warfarin and Venous-Thrombosis

Ovarian vein thrombosis (OVT) often presents in the post-partum period and is associated with significant complications including inferior vena cava extension, pulmonary embolism, sepsis, and renal obstruction. Idiopathic OVT is rare, and no consensus has been agreed upon regarding its diagnosis and management. This case presents a patient who was diagnosed with idiopathic OVT and was treated with apixaban. A literature review was performed collating reported cases of idiopathic OVT to form a recommendation regarding optimal management and follow up.. A 42-year-old Chinese woman presenting with right lower quadrant pain underwent a CT abdomen after urinary tract obstruction was excluded on ultrasound. She was subsequently diagnosed with an idiopathic 35 mm ovarian vein thrombus (OVT) given no history of primary coagulopathy nor secondary aetiology. A literature review was performed collating 18 case reports with method of diagnosis and management summarized. Treatment alternatives included low molecular weight heparin, warfarin, rivaroxaban and apixaban. Most were diagnosed after work up for suspected renal calculus or appendicitis. Follow up imaging was performed from between 6 weeks to 6 months after initiation of anticoagulation.. Direct oral anticoagulants were an effective treatment for OVT, however warfarin should be commenced in those suspected of antiphospholipid syndrome awaiting confirmation or exclusion of the diagnosis.

Topics: Adult; Anticoagulants; Female; Humans; Ovary; Thrombosis; Venous Thrombosis; Warfarin

The aim of this study was to evaluate the efficacy and safety of the anticoagulants for the prevention of portal vein system thrombosis (PVST) in patients with cirrhosis after splenectomy and explore the optimal time of anticoagulant administration.. A systematic literature search was performed using PubMed, Embase and China Biology Medicine disc (CBM)databases, so as to screen out studies comparing the prognoses between cirrhotic post-splenectomy patients treated with and without anticoagulants. The parameters that were analyzed included the incidence of PVST and postoperative bleeding.. With a total of 592 subjects, we included 8 studies (6 observational and 2 randomized trials) that fulfilled the inclusion criteria. We found that the incidence of PVST was significantly lower in the anticoagulation group during the first 6 months of anticoagulant administration. And the largest difference in the incidence of PVST between the anticoagulation and control groups was observed at 3 months (odds ratio 0.17(0.11~0.27); P = 0.767; I2 = 0.0%) and 6 months (OR = 0.21(0.11~0.40); P = 0.714; I2 = 0.0%) postoperatively. The incidence of bleeding was not significantly higher in the anticoagulation group (odds ratio 0.71 (0.30~1.71); P = 0.580; I2 = 0.0%).. Low-molecular weight heparin (LMWH) and warfarin can decrease the incidence of PVST in post-splenectomy cirrhotic patients without an increased risk of bleeding. And the optimal use time of warfarin is 6 months after splenectomy.

Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Liver Cirrhosis; Portal Vein; Postoperative Complications; Splenectomy; Venous Thrombosis; Warfarin

Advancing age is a risk factor for developing non-valvular atrial fibrillation (NVAF) or acute venous thromboembolism (VTE). We assessed the comparative effectiveness, safety, costs, and healthcare utilization associated with rivaroxaban versus warfarin in patients of advanced age managed in the United States (US).. We conducted a systematic review of Medline and Embase through April 2023 to identify real-world evidence (RWE) studies of older adults (at least 65+ years of age) with either NVAF or VTE who received either rivaroxaban or warfarin in the US and reported an outcome of stroke or systemic embolism (SSE), ischemic stroke (IS), recurrent VTE, major bleeding, intracranial hemorrhage, costs, or healthcare resource utilization. We classified each outcome of interest per study as "positive" (lower risk), "negative" (higher risk), or "neutral" based upon the summary effect size of rivaroxaban versus warfarin.. Twenty-nine RWE studies met inclusion criteria, mostly (83%) in NVAF populations. For SSE with rivaroxaban versus warfarin, 68.8% of studies showed positive effects and 31.2% showed neutral outcome. For major bleeding, 57.7% showed neutral effects, 38.5% showed negative effects, and 3.8% of studies showed positive effects with rivaroxaban versus warfarin. Of the two studies reporting cost data, both were positive, showing lower costs for SSE for rivaroxaban versus warfarin and neutral cost for major bleeding costs.. This systematic review supports findings from subgroup analyses of randomized controlled trials that, compared with warfarin, rivaroxaban is associated with generally neutral or positive effects on thrombosis and a mixed picture on bleeding outcomes in older adults with either NVAF or VTE treated in the United States.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Embolism; Hemorrhage; Humans; Retrospective Studies; Rivaroxaban; Stroke; United States; Venous Thromboembolism; Venous Thrombosis; Warfarin

Management of cerebral venous thrombosis (CVT) involves minimizing expansion of the thrombus and promoting the recanalization of the venous sinus. While current guidelines include indications of endovascular management and anticoagulation with heparin and warfarin, the use of direct-acting oral anticoagulants (DOACs) has increased. In this study, we aim to conduct a network meta-analysis comparing these 3 therapeutic options: standard anticoagulation, DOACs, and endovascular treatments (EVTs).. Seventeen of 2265 studies identified from 4 publication databases met inclusion criteria for this network meta-analysis. Outcomes analyzed included modified Rankin Scale score, complications, mortality, and 6-month recanalization rates using a frequentist network meta-analysis approach. For each outcome, the preferential order of each intervention was ranked hierarchically based on P-score calculations used for frequentist network meta-analyses.. Modified Rankin Scale outcomes were not significantly different based on the type of treatment modality (i.e., standard anticoagulation, DOACs, or EVT). Evaluation of complications demonstrated that patients treated with EVT were significantly more likely to experience a worse outcome than individuals treated with standard anticoagulation (odds ratio [OR] = 1.83, P = 0.04). Other comparisons did not demonstrate a significant difference in adverse events. For all-cause mortality outcomes, EVT demonstrated significantly greater odds of mortality than standard anticoagulation (OR = 1.89, P = 0.02). Mortality between DOACs and standard anticoagulation was not significantly different. When comparing 6-month recanalization rates, DOACs and EVT were significantly more effective than standard anticoagulation (OR = 1.93, OR = 2.2, P < 0.05). EVT followed by DOACs was preferred over standard anticoagulation for 6-month recanalization rates.. This network meta-analysis evaluates the outcomes in CVT treatment, comparing standard anticoagulation, DOACs, and EVT, with evidence that DOACs have similar outcomes to standard anticoagulation in the treatment of CVT. EVT resulted in an increased risk of overall mortality but improved 6-month recanalization rates.

Topics: Administration, Oral; Anticoagulants; Factor Xa Inhibitors; Heparin; Humans; Intracranial Thrombosis; Network Meta-Analysis; Venous Thrombosis; Warfarin

High level evidence for direct oral anticoagulants (DOACs) in patients with cerebral venous thrombosis is lacking. We performed a systematic review and meta-analysis to assess the efficacy and safety of DOACs versus vitamin K antagonists in patients with cerebral venous thrombosis.. This systematic review was registered in PROSPERO (CRD42021228800). We searched MEDLINE (via Ovid), EMBASE, CINAHL, and the Web of Science Core Collection between January 1, 2007 and Feb 22, 2022. Search terms included a combination of keywords and controlled vocabulary terms for cerebral venous thrombosis, vitamin K antagonists/warfarin, and DOACs. We included both randomized and nonrandomized studies that compared vitamin K antagonists and DOACs in 5 or more patients with cerebral venous thrombosis. Where studies were sufficiently similar, we performed meta-analyses for efficacy (recurrent venous thromboembolism and complete recanalization) and safety (major hemorrhage) outcomes, using relative risks (RRs).. This systematic review and meta-analysis suggest that in patients with cerebral venous thrombosis, DOACs, and warfarin may have comparable efficacy and safety. Given the limitations of the studies included (low number of randomized controlled trials, modest total sample size, rare outcome events), our findings should be interpreted with caution pending confirmation by ongoing randomized controlled trials and large, prospective, observational studies.

Topics: Administration, Oral; Anticoagulants; Fibrinolytic Agents; Hemorrhage; Humans; Intracranial Thrombosis; Prospective Studies; Venous Thromboembolism; Venous Thrombosis; Vitamin K; Warfarin

Infection following arthroplasty can have devastating effects for the patient and necessitate further surgery. Venous thromboembolism (VTE) prophylaxis is required to minimize the risk of deep venous thrombosis and pulmonary embolism. Anticoagulation has been demonstrated to interfere with wound-healing and increase the risk of infection. We hypothesized that different anticoagulation regimes will have differing effects on rates of periprosthetic joint infection. The aim of this study was to compare the surgical site infection risk between the use of warfarin, low-molecular-weight heparin (LMWH), and aspirin for VTE prophylaxis following total knee or hip arthroplasty.. A systematic literature search was conducted in November 2018 using the PubMed, CINAHL, and Cochrane Central Register of Controlled Trials (CENTRAL) databases to identify studies that compared warfarin, LMWH, and/or aspirin with regard to surgical site infection rates following hip or knee arthroplasty. Meta-analyses were performed to compare the infection and VTE risks between groups.. Nine articles involving 184,037 patients met the inclusion criteria. Meta-analysis showed that warfarin prophylaxis was associated with a higher risk of deep infection (or infection requiring reoperation) (odds ratio [OR] = 1.929, 95% confidence interval [CI] = 1.197 to 3.109, p = 0.007) and surgical site infection overall (OR = 1.610, 95% CI = 1.028 to 2.522, p = 0.038) compared with aspirin in primary total joint arthroplasty, with similar findings also seen when primary and revision procedures were combined. There was no significant difference in infection risk between warfarin and LMWH and between LMWH and aspirin. There was a nonsignificant trend for VTE risk to be higher with warfarin compared with aspirin therapy for primary procedures (OR = 1.600, 95% CI = 0.875 to 2.926, p = 0.127), and this was significant when both primary and revision cases were included (OR = 2.674, 95% CI = 1.143 to 6.255, p = 0.023).. These findings caution against the use of warfarin for VTE prophylaxis for hip and knee arthroplasty. Further randomized head-to-head trials and mechanistic studies are warranted to determine how specific anticoagulants impact infection risk.. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Heparin, Low-Molecular-Weight; Humans; Surgical Wound Infection; Venous Thrombosis; Warfarin

This article aims to review the latest literature on prophylactic and therapeutic anticoagulation and the safety profile of anticoagulants in patients with cirrhosis.. The understanding of hematological hemostasis is cirrhotic patients has changed drastically in recent years. Although in the past, cirrhotic patients were often considered to be 'auto-anticoagulated' and at higher risk of bleeding, recent studies have demonstrated that there may be a rebalance in procoagulation and anticoagulation factors in patients with cirrhosis. This, and clinical experience, suggest that cirrhotic patients are at risk of development of venous thrombosis, pulmonary embolism and ischemic strokes and as such, the best management approaches in these patients remains controversial. The bulk of the data suggest that patients with cirrhosis who are at risk for thrombotic or embolic complications should be anticoagulated. However, it is imperative that they be closely monitored.. The medical literature on anticoagulation in patients with liver cirrhosis is conflicting and limited to small sample observational studies. However, most studies suggest that in patients with early stages of liver cirrhosis and no history of varices, anticoagulation appears to be well tolerated.

Topics: Anticoagulants; Atrial Fibrillation; Blood Coagulation Disorders; Blood Coagulation Factors; Comorbidity; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Liver Cirrhosis; Partial Thromboplastin Time; Portal Vein; Prothrombin Time; Pulmonary Embolism; Stroke; Thrombosis; Venous Thrombosis; Warfarin

Venous thromboembolism (VTE) is a common problem in cancer patients and the incidence is increasing, especially for patients with lung cancer. Common features of these patients, like advanced stage, male gender, old age and chemotherapy, are risk factors of VTE. Here we reported a case in which the patient with lung cancer developed deep vein thrombosis (DVT) when receiving chemotherapy.. A 53-year-old male who was diagnosed with lung cancer with multiple metastasis developed severe DVT during chemotherapy. Despite the use of aspirin, warfarin and low molecular weight heparin (LMWH) for anticoagulant and thrombolytic therapy, the condition was still deteriorating, resulting in amputation finally.. It's rare that the conditions of cancer patients who develop venous thromboembolism (VTE) keep deteriorating despite the administration of aspirin, warfarin and low weight molecular heparin. Both early diagnosis and prophylactic use of anticoagulants are suggested for cancer patients to improve the prognosis.

Topics: Amputation, Surgical; Anticoagulants; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Humans; Lung Neoplasms; Male; Middle Aged; Paclitaxel; Treatment Failure; Venous Thrombosis; Warfarin

Extended treatment is preconized in a significant proportion of patients with unprovoked venous thromboembolism (VTE). However, limited direct/indirect comparisons are available to appropriately weight the benefit/risk ratio of the diverse treatments available. We aimed to compare the rate of symptomatic recurrent VTE and major bleeding (MB), the net clinical benefit (VTE+MB) and death on vitamin-K antagonist (VKA), direct oral anticoagulants (DOAC) and antiplatelet drugs for extended anticoagulation.. A systematic literature search through September 2018 identified randomized trials studying these pharmacologic therapies for extended anticoagulation following VTE. Treatment effects were calculated using network meta-analysis with frequentist fixed-effects model.. 18 trials (18,221 patients) were included in the analysis. All treatments reduced the risk of recurrence compared to placebo/observation. Nonetheless, VKA (RR 0.22; 95%CI 0.13-0.39) and DOAC (RRs ranging from 0.25-0.32; 95%CI ranging from 0.13-0.52) were more effective than aspirin, whereas low-dose VKA was less effective than standard-dose VKA (RR 2.47; 95%CI 1.34-4.55). The efficacy of DOAC was globally comparable to standard-adjusted dose VKA. Low- (RR 3.13; 95%CI 1.37-7.16) and standard-dose (RR 3.23; 95%CI 1.16-8.99) VKA also increased the risk of MB, which was not the case for any DOAC. Low-dose VKA and low-dose DOAC had similar effects on MB compared to standard-doses. Although there was a trend for reduced MB and enhanced net clinical benefit for DOAC compared to VKA, this was not statistically significant. The specific anticoagulant therapies had no significant effects on deaths.. Standard-dose VKA and low/standard-dose DOAC share similar effects on VTE recurrence and MB, whereas aspirin and low-dose VKA were associated with lower benefit/risk ratio.

Topics: Administration, Oral; Anticoagulants; Aspirin; Blood Coagulation; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Network Meta-Analysis; Platelet Aggregation Inhibitors; Secondary Prevention; Venous Thromboembolism; Venous Thrombosis; Vitamin K; Warfarin

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hospitalization; Humans; Medication Adherence; Pulmonary Embolism; Venous Thrombosis; Warfarin

Portal vein thrombosis (PVT) is caused by several conditions including infection, malignancies, surgery, medications, and coagulation disorders. However, PVT caused by low-energy injury is very rare. A 51-year-old man visited a clinic with a 2-day history of abdominal pain following blunt abdominal trauma. Contrast-enhanced computed tomography (CT) revealed thrombosis in both the portal vein and splenic vein, and he was transferred to our hospital with a diagnosis of PVT. Anticoagulant therapy was initiated using unfractionated heparin. A repeat CT scan revealed enlargement of the thrombus, which occluded the main trunk and first right branch of the portal vein. Laboratory data before heparin administration suggested low protein C activity. Anticoagulation therapy was continued with intermittent assessment of the size of the thrombus and degree of coagulation. On day 23, enhanced CT showed marked shrinkage of the thrombus compared with that on day 8. On day 30, the patient was discharged with a therapeutic prothrombin time-international normalized ratio. Here we present a case of PVT caused by low-energy trauma of the upper abdomen in a patient with a background of low protein C activity that was successfully treated without invasive surgery.

Topics: Abdominal Injuries; Anticoagulants; Drug Therapy, Combination; Heparin; Humans; Male; Middle Aged; Portal Vein; Protein C Deficiency; Venous Thrombosis; Warfarin; Wounds, Nonpenetrating

The traditional treatment of venous thromboembolism (VTE) with heparin and warfarin has numerous limitations. New oral anticoagulants represent the promising alternative with the potential to overcome the limitations of traditional treatment.. Apixaban is an oral factor Xa inhibitor with a rapid onset of action and predictable pharmacokinetics that allows a fixed dose regimen. With this characteristic apixaban overcomes many limitations and simplifies treatment of VTE eliminating the need for initial parenteral anticoagulant therapy and laboratory monitoring.. Fixed-dose regimen of oral apixaban alone is as effective as conventional treatment regimen and is associated with a clinically relevant reduction of major bleeding. Extended anticoagulation with apixaban with either a treatment dose (5 mg twice daily) or thromboprophylactic dose (2.5 mg twice daily) reduces the risk of recurrent venous thromboembolism without increase in the rate of major bleeding.. Therefore, apixaban provides a simple, effective and safe alternative to conventional acute or long-term treatment of VTE.

Topics: Administration, Oral; Anticoagulants; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Hemorrhage; Heparin; Humans; Pulmonary Embolism; Pyrazoles; Pyridones; Venous Thromboembolism; Venous Thrombosis; Warfarin

The optimal strategy for postoperative deep venous thrombosis prophylaxis remains controversial in hip and knee arthroplasty. Warfarin causes transient hypercoagulability; however, the optimal timing of treatment remains unclear. We evaluated the effects of preoperative versus postoperative warfarin therapy with a primary endpoint of perioperative change in hemoglobin. Warfarin was dosed according to a standard nomogram. No difference in perioperative hemoglobin change was observed. The preoperative group demonstrated higher INRs. Initiation of warfarin preoperatively was not associated with any difference in perioperative hemoglobin change. Larger studies are needed to determine whether the risk of adverse events is increased with either strategy.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Humans; Postoperative Care; Preoperative Care; Venous Thrombosis; Warfarin

Venous thromboembolism (VTE) is a common condition in hospital patients. Considerable controversy is ongoing regarding optimal initial warfarin dosing for patients with acute deep venous thrombosis (DVT) and pulmonary embolism (PE). Achieving a therapeutic international normalized ratio (INR) with warfarin as soon as possible is important because this minimizes the duration of parenteral medication necessary to attain immediate anticoagulation, and it potentially decreases the cost and inconvenience of treatment. Although a 5-mg loading-dose nomogram tends to prevent excessive anticoagulation, a 10-mg loading-dose nomogram may achieve a therapeutic INR more quickly. This is an update of a review first published in 2013.. To evaluate the efficacy of a 10-mg warfarin nomogram compared with a 5-mg warfarin nomogram among patients with VTE.. For this update the Cochrane Vascular Trials Search Co-ordinator searched the Specialised Register (last searched September 2015) and the Cochrane Register of Studies (CENTRAL (2015, Issue 8). Clinical trials databases were also searched. The review authors searched PubMed (last searched 11 June 2015) and LILACS (last searched 11 June 2015). In addition, the review authors contacted pharmaceutical companies.. Randomized controlled studies comparing warfarin initiation nomograms of 10 and 5 mg in patients with VTE.. Two review authors independently assessed trial quality and extracted data. The review authors contacted study authors for additional information.. Four trials involving 494 participants were included. Three studies involving 383 participants provided data on the proportion of participants who had achieved a therapeutic INR by day five. Significant benefit of a 10-mg warfarin nomogram was observed (risk ratio (RR) 1.27, 95% confidence interval (CI) 1.05 to 1.54; moderate quality evidence), although with substantial heterogeneity (I(2) = 90%). The review authors analyzed each study separately because it was not possible to perform a subgroup analysis by inpatient or outpatient status. One study showed significant benefit of a 10-mg warfarin nomogram for the proportion of outpatients with VTE who had achieved a therapeutic INR by day five (RR 1.78, 95% CI 1.41 to 2.25), with the number needed to treat for an additional beneficial outcome (NNTB = 3, 95% CI 2 to 4); another study showed significant benefit of a 5-mg warfarin nomogram in outpatients with VTE (RR 0.58, 95% CI 0.36 to 0.93) with NNTB = 5 (95% CI 3 to 28); a third study, consisting of both inpatients and outpatients, showed no difference (RR 1.08, 95% CI 0.65 to 1.80).No difference was observed in recurrent venous thromboembolism at 90 days when the warfarin nomogram of 10 mg was compared with the warfarin nomogram of 5 mg (RR 1.48, 95% CI 0.39 to 5.56; 3 studies, 362 participants, low quality evidence); no difference was observed in major bleeding at 14 to 90 days (RR 0.97, 95% CI 0.27 to 3.51; 4 studies, 494 participants, moderate quality evidence). No difference was observed in minor bleeding at 14 to 90 days (RR 0.52, 95% CI 0.15 to 1.83; 2 studies, 243 participants, very low quality evidence) or in length of hospital stay (mean difference (MD) -2.3 days, 95% CI -7.96 to 3.36; 1 study, 111 participants, low quality evidence).. In patients with acute thromboembolism (DVT or PE) aged 18 years or older, considerable uncertainty surrounds the use of a 10-mg or a 5-mg loading dose for initiation of warfarin to achieve an INR of 2.0 to 3.0 on the fifth day of therapy. Heterogeneity among analyzed studies, mainly caused by differences in types of study participants and length of follow-up, limits certainty surrounding optimal warfarin initiation nomograms.

Topics: Adult; Anticoagulants; Humans; International Normalized Ratio; Nomograms; Pulmonary Embolism; Time Factors; Venous Thromboembolism; Venous Thrombosis; Warfarin

To review current literature for anticoagulation in patients with cirrhosis and provide a summary of the effects of cirrhosis on the coagulation cascade, therapeutic monitoring through interpretation of antifactor Xa (anti-Xa), activated partial thromboplastin time (aPTT), and international normalized ratio (INR) as well as current prophylaxis and treatment recommendations in cirrhotic patients.. A systematic electronic literature search was conducted in PubMed using the key termsanticoagulation, warfarin, low-molecular-weight heparin(LMWH),unfractionated heparin(UFH),target-specific oral anticoagulants, deep-vein thrombosis(DVT),pulmonary embolism(PE),portal vein thrombosis(PVT),venous thromboembolism, anti-Xa, activated partial thromboplastin time, anticoagulation therapeutic monitoring, coagulopathy, coagulation cascade, chronic liver disease, cirrhosis, anddecompensated liver disease. Studies written in the English language from January 2000 to December 2015 were considered for this review article. All search results were reviewed, and the relevance of each article was determined by authors independently.. Patients with cirrhosis are at higher risk for both bleeding and thrombosis-related complications. Cirrhosis affects production of both procoagulant and anticoagulant factors, thus resulting in increased INR and aPTT levels and decreased anti-Xa levels. LMWH is the treatment of choice for the prevention and treatment of DVT/PE/PVT in patients with cirrhosis, and monitoring with anti-Xa levels for dose adjustment is not recommended. UFH is an alternative in cirrhotic patients for shorter-term use and in cases of severe renal dysfunction and/or hemodynamic instability. Cirrhotic patients on anticoagulation therapy should be monitored closely for signs and symptoms of bleeding and thrombosis.

Topics: Anticoagulants; Hemorrhage; Heparin; Humans; International Normalized Ratio; Liver Cirrhosis; Partial Thromboplastin Time; Pulmonary Embolism; Venous Thromboembolism; Venous Thrombosis; Warfarin

Venous thromboembolism (VTE) is a common condition with potentially serious and life-threatening consequences. The standard method of thromboprophylaxis uses an anticoagulant such as low molecular weight heparin (LMWH) or warfarin. In recent years, another type of anticoagulant, pentasaccharide, an indirect factor Xa inhibitor, has shown good anticoagulative effect in clinical trials. Three types of pentasaccharides are available: short-acting fondaparinux, long-acting idraparinux and idrabiotaparinux. Pentasaccharides cause little heparin-induced thrombocytopenia and are better tolerated than unfractionated heparin, LMWH and warfarin. However, no consensus has been reached on whether pentasaccharides are superior or inferior to other anticoagulative methods.. To assess effects of pentasaccharides versus other methods of thromboembolic prevention (thromboprophylaxis) in people who require anticoagulant treatment to prevent venous thromboembolism.. The Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (last searched March 2016) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 2). The CIS searched trial databases for details of ongoing and unpublished studies. Review authors searched LILACS (Latin American and Caribbean Health Sciences) and the reference lists of relevant studies and reviews identified by electronic searches.. We included randomised controlled trials on any type of pentasaccharide versus other anticoagulation methods (pharmaceutical or mechanical) for VTE prevention.. Two review authors independently selected trials, assessed methodological quality and extracted data in predesigned tables.. We included in this review 25 studies with a total of 21,004 participants. All investigated fondaparinux for VTE prevention; none investigated idraparinux or idrabiotaparinux. Studies included participants undergoing abdominal surgery, thoracic surgery, bariatric surgery or coronary bypass surgery; acutely ill hospitalised medical patients; people requiring rigid or semirigid immobilisation; and those with superficial venous thrombosis. Most studies focused on orthopaedic patients. We lowered the quality of the evidence because of heterogeneity between studies and a small number of events causing imprecision.When comparing fondaparinux with placebo, we found less total VTE (risk ratio (RR) 0.24, 95% confidence interval (CI) 0.15 to 0.38; 5717 participants; 8 studies; I. Moderate to high quality evidence shows that fondaparinux is effective for short-term prevention of VTE when compared with placebo. It can reduce total VTE, DVT, total PE and symptomatic VTE, and does not demonstrate a reduction in deaths compared with placebo. Low to moderate quality evidence shows that fondaparinux is more effective for short-term VTE prevention when compared with LMWH. It can reduce total VTE and total DVT and does not demonstrate a reduction in deaths when compared with LMWH. However, at the same time, moderate to high quality evidence shows that fondaparinux increases major bleeding when compared with placebo and LMWH. Therefore, when fondaparinux is chosen for the prevention of VTE, attention should be paid to the person's bleeding and thrombosis risks. Most data were derived from patients undergoing orthopaedic surgery. Therefore, the conclusion predominantly pertains to these patients. Data on fondaparinux for other clinical conditions are sparse.

Topics: Anticoagulants; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Randomized Controlled Trials as Topic; Venous Thromboembolism; Venous Thrombosis; Warfarin

As a class, the target-specific oral anticoagulants (TSOACs) are at least as effective as warfarin, often with superior safety for the prevention of stroke in patients with nonvalvular atrial fibrillation (AF) and the treatment of acute venous thromboembolism (VTE) and prevention of recurrent VTE. Currently, dabigatran, the direct thrombin inhibitor, along with rivaroxaban and apixaban, direct factor Xa inhibitors, has been approved in multiple countries for these indications. Edoxaban, which has received approval for the abovementioned indications in Japan, has demonstrated efficacy and safety comparable to or better than warfarin in Phase III clinical trials and is under further regulatory consideration. It is anticipated that the use of TSOACs will increase as practitioners and healthcare systems gain familiarity with these drugs and adopt their use into clinical practice. This review will provide a brief overview of the TSOAC Phase III clinical trials for prevention of stroke and systemic embolic events in patients with AF and the Phase III clinical trials for the prevention of recurrent VTE, discuss current treatment guidelines, address how TSOACs may help meet national safety goals, and provide clinical decision-making guidance regarding the use of TSOACs for hospitalists.

Topics: Anticoagulants; Antithrombins; Atrial Fibrillation; Clinical Trials, Phase III as Topic; Dabigatran; Factor Xa Inhibitors; Hospitalists; Humans; International Normalized Ratio; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Venous Thrombosis; Warfarin

Although the current therapeutic armamentarium of venous thrombosis encompasses the use of vitamin K antagonists, heparins, and direct oral anticoagulants, these drugs have several important drawbacks. Antisense oligonucleotides are relatively short single-stranded nucleic acid sequences, which hybridize with a target messenger RNA (mRNA) and suppress protein synthesis. Coagulation factor XI is a key player in blood coagulation, and thus represents a potential target for antisense therapy. The available evidence reviewed in this article suggests that factor XI antisense oligonucleotides may be more effective than conventional anticoagulants in preventing the onset and propagation of thrombosis, do not require factor measurement since the reduction of mRNA synthesis appears dose-dependently, robustly, and stably decreased for 3 to 5 weeks after the end of administration, with an incidence of major bleeding that is at least not greater than that associated with warfarin or low-molecular-weight heparin therapy. Despite conceptual simplicity, rational design, and relatively inexpensive cost, the preliminary findings in animal models and in patients undergoing knee surgery need to be validated in other prospective trials and cost-effective analyses before this attractive treatment option can be advocated as a new paradigm in prevention and treatment of venous thrombosis.

Topics: Animals; Clinical Trials as Topic; Disease Models, Animal; Factor XI; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Oligodeoxyribonucleotides, Antisense; RNA, Messenger; Venous Thrombosis; Warfarin

Venous thromboembolism (VTE), manifesting as either deep vein thrombosis or pulmonary embolism, is common worldwide including in Japan. The number of patients clinically diagnosed with VTE is increasing with the majority of cases occurring out-of-hospital and of milder severity. Cancer is the largest risk factor for VTE and VTE in cancer patients confers an increased 1-year mortality rate. However, the majority of VTE cases are considered "idiopathic" or "unprovoked." The limited efficacies of unfractionated heparin and warfarin have stimulated the development of new anticoagulant therapies. Recently, parenteral and oral administration of the Xa inhibitors fondaparinux and edoxaban, respectively, was approved in Japan. These agents have the potential to provide safer and more efficacious treatment options for VTE. Although further randomized studies are required to validate the utility of these agents, they are expected to substantially improve quality of life in VTE patients. This review summarizes the current status of VTE management in Japan focusing on current epidemiology and recent advances in anticoagulant therapy.

Topics: Anticoagulants; Fondaparinux; Heparin; Humans; Japan; Polysaccharides; Pulmonary Embolism; Pyridines; Quality of Life; Risk Factors; Thiazoles; Venous Thromboembolism; Venous Thrombosis; Warfarin

Recent studies have greatly expanded our understanding of the coagulopathy of cirrhosis. It is clear that cirrhosis patients are at a risk of both bleeding and thrombosis. While prediction of these events remains challenging, cirrhosis patients are not protected from the development of venous and arterial thrombosis. In fact, studies show that hypercoagulability may promote hepatic decompensation and development of fibrosis. Anticoagulation for thrombosis is now becoming a common prospect in many clinical situations. Our understanding of the efficacy and safety of commonly used therapeutics is only beginning to emerge and the risks and benefits remain unclear in this unique population. In this review, we discuss the role of anticoagulation in the treatment and prevention peripheral and splanchnic thrombosis in patients with cirrhosis, as well as examine the potential role of anticoagulants in altering the progression of chronic liver disease.

Topics: Anticoagulants; Blood Coagulation Disorders; Heparin; Humans; Liver Cirrhosis; Venous Thrombosis; Warfarin

The risk of recurrent thromboembolic disorders in the 10-year period following an episode of unprovoked venous thromboembolism (VTE) ranges between 30 and 50%, the rate being higher in patients with primary deep venous thrombosis (DVT) than in those with primary pulmonary embolism (PE). The clinical presentation with primary PE increases by more than three times the risk of a new PE episode over that with isolated DVT. Baseline parameters that increase this risk are the proximal location of DVT, obesity, old age and male sex, whereas the role of thrombophilia is controversial. An increasing role is played by post-baseline parameters such as the ultrasound assessment of residual vein thrombosis and the determination of D-dimer. While the latest international guidelines suggest indefinite anticoagulation for most patients with the first episode of unprovoked VTE, new scenarios are being offered by the identification of risk stratification models and by strategies that have the potential to help identify patients in whom anticoagulation can be safely discontinued, such as those that incorporate the assessment of D-dimer and residual vein thrombosis. New opportunities are being offered by low-dose aspirin, which has recently been reported to decrease by more than 30% the risk of recurrent events without increasing the bleeding risk; and especially by a few emerging anti-Xa and anti-IIa oral compounds, which are likely to induce fewer haemorrhagic complications than vitamin K antagonists while preserving at least the same effectiveness, do not require laboratory monitoring, and can be used immediately after the thrombotic episode.

Topics: Age Factors; Anticoagulants; Aspirin; Benzimidazoles; beta-Alanine; Dabigatran; Disease Management; Female; Fibrin Fibrinogen Degradation Products; Fibrinolytic Agents; Fondaparinux; Humans; Male; Morpholines; Obesity; Polysaccharides; Postthrombotic Syndrome; Pulmonary Embolism; Risk Assessment; Risk Factors; Rivaroxaban; Secondary Prevention; Sex Factors; Thiophenes; Thrombophilia; Ultrasonography; Venous Thromboembolism; Venous Thrombosis; Warfarin

Topics: Adult; Aged; Anticoagulants; Atrial Fibrillation; Female; Humans; Male; Stroke; Venous Thrombosis; Warfarin

Vitamin K antagonists (VKAs) remain the standard therapy for anticoagulation in prevention and treatment of venous thromboembolism (VTE) and for the prevention of stroke in atrial fibrillation (AF). Due to numerous limitations of VKAs, target-specific oral anticoagulants have been developed. Edoxaban is a direct activated factor X inhibitor with attractive features among which are once daily dosing, no need for routine monitoring, and minimal drug-drug interactions. In patients undergoing orthopedic surgery, edoxaban was superior to enoxaparin in preventing VTE. Furthermore, a recent large-scale phase III trial in patients with symptomatic VTE demonstrated that edoxaban was noninferior to warfarin in preventing recurrent VTE and reduced bleeding. In the largest trial of anticoagulation in patients with AF to date, edoxaban was noninferior to warfarin in the prevention of stroke or systemic embolism and reduced bleeding and cardiovascular mortality. This review provides an overview of the pharmacology, clinical trial results, and potential indications for edoxaban.

Topics: Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Factor Xa Inhibitors; Hemorrhage; Humans; Pyridines; Randomized Controlled Trials as Topic; Thiazoles; Treatment Outcome; Venous Thrombosis; Warfarin

Portal vein thrombosis is an unusual condition and its association with an acute cytomegalovirus (CMV) infection is known but rarely reported. We present here the case of a 24-year-old woman suffering from a symptomatic portal vein thrombosis, confirmed by CT angiography, and acute CMV-related hepatitis. Besides a second generation oral contraceptive with estrogen and progesterone, not associated with smoking, the acute CMV infection was the only cause found to have provoked the venous thrombosis; a myeloproliferative disorder or biological thrombophilia were ruled out. The patient rapidly recovered with vitamin K antagonists (VKA) anticoagulant treatment. Eighteen cases of splanchnic vein thrombosis complicating acute CMV infection were found in the literature. All patients had acute hepatitis. The outcome was usually favorable with warfarin therapy for a period lasting 3 to 7 months. Antiviral treatment (anti-CMV) was used in three cases of severe infection. The antiviral therapy was given only in immunosuppressed patients. For immunocompetent patients, CMV infection is usually asymptomatic and clinical signs are often non-specific and mild, not requiring treatment.. This case report and the review of the literature recall the need to search for acute CMV infection in patients with portal thrombosis so a possible transient trigger for venous thromboembolism can be identified, avoiding extended anticoagulation.

Topics: Acute Disease; Anticoagulants; Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Cytomegalovirus Infections; Ethinyl Estradiol; Female; Heparin, Low-Molecular-Weight; Hepatitis, Viral, Human; Humans; Levonorgestrel; Portal Vein; Venous Thrombosis; Warfarin; Young Adult

Perioperative pulmonary thromboembolism (PTE) occurred in 2.93 per 10,000 cases and mortality of PTE was 14% in Japan according to the surveillance of Japanese Society of Anesthesiologists from 2009 to 2011. Anesthesiologists have to evaluate perioperative venous thromboembolism (VTE) risk carefully and take adequate measures to prevent PTE. The first step is the assessment of the preoperative probability of VTE and the next step is the assessment of the risk for VTE during and after operation. If a patient has moderate probability of VTE preoperatively, diagnostic procedures are recommended. If the d-dimer is positive, whole-leg ultrasound is recommended. If DVT is positive in proximal vein, further investigation or anticoagulant therapy are considered. Primary preventions of VTE during and after surgeries are as follows. In patients with low or moderate risks for VTE, intermittent pneumatic compression is recommended. In patients with high risks for VTE, pharmacologic prophylaxes are recommended. In recent years newly developed anticoagulants can be available other than low-dose unfractionated heparin. However, the incidence of VTE in Japanese populations is different from western countries. Moreover our own evidence has not fully been accumulated yet. Therefore further investigations for prevention of perioperative VTE in Japan are expected for our own new guidelines.

Topics: Anesthesia, Epidural; Anticoagulants; Biomarkers; Diagnostic Imaging; Fibrin Fibrinogen Degradation Products; Heparin; Humans; Intraoperative Complications; Perioperative Care; Postoperative Complications; Practice Guidelines as Topic; Pulmonary Embolism; Pyridines; Risk Factors; Thiazoles; Venous Thromboembolism; Venous Thrombosis; Warfarin

In the past, unfractionated heparin and warfarin have been used as anticoagulants for treatment of venous thromboembolism in Japan. Although it has been effective anticoagulants, these uses are accompanied by several pitfalls, which have led to research and the discovery of new additional groups of anticoagulants: parenteral factor Xa inhibitors, such as fondaparinux, and oral direct factor Xa inhibitors, such as rivaroxaban, apixaban and edoxaban. These new anticoagulants are fast-acting, noninferior to heparin and warfarin in preventing recurrence of venous thromboembolism, and do not require monitoring. These new anticoagulants show promise for improvement of long-term outcome for venous thromboembolism.

Topics: Anticoagulants; Heparin; Humans; Japan; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis; Warfarin

The severity of side effects that may occur with vitamin K antagonists due to their narrow therapeutic window requires great attention in finding out the most appropriate dose for these drugs. Pharmacogenetic research has now considerably helped clarifying the relationships between genetic variants and sensitivity to such therapy, paving the ground to predictive algorithms that include clinical and genetic variables to establish the best doses to start and maintain an adequate anticoagulation. Pharmacogenetic algorithms indeed aim at identifying tailored regimens, reducing adverse drug reactions and subsequent hospitalizations, optimizing therapeutic efficacy and containing costs. Here we describe the results so far achieved in pharmacogenetic research with vitamin K antagonists, analyzing studies that have assessed the usefulness of such algorithms.

Topics: Algorithms; Anticoagulants; Biomarkers; Clinical Trials as Topic; Cytochrome P-450 CYP2C9; Dose-Response Relationship, Drug; Humans; Pharmacogenetics; Polymorphism, Single Nucleotide; Randomized Controlled Trials as Topic; Thromboembolism; Venous Thrombosis; Vitamin K; Vitamin K Epoxide Reductases; Warfarin

Hypercoagulable states (HS) are inherited or acquired conditions that predispose an individual to venous and/or arterial thrombosis. The dermatologist can play a vital role in diagnosing a patient's HS by recognizing the associated cutaneous manifestations, such as purpura, purpura fulminans, livedo reticularis, livedo vasculopathy (atrophie blanche), anetoderma, chronic venous ulcers, and superficial venous thrombosis. The cutaneous manifestations of HS are generally nonspecific, but identification of an abnormal finding can warrant a further workup for an underlying thrombophilic disorder. This review will focus on the basic science of hemostasis, the evaluation of HS, the skin manifestations associated with hypercoagulability, and the use of antiplatelet and anticoagulant therapy in dermatology.

Topics: Anetoderma; Anticoagulants; Antiphospholipid Syndrome; Calciphylaxis; Hemostasis; Heparin; Humans; Livedo Reticularis; Necrosis; Platelet Aggregation Inhibitors; Purpura; Skin; Skin Diseases; Thrombophilia; Varicose Ulcer; Venous Thrombosis; Warfarin

In patients with deep venous thrombosis or pulmonary embolism, initial treatment with low-molecular-weight heparin (LMWH) is primarily aimed at preventing thrombus extension. After this initial phase, the goal of treatment is to prevent recurrences, which can be fatal. Is it better to continue treatment of deep venous thrombosis or pulmonary embolism with LMWH or switch to an oral anticoagulant? What is the optimal duration of treatment? To answer these questions, we conducted a review of the literature using the standard Prescrire methodology. In non-cancer patients, two meta-analyses of trials in which treatment was not double blinded showed that severe bleeding was slightly less frequent with LMWH than with a vitamin K antagonist, but no data on mortality or the recurrence rate were provided. In cancer patients, LMWH prevented more recurrences than vitamin K antagonists; LMWH did not reduce overall mortality and did not increase the risk of serious bleeding compared to vitamin K antagonists. Treatment with LMWH requires daily injections and renal monitoring.Treatment with warfarin, the standard vitamin K antagonist, requires regular INR monitoring. There is no evidence that rivaroxaban or dabigatran has a better harm-benefit balance than warfarin for long-term treatment. After a first episode of proximal deep venous thrombosis or pulmonary embolism associated with an identified reversible trigger, several meta-analyses support a 3-month course of anticoagulation. Prolonged anticoagulant therapy is generally considered when there is no identified trigger or in case of a recurrence. Two double-blind randomised placebo-controlled trials failed to establish whether or not aspirin-based antiplatelet therapy given after discontinuation of anticoagulant therapy has a favourable harm-benefit balance. Various clinical practice guidelines published since 2006 recommend first-line treatment with a vitamin K antagonist for at least 3 months in patients without cancer, and continuation of LMWH therapy in patients with cancer. Overall, LMWH and warfarin have similar harm-benefit balances. In practice, it is best to choose between these drugs on a case-by-case basis, taking into account patient preferences, monitoring constraints, difficulty controlling the INR, the risk of bleeding and interactions, and the cost of treatment.

Topics: Anticoagulants; Aspirin; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Pulmonary Embolism; Randomized Controlled Trials as Topic; Secondary Prevention; Venous Thrombosis; Vitamin K; Warfarin

Venous thromboembolism (VTE) is a common condition in hospital patients. Considerable controversy is ongoing regarding optimal initial warfarin dosing for patients with acute deep venous thrombosis (DVT) and pulmonary embolism (PE). Achieving a therapeutic international normalized ratio (INR) with warfarin as soon as possible is important because this minimizes the duration of parenteral medication necessary to attain immediate anticoagulation, and it potentially decreases the cost and inconvenience of treatment. Although a 5-mg loading-dose nomogram tends to prevent excessive anticoagulation, a 10-mg loading-dose nomogram may achieve a therapeutic INR more quickly.. To evaluate the efficacy of a 10-mg warfarin nomogram compared with a 5-mg warfarin nomogram among patients with VTE.. The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched January 2013) and the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 12). The review authors searched PubMed (last searched 10 April 2013) and LILACS (last searched 28 February 2013). In addition, the review authors contacted pharmaceutical companies.. Randomized controlled studies comparing warfarin initiation nomograms of 10 and 5 mg in patients with VTE.. Two review authors independently assessed trial quality and extracted data. The review authors contacted study authors for additional information.. Four trials involving 494 participants were included. Three studies involving 383 participants provided data on the proportion of participants who had achieved a therapeutic INR by day five. Significant benefit of a 10-mg warfarin nomogram was observed (risk ratio [RR] 1.27, 95% confidence interval [CI] 1.05 to 1.54), although with substantial heterogeneity (I(2) = 90%). The review authors analyzed each study separately because it was not possible to perform a subgroup analysis. One study showed significant benefit of a 10-mg warfarin nomogram for the proportion of outpatients with VTE who had achieved a therapeutic INR by day five (RR 1.78, 95% CI 1.41 to 2.25), with the number needed to treat for an additional beneficial outcome (NNTB = 3, 95% CI 2 to 4); another study showed significant benefit of a 5-mg warfarin nomogram in outpatients with VTE (RR 0.58, 95% CI 0.36 to 0.93) with NNTB = 5 (95% CI 3 to 28); a third study showed no difference (RR 1.08, 95% CI 0.65 to 1.80). No difference was observed in recurrent venous thromboembolism (RVTE) at 90 days when the warfarin nomogram of 10 mg was compared with the warfarin nomogram of 5 mg (RR 1.48, 95% CI 0.39 to 5.56); no difference was observed in major bleeding at 14 days (RR 1.69, 95% CI 0.22 to 13.04) and at 90 days (RR 0.62, 95% CI 0.10 to 3.78). No difference was observed in minor bleeding at 14 to 90 days (RR 0.32, 95% CI 0.15 to 1.83) or in length of hospital stay (mean difference [MD] -2.30 days, 95% CI -7.96 to 3.36).. In patients with acute thromboembolism (DVT or PE) aged 18 years or older, considerable uncertainty surrounds the use of a 10-mg or a 5-mg loading dose for initiation of warfarin to achieve an INR of 2.0 to 3.0 on the fifth day of therapy. Heterogeneity among analyzed studies limits certainty surrounding optimal warfarin initiation nomograms.

Topics: Anticoagulants; Humans; International Normalized Ratio; Nomograms; Pulmonary Embolism; Time Factors; Venous Thromboembolism; Venous Thrombosis; Warfarin

A 60-year-old man was treated in the hospital for mesenteric vein thrombosis and discharged home on anticoagulation. On warfarin the patient started to bleed profusely from the nose and tongue. He was evaluated by ENT (ears, nose and throat); a nasal endoscopy revealed several vascular ectasias. Subsequent detailed history and general physical examination established the diagnosis of hereditary haemorrhagic telangiectasia also known as Osler-Weber-Rendu syndrome. On further evaluation, pulmonary arteriovenous malformations were diagnosed on imaging and treated by intervention radiology. In hindsight, the diagnosis could have been made in the general practitioner's office with just a routine thorough history and a physical examination at a new patient visit. We report this case to stress upon the importance of vigilant clinical, medical and family history and a thorough examination to establish an early diagnosis of this not-so-rare entity.

Topics: Angiography; Anticoagulants; Combined Modality Therapy; Diagnosis, Differential; Emergency Service, Hospital; Follow-Up Studies; Hemorrhage; Humans; Male; Mesenteric Vascular Occlusion; Mesenteric Veins; Middle Aged; Risk Assessment; Severity of Illness Index; Telangiectasia, Hereditary Hemorrhagic; Tomography, X-Ray Computed; Treatment Outcome; Venous Thrombosis; Warfarin

Randomized clinical trials have defined anticoagulation with unfractionated or low-molecular-weight heparin followed by warfarin as a standard therapy for acute deep venous thrombosis (DVT). Such treatment is highly effective in preventing recurrent venous thromboembolism with a low risk of bleeding, but provides imperfect protection against development of the post-thrombotic syndrome. Several strategies of early thrombus removal, including surgical venous thrombectomy, catheter-directed thrombolysis and pharmacomechanical thrombectomy have been developed with the goal of reducing the incidence of the post-thrombotic syndrome by restoring venous patency and preserving valvular function. Although clinical judgement and a consideration of the individual patient's medical condition and values are required, early thrombus removal strategies should be considered in selected patients with phlegmasia cerulea dolens and those with a first episode of acute iliofemoral thrombosis of less than 14 days duration.

Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Mechanical Thrombolysis; Time Factors; Venous Thrombosis; Warfarin

Improved techniques in microvascular surgery over the last several decades have led to the increased use of free tissue transfers as a mode of reconstructing difficult problems with a high success rate. However, undiagnosed thrombophilias have been associated with microsurgery free flap failures. We present a case of successful free tissue transfer in a patient with lupus anticoagulant and review the literature.

Topics: Accidents, Traffic; Adult; Algorithms; Anticoagulants; Dextrans; Free Tissue Flaps; Humans; Lower Extremity; Lupus Coagulation Inhibitor; Male; Microsurgery; Motorcycles; Muscle, Skeletal; Venous Thrombosis; Warfarin

The standard multipotent anticoagulants (unfractionated and low molecular weight heparins, antagonists of vitamin K) are commonly used for treatment and/or prophylaxis of different thrombotic complications, such as deep vein thrombosis, thrombophilia, pulmonary embolism, myocardial infarction, stroke and so on. Advantages and shortcomings of these anticoagulants are considered. The modern tendencies to use small selective direct inhibitors of thrombin or factor Xa are surveyed. The search of the new targets in the coagulation cascade for development of new promising anticoagulants and improvement in antithrombotic therapy is discussed.

Topics: Anticoagulants; Benzimidazoles; beta-Alanine; Blood Coagulation; Dabigatran; Factor Xa; Factor Xa Inhibitors; Heparin, Low-Molecular-Weight; Hirudins; Humans; Platelet Aggregation Inhibitors; Thrombin; Thromboembolism; Thrombophilia; Venous Thrombosis; Vitamin K; Warfarin

Topics: Aged; Anaphylaxis; Anticoagulants; Enoxaparin; Female; Fibrinolytic Agents; Glucocorticoids; Humans; Injections, Intravenous; Male; Middle Aged; Tissue Plasminogen Activator; Venous Thrombosis; Warfarin; Young Adult

The past decade has witnessed important advances in the diagnosis and treatment of venous thromboembolism with excellent opportunities to apply evidence-based medicine for many of the steps in the management of the disease. This review discusses the clinical prediction rules that should be used to reduce utilization of imaging diagnosis for deep vein thrombosis or pulmonary embolism and the risk stratification for thrombolytic therapy or outpatient management of pulmonary embolism. The treatment options have increased and include low-molecular-weight heparin (LMWH), intravenous or subcutaneous unfractionated heparin - the latter either monitored or not monitored, fondaparinux and rivaroxaban for the initial phase. Thereafter, vitamin K antagonists (VKAs), LMWH, oral factor Xa or thrombin inhibitors are or will soon become available. The VKAs have been subjected to many randomised trial addressing the initiation, intensity, monitoring and self-management. Extended anticoagulation and the selection for that is finally reviewed.

Topics: Anticoagulants; Antithrombins; Clinical Trials as Topic; Diagnostic Imaging; Disease Management; Factor Xa Inhibitors; Heparin, Low-Molecular-Weight; Humans; Morpholines; Radiography; Risk; Rivaroxaban; Thiophenes; Thrombin; Venous Thromboembolism; Venous Thrombosis; Vitamin K; Warfarin

A number of novel oral anticoagulants that directly target factor Xa or thrombin have been developed in recent years. Rivaroxaban and apixaban (direct factor Xa inhibitors) and dabigatran etexilate (a direct thrombin inhibitor) have shown considerable promise in large-scale, randomised clinical studies for the management of thromboembolic disorders, and have been approved for clinical use in specific indications. Rivaroxaban is licensed for the prevention of venous thromboembolism in patients undergoing elective hip or knee replacement surgery, the treatment of deep-vein thrombosis and prevention of recurrent venous thromboembolism, and for stroke prevention in patients with non-valvular atrial fibrillation. Based on the clinical trial data for rivaroxaban, feedback on its use in clinical practice and the authors' experience with the use of rivaroxaban, practical guidance for the use of rivaroxaban in special patient populations and specific clinical situations is provided. Although most recommendations are in line with the European summary of product characteristics for the approved indications, additional and, in several areas, different recommendations are given based on review of the literature and the authors' clinical experience.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Blood Loss, Surgical; Clinical Trials as Topic; Dabigatran; Factor Xa Inhibitors; Female; Humans; Male; Morpholines; Practice Guidelines as Topic; Pregnancy; Rivaroxaban; Stroke; Thiophenes; Venous Thromboembolism; Venous Thrombosis; Warfarin

Thromboembolic disorders are among the major causes of morbidity and mortality, and anticoagulation remains the cornerstone of prevention and treatment of these disorders. Although effective, the well-established agents have significant drawbacks. Heparin, low molecular weight heparin, and fondaparinux must be given parenterally, which is inconvenient for long-term or home use. The orally administered vitamin K antagonists (such as warfarin) have a slow onset of action, thus requiring bridging therapy with a parenteral agent when immediate anticoagulation is needed (e.g. inpatients with acute deep vein thrombosis). Because vitamin K antagonists produce a variable anticoagulant response as a result of multiple drug-drug and food-drug interactions and genetic polymorphisms, frequent coagulation monitoring and dose adjustment are required to ensure a therapeutic level of anticoagulation, which is inconvenient for both patients and physicians. In the search for new agents to overcome the drawbacks associated with traditional agents, direct Factor Xa inhibitors (e.g. rivaroxaban, apixaban, and edoxaban) and direct thrombin inhibitors (e.g. dabigatran etexilate) have been developed and are undergoing late-stage clinical evaluation for the prevention and treatment of thromboembolic disorders. These new oral agents have already shown promise in large-scale clinical studies and data suggest that we have entered a new era with novel drugs that are closer than ever to the 'ideal anticoagulant'. Because these new oral agents have a rapid onset of action and can be given at fixed doses without the need for routine coagulation monitoring, they may simplify treatment paradigms and are expected to improve overall clinical outcome.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Food-Drug Interactions; Heparin, Low-Molecular-Weight; Humans; Thromboembolism; Venous Thrombosis; Warfarin

To critically evaluate the benefit/risk ratio of some strategies for venous thromboembolism prophylaxis (VTE) RECENT FINDINGS: A growing body of evidence shows that graduated elastic stockings are not effective in medical patients. Special surgical settings as bariatric surgery deserve attention with a high VTE risk and no evidence-based data with regard to prophylaxis. Extended prophylaxis is being evaluated in these patients, whereas its efficacy has been demonstrated in abdominal and pelvic surgery for cancer. New oral anticoagulants are about to change the clinical landscape but yet some issues are not solved: no antidote, no monitoring, no standardization for the perioperative bridging in patients with therapeutic doses. In addition, they have not been tested in fragile patients in whom an increased bleeding risk could be feared. Finally, a large bunch of guidelines are now available to help the physician in the decision-making process.. Studies evaluating the benefit/risk ratio of graduated elastic stockings should now take place in surgery. Increasing and splitting the anticoagulant dose (mainly low molecular weight heparins) by two injections a day could be recommended in bariatric surgery and morbidly obese patients. New anticoagulant agents should also be tested in special populations, following the European Medicines Agency guidance. The methodology of clinical trials in VTE prophylaxis has to be moved forward, pending the choice of debatable surrogate end-points as asymptomatic venous thrombosis and disputed issues on the assessment of major bleeding.

Topics: Anticoagulants; Bariatric Surgery; Enoxaparin; Guidelines as Topic; Humans; Neoplasms; Perioperative Care; Stockings, Compression; Treatment Outcome; Venous Thrombosis; Warfarin

Deep venous thrombosis (DVT) or pulmonary embolism may occur in almost 2 in 1000 people each year, with up to 25% of those having a recurrence. Around 5% to 15% of people with untreated DVT may die from pulmonary embolism. Risk factors for DVT include immobility, surgery (particularly orthopaedic), malignancy, pregnancy, older age, and inherited or acquired prothrombotic clotting disorders.. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for proximal DVT? What are the effects of treatments for isolated calf DVT? What are the effects of treatments for pulmonary embolism? What are the effects of interventions on oral anticoagulation management in people with thromboembolism? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).. We found 45 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.. In this systematic review we present information relating to the effectiveness and safety of the following interventions: anticoagulation; compression stockings; low molecular weight heparin (short and long term, once or twice daily, and home treatment); oral anticoagulants (short and long term, high intensity, abrupt discontinuation, and computerised decision support); prolonged duration of anticoagulation; thrombolysis; vena cava filters; and warfarin.

Topics: Administration, Oral; Animals; Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Pulmonary Embolism; Thromboembolism; Venous Thrombosis; Warfarin

Venous thromboembolic events, including deep venous thromboses and pulmonary embolisms, have a high risk of occurrence in patients treated with lower extremity arthroplasty and hip fracture surgery. Although the prevalence of these complications has been lowered with the use of venous thromboembolic prophylaxis, the current rate is still troublesome because of the possibility of death or the need for lifetime treatment of postthrombotic syndrome and/or pulmonary hypertension. Prophylactic methods currently include mechanical devices and pharmacologic agents. Mechanical devices are difficult to compare because they are not standardized, the devices are often used in multimodal prophylactic regimens, and the devices cannot be used when the patient is ambulating or at home. A new portable compression device allows use during ambulation and can be used by the patient at home. A recent study of this portable device in patients treated with total hip arthroplasty showed an efficacy similar to that of low-molecular-weight heparin, with fewer major bleeding complications. Pharmacologic prophylaxis includes low-molecular-weight heparin, synthetic pentasaccharide, warfarin, and aspirin. All of these agents have different degrees of efficacy and safety. New oral agents for thromboprophylaxis are on the horizon but are not yet approved by the Food and Drug Administration.

Topics: Anticoagulants; Arthroplasty, Replacement, Knee; Early Ambulation; Heparin, Low-Molecular-Weight; Hip Fractures; Humans; Intermittent Pneumatic Compression Devices; Orthopedic Procedures; Patient Compliance; Plastic Surgery Procedures; Vena Cava Filters; Venous Thrombosis; Warfarin

We consider in this review traditional and novel approaches to drug prevention of pulmonary embolism (PE) which in predominant number of cases is related to deep vein thrombosis of lower extremities. Risk of PE development is especially high in patients after orthopedic hip or knee surgery. Modern recommendations contemplate use of unfractionated and low molecular weight heparins, vitamin K antagonists (warfarin in the first place), fondaparinux. Oral direct anticoagulants related to selective inhibitors of blood coagulation factors IIa (thrombin) and Xa have appeared recently and proved their preventive efficacy and safety in randomized controlled studies. Preventive efficacy and safety of dabigatran among direct selective factor IIa (thrombin) inhibitors and of rivaroxaban, apixaban, and edoxaban among direct selective factor IIa inhibitors have been studied best.

Topics: Anticoagulants; Drug Administration Routes; Drug Substitution; Factor Xa Inhibitors; Heparin; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Lower Extremity; Orthopedic Procedures; Postoperative Complications; Pulmonary Embolism; Randomized Controlled Trials as Topic; Risk Factors; Secondary Prevention; Therapies, Investigational; Thrombin; Venous Thrombosis; Warfarin

Topics: Administration, Oral; Anticoagulants; Craniocerebral Trauma; Drug Administration Schedule; Drug Interactions; Drug Monitoring; Hemorrhage; Humans; International Normalized Ratio; Perioperative Care; Platelet Aggregation Inhibitors; Pulmonary Embolism; Venous Thrombosis; Warfarin

Topics: Administration, Oral; Anticoagulants; Humans; International Normalized Ratio; Recurrence; Self Care; Venous Thrombosis; Warfarin

The prevalence of obesity has increased substantially over recent years. Clinicians are increasingly being challenged with making uncertain anticoagulant dosing decisions, as the optimal dosing strategy for most anticoagulants in the obese patient population remains unknown. Research published to date suggests that the clearance of anticoagulants increases with weight. As obesity is associated with an increased risk of venous thromboembolism and arterial disease, there is an urgent need to establish appropriate anticoagulation regimens for this patient group. Research studies applying the method of pharmacokinetic-pharmacodynamic modelling and simulation could establish an appropriate evidence base and provide direction and reassurance to prescribing clinicians.

Topics: Acute Coronary Syndrome; Anticoagulants; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Dabigatran; Double-Blind Method; Factor Xa Inhibitors; Fondaparinux; Hemorrhage; Heparin; Humans; Morpholines; Multicenter Studies as Topic; Obesity; Polysaccharides; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Thrombin; Thrombophilia; Venous Thrombosis; Warfarin

Thrombosis in children is becoming more prevalent due to increased awareness of these issues in the pediatric population and advances in medicine. Management of affected children are challenging due to differences in their hemostatic system compared with adults. Prospective, controlled trials for management/treatment of children with thrombosis are lacking. Many of the available guidelines for treatment of thrombosis in children are extrapolated from adult data and do not account for the uniqueness of the pediatric hemostatic system, although more research and data are becoming available. This review will focus on children over 1 year of age, including adolescents, looking at the etiology of thrombosis, diagnosis, management options, and any associated complications in this pediatric population.

Topics: Adolescent; Anticoagulants; Catheterization, Central Venous; Child; Child, Preschool; Factor V; Fibrinolytic Agents; Hemostasis; Heparin; Humans; Iliac Vein; Infant; Prothrombin; Pulmonary Embolism; Thrombosis; Venous Thrombosis; Vitamin K; Warfarin

Topics: Accidental Falls; Adolescent; Anticoagulants; Bed Rest; Bicycling; Hematoma; Humans; Lacerations; Liver; Male; Retroperitoneal Space; Spleen; Tomography, X-Ray Computed; Vena Cava, Inferior; Venous Thrombosis; Warfarin

Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism, represents a significant source of morbidity and mortality. It is readily diagnosed with noninvasive modalities when there is a clinical suspicion. Most patients presenting with signs and symptoms of DVT have well-known risk factors, such as a history of VTE, malignancy, recent illness, or immobilization. A subset of individuals with idiopathic VTE have no readily identifiable risk factors. Therapeutic anticoagulation is the cornerstone of management in all patients with VTE. Adjunctive measures, such as thrombolysis and the use of vena cava filters, are indicated in select cases. The ideal duration of anticoagulation is unknown, but is often maintained long-term in patients with acquired or inherited thrombophilia. Warfarin is the only oral anticoagulant approved by the US Food and Drug Administration. Warfarin carries a substantial annual risk of bleeding complications, requires ongoing monitoring, and has extensive drug-drug interactions, which are causes for concern in patients requiring long-term anticoagulation. Alternative oral anticoagulants, such as direct thrombin inhibitors and factor Xa inhibitors, are subjects of active research in alternative agents for oral anticoagulation, and have been recently approved for prophylaxis in Canada and the European Union.

Topics: Anticoagulants; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Pulmonary Embolism; Risk Factors; Vena Cava Filters; Venous Thromboembolism; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Child; Hemostasis; Heparin; Humans; International Normalized Ratio; Risk Assessment; Risk Factors; Venous Thromboembolism; Venous Thrombosis; Warfarin

Deep venous thrombosis (DVT) is the end result of a complex interaction of events including the activation of the clotting cascade in conjunction with platelet aggregation. Patients undergoing major lower extremity orthopedic surgery, especially total joint arthroplasty (TJA), are at high risk for developing a postoperative DVT or a subsequent pulmonary embolus. Venous thromboembolic (VTE) prophylaxis, most commonly pharmacologic prophylaxis, has become the standard of care for patients undergoing elective TJA. However, the controversy between the efficacy of VTE prophylaxis and the increased risk for bleeding in the postoperative period continues to exist. This review addresses the controversy underlying VTE prophylaxis by outlining 2 guidelines and demonstrating the pros and cons of different DVT prophylaxis regimens based on the available evidence-based literature.

Topics: Anticoagulants; Arthroplasty, Replacement; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Drug Interactions; Humans; International Normalized Ratio; Postoperative Complications; Practice Guidelines as Topic; Venous Thrombosis; Warfarin

Thromboembolic complications are much higher in pregnancy due to procoagulant changes. Heparin does not cross the placenta and the use of unfractionated heparin (UFH) is the current established practice in prophylaxis and treatment for thromboembolism in pregnancy.. To compare the effectiveness of anticoagulant therapies for the treatment of deep vein thrombosis in pregnancy. The anticoagulant drugs included are UFH, low molecular weight heparin (LMWH) and warfarin.. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (March 2010) and reference lists of retrieved studies.. Randomised controlled trials comparing any combination of warfarin, UFH, LMWH and placebo in pregnant women.. We used methods described in the Cochrane Handbooks for Systemic Reviews of Interventions for assessing the eligibility of studies identified by the search strategy. A minimum of two review authors independently assessed each study.. We did not identify any eligible studies for inclusion in the review.We identified three potential studies; after assessing eligibility, we excluded all three as they did not meet the prespecified inclusion criteria. One study compared LMWH and UFH in pregnant women with previous thromboembolic events and, for most of these women, anticoagulants were used as thromboprophylaxis. There were only three women who had a thromboembolic event during the current pregnancy and it was unclear whether the anticoagulant was used as therapy or prophylaxis. We excluded one study because it included only women undergoing caesarean birth. The third study was not a randomised trial.. There is no evidence from randomised controlled trials on the effectiveness of anticoagulation for deep vein thrombosis in pregnancy. Further studies are required.

Topics: Anticoagulants; Female; Heparin; Heparin, Low-Molecular-Weight; Humans; Pregnancy; Pregnancy Complications, Hematologic; Venous Thrombosis; Warfarin

Standard management is best: start with unfractionated heparin or low-molecular-weight heparin and follow with long-term therapy with a vitamin K antagonist. Some evidence supports thrombolytic therapy, placement of a superior vena cava filter, or surgical thrombectomy in selected patients. Whether to remove venous catheters during initial treatment for catheter-induced venous thrombosis remains unclear, because limited studies address this issue specifically.

Topics: Anticoagulants; Arm; Evidence-Based Medicine; Heparin; Heparin, Low-Molecular-Weight; Humans; Thrombectomy; Thrombolytic Therapy; Vena Cava Filters; Venous Thrombosis; Warfarin

The aim was to determine the validity of the international normalized ratio (INR) and prothrombin time (PT) as a monitor for warfarin therapy in patients with lupus anticoagulants and recurrent thrombosis, and to investigate alternative approaches to monitoring warfarin therapy and new treatment options in these patients. A case is described of a 63-year-old female with antiphospholipid syndrome and recurrent venous thrombosis despite optimal adjusted warfarin therapy. In patients with lupus anticoagulants, the INRs obtained while receiving warfarin vary and often overestimate the extent of anticoagulation, while PT without receiving warfarin is often prolonged. In conclusion, lupus anticoagulants can influence PT and lead to INR that does not accurately reflect the true level of anticoagulation. Optimizing of (warfarin) oral anticoagulation therapy could be achieved by individual monitoring of anticoagulation effect with a test thatis insensitive to lupus anticoagulants (chromogenic factor X assay). Emerging oral anticoagulants, direct thrombin inhibitors and direct factor Xa inhibitors, such as dabigatran and rivaroxaban, with a predictable anticoagulant response and little potential for food or drug interactions, have been designed to be administered in fixed doses without coagulation monitoring and could be the treatment choice for these patients.

Topics: Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Antithrombins; Factor Xa Inhibitors; Female; Humans; International Normalized Ratio; Middle Aged; Prothrombin Time; Recurrence; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Drug Administration Schedule; Humans; Practice Guidelines as Topic; Risk Factors; Secondary Prevention; Venous Thrombosis; Warfarin

Antiphospholipid syndrome (APS) is characterised by vascular thrombosis and/or obstetric morbidity in the presence of persistently positive antiphospholipid antibodies (aPL). Balancing an individuals' risk of thrombosis against the benefits and risks of antithrombotic therapies is crucial for optimising management and preventing morbidity in APS and asymptomatic aPL. Limitations in research studies have led to debate regarding best-practice. This review of the available literature makes the following recommendations. Those with asymptomatic aPL should only be treated with aspirin if they have persistently positive aPL, obstetric APS, or co-existent systemic lupus erythematosus. For those with APS, lower risk patients (i.e. first venous thrombosis) should be treated with warfarin to an INR 2.0-3.0. Those at higher risk (i.e. arterial thrombosis or recurrent events) should be treated with warfarin to an INR of >3.0. During pregnancy in APS, low molecular weight heparin (LMWH) and aspirin should be used and women should be under the care of obstetricians and physicians specialising in APS. Additional vascular and thrombotic risk factors should be actively reduced in all patient groups. Further randomised controlled trials are required, which should involve larger patient groups with APS diagnosed according to accepted criteria. This may mean that international and multi-centre trials are needed to ascertain the best treatment regimens.

Topics: Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Aspirin; Female; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Pregnancy; Pregnancy Complications, Hematologic; Venous Thrombosis; Warfarin

This systematic review aims to assess the risks (both thromboembolic and bleeding) of an oral anticoagulation therapy (OAT) patient undergoing implant therapy and to provide a management protocol to patients under OAT undergoing implant therapy.. Medline, Cochrane Data Base of Systematic Reviews, the Cochrane Central Register of Controlled Trials and EMBASE (from 1980 to December 2008) were searched for English-language articles published between 1966 and 2008. This search was completed by a hand research accessing the references cited in all identified publications.. Nineteen studies were identified reporting outcomes after oral surgery procedures (mostly dental extractions in patients on OAT following different management protocols and haemostatic therapies). Five studies were randomized-controlled trials (RCTs), 11 were controlled clinical trials (CCTs) and three were prospective case series. The OAT management strategies as well as the protocols during and after surgery were different. This heterogeneity prevented any possible data aggregation and synthesis. The results from these studies are very homogeneous, reporting minor bleeding in very few patients, without a significant difference between the OAT patients who continue with the vitamin K antagonists vs. the patients who stopped this medication before surgery. These post-operative bleeding events were controlled only with local haemostatic measures: tranexamic acid mouthwashes, gelatine sponges and cellulose gauzes's application were effective. Post-operative bleeding did not correlate with the international normalised ratio (INR) status. In none of the studies was a thromboembolic event reported.. OAT patients (INR 2-4) who do not discontinue the AC medication do not have a significantly higher risk of post-operative bleeding than non-OAT patients and they also do not have a higher risk of post-operative bleeding than OAT patients who discontinue the medication. In patients with OAT (INR 2-4) without discontinuation, topical haemostatic agents were effective in preventing post-operative bleeding. OAT discontinuation is not recommended for minor oral surgery, such as single tooth extraction or implant placement, provided that this does not involve autogenous bone grafts, extensive flaps or osteotomy preparations extending outside the bony envelope. Evidence does not support that dental implant placement in patients on OAT is contraindicated.

Topics: Administration, Oral; Administration, Topical; Anticoagulants; Atrial Fibrillation; Contraindications; Dental Care for Chronically Ill; Dental Implantation, Endosseous; Gelatin; Heart Valve Prosthesis; Hemostatics; Humans; International Normalized Ratio; Mouthwashes; Oral Surgical Procedures; Postoperative Hemorrhage; Thromboembolism; Tranexamic Acid; Venous Thrombosis; Warfarin

Deep vein thrombosis (DVT) is a cause of preventable morbidity and mortality in hospitalized surgical patients. The occurrence of the disease is related to presence of risk factors, which are related primarily to trauma, venous stasis and hyper-coagulability. DVT seems not to be taken seriously by many surgeons in Nigeria. This is despite comprehensive studies that show no real differences in racial demography of the disease.. To highlight the importance of physician awareness about DVT especially its risks and prevention methods.. A detailed literature search was completed to extrapolate articles that described DVT risks and prevention. This involved hand and online searches. Specific search terms used included DVT/risk factors/prevention. The searches generated 468 papers. Of these 57 papers were included in the review.. Predominant risk factors for DVT include middle or old age, prolonged surgery, trauma, confinement, presence of malignancy and insertion of deep venous catheters. In women, contraceptive use, hormone replacement therapy, pregnancy and the puepernum are a additional risk factors. Prophylactic measures include those directed at eliminating venous stasis and those directed at changes in blood coagulability.. Deep Venous Thrombosis is a common disease with fatal and serious long term burdensome complications. We must target primary and secondary prophylaxis to improve survival and reduce morbidity from this preventable disease.

Topics: Anticoagulants; Aspirin; Awareness; Clinical Competence; Cyclooxygenase Inhibitors; Dextrans; Dihydroergotamine; Fibrinolytic Agents; Heparin; Humans; Nigeria; Postoperative Complications; Risk Factors; Vasoconstrictor Agents; Venous Thrombosis; Warfarin

There is a perception in the orthopaedic and thromboembolism community that the incidence of deep vein thrombosis (DVT) has decreased in patients undergoing total knee arthroplasty (TKA) or total hip arthroplasty (THA).. To assess the incidence of DVT with warfarin thromboprophylaxis over time in patients undergoing elective TKA or THA.. The MEDLINE, EMBASE, and Cochrane Library databases were searched to October 2006, supplemented by a manual search of reference lists. Two reviewers independently extracted data on study characteristics, quality and the frequency of total, symptomatic and proximal DVT.. Fourteen studies (4,423 patients) were included. Total and proximal DVT after TKA declined over time (r=-0.75, p=0.031; r=-0.86, p=0.007 respectively). Total and proximal DVT after THA did not change. The risk of developing DVT after TKA was significantly higher than after THA (OR 1.85, 95% CI 1.6-2.14; p<0.0001). The risk of developing symptomatic DVT after THA was significantly higher than after TKA (OR 2.18, 95% CI 1.11-4.27; p=0.012).. The incidence of DVT in patients undergoing elective TKA appears to have declined in patients receiving warfarin thromboprophylaxis.

Topics: Adult; Age Factors; Aged; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Humans; Incidence; Middle Aged; Postoperative Complications; Randomized Controlled Trials as Topic; Time Factors; Venous Thrombosis; Warfarin

Currently available anticoagulants are effective in reducing the recurrence rate of venous thromboembolism (VTE). However, anticoagulant treatment is associated with an increased risk for bleeding complications. Thus, anticoagulation has to be discontinued when benefit of treatment no longer clearly outweigh its risks. The duration of anticoagulant treatment is currently framed based on the estimated individual risk for recurrent VTE. The incidence of recurrent VTE can be estimated through a two-step decision algorithm. Firstly, the features of the patient (gender), of the initial event (proximal or distal deep vein thrombosis or pulmonary embolism), and the associated conditions (cancer, surgery, etc) provide essential information on the risk for recurrence after anticoagulant treatment discontinuation. Secondly, at time of anticoagulant treatment discontinuation, D: -dimer levels and residual thrombosis have been indicated as predictors of recurrent VTE. Current evidence suggests that the risk of recurrence after stopping therapy is largely determined by whether the acute episode of VTE has been effectively treated and by the patient's intrinsic risk of having a new episode of VTE. All patients with acute VTE should receive oral anticoagulant treatment for three months. At the end of this treatment period, physicians should decide for withdrawal or indefinite anticoagulation. Based on intrinsic patient's risk for recurrent VTE and for bleeding complications and on patient preference, selected patients could be allocated to indefinite treatment with VKA with scheduled periodic re-assessment of the benefit from extending anticoagulation. Alternative strategies for secondary prevention of VTE to be used after conventional anticoagulation are currently under evaluation. Cancer patients should receive low molecular-weight heparin over warfarin in the long-term treatment of VTE. These patients should be considered for extended anticoagulation at least until resolution of underlying disease. The risk for recurrent venous thromboembolism can be estimated through a two-step algorithm. Firstly, the features of the patient (gender), of the initial event (proximal or distal deep vein thrombosis or pulmonary embolism), and the associated conditions (cancer, surgery, etc) are essential to estimate the risk for recurrence after anticoagulant treatment discontinuation. Secondly, a correlation has been shown between D: -dimer levels and residual thrombosis at time of an

Topics: Algorithms; Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Pulmonary Embolism; Risk Assessment; Secondary Prevention; Time Factors; Venous Thromboembolism; Venous Thrombosis; Warfarin

The association of cancer and venous thromboembolism (VTE) becomes increasingly important. VTE has been recognised as an increasingly frequent complication in cancer care. Furthermore, recent clinical trials have shown that therapy and prophylaxis of VTEs with low-molecular weight heparin (LMWH) is, in general, superior to oral anticoagulation with warfarin. Also, prolonged therapy of or prophylaxis for VTE in cancer patients seems to be associated with an improved outcome.. Research on patient preferences for therapy and prophylaxis of VTE is still rare; but it seems clear that, as in other areas, cancer patients wish to be involved in the decision-making process. Patients seem to accept LMWH over oral anticoagulation despite the need for subcutaneous injections.. Cancer and thrombosis/hypercoagulability is an increasingly important association. The use of antithrombotics in cancer patients warrants increased attention since it's importance seems underrecognized.

Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Primary Prevention; Prognosis; Quality of Life; Venous Thrombosis; Warfarin

This review describes recent evidence relevant to the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). Because venous thromboembolism (VTE) is a spectrum of disease that includes both of these disorders, many of the therapeutic options are common to both. At the time of diagnosis, effective treatment options for patients with VTE include unfractionated heparin, low molecular weight heparins (e.g., dalteparin, enoxaparin, tinzaparin), and pentasaccharides (e.g., fondaparinux). Many patients with VTE, especially DVT, can receive most or all of their initial treatment as outpatients. Other treatment strategies such as vena caval filter placement and mechanical (or chemical) clot dissolution are discussed briefly. Anticoagulation with warfarin (or other oral vitamin K antagonists) is a highly effective strategy for the long-term prevention of VTE recurrence in most patients. In addition to presenting evidence relevant to the optimal duration of warfarin therapy, we highlight circumstances under which extended therapy with a parenteral agent such as a low molecular weight heparin might be preferable.

Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Pulmonary Embolism; Venous Thromboembolism; Venous Thrombosis; Warfarin

Long-term parenteral nutrition (PN) is administered to patients who are unable to use their gastrointestinal tract to absorb sufficient nutrients and water to maintain their nutritional status. Patients receiving long-term parenteral nutrition are at risk of numerous complications including thrombosis of the central venous catheter used to provide nutrition. Central venous access is essential to the successful delivery of long-term PN. One of the strategies to lessen the frequency of this complication is anticoagulation therapy with warfarin. The effect of warfarin in preventing this complication may be modified by vitamin K intake. Individuals with gastrointestinal failure may receive vitamin K from a variety of sources. This review summarizes the role of warfarin in preventing central venous access thrombosis. It also summarizes potential sources of vitamin K intake in home parenteral nutrition patients, examines the evidence for recommendations regarding vitamin K intake, and considers the potential impact of increased vitamin K intake on home PN patients, particularly on the prevention of central venous thrombosis.

Topics: Anticoagulants; Antifibrinolytic Agents; Catheterization, Central Venous; Gastrointestinal Diseases; Humans; Parenteral Nutrition, Home; Time Factors; Venous Thrombosis; Vitamin K; Warfarin

Venous thromboembolism (VTE) disease, as defined by the occurrence of deep venous thrombosis or pulmonary embolism, occurs among 4 to 20% of patients with cancer and is a leading cause of death among these patients. Use of classical anticoagulation to treat VTE in a cancer patient is associated with a higher risk of major bleeding and of VTE recurrence as compared to noncancer patients. Updated comprehensive and systematic review of current data from the medical literature allows to reconsider the classical approach used for anticoagulant treatment in cancer patients and to implement adapted recommendations. In 2008, the use of daily subcutaneous low-molecular-weight heparin (LMWH) for at least three to six months is recommended as first line therapy to treat VTE disease in cancer patients. If LMWH are contra-indicated (renal insufficiency), other therapeutic approaches are warranted, such as use of unfractionated heparin (UFH) with early introduction of anti-vitamin K for at least three months or venous cava filter in case of absolute contra-indications to anticoagulation. VTE prophylaxis in cancer patients relies on the same therapeutic approaches as currently used for noncancer patients at high risk of VTE. The definition of more specific prophylactic approaches for patients with cancer considered at higher risks of VTE, will be the subject of many clinical trials in the forthcoming years.

Topics: Anticoagulants; Brain Neoplasms; Heparin; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Pulmonary Embolism; Risk Factors; Venous Thromboembolism; Venous Thrombosis; Warfarin

Venous thrombosis is a common disease. As the mean age of the population increases, so does the incidence of venous thromboembolism. Anticoagulant therapy is equally effective in young and older patients, and can reduce substantially the associated morbidity and mortality. When considering long-term oral anticoagulant therapy in older patients, however, careful ongoing evaluation is imperative to ensure that the risk of bleeding does not outweigh the antithrombotic benefits.

Topics: Anticoagulants; Antithrombin III; Enoxaparin; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Pulmonary Embolism; Stockings, Compression; Thrombolytic Therapy; Venous Thrombosis; Warfarin

Based on an individual assessment of risk factors for arterial or venous thrombosis and the risk of postoperative bleeding, this article outlines the preoperative and postoperative approach to anticoagulant management. Preceding this is a brief description of the therapies most commonly used in the perioperative period. The prevention of arterial thromboembolism is considered separately from the prevention of venous thrombosis. Perioperative management of anticoagulation can cause anxiety for patients, surgeons, anesthetists, and those who manage long-term anticoagulant therapy. Good communication between all of these parties is essential to ensure that an optimal management strategy is identified and executed.

Topics: Algorithms; Anticoagulants; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Perioperative Care; Pulmonary Embolism; Recurrence; Risk Factors; Vena Cava Filters; Venous Thrombosis; Warfarin

The aim of this study was to report our experience and review the published data on argatroban administration during adult cardiac surgery.. The information on all reported cases of argatroban use in adults, during cardiac surgery was reviewed, including that of the patient described here. This analysis focused on patient characteristics, type of surgery, argatroban dosing schedule, monitoring of anticoagulation and outcomes.. Twenty-one cases have been reported. Fifteen patients underwent off-pump surgical procedures with the argatroban dose adjusted to maintain an activated clotting time (ACT) range between 200 and 300 s. Three intraoperative thrombi occurred in two patients when the ACT was <280 s. None had coagulopathy. Six cases reported the use of argatroban during on-pump cardiac surgery dosed to keep the ACT >400 s. Intraoperative thrombotic complications were not reported in this group; however, one clot in the pump was noted after the procedure when the ACT was between 300 and 350 s. All six cases required larger volumes of perioperative blood products and three had severe coagulopathy. Of the 21 cases, seven had an indication for continued anticoagulation following surgery. Four cases did not report further use of argatroban after surgery. Three patients received argatroban after surgery without complications. Recommendations for how to use argatroban during cardiac surgery are proposed.. Argatroban, with ACT monitoring, might be safely used for anticoagulation during cardiac surgery.

Topics: Adult; Aged; Anticoagulants; Arginine; Cardiac Surgical Procedures; Coronary Artery Bypass; Coronary Artery Bypass, Off-Pump; Drug Monitoring; Endocarditis, Bacterial; Female; Heart Valve Prosthesis Implantation; Heparin; Humans; Intra-Aortic Balloon Pumping; Intraoperative Complications; Male; Middle Aged; Mitral Valve; Pipecolic Acids; Postoperative Complications; Retrospective Studies; Staphylococcal Infections; Subclavian Vein; Sulfonamides; Thrombosis; Venous Thrombosis; Warfarin; Whole Blood Coagulation Time

Venous thromboembolic disease (VTE) remains the most common and potentially fatal complication following total knee replacement (TKR). Its incidence has been reported in excess of 50% if no prophylaxis is used. Even with current prophylaxis regimens, VTE incidence remains high in the range of 25% to 30%. Three prophylaxis regimens are recommended according to the guidelines put forth by the American College of Chest Physicians: 1) low-molecular-weight heparin, 2) indirect factor Xa inhibitor, and 3) adjusted-dose warfarin. Phase II and III clinical trials are currently underway to evaluate the efficacy and safety of newer antithrombotic agents as prophylaxis against VTE following TKR.

Topics: Anticoagulants; Arthroplasty, Replacement, Knee; Factor Xa Inhibitors; Heparin, Low-Molecular-Weight; Humans; Intermittent Pneumatic Compression Devices; Thromboembolism; Venous Thrombosis; Warfarin

The Seventh American College of Chest Physicians (ACCP) Conference on Antithrombotic and Thrombolytic Therapy provides guidelines for outpatient management of anticoagulation therapy. The ACCP guidelines recommend short-term warfarin therapy, with the goal of maintaining an International Normalized Ratio (INR) of 2.5 +/- 0.5, after major orthopedic surgery. Therapy for venous thromboembolism includes an INR of 2.5 +/- 0.5, with the length of therapy determined by associated conditions. For patients with atrial fibrillation, the INR is maintained at 2.5 +/- 0.5 indefinitely; for most patients with mechanical valves, the recommended INR is 3.0 +/- 0.5 indefinitely. Use of outpatient low-molecular-weight heparin (LMWH) is as safe and effective as inpatient unfractionated heparin for treatment of venous thromboembolism. The ACCP recommends starting warfarin with unfractionated heparin or LMWH for at least five days and continuing until a therapeutic INR is achieved. Because patients with venous thromboembolism and cancer who have been treated with LMWH have a survival advantage that extends beyond their venous thromboembolism treatment, the ACCP recommends beginning their therapy with three to six months of LMWH. When invasive procedures require the interruption of oral anticoagulation therapy, recommendations for bridge therapy are determined by balancing the risk of bleeding against the risk of thromboembolism. Patients at higher risk of thromboembolization should stop warfarin therapy four to five days before surgery and start LMWH or unfractionated heparin two to three days before surgery.

Topics: Ambulatory Care; Anticoagulants; Drug Administration Schedule; Drug Interactions; Evidence-Based Medicine; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Pulmonary Embolism; Risk; Venous Thrombosis; Warfarin

Topics: Administration, Oral; Anticoagulants; Drug Monitoring; Heparin, Low-Molecular-Weight; Humans; Injections, Subcutaneous; International Normalized Ratio; Nurse's Role; Patient Compliance; Patient Education as Topic; Patient Selection; Risk Factors; Self Administration; Venous Thrombosis; Warfarin

The long-term complications of deep vein thrombosis (DVT), assessment of risk for venous thromboembolism (VTE) in medical and surgical patients, recommendations in evidence-based guidelines for VTE prophylaxis in surgical and medical patients and the treatment of VTE, and a new alternative for VTE prophylaxis and treatment are discussed.. Pulmonary embolism (PE) is an acute complication of DVT, and recurrent DVT, post-thrombotic syndrome, and death are long-term complications of DVT. The need to assess VTE risk and provide VTE prophylaxis are well recognized in surgical patients. However, VTE prophylaxis is underutilized in medical patients despite the fact that DVT is common and guidelines for prophylaxis are available, partly because the condition often is asymptomatic in these patients. The risk for VTE increases as the number of risk factors increases, so the aggressiveness of VTE prophylaxis in medical and surgical patients increases as the risk of VTE increases. The most recent American College of Chest Physicians (ACCP) guidelines recommend low-dose unfractionated heparin or low-molecular-weight heparin (LMWH) for VTE prophylaxis in acutely ill medical patients. The treatment of VTE recommended by ACCP involves short-term LMWH or unfractionated heparin therapy plus long-term oral warfarin therapy. The pentasaccharide, factor Xa inhibitor, fondaparinux is a new alternative for VTE prophylaxis and treatment. Reducing LMWH doses for patients with severe renal impairment may offer a safety advantage. Fixed doses of LMWH are customarily used for VTE prophylaxis regardless of body weight or body mass index, but weight-based dosing with larger doses for obese patients may be more effective than fixed doses.. Efforts to assess VTE risk and apply evidence-based guidelines for VTE prophylaxis and treatment in medical patients as well as surgical patients can improve patient care and outcomes. Findings from recent clinical research provide clinicians with clarification about the optimal prophylactic and treatment strategies, and future guidelines will reflect these findings.

Topics: Adult; Aged; Anticoagulants; Clinical Protocols; Drug Therapy, Combination; Evidence-Based Medicine; Female; Fibrinolytic Agents; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Outcome Assessment, Health Care; Polysaccharides; Pulmonary Embolism; Risk; Thromboembolism; Venous Thrombosis; Warfarin

A 79-year-old man with a history of deep vein thrombosis and pulmonary embolism received anticoagulation therapy with warfarin 5 mg daily for 8 months. He was diagnosed with osteomyelitis and underwent partial metatarsal resection of his right foot. After surgery, antibiotics were initiated, including ertapenem sodium 1 g intravenously every 24 hours, vancomycin 1400 mg intravenously every 24 hours, and rifampin 300 mg by mouth twice daily. Achieving a therapeutic level of anticoagulation was difficult despite escalating doses of warfarin, because of the interaction with rifampin. A 5- to 6-fold increase in warfarin dose was prescribed to reach therapeutic international normalized ratios (INRs), but even these increases were insufficient to maintain his INR in the therapeutic range. After rifampin was discontinued, warfarin doses were gradually reduced over the next 2 months. When concurrent warfarin-rifampin therapy is necessary, vigilant monitoring is imperative and significant increases in warfarin doses are likely.

Topics: Aged; Antibiotics, Antitubercular; Anticoagulants; Drug Administration Schedule; Drug Interactions; Drug Monitoring; Humans; International Normalized Ratio; Male; Nursing Assessment; Osteomyelitis; Postoperative Care; Pulmonary Embolism; Rifampin; Risk Assessment; Venous Thrombosis; Warfarin

Topics: Animals; Biomarkers, Tumor; Blood Coagulation Factors; Disseminated Intravascular Coagulation; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Prognosis; Pulmonary Embolism; Venous Thrombosis; Warfarin

The antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterised by autoantibody production and vascular thrombosis or pregnancy morbidity. Autoantibodies generated against phospholipid and phospholipid-binding proteins often impair phospholipid-dependent clotting assays (lupus anticoagulants). These autoantibodies activate endothelial cells, platelets and biochemical cascades and can exist in autoimmune disorders such as lupus. Consistently positive antibodies may worsen the severity of thrombo-occlusive disease. The most common neurological manifestations of APS include stroke and transient ischaemic attacks due to arterial thromboses. Antiphospholipid antibodies may cause additional neurological impairments through both vascular and immune mechanisms. Antiaggregant or anticoagulant therapies are indicated for APS-related ischaemic strokes. Treatment regimens for asymptomatic antibody-positive patients and those with refractory disease remain controversial. There is scant literature on neurological APS manifestations in paediatric patients. Assessment of traditional cardiovascular and inherited thrombophilia risk factors is essential in patients with APS. Modifiable risk factors and valvular heart disease may worsen thrombotic and cerebrovascular outcomes. Alternative therapies such as statins, anti-malarials, angiotensin-converting enzyme inhibitors and thrombin inhibitors warrant further research.

Topics: Anticoagulants; Antiphospholipid Syndrome; Humans; Lupus Coagulation Inhibitor; Risk Assessment; Risk Factors; Stroke; Venous Thrombosis; Warfarin

Venous thromboembolism, including deep vein thrombosis and pulmonary thromboembolism, is a common illness during postoperative period. Pharmacological antithrombotic therapy is the cornerstone for the treatment of venous thromboembolism. However, management of venous thromboembolism during postoperative period can be challenging, because of increased risk of bleeding associated with antithrombotic agents. Therefore, we should devise a strategy with mechanical support such as catheter intervention, inferior vena cava filter and percutaneous cardiopulmonary support during the period with increased bleeding risk.

Topics: Anticoagulants; Catheterization; Extracorporeal Membrane Oxygenation; Heparin; Humans; Perioperative Care; Postoperative Complications; Practice Guidelines as Topic; Pulmonary Embolism; Vena Cava Filters; Venous Thrombosis; Warfarin

The reported overall risk of deep venous thrombosis in gynaecological surgery ranges from 7 to 45%. Fatal pulmonary embolism is estimated to occur in nearly 1% of these women. Pharmaceutical interventions are one possible prophylactic measure for preventing emboli in women undergoing major gynaecological surgery. Agents include unfractionated heparin (low -dose and adjusted-dose), low-molecular-weight heparins, heparinoids and warfarin.. The objective of this review was to evaluate the effectiveness of warfarin, heparin and aspirin in preventing thromboembolism after major gynaecological surgery.. We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (searched 15 August 2003), the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library issue 2, 2003), MEDLINE (1966 to April 2003), EMBASE (1985 to April 2003), and CINAHL (1982 to April 2003). References from relevant articles were searched and authors contacted where necessary. In addition we contacted experts in the field for unpublished works.. Randomised controlled trials of heparins, warfarin or aspirin to prevent thromboembolism after major gynaecological surgery were eligible for inclusion.. Thirty-three trials were identified in the initial search. On careful inspection only eight of these met the inclusion criteria. Trials were data extracted and assessed for quality by at least two reviewers. Data were combined for meta-analysis using odds ratios for dichotomous data or weighted mean difference for continuous data. A random effects statistical model was used.. The meta-analysis of heparin versus placebo found a statistically significant decrease in the number of DVTs in both the all women group (including those with and without malignancy) (OR 0.30, 95% CI 0.12 to 0.76) and the subgroup of only women with malignancy (OR 0.30, 95% CI 0.10 to 0.89). There was no significant difference in the incidence of PE. Oral warfarin reduced DVT when compared to placebo in all women (OR 0.22, 95% CI 0.06 to 0.86) and in women with malignancy (OR 0.18, 95% CI 0.04 to 0.87). Meta-analyses of UH and LMWH showed no statistical difference in any comparison. No studies compared aspirin alone to placebo, heparin or warfarin. There was a statistically significant increase in injection site haematomas associated with heparin compared to placebo (OR 0.30, 95% CI 0.10 to 0.89).. Women, undergoing major gynaecological surgery and without contraindications to anticoagulants should be offered thromboprophylaxis. Evidence suggests that UH and LMWH are equally as effective in preventing DVT and the one trial available suggests that warfarin is as effective as UH. There is no evidence as yet to suggest that warfarin, heparin or aspirin reduce incidence of PE.

Topics: Anticoagulants; Aspirin; Female; Gynecologic Surgical Procedures; Heparin; Humans; Postoperative Complications; Pulmonary Embolism; Venous Thrombosis; Warfarin

The objectives of this study were to review perioperative bridging strategies for anticoagulated patients and to describe a novel bridging strategy for tonsillectomy in an anticoagulated patient that addresses both primary and secondary hemorrhage risks.. A literature review and a case report are presented. PubMed was reviewed for evidence-based recommendations on perioperative management of anticoagulated patients. A case report is detailed of a 28-year-old woman with antiphospholipid syndrome on warfarin for high risk of venous thrombosis who underwent tonsillectomy. A perioperative bridging strategy incorporating outpatient low-molecular weight heparin and inpatient unfractionated heparin was implemented to minimize risks of thrombosis and primary and secondary posttonsillectomy hemorrhage.. Limited evidence supports a consensus on the best perioperative management of anticoagulated patients. Tonsillectomy in an anticoagulated patient has not been described previously. The patient in this case underwent successful tonsillectomy with no thrombosis or bleeding after 1 month of follow-up.. Tonsillectomy can be done relatively safely in an anticoagulated patient at high risk for thrombosis. The perioperative bridging strategy should account for its unique risk of primary and secondary postoperative hemorrhage. A proposed algorithm for managing these competing risks is presented.

Topics: Adult; Algorithms; Anticoagulants; Antiphospholipid Syndrome; Blood Loss, Surgical; Dose-Response Relationship, Drug; Drug Administration Schedule; Enoxaparin; Evidence-Based Medicine; Female; Heparin; Heparin, Low-Molecular-Weight; Humans; Long-Term Care; Perioperative Care; Peritonsillar Abscess; Postoperative Hemorrhage; Risk Factors; Tonsillectomy; Venous Thrombosis; Warfarin

Venous thromboembolism (VTE) occurs more frequently in cancer patients than in non-cancer patients and outcomes are poor in patients with both cancer and thrombosis. Patients with cancer who develop thrombosis are more likely to experience a recurrence of VTE and have increased bleeding complications while receiving oral anticoagulant treatment. The purpose of this paper is to discuss the causes and outcomes of thrombosis in cancer patients, the limitations of warfarin therapy, the guidelines and data for the use of low-molecular-weight heparins (LMWHs) in the treatment and secondary prevention of thrombosis in cancer patients, and emerging data regarding survival with the use of LMWH in cancer patients.. Literature for this paper has been collected using multiple sources, including primary, secondary, and tertiary references. Online searches have been conducted utilizing the PubMed and OVID databases, and abstracts from the Proceedings of the American Society of Clinical Oncology and the American Society of Hematology Annual Meeting and Exhibition. The following key terms were used in the search: cancer, deep vein thrombosis, pulmonary embolism, anticoagulation, LMWHs, guidelines, survival, cost.. The long-term use of LMWHs in the settings of cancer and thrombosis are supported by recent clinical trial evidence that demonstrate their equivalent safety and improved efficacy when compared to oral anticoagulants resulting in their inclusion in current guidelines. Finally, newer studies offer further evidence of improved outcomes with dalteparin and nadroparin, including possible survival benefits.. Treatment with LMWHs has been shown to be more effective than warfarin in the extended treatment of VTE in patients with cancer and is safe in this setting. Use of a LMWH for at least the first 3-6 months of long-term treatment is now considered the standard of care for patients with cancer and is recommended in numerous guidelines. Additionally, further evaluation of the survival benefits of LMWH in cancer patients is warranted.

Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Survival Analysis; Thromboembolism; Treatment Outcome; Venous Thrombosis; Warfarin

To determine whether the use of low-dose warfarin could reduce the incidence of thrombosis in patients with cancer who have a central venous catheter (CVC).. MEDLINE, CINAHL, CANCERLIT, EMBASE, and the Cochrane Library.. Meta-analysis of four studies (N = 1,236 patients) revealed that 6.4% of warfarin-treated patients experienced a thrombotic event compared with 7.5% in the control (no treatment) group. The risk difference for thrombus formation was not significant (2.0%, confidence interval = -9.0% to 5.0%).. The administration of warfarin did not reduce the incidence of symptomatic or asymptomatic CVC-associated thrombosis in patients with cancer.. Using research findings to inform clinical nursing practice is important in caring for patients and providing optimal and improved patient outcomes. Prophylactic use of low-dose warfarin may not prevent thrombus formation and is associated with potentially adverse patient outcomes.

Topics: Anticoagulants; Catheterization, Central Venous; Humans; Neoplasms; Venous Thrombosis; Warfarin

A 39-year-old man with a history of deep vein thrombosis and septic arthritis of the left knee was treated with warfarin and cefazolin. Therapeutic prothrombin times and international normalized ratios (INRs) were maintained with warfarin 32 mg/week for approximately 1 month. When the patient's antibiotic regimen was changed from cefazolin to nafcillin 2 g every 4 hours, his INR declined significantly. His warfarin dosage had to be increased to a maximum of 88 mg/week to achieve a therapeutic INR. After completion of antibiotic therapy with nafcillin, the patient's warfarin requirements slowly declined over several weeks. A maintenance dosage of warfarin 42-48 mg/week was necessary after nafcillin discontinuation. Hepatic cytochrome P450 isoenzyme induction by nafcillin is likely the mechanism of a warfarin-nafcillin interaction. The usual onset of effect is within 1 week after starting nafcillin, and the offset of the effect is usually evident within 4 weeks after nafcillin discontinuation. In patients taking warfarin who are prescribed nafcillin, a 2-4-fold increase in the warfarin dose may be necessary, and clinicians should closely monitor INRs.

Topics: Adult; Anti-Bacterial Agents; Anticoagulants; Drug Interactions; Humans; International Normalized Ratio; Male; Nafcillin; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Evidence-Based Medicine; Heparin; Humans; Intermittent Pneumatic Compression Devices; Laparoscopy; Risk Assessment; Stockings, Compression; Time Factors; Vena Cava Filters; Venous Thrombosis; Warfarin

Without prophylaxis, rates of deep vein thrombosis (DVT) after major orthopedic surgery range from 40% to 60%. Randomized clinical trials over the past 30 years have provided evidence that primary thromboprophylaxis reduces DVT, pulmonary embolism (PE), and fatal PE, and prophylaxis to prevent venous thromboembolism (VTE) in patients at risk has been ranked as the highest safety practice for hospitalized patients. Since 1986, some type of prophylaxis has been recommended for total knee arthroplasty (TKA), total hip arthroplasty (THA), and hip fracture surgery. Orthopedic guidelines published in Chest provide a current evidence-based guide for prophylaxis for TKA, THA, and hip fracture surgery. In addition to following these recommendations for routine prophylaxis, surgeons should assess patients for additional VTE risk. Patients at higher risk may need more intense prophylaxis. Data from meta-analyses and placebo-controlled, blinded, randomized clinical trials have demonstrated little or no increase in rates of clinically important bleeding with prophylaxis.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Hip Fractures; Humans; Postoperative Complications; Practice Guidelines as Topic; Pulmonary Embolism; Risk Factors; Venous Thrombosis; Warfarin

We presented a patient suffered from stroke related to thalidomide therapy. The patient was a 74-year-old man who had about two-year history of multiple myeloma and treated with 100 mg of oral thalidomide daily. He was diagnosed as having cryptogenic stroke attributable to patent foramen ovale, when he admitted to our hospital with sudden onset left-side hemiparesis. Antiplatelet and neuroprotective therapies were commenced along with the use of elastic stocking to prevent further embolic event. Then, warfarin was selected as secondary prevention to reduce the risk of paradoxical embolism during thalidomide therapy. Although the risk of deep vein thrombosis on thalidomide therapy has been well documented, only a few cases have been noted documenting the risk of stroke during thalidomide therapy. We need to be careful about the risk of deep vein thrombosis on thalidomide therapy, even as monotherapy, and consider using anticoagulant therapy while prescribing thalidomide.

Topics: Aged; Anticoagulants; Aspirin; Embolism, Paradoxical; Foramen Ovale, Patent; Humans; Male; Multiple Myeloma; Neuroprotective Agents; Risk; Stockings, Compression; Stroke; Thalidomide; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Antineoplastic Agents; Catheterization; Catheters, Indwelling; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Venous Thrombosis; Warfarin

The antiphospholipid syndrome is described with a review of its historical development as a recognized syndrome, what constitutes an antiphospholipid antibody, how it is measured, and how the syndrome is treated. Antiphospholipid antibodies are actually antibodies to a protein, most often beta-2-glycoprotein 1, that is usually bound to a phospholipid. Some antibodies are directed towards lipid-bound prothrombin. The antibodies are measured by immunologic assays or by antibody-dependent abnormalities detected in coagulation assays. Although they prolong coagulation assays, they are associated with a thrombotic tendency rather than a bleeding disorder. There are numerous postulated mechanisms to account for the thrombotic tendency. Patients with the antiphospholipid syndrome are treated with long-term oral anticoagulation to prolong the INR to 2.0 to 3.0. For most patients, a more intense level of treatment with a higher INR is not needed.

Topics: Aged; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; beta 2-Glycoprotein I; Enoxaparin; False Positive Reactions; Female; Glycoproteins; Humans; Stroke; Time Factors; Venous Thrombosis; Warfarin

Venous thromboembolic disease (VTD), which consists primarily of deep venous thrombosis (DVT) and pulmonary embolism (PE), is of significant concern to orthopedic surgeons who perform total hip and total knee arthroplasties. DVT and PE can be prevented in multiple ways; each method or combination of methods has its benefits and drawbacks. Seemingly, the more efficacious a medication or method for preventing VTD, the higher the associated risk for adverse events such as bleeding and wound complications. For each patient, then, the balance or homeostasis between significant clotting event and bleeding must be determined. Examining this balance and understanding the benefits and risks associated with each medication or intervention may allow surgeons to make educated decisions about prophylaxis for their patients. Furthermore, risk stratification and multimodal management may prove to be the safest and most effective way to manage VTD prevention.

Topics: Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Heparin; Humans; Male; Phlebography; Platelet Aggregation Inhibitors; Postoperative Complications; Pulmonary Embolism; Reoperation; Risk Assessment; Venous Thrombosis; Warfarin

Despite the significant advances over the last 50 years with regard to anticoagulant therapy, warfarin remains the definitive standard for the long-term prevention of thromboembolic events in at-risk patients, except those with acute coronary syndromes, in which antiplatelets are preferred. Ximelagatran, a prodrug of melagatran, is an orally administered direct thrombin inhibitor whose therapeutic potential has been investigated in venous thromboembolism, acute coronary syndromes and prevention of stroke in atrial fibrillation. Clinical studies have demonstrated ximelagatran to be comparable in efficacy to the oral vitamin K antagonist warfarin and low molecular weight heparin for prophylaxis of venous thromboembolism, comparable to warfarin for stroke prevention in the setting of atrial fibrillation, and, when combined with aspirin, more effective than aspirin alone at preventing major adverse cardiovascular events in patients with a recent myocardial infarction. Double-blind trials have also revealed the efficacy of ximelagatran in the secondary prevention of venous thromboembolism and shown the agent to be as effective as enoxaparin/warfarin in treating patients with acute deep vein thrombosis. Adverse effects with ximelagatran include elevations in alanine transaminase (ALT), which may require monitoring, and bleeding complications. Bleeding complications appear to be less than or at least comparable to those occurring with standard anticoagulant treatments like warfarin or low molecular weight heparin. In addition to its favorable efficacy and safety profile in comparison with standard anticoagulant therapy, the convenience of its oral, fixed-dose administration without the need for anticoagulation monitoring might help encourage a wider use of appropriate anticoagulation using ximelagatran across the population at risk, reducing the incidence of thromboembolic events.

Topics: Administration, Oral; Anticoagulants; Azetidines; Benzylamines; Drug Administration Schedule; Humans; Myocardial Infarction; Randomized Controlled Trials as Topic; Secondary Prevention; Stroke; Thrombin; Thromboembolism; Venous Thrombosis; Warfarin

Venous thromboembolism (VTE) constitutes an important health problem in developed countries. Owing to their underlying malignancies, people with cancer are at particularly high risk of VTE. The level of this risk is influenced by several factors, including type of cancer and the presence or absence of metastases. However, different types of oncology treatment can also further increase the thrombotic risk. Consequently, primary and secondary thromboprophylaxis in people with cancer should be considered as part of any integrated oncology treatment. Moreover, recent exciting studies have suggested that low molecular weight heparins (LMWH) may also influence overall survival in people with cancer. Clearly, these findings raise the likelihood that the use of LMWH in oncology practice may increase significantly in the near future. However, it is important to appreciate that the use of thromboprophylaxis in people with cancer is complicated by a number of specific problems. In this overview, we have systematically addressed the difficult clinical issues that are involved in the selection of appropriate primary and secondary thromboprophylaxis for people with cancer.

Topics: Anticoagulants; Heparin; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Pulmonary Embolism; Risk Factors; Venous Thrombosis; Warfarin

Anticoagulant therapy includes unfractionated heparin and vitamin K antagonists' administration. In both of these two types of drugs a treatment failure could occur. Currently available anticoagulants have a numerous disadvantages which could be involved in causes of their malfunctioning. During every new event of the re-thrombosis it is necessary to analyse all circumstances which influence this unfavourable outcome. Firstly, cases during adequate and non-adequate therapy should be distinguished. Secondly, it is important to identify the reasons of the treatment failure. Cancer and/or antiphospholipid antibodies are the main causes of re-thrombosis during adequate therapy. The conditions, which could steer for to non-adequate anticoagulation are various, and their identification could be difficult. The most important thing in this process is the objective documentation of the re-thrombosis. More efficacious, safer, and easier to use anticoagulants are under development. Some of them could bring a problem solution for these patients who underwent anticoagulant treatment failure.

Topics: Anticoagulants; Heparin; Humans; Pulmonary Embolism; Recurrence; Thromboembolism; Treatment Failure; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Thromboembolism; Venous Thrombosis; Warfarin

Warfarin and azathioprine may be prescribed concurrently in patients requiring both anticoagulation and immunosuppression. However, a potential interaction between the 2 drugs, resulting in an increased warfarin requirement, may be overlooked in clinical practice.. A 67-year-old woman was treated with warfarin (initial mean dose, 24 mg/wk [3.5 mg/d]) for >3 years for recurrent deep vein thrombosis associated with systemic lupus erythematosus. Soon after commencing warfarin, azathioprine 150 mg/d was introduced for its steroid-sparing effect. Warfarin was titrated to a mean dose of 60 to 75 mg/wk (8.5-10.5 mg/d) over the next 18 months. Her dose of azathioprine was then increased to 200 mg/d. Subtherapeutic international normalized ratio (INR) levels required an increase in the warfarin dose to a mean of 130 mg/wk (18.5 mg/d). Subsequent discontinuation of azathioprine resulted in a dramatic increase in her INR levels (from 1.8 to 14.0 four weeks after discontinuation).. A temporal relationship, demonstrating the interaction between warfarin and azathioprine, was evident at various times during therapy for our patient. This case, together with 7 additional published cases, is comprehensively reviewed here using previously described criteria for establishing a definite interaction between warfarin and other drugs.. The evidence supports a clinically important inhibitory action of azathioprine on warfarin and calls for closer monitoring of INR levels when azathioprine doses are altered during concurrent administration with warfarin.

Topics: Aged; Anticoagulants; Azathioprine; Drug Antagonism; Female; Humans; Immunosuppressive Agents; International Normalized Ratio; Lupus Erythematosus, Systemic; Venous Thrombosis; Warfarin

Deep vein thrombosis and its lethal complication pulmonary embolism are manifestations of venous thromboembolism (VTE), which is typically associated with cancer and recent major surgery. Certain solid tumors and hematologic malignancies impose an inherently elevated risk of VTE that is compounded by chemotherapy and other risk factors. Multiple myeloma (MM) and other plasma cell dyscrasias are thrombogenic as a consequence of their multiple hemostatic effects, including elevated interleukin-6 levels, pro-coagulant antibody formation, paraprotein interference with fibrin structure, activated protein C resistance, and endothelial damage. The oral immunomodulatory drugs thalidomide and lenalidomide have produced major therapeutic responses in patients with MM when used in combination with oral steroids and chemotherapy, but a high incidence of VTE has been reported. Various VTE prophylaxis strategies with thalidomide- and lenalidomide-containing combinations have been investigated in clinical studies. This review discusses emerging results on the use of VTE prophylaxis to minimize VTE risks associated with MM treatment regimens containing thalidomide and lenalidomide.

Topics: Anticoagulants; Aspirin; Clinical Trials as Topic; Drug Therapy, Combination; Embolism; Factor V; Heparin, Low-Molecular-Weight; Humans; Immunologic Factors; Multiple Myeloma; Mutation; Prothrombin; Risk Reduction Behavior; Treatment Outcome; Venous Thrombosis; Warfarin

Venous thromboembolism (VTE), which is manifested as deep vein thrombosis (DVT) and pulmonary embolism (PE), represents a significant cause of death, disability, and discomfort. They are frequent complications of various surgical procedures. The aging population and the survival of more severely injured patients may suggest an increasing risk of thromboembolism in the trauma patients. Expanded understanding of the population at risk challenges physicians to carefully examine risk factors for VTE to identify high-risk patients who can benefit from prophylaxis. An accurate knowledge of evidence-based risk factors is important in predicting and preventing postoperative DVT, and can be incorporated into a decision support system for appropriate thromboprophylaxis use. Standard use of DVT prophylaxis in a high-risk trauma population leads to a low incidence of DVT. The incidence of VTE is common in Asia. The evaluation includes laboratory tests, Doppler test and phlebography. Screening Doppler sonography should be performed for surveillance on all critically injured patients to identify DVT. D-Dimer is a useful marker to monitor prophylaxis in trauma surgery patients. The optimal time to start prophylaxis is between 2 hours before and 10 hours after surgery, but the risk of PE continues for several weeks. Thromboprophylaxis includes graduated compression stockings and anticoagulants for prophylaxis. Anticoagulants include Warfarin, which belongs to Vitamin K antagonists, unfractionated heparin, low molecular weight heparins, factor Xa indirect inhibitor Fondaparinux, and the oral IIa inhibitor Melagatran and ximelagatran. Recombinant human soluble thrombomodulin is a new and highly effective antithrombotic agent. Prophylactic placement of vena caval filters in selected trauma patients may decrease the incidence of PE. The indications for prophylactic inferior vena cava filter insertion include prolonged immobilization with multiple injuries, closed head injury, pelvic fracture, spine fracture, multiple long bone fracture, and attending discretion. Multiple-trauma patients are at increased risk for DVT but are also at increased risk of bleeding, and the use of heparin may be contraindicated. Serial compression devices (SCDs) are an alternative for DVT prophylaxis. Compression devices provide adequate DVT prophylaxis with a low failure rate and no device-related complications. Immobilization is one of important reasons of VTE. The ambulant patient is far less li

Topics: Anticoagulants; Factor Xa Inhibitors; Heparin; Heparin, Low-Molecular-Weight; Humans; Orthopedic Procedures; Postoperative Complications; Pulmonary Embolism; Recombinant Proteins; Risk Factors; Thrombomodulin; Vena Cava Filters; Venous Thrombosis; Vitamin K; Warfarin

Anticoagulant therapy is the cornerstone of treatment of venous thromboembolism (VTE). Such treatment is divided into two stages. Rapid initial anticoagulation is given to minimize the risk of thrombus extension and fatal pulmonary embolism, whereas extended anticoagulation is aimed at preventing recurrent VTE, thereby reducing the risk of postphlebitic syndrome. With currently available drugs, immediate anticoagulation can only be achieved with parenteral agents, such as heparin, low-molecular-weight heparin, or fondaparinux. Extended treatment usually involves the administration of vitamin K antagonists, such as warfarin. Emerging anticoagulants have the potential to streamline VTE treatment. These agents include idraparinux, a long-acting synthetic pentasaccharide that is given subcutaneously on a once-weekly basis, and new oral anticoagulants that target thrombin or factor Xa. This paper i) reviews the pharmacology of these agents, ii) outlines their potential strengths and weaknesses, iii) describes the results of clinical trials with these new drugs, and iv) identifies the evolving role of new anticoagulants in the management of VTE.

Topics: Anticoagulants; Fondaparinux; Glycosaminoglycans; Heparin, Low-Molecular-Weight; Humans; Models, Chemical; Oligosaccharides; Polysaccharides; Postphlebitic Syndrome; Pulmonary Embolism; Thromboembolism; Venous Thrombosis; Vitamin K; Warfarin

Topics: Anticoagulants; Aspirin; Chemoprevention; Heparin; Hip Fractures; Humans; Risk Assessment; Risk Factors; Thromboembolism; Time Factors; Venous Thrombosis; Warfarin

Antiplatelet therapy with aspirin and clopidogrel is standard care following revascularization by percutaneous coronary intervention with stent insertion. This so-called dual therapy is recommended for up to 4 weeks after intervention for bare-metal stents and for 6-12 months after intervention for drug-eluting stents. Although it is estimated that 5% of patients undergoing percutaneous coronary intervention require long-term anticoagulation because of an underlying chronic medical condition, continuing treatment with triple therapy (warfarin, aspirin and clopidogrel) increases the risk of bleeding. In most patients triple antithrombotic therapy seems justified for a short period of time. In some patients, however, a more considered judgment based on absolute need for triple therapy, risk of bleeding and risk of stent thrombosis is required, but the optimum antithrombotic treatment for these patients who require long-term anticoagulation has not been defined. This Review summarizes the existing literature concerning antithrombotic therapy and makes recommendations for initiation and duration of triple therapy in the small proportion of patients already receiving anticoagulant therapy who require percutaneous coronary intervention.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Drug Administration Schedule; Drug Therapy, Combination; Heart Valve Prosthesis Implantation; Heparin; Humans; Platelet Aggregation Inhibitors; Postoperative Hemorrhage; Practice Guidelines as Topic; Risk Factors; Stents; Thrombosis; Ticlopidine; Venous Thrombosis; Warfarin

Topics: Abdomen; Anticoagulants; Aspirin; Heparin; Humans; Pelvis; Postoperative Complications; Venous Thrombosis; Warfarin

Ximelagatran has been recently studied for prophylaxis in surgical orthopedic cases.. We proposed to establish whether interventions involving ximelagatran, as compared with warfarin, would increase thromboembolic prophylaxis in patients undergoing major orthopedic knee surgery.. Studies with random assignment were identified by an electronic search of the medical literature up to 2006. Data were double-entered into the Review Manager software, version 4.2.5.. We included three well-conducted clinical trials involving 4,914 participants. Sub-groups with two dosages of ximelagatran (24 mg and 36 mg, b.i.d.), were defined. Ximelagatran showed significantly lower frequency of total venous thromboembolism (VTE) than warfarin, but only with the 36-mg dosage (risk relative, RR: 0.72; 95% confidence interval, CI: 0.64-0.81; p < 0.00001). For the 24-mg subgroup, total VTE frequency was similar (RR: 0.86; 95% CI: 0.73-1.01; p = 0.06). No significant differences were shown with either ximelagatran dosage for deep vein thrombosis (DVT), pulmonary embolism, any bleeding or severe bleeding. At the end of the treatment, alanine aminotransferase (ALT) elevation was less frequent in the 24-mg ximelagatran sub-group (RR: 0.33; 95% CI: 0.12-0.91; p = 0.03], but during the follow-up period, the ALT elevation rate was greater in the 36-mg ximelagatran group (RR: 6.97; 95% CI: 1.26-38.50; p = 0.03].. Ximelagatran appears to be more effective than warfarin when used in higher dosages (36 mg b.i.d.), but at the expense of increased frequency of ALT elevation during the follow-up period.

Topics: Aged; Anticoagulants; Azetidines; Benzylamines; Brazil; Epidemiologic Methods; Hemorrhage; Humans; Knee; Orthopedic Procedures; Pulmonary Embolism; Thromboembolism; Venous Thrombosis; Warfarin

Patients undergoing general surgery present an inherent risk of deep vein thrombosis (DVT). Evidence-based strategies for prevention and treatment of DVT should be continuously upgraded on the basis of good-quality recent trials.. Articles were identified using MEDLINE, EMBASE, and the Cochrane Library databases (January 1980 to July 2003). Randomized clinical trials and meta-analyses in which different prophylactic and treatment methods were compared for general surgery patients were selected.. In general surgery, low-molecular weight heparins (LMWHs) are relied upon more and more for prophylaxis and initial anticoagulant treatment of DVT, because of their multiple advantages in efficacy, safety, and convenience in handling. For cost-effective reasons, full-dose vitamin K antagonists are still preferred as the standard long-term anticoagulation method, while LMWHs represent the exception. Long-term use of low-intensity warfarin should be considered a new standard of care for the management of venous thrombosis. Compared to LMWH, the new anticoagulant molecules fondaparinux and ximelagatran seem to have similar efficacy in the treatment of venous thromboembolism, but they have a 2-fold increased efficacy in its prophylaxis. Clinical implementation of these new anticoagulant molecules depends on their cost-effectiveness; however, they have the potential to become the treatment of choice in the next decade. Thrombolysis has an unacceptable risk of hemorrhagic complications when used in the treatment of postoperative DVT. Furthermore, there are no data to prove that thrombolysis reduces the incidence of postthrombotic syndrome (PTS), despite early and complete recanalization achieved by thrombolysis. Surgical thrombectomy is only meant to decompress the venous hypertension consecutive to massive thrombosis (phlegmasia cerulea dolens) and thus to avoid venous gangrene. Other mechanical percutaneous thrombectomy devices are under evaluation. In selected cases, a combination treatment consisting of locoregional thrombolysis of the crurofemoral venous axis and mechanical thrombectomy of the pelvic venous axis achieves high rates of complete desobliteration.

Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Postoperative Complications; Risk Assessment; Surgical Procedures, Operative; Thrombectomy; Thrombolytic Therapy; Venous Thrombosis; Vitamin K; Warfarin

The limitations of traditional anticoagulants, heparin and warfarin, have prompted the development of new anticoagulant drugs for prevention and treatment of both venous and arterial thromboembolism. After a brief review of thrombogenesis and its regulation, this paper focuses on new anticoagulant agents in more advanced stages of clinical testing.

Topics: Animals; Anticoagulants; Drugs, Investigational; Heparin, Low-Molecular-Weight; Humans; Venous Thrombosis; Warfarin

Venous thromboembolic disease has an estimated annual incidence of one in 1000 people. However, thrombosis of the superior mediastinum and neck veins is less frequent and it is usually due to direct trauma to the neck by intravenous catheters, drug abusers or neck dissection surgery. Local or distant malignancy (Trousseau's syndrome) is also an important cause. Thrombosis of the superior mediastinal and internal jugular veins is rarely a cause of primary referral to the otolaryngologist. On these rare occasions, it can present as a painful neck mass, but may also present with stridor, dysphonia or dysphagia. The four patients presented here illustrate different ways of presentation. Different imaging techniques such as ultrasound, computed tomography (CT) scan, magnetic resonance imaging (MRI) and venogram, will produce a diagnosis of thrombosis, occasionally with a mass, but only a biopsy will confirm or rule-out malignancy. Spontaneous thrombophlebitis can be the first manifestation of an occult neoplasm and any investigation into venous thrombosis must include a thorough general examination and follow up.

Topics: Aged; Anticoagulants; Fatal Outcome; Female; Heparin; Humans; Jugular Veins; Male; Mediastinum; Middle Aged; Superior Vena Cava Syndrome; Tomography, X-Ray Computed; Treatment Outcome; Venous Thrombosis; Warfarin

Because the costs of anticoagulation therapy are substantial and the difference between the risks and benefits of this therapy are often narrow, economic analyses are particularly valuable when weighing anticoagulation options. Economic analyses to date suggest that anticoagulation is most effective and results in the greatest cost savings when applied to populations at highest risk for thrombotic events. They also suggest that in situations where a more costly anticoagulant agent is available, that agent is cost-effective only if it is clearly more efficacious or if it substantially reduces costs in other areas, such as hospitalization. These principles should guide clinicians' choices of anticoagulation strategies.

Topics: Anticoagulants; Cost-Benefit Analysis; Drug Costs; Fondaparinux; Health Care Costs; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Thromboembolism; Venous Thrombosis; Warfarin

The management of spontaneous intracerebral haemorrhage (ICH) can be challenging for hospital doctors. Although the management of ICH is covered in stroke guidelines, many difficult clinical questions remain. In this article the authors suggest approaches to ten common and difficult questions.

Topics: Anticoagulants; Aspirin; Brain Ischemia; Cerebral Hemorrhage; Hospitalization; Humans; Magnetic Resonance Angiography; Medical Records; Myocardial Infarction; Neurosurgical Procedures; Patient Education as Topic; Patient Selection; Platelet Aggregation Inhibitors; Pulmonary Embolism; Referral and Consultation; Terminology as Topic; Venous Thrombosis; Warfarin

Topics: Administration, Oral; Anticoagulants; Evidence-Based Medicine; Humans; International Normalized Ratio; Thromboembolism; Venous Thrombosis; Warfarin

Topics: Algorithms; Anticoagulants; Blood Coagulation; Drug Interactions; Drug Monitoring; Heparin; Humans; Nursing Assessment; Patient Education as Topic; Practice Guidelines as Topic; Risk Factors; Thromboembolism; Time Factors; Venous Thrombosis; Warfarin

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, dosage and administration, contraindications, and adverse effects of ximelagatran are reviewed.. Ximelagatran is the first orally active direct thrombin inhibitor to be tested in Phase III clinical trials. After oral administration, ximelagatran is rapidly converted to its active metabolite, melagatran. Melagatran (after oral ximelagatran administration) predictably inhibits thrombin function without need for routine anticoagulation monitoring. Melagatran effectively inhibits both free and clot-bound thrombin-a potential pharmacodynamic advantage over heparin products. Melagatran has a half-life of 2.4-4.6 hours, necessitating twice-daily administration. Melagatran is primarily eliminated by the kidneys and has not been studied clinically in patients with severe renal failure. Ximelagatran has undergone 10 Phase III trials (6 for prophylaxis of venous thromboembolism [VTE] due to orthopedic surgery, 1 for initial treatment of VTE, 1 for long-term prevention of VTE recurrence, and 2 for stroke prophylaxis due to atrial fibrillation). Results were generally positive. AstraZeneca applied in December 2003 for marketing approval of ximelagatran for prevention of VTE after total knee replacement surgery, long-term prevention of VTE recurrence after standard therapy, and stroke prevention due to atrial fibrillation. FDA denied approval of ximelagatran for all indications, mainly because of increased rates of coronary artery disease events in ximelagatran recipients in some studies and the possibility of hepatic failure when the medication is used for long-term therapy.. Ximelagatran has shown promise as a possible alternative to warfarin and other anticoagulants but will require further study to ensure its safety.

Topics: Anticoagulants; Atrial Fibrillation; Azetidines; Benzylamines; Biological Availability; Clinical Trials, Phase III as Topic; Drug Interactions; Half-Life; Humans; Metabolic Clearance Rate; Stroke; Thrombin; Thromboembolism; Venous Thrombosis; Warfarin

Vitamin K antagonists (coumarins) are widely-used oral anticoagulants for the prevention of venous thromboembolism and strokes. Wide inter-individual variation in dose response and frequent bleeds characterize the initiation of coumarin therapy. Over the past 10 years both genetic and nongenetic determinants of coumarin dose response have been identified. A comprehensive pharmacogenetics approach to warfarin therapy has the potential to improve the safety and efficiency of warfarin initiation.

Topics: Anticoagulants; Blood Coagulation; Coumarins; Humans; Models, Biological; Pharmacogenetics; Stroke; Venous Thrombosis; Warfarin

Ximelagatran is a direct thrombin inhibitor that offers numerous potential advantages compared with traditional anticoagulants. It is given orally, has a rapid onset of action, does not require laboratory monitoring, and is not associated with immune-mediated thrombocytopenia. Numerous phase III trials with ximelagatran focusing on deep vein thrombosis prophylaxis and treatment, stroke prevention in patients with atrial fibrillation, and secondary prevention after acute myocardial infarction have been conducted. Results of these trials indicate that ximelagatran has similar efficacy and risk of bleeding compared with currently used anticoagulants. Accordingly, the potential of this agent to replace warfarin therapy for a variety of indications has been widely touted. Ximelagatran has already been approved in Europe for prophylaxis of venous thromboembolism in patients undergoing hip or knee surgery. However, an adverse effect of ximelagatran is liver enzyme elevation, which has been observed in 5% to 10% of patients with chronic administration of the drug. Although initially felt to be transient in nature, subsequent data presented to the Federal Drug Administration suggest a small but real risk of significant hepatotoxicity. These data led the advisory committee to the Federal Drug Administration to recommend against immediate approval of ximelagatran pending further information. The consistent results of completed trials with ximelagatran suggest that it has the potential to be used in many conditions that currently require treatment with warfarin and heparin products. The potential benefit that may be achieved by the replacement of these historically problematic narrow therapeutic index agents must be weighed against as yet undetermined long-term risks of hepatotoxicity.

Topics: Administration, Oral; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Azetidines; Benzylamines; Humans; Myocardial Infarction; Stroke; Thrombin; Thromboembolism; Venous Thrombosis; Warfarin

Intravenous (IV) infusion of unfractionated heparin (UFH) followed by oral administration of warfarin remains the cornerstone of clinical treatment of deep vein thrombosis (DVT). Results from numerous clinical trials demonstrate that subcutaneously administered low-molecular-weight heparin (LMWH) is at least as effective and as safe as IV UFH. Treatment with LMWH has several clinical advantages over treatment with UFH, including less-frequent dosing and elimination of the need for monitoring. The introduction of LMWHs has made it possible for physicians to offer outpatient treatment of DVT, with the associated advantage of reduced costs due to shortened hospital stays. However, the optimal duration of anticoagulant therapy after DVT is still debated, as it depends on an individual patient's potential risk for recurrence or treatment-associated complications. Patients are usually risk stratified on the basis of multiple clinical characteristics, including the location of thromboemboli, the presence or absence of cancer, the assumed etiology or cause of DVT (idiopathic vs. due to a transient risk factor), and the presence of certain thrombophilic conditions. High-risk patients often receive inpatient treatment with UFH or LMWH and are candidates for long-term (> or = 6 months) oral anticoagulation, whereas short-term anticoagulation (3 to 6 months) is usually indicated for patients who are at lower risk of recurrence or therapeutic complications and who can be treated with LMWH on an outpatient basis. The introduction of LMWHs has resulted in significant clinical progress for the treatment of DVT.

Topics: Ambulatory Care; Anticoagulants; Clinical Trials as Topic; Contraindications; Drug Administration Schedule; Heparin; Hospitalization; Humans; Venous Thrombosis; Warfarin

Topics: Chemoprevention; Heparin, Low-Molecular-Weight; Humans; Perioperative Care; Postoperative Complications; Pulmonary Embolism; Risk Assessment; Risk Factors; Venous Thrombosis; Warfarin

Recent clinical trials are answering some of the perplexing clinical questions about venous thromboembolism (VTE), such as the length and intensity of anticoagulation needed to prevent recurrence. We review some of these clinical trials and their implications for physicians and patients.

Topics: Anticoagulants; Clinical Trials as Topic; Factor V; Humans; Risk Factors; Secondary Prevention; Thromboembolism; Venous Thrombosis; Warfarin

Acutely ill general medical patients are at moderate-to-high risk of venous thromboembolism (VTE); approximately 10-30% may develop deep vein thrombosis or pulmonary embolism, the latter being a leading contributor to deaths in hospital. Medical conditions associated with a high risk of VTE include cardiac disease, cancer, respiratory disease, inflammatory bowel disease, and infectious disease. Predisposing risk factors for VTE in medical patients include history of VTE, history of malignancy, complicating infections, increasing age, thrombophilia, prolonged immobility, and obesity. Unfractionated heparin (UFH), low-molecular weight heparin (LMWH), and fondaparinux sodium have been shown to be effective agents in the prevention of VTE in medical patients. In this setting, UFH has a higher rate of bleeding complications than LMWH. There is no evidence supporting the use of aspirin, warfarin, or mechanical methods to prevent VTE in medical patients. We recommend either LMWH or fondaparinux sodium as well tolerated and effective thromboprophylactic agents in medical patients.

Topics: Anticoagulants; Aspirin; Bandages; Clinical Trials as Topic; Heparin; Humans; Intermittent Pneumatic Compression Devices; Risk Factors; Thromboembolism; Venous Thrombosis; Warfarin

To provide oncology nurses with an understanding of therapeutic options for cancer-associated thrombosis, strategies to prevent recurrence, and practical issues in patient management.. Primary and tertiary literature and the author's clinical experience.. Oncology nurses monitor patients throughout the care continuum for signs and symptoms indicating vascular thromboembolism and need to know the steps to take to expedite an accurate diagnosis and ensure prompt treatment.. Oncology nurses must keep informed about the evolving evidence that leads to practice changes. They should be able to teach patients about therapeutic options and their potential for improving outcomes.

Topics: Anticoagulants; Hemorrhage; Humans; Neoplasms; Oncology Nursing; Risk Factors; Vena Cava Filters; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Dose-Response Relationship, Drug; Humans; Long-Term Care; Secondary Prevention; Thromboembolism; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Dose-Response Relationship, Drug; Humans; Recurrence; Risk Factors; Thromboembolism; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Thromboembolism; Thrombolytic Therapy; Venous Thrombosis; Warfarin

Venous thromboembolism (VTE) is a serious disorder and a major cause of morbidity and mortality among acutely ill medical patients. However, despite the growing number of patients with acute medical illnesses who have an associated risk of VTE, the widespread use of VTE prophylaxis does not yet occur for both surgical and nonsurgical patients. Although individuals at greatest risk for VTE include patients undergoing major orthopedic surgery and those with medical conditions that require prolonged immobilization, all patients who have acute medical illnesses should be considered for VTE prophylaxis. Several strategies, including various mechanical and pharmacologic approaches, are currently used for VTE prophylaxis. Increased awareness about the full range of options for VTE prophylaxis can help health care providers select the appropriate course of action to help reduce the incidence of VTE among patients with acute medical illnesses.

Topics: Anticoagulants; Aspirin; Bandages; Combined Modality Therapy; Heparin, Low-Molecular-Weight; Intermittent Pneumatic Compression Devices; Platelet Aggregation Inhibitors; Postoperative Complications; Randomized Controlled Trials as Topic; Thromboembolism; Vena Cava Filters; Venous Thrombosis; Warfarin

Atrial fibrillation is the most frequently encountered tachyarrhythmia requiring therapy. Treatment issues include therapy for any reversible cause; the identification and treatment of any underlying structural disorder; control of the ventricular rate, both for symptom reduction and prevention of tachycardic-induced cardiomyopathy; restoration and maintenance of sinus rhythm when symptoms persist despite rhythm control; and anticoagulation in patients with high-risk markers for systemic embolization: age over 65 years, hypertension, diabetes, ventricular failure, rheumatic valvular disease, and prior stroke or other embolic event. In such patients, anticoagulation with warfarin is currently recommended. Warfarin therapy carries significant risks (especially bleeding), inconveniences (the cost of prothrombin time monitoring, the need for rigid dietary stability, the concerns of drug and herbal interactions), and other concerns (the issue of generic formulation substitution).. Under development are oral thrombin inhibitors. The first to reach clinical approval will likely be ximelagatran. In clinical trials to date, ximelagatran has proven to be equal to or superior to warfarin in the prevention and treatment of thrombophlebitis. In atrial fibrillation patients, the Stroke Prevention Using Oral Thrombin Inhibitor in Atrial Fibrillation (SPORTIF) trials completed so far appear to show a similar or better efficacy for ximelagatran versus warfarin as regards both prevention of embolic events and lower risks of major bleeding, with no serious adverse effects except for apparently reversible alterations in liver function tests in approximately 6% of subjects, all occurring early in therapy to date. If the remaining SPORTIF trial (SPORTIF V) is confirmatory (results to be available in late 2003), it is expected that this exciting new product will be submitted this winter to the Food and Drug Administration for approval. Recent findings also include the observations in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) and Rate Control Versus Electrical Cardioversion (RACE) trials that anticoagulation should not be discontinued despite the restoration and maintenance of sinus rhythm.. Oral direct thrombin inhibitors, such as ximelagatran, appear likely to replace the use of warfarin in most patients in the near future, because of a better risk-benefit profile.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Azetidines; Benzylamines; Clinical Trials as Topic; Embolism; Fibrinolytic Agents; Humans; Prothrombin Time; Randomized Controlled Trials as Topic; Stroke; Venous Thrombosis; Warfarin

A 67-year-old man receiving a stable maintenance dosage of warfarin experienced an increased international normalized ratio (INR) without bleeding when his atorvastatin therapy was switched to fluvastatin. His warfarin dosage was reduced and his INR stabilized. The fluvastatin was switched back to atorvastatin, and the warfarin dosage was increased to maintain the patient's goal INR. The literature supports a drug interaction between warfarin and fluvastatin due to the strong affinity of fluvastatin for the cytochrome P450 enzyme 2D6. This interaction has not been seen with atorvastatin. Lovastatin also reportedly has caused increases in INR when coadministered with warfarin. It is unclear whether simvastatin interacts with warfarin, but it may increase INRs slightly or increase serum simvastatin levels. One case report describes an interaction between simvastatin and the anticoagulant acenocoumarol, which resulted in an elevated INR. Pravastatin does not appear to interact with warfarin but has caused an increased INR when combined with the anticoagulant fluindione. Thus, until more definitive data are available, clinicians should monitor the INR closely after starting statin therapy in any patient receiving anticoagulation therapy.

Topics: Acenocoumarol; Administration, Oral; Aged; Anticoagulants; Atorvastatin; Drug Interactions; Fatty Acids, Monounsaturated; Fluvastatin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; International Normalized Ratio; Male; Patient Compliance; Pyrroles; Simvastatin; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Clinical Trials as Topic; Humans; Immobilization; Neoplasms; Risk Factors; Venous Thrombosis; Warfarin

Ximelagatran (Exanta), the first available oral direct thrombin inhibitor, and its active form, melagatran, have been evaluated in the prevention of venous thromboembolism (VTE) in patients undergoing hip or knee replacement. After oral administration ximelagatran is rapidly bioconverted to melagatran. Melagatran inactivates both circulating and clot-bound thrombin by binding to the thrombin active site, thus, inhibiting platelet activation and/or aggregation and reducing fibrinolysis time. The efficacy of subcutaneous melagatran followed by oral ximelagatran has been investigated in four European trials and the efficacy of an all oral ximelagatran regimen has been investigated in five US trials. In a dose-ranging European study, preoperatively initiated subcutaneous melagatran 3 mg twice daily followed by oral ximelagatran 24 mg twice daily was significantly more effective than subcutaneous dalteparin sodium 5000IU once daily in preventing the occurrence of VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients undergoing hip or knee replacement. In one study, there were no significant differences in VTE prevention between subcutaneous melagatran 3 mg administered after surgery followed by ximelagatran 24 mg twice daily and enoxaparin sodium (enoxaparin) 40 mg once daily. Compared with enoxaparin, significantly lower rates of proximal DVT and/or PE (major VTE) and total VTE were observed when melagatran was initiated preoperatively (2mg) then postoperatively (3mg) and followed by ximelagatran 24 mg twice daily. In the US, four studies showed that postoperatively initiated ximelagatran 24 mg twice daily was of similar efficacy to enoxaparin or warfarin in the prevention of VTE in patients undergoing hip or knee replacement. However, ximelagatran 36 mg twice daily was superior to warfarin (target international normalised ratio of 2.5) at preventing the incidence of VTE in patients undergoing total knee replacement in two studies.Ximelagatran alone or after melagatran was generally well tolerated. Overall, the incidence of bleeding events and transfusion rates were not markedly different from those documented for comparator anticoagulants. In a post-hoc analysis of one study, transfusion rates were lower in ximelagatran than enoxaparin recipients.. Oral ximelagatran alone or in conjunction with subcutaneous melagatran has shown good efficacy and was generally well tolerated in the prevention of VTE in patients undergoing orthopaedic surgery. Furthermore, patients receiving ximelagatran/melagatran do not require anticoagulant monitoring. The drug has a low potential for drug interactions and can be administered either by subcutaneous injection or orally. Thus, on the basis of available evidence, ximelagatran/melagatran appears poised to play an important role in the prophylaxis of VTE in patients undergoing orthopaedic surgery.

Topics: Anticoagulants; Azetidines; Benzylamines; Drug Interactions; Drug Therapy, Combination; Enoxaparin; Glycine; Humans; Orthopedic Procedures; Randomized Controlled Trials as Topic; Thrombin; Thromboembolism; Venous Thrombosis; Warfarin

Central venous catheters (CVCs), such as the tunneled catheters and the totally implanted ports, play a major role in general medicine and oncology. Aside from the complications (pneumothorax, hemorrhage) associated with their initial insertion, all of these CVCs are associated with the long-term risks of infection and thrombosis. Despite routine flushing with heparin or saline, 41% of CVCs result in thrombosis of the blood vessel, and this markedly increases the risk of infection. Only one-third of these clots are symptomatic. Within days of insertion, almost all CVCs are coated with a fibrin sheath, and within 30 days, most CVC-related thrombi arise. Aside from reducing the function of the catheter, these CVC-related thrombi can cause postphlebitic syndrome in 15%-30% of cases and pulmonary embolism in 11% (only half of which are symptomatic). Risk factors for CVC thrombosis include the type of malignancy, type of chemotherapy, type of CVC, and locations of insertion site and catheter tip, but not inherited thrombophilic risk factors. Efforts to reduce CVC thrombosis with systemic prophylactic anticoagulation with low-molecular-weight heparin have failed. Low-dose warfarin prophylaxis remains controversial; all studies are flawed, with older studies, but not newer ones, showing benefit. Currently, less than 10% of patients with CVCs receive any systemic prophylaxis. Although its general use cannot be recommended, low-dose warfarin may be a low-risk treatment in patients with good nutrition and adequate hepatic function. Clearly, additional studies are required to substantiate the prophylactic use of low-dose warfarin. Newer anticoagulant treatments, such as pentasaccharide and direct thrombin inhibitors, need to be explored to address this major medical problem.

Topics: Anticoagulants; Catheterization; Catheterization, Central Venous; Catheters, Indwelling; Costs and Cost Analysis; Heparin; History, 17th Century; Humans; Neoplasms; Risk Factors; Thrombosis; Venous Thrombosis; Warfarin

All patients with neurologic diseases should receive perioperative VTE prophylaxis. The choice of mechanical, pharmacologic, or combined modalities of prophylaxis depends on both the underlying risk factors and surgical VTE risks. Prophylaxis and treatment options must be individualized to the patient. Prevention of VTE will help minimize the need for therapeutic treatment. Options for treatment include both inpatient and outpatient regimens using UFH or LMWH. In patients with an absolute or relative contraindication to anticoagulation, an IVC filter is an appropriate management strategy. Perioperative bridging therapy should be considered in patients with high or moderate risks for recurrent VTE.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Brain Diseases; Chondroitin Sulfates; Dermatan Sulfate; Dose-Response Relationship, Drug; Drug Combinations; Fibrinolytic Agents; Heparin; Heparitin Sulfate; Humans; Postoperative Complications; Venous Thrombosis; Warfarin

Topics: Confidence Intervals; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Hemorrhage; Humans; Incidence; Male; Probability; Randomized Controlled Trials as Topic; Risk Assessment; Severity of Illness Index; Survival Rate; Venous Thrombosis; Warfarin

Patients who have undergone total hip arthroplasty are at risk for venous thromboembolic disease, including deep venous thrombosis, pulmonary embolism, and postphlebitic syndrome. Although the number of annual total hip arthroplasties in the United States has steadily risen in the past decade, the rate of venous thromboembolic disease within that patient group has declined as a result of advances in surgical and postoperative procedures, including prompt mobilization and safety and efficacy of thromboprophylactic alternatives. This paper reviews the therapeutic options for deep venous thrombosis prophylaxis following total hip arthroplasty, with an emphasis on recommendations of the Sixth American College of Chest Physicians Consensus Conference on Antithrombotic Therapy. The implications of recent randomized clinical trials on care provided by physiatrists in the rehabilitation facility setting are also discussed. The low-molecular-weight heparins have become widely accepted alternatives to aspirin, heparin, and warfarin as results from randomized clinical trials have proved their superior safety and efficacy in the postoperative period. Prolonged prophylaxis up to 30 to 35 days postoperatively in total hip arthroplasty may offer additional protection against venous thrombosis. Therefore, to prescribe optimal thromboprophylactic regimens following total hip arthroplasty, physicians require an understanding of the current recommendations of the Sixth American College of Chest Physicians Consensus Conference on Antithrombotic Therapy and the implications of recently concluded clinical trials.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Chemoprevention; Clinical Trials as Topic; Continuity of Patient Care; Health Planning Guidelines; Heparin, Low-Molecular-Weight; Humans; Outpatients; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Female; Fibrinolytic Agents; Heparin; Humans; Middle Aged; Practice Guidelines as Topic; Secondary Prevention; Thrombolytic Therapy; Venous Thrombosis; Warfarin

Current treatment and secondary prophylaxis of venous thromboembolism has two major drawbacks. During vitamin K antagonist therapy, patients need to be monitored closely to maintain efficacy and minimize the bleeding risk due to fluctuations of the prothrombin time (international normalized ratio, INR), and after cessation of therapy there is the problem of recurrent thrombosis, ie, the catch-up phenomenon. Recent studies indicate that for most patients, vitamin K antagonist therapy aimed at an INR of 2.0 to 3.0 is optimal. For patients with thrombosis due to a temporary risk factor, extending treatment beyond 3 months is not needed, whereas for other patients a minimal duration of 1 year can be advocated. For patients with cancer, it is beneficial to postpone therapy with vitamin K antagonists and prolong initial low-molecular-weight therapy for 3 to 6 months. New developments are aimed at further individualization of the duration of treatment and at the introduction of agents that are suitable for long-term treatment and do not require monitoring.

Topics: Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Thromboembolism; Venous Thrombosis; Vitamin K; Warfarin

Venous thromboembolism is a multifactorial silent disease and tends not to be suspected by physicians, especially in medical patients. Pulmonary embolism is the most preventable cause of death among hospitalized patients. It is of major importance to assess the risk for venous thromboembolism and to adapt the prophylactic strategy with the aim of improving the risk-benefit ratio of the prophylaxis.. Prophylaxis of venous thromboembolism can be done by either mechanical means or pharmacologic agents or both. The Medenox trial, the Prime study, the Prince study, the Prevent study, and the Artemis trial demonstrated that acutely ill medical patients are at increased risk of venous thromboembolism and that low molecular weight heparins (enoxaparin 40 mg or dalteparin 5000 IU subcutaneously once daily for 10 days) as well as fondaparinux 2,5 mg subcutaneously once daily for 10 days have a favorable risk-benefit ratio in the prevention of venous thromboembolism in acutely ill medical patients. The publication of the results of the Exclaim study is expected to clarify the optimal duration of prophylaxis in this group of patients. Patients hospitalized in medical intensive care units as well as patients with active cancer or central venous catheters are at increased risk of venous thromboembolism, and the studies published so far demonstrate the favorable risk-benefit ratio of thromboprophylaxis with either low molecular weight heparins or low-dose warfarin.. Acutely ill medical patients are at increased risk of venous thromboembolism. Prophylaxis with low molecular weight heparins and fondaparinux is effective and safe. Initiatives to improve venous thromboembolism prophylaxis should be based on the education of physicians regarding the individualized risk assessment.

Topics: Anticoagulants; Dalteparin; Enoxaparin; Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Humans; Polysaccharides; Risk Factors; Thromboembolism; Venous Thrombosis; Warfarin

Every year, approximately 2 million people experience a deep venous thrombosis (DVT). Approximately 600,000 of these people are diagnosed with a pulmonary embolism and about 10% of these die. It has been established that surgery, anesthesia, and bed rest increase the risk of DVT, and therefore, patients who undergo a major lower-extremity procedure should receive prophylaxis. During the past 10 years, the choices of pharmacological and mechanical prophylaxis have increased greatly. Warfarin is probably the most widely used prophylactic method in the U.S., but low-molecular-weight heparin (LMWH) use has increased. Also available is a synthetic pentasaccharide that acts as an anti-Xa inhibitor to decrease DVT without increase in bleeding. All but warfarin are given by subcutaneous injection and require no laboratory management to adjust the medication. Another drug in clinical trials is a direct thrombin inhibitor taken orally in a fixed dose that does not require monitoring. Non-pharmacological prophylaxis and/or stacked modalities, although used, have not shown the efficacy of pharmacological prophylaxis. With the incidence of DVT reported in the range of 41% to 85% without prophylaxis in joint replacement and hip-fracture surgery, prophylaxis is warranted in all lower-extremity joint replacement and hip-fracture patients.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Azetidines; Benzylamines; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Postoperative Complications; Pulmonary Embolism; Venous Thrombosis; Warfarin

The literature suggests that unresponsiveness to warfarin can continue for 1 week or longer after administration of high-dose vitamin K1 10 mg or greater; however, there is a lack of supporting data to define the duration and clinical consequences of impaired warfarin response with high doses of vitamin K1. This case series describes four patients receiving indefinite warfarin therapy who received high and, in most cases, repeated doses of vitamin K1 for urgent reversal of therapeutic anticoagulation for an invasive procedure or surgery. The patients displayed impaired warfarin response for 11 days-3.5 weeks after administration of vitamin K1 10-40 mg. The associated financial burden for the patients was substantial. We reviewed the literature to examine the mechanism of impaired warfarin response, and the clinical efficacy, safety, and appropriateness of vitamin K1 and fresh-frozen plasma in urgent reversal of anticoagulation.

Topics: Adult; Anticoagulants; Antifibrinolytic Agents; Drug Interactions; Female; Humans; International Normalized Ratio; Male; Middle Aged; Venous Thrombosis; Vitamin K; Warfarin

A short cut review was carried out to establish whether low molecular weight heparins were safer and more effective anticoagulants than coumarins in injecting drug users (IDUs) with deep venous thrombosis (DVT). Altogether 276 papers were found using the reported search, of which two presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. A clinical bottom line is stated.

Topics: Adult; Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Substance Abuse, Intravenous; Venous Thrombosis; Warfarin

Patients with antiphospholipid antibodies (APLA) are at risk of arterial thromboembolism (ATE) or venous thromboembolism (VTE). The true strength of the association between APLA and first TE is unknown as there are no prospective studies of a large, well-characterized inception cohort of matched patients with and without APLA. Thus, evidence-based treatment recommendations for primary prophylaxis of TE in such patients cannot be made. Optimal therapy of patients with recent TE and APLA remains controversial; although there is no doubt that some such patients have a malignant hypercoagulable state characterized by resistance to "usual intensity" anticoagulation; recent evidence suggests that most such patients are adequately treated with "usual therapy". After warfarin discontinuation, such patients appear to be at increased risk of recurrent TE, as demonstrated in a series of studies of discontinuation of secondary TE prophylaxis in patients with APLA and venous TE (VTE). Because of this increased risk of recurrent TE, after anticoagulants are discontinued, most "experts" recommend extended duration therapeutic dose warfarin for such patients. This paper will briefly review this evidence.

Topics: Anticoagulants; Antiphospholipid Syndrome; Clinical Trials as Topic; Humans; Random Allocation; Research Design; Risk; Venous Thrombosis; Warfarin

To review the literature investigating initial dosing of warfarin at 5 or 10 mg for treatment of acute venous thromboembolism.. Articles were identified through searches of MEDLINE (1966-December 2003) using the key words warfarin, oral anticoagulation, warfarin dose, warfarin initiation, venous thromboembolism, and anticoagulation. Additional references were located through review of the bibliographies of the articles cited.. Studies of the initial dosing of warfarin at 5 or 10 mg were evaluated and relevant information was included, as were those that identified known factors that influence the maintenance dose of warfarin.. For the treatment of acute venous thromboembolism, warfarin dosing is often provider dependent. Until recently, studies suggested that 5 mg initiation was as effective as 10 mg, without increasing the risk of bleeding. However, the most recent study comparing a 5- versus 10-mg initial dosing nomogram supports an initial dose of 10 mg. These results should be interpreted with caution, however, since patients at high risk for bleeding were excluded from the study. Several patient-specific factors will affect the maintenance dose, guiding clinicians to start with lower (<5 mg) or higher (>5 mg) doses.. Although recent evidence supports a 10-mg initiation nomogram, clinicians should consider patient-specific factors prior to deciding an initial warfarin dose. If a 10-mg loading dose is utilized, strict compliance with the protocol is necessary.

Topics: Acute Disease; Anticoagulants; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Administration Schedule; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Thromboembolism; Time Factors; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Bed Rest; Blood Coagulation; Blood Coagulation Factors; Female; Heparin, Low-Molecular-Weight; Humans; Male; Neoplasms; Prognosis; Pulmonary Embolism; Risk; Thrombectomy; Thrombolytic Therapy; Tissue Plasminogen Activator; Urokinase-Type Plasminogen Activator; Vena Cava Filters; Venous Thrombosis; Warfarin

Topics: Activities of Daily Living; Anticoagulants; Bandages; Female; Heparin; Humans; Massage; Perioperative Care; Postoperative Complications; Posture; Pulmonary Embolism; Risk Factors; Vena Cava Filters; Venous Thrombosis; Warfarin

Neuraxial anesthesia during major orthopedic surgery, combined with venous thromboembolism prophylaxis, is generally safe and well tolerated, with potential benefits over general anesthesia. The risk of spinal/epidural hematoma, a rare but very serious complication, can be minimized by careful patient selection and attention to anesthetic technique. This risk is further reduced with the use of peripheral nerve blocks in place of neuraxial anesthesia.

Topics: Anesthesia, Conduction; Anesthesia, General; Aspirin; Factor Xa Inhibitors; Heparin; Humans; Orthopedic Procedures; Venous Thrombosis; Vitamin K; Warfarin

Despite the effectiveness of anticoagulant therapy for the treatment of acute venous thromboembolism and the prevention of recurrent venous thromboembolism, existing antithrombotic therapies are suboptimal. Unfractionated heparin, low-molecular-weight heparin (LMWH) and warfarin have practical limitations and carry the risk of treatment-related adverse events that restrict their clinical benefits and reduce cost-effectiveness. Efforts to achieve optimal venous thromboembolism prophylaxis by modifying the intensity of oral warfarin treatment have produced equivocal results, and there is a need for new, efficacious antithrombotic drugs providing predictable, well-tolerated oral dosing without the need for coagulation monitoring. Such agents would ideally have no significant food or drug interactions, and be suitable for both short- and long-term treatment. Ximelagatran, the first oral direct thrombin inhibitor, has the potential to fulfill many of the unmet needs in the management of venous thromboembolism.

Topics: Administration, Oral; Anticoagulants; Azetidines; Benzylamines; Clinical Trials as Topic; Heparin, Low-Molecular-Weight; Humans; Secondary Prevention; Thrombin; Venous Thrombosis; Warfarin

The risk factors for venous thromboembolism (VTE), recommendations for risk stratification and prophylaxis of VTE based on risk, nonpharmacologic and pharmacologic interventions used for prophylaxis, and clinical controversies surrounding VTE prophylaxis are discussed.. Risk factors for VTE are common in hospitalized patients and readily identifiable in patients' medical history. The recommended prophylactic strategy depends on the degree of risk. Nonpharmacologic interventions may suffice for patients at low risk for VTE, but antithrombotic drug therapy is recommended for patients at moderate or higher risk. Newer antithrombotic agents with more specific activity on the coagulation cascade than older agents have been developed to improve on efficacy, safety, and convenience. Current recommendations of the American College of Chest Physicians (ACCP) do not reflect the availability of the newest agents; these agents are likely to be included as options for patients at the highest risk for VTE when ACCP updates its recommendations in the near future.. The optimal agent, timing of initiation, and duration of prophylaxis in patients at the highest risk for VTE are ongoing controversies.

Topics: Fibrinolytic Agents; Humans; Inpatients; Randomized Controlled Trials as Topic; Risk Factors; Thromboembolism; Venous Thrombosis; Warfarin

The long-term consequences of recurrent venous thromboembolism (VTE) and post-thrombotic syndrome, clinical profiles of traditional and novel antithrombotic agents used to treat VTE, current treatment recommendations for acute symptomatic VTE, clinical experience with newer antithrombotic agents for acute treatment and extended secondary prevention of VTE, and an emerging VTE treatment paradigm are discussed.. Novel antithrombotic agents, with more specific activity on the coagulation cascade, more predictable pharmacodynamics and pharmacokinetics, simpler dosing regimens, and few or no laboratory monitoring requirements, have been developed to overcome limitations associated with some of the nonspecific traditional anticoagulants. Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are currently the recommended options for initial anticoagulation in patients with acute VTE. Warfarin is the most commonly used agent for chronic anticoagulation. Emerging evidence now also supports the role of factor-Xa inhibitors and oral direct thrombin inhibitors in the acute treatment and extended secondary prevention of VTE. In recent clinical trials, fondaparinux (a synthetic factor-Xa inhibitor) was comparable in efficacy and safety to unfractionated heparin for the treatment of acute symptomatic PE and to the LMWH enoxaparin for treating acute DVT. Ximelagatran, an oral direct thrombin inhibitor, was comparable in safety and efficacy to enoxaparin plus warfarin for treatment of acute VTE (DVT with or without PE). In addition, ximelagatran has been demonstrated to be superior to placebo for the extended secondary prevention of VTE, when continued for an additional 18 months beyond an initial six months of therapy. The benefits of extended anticoagulation for secondary VTE prevention have also been recently demonstrated with both low (INR 1.5-2.0) and regular intensity (INR 2.0-3.0) warfarin therapy.. A new paradigm for treating VTE is evolving based on the results of recent research to incorporate the use of emerging antithrombotic therapies in the acute treatment period and both traditional and novel agents in the chronic, extended-treatment period.

Topics: Clinical Trials as Topic; Fibrinolytic Agents; Humans; Thromboembolism; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Chemoprevention; Drug Monitoring; Economics, Pharmaceutical; Guideline Adherence; Humans; Managed Care Programs; Pulmonary Embolism; Stroke; Thromboembolism; Venous Thrombosis; Warfarin

Atrial fibrillation (AF) greatly increases the risk of stroke. Long-term oral therapy with warfarin reduces the risk of AF-related stroke by 62%, and national guidelines now call for warfarin therapy in most patients without specific contraindications to anticoagulation. However, the drug's narrow therapeutic index means that warfarin therapy must be guided by coagulation monitoring. This requirement and other inherent limitations of warfarin have led to widespread underutilization and underanticoagulation in AF patients who require antithrombotic therapy for stroke prevention. Recent studies indicate that in many health systems less than half of warfarin-eligible patients take the drug and even fewer are adequately maintained within a protective therapeutic range. Similarly, despite the documented efficacy of anticoagulation in patients at risk for deep vein thrombosis (DVT) and related pulmonary embolism, prophylaxis for DVT, even in high-risk situations such as following orthopedic surgery, is suboptimal. This article explores the scope of warfarin underutilization and underanticoagulation that exists in current clinical practice. The clinical consequences of warfarin underuse are also described. Discussion in the roundtable after this review explores the causes for the wide treatment gap between anticoagulation clinical trial results and clinical practice outcomes. The economic implications of such a gap and strategies for closing the gap are also discussed by the panelists.

Topics: Anticoagulants; Atrial Fibrillation; Chemoprevention; Drug Monitoring; Drug Utilization; Evidence-Based Medicine; Guideline Adherence; Humans; Practice Patterns, Physicians'; Pulmonary Embolism; Risk Factors; Stroke; Thromboembolism; Venous Thrombosis; Warfarin

It is now possible to identify hereditary risk factors in a substantial percentage of patients presenting with a venous thrombotic event. Discovery of the factor V Leiden and prothrombin G20210A mutations has greatly increased the percentage of patients in whom venous thrombosis can be attributed to hereditary thrombophilia. There is considerable uncertainty, however, as to how this information should be used in patient management. Although prolonged anticoagulation at an international normalized ratio (INR) of 2 to 3 is highly effective in preventing thrombotic recurrences, this benefit is partially offset by the risk of major bleeding and the inconvenience associated with oral vitamin K antagonists. Although low-intensity anticoagulation at a target INR of 1.5 to 2 has recently been shown to be effective in preventing recurrent venous thromboembolism after 3 to 6 months of treatment at an INR of 2 to 3, it has not been demonstrated to reduce the risk of major bleeding complications. A decision as to the overall benefit of extended anticoagulation therefore continues to require clinical assessment of an individual patient's risk of recurrence in the absence of treatment and the risk of bleeding at the chosen INR target range.

Topics: Anticoagulants; Factor V; Humans; International Normalized Ratio; Mutation; Prothrombin; Recurrence; Risk; Risk Factors; Thromboembolism; Thrombophilia; Time Factors; Venous Thrombosis; Vitamin K; Warfarin

Topics: Anticoagulants; Decision Support Systems, Clinical; Drug Therapy, Combination; Heparin, Low-Molecular-Weight; Humans; Pulmonary Embolism; Thromboembolism; Thrombolytic Therapy; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Education, Nursing, Continuing; Hemorrhage; Heparin; Humans; Information Services; Nurse Clinicians; Risk Factors; Venous Thrombosis; Warfarin

Atrial fibrillation and venous thromboembolism are particularly frequent in the elderly. Whether or not prescribe oral anticoagulant treatment in the elderly is therefore a common question for the physician. Despite the benefits of anticoagulation demonstrated in clinical trials, oral anticoagulant therapy is underused in the elderly.. Indications for oral anticoagulation are discussed specifically in the elderly with a literature review. Only the length of anticoagulation treatment after a venous thromboembolism remained a purpose of discussion regarding the severity of the pathology. The frequency of systemic thromboembolism in nonvalvular atrial fibrillation is increasing with age. Oral anticoagulation reduces this risk. This benefice is to compare with the increasing rate of major bleeding complications in the elderly and in patient who had stroke, hyper-tension, diabetes mellitus or gastrointestinal bleeding. The objective of this article is to focus on the mode to measure oral anticoagulant benefice/risk ratio in the elderly and to propose several ways to minimize the risk for bleeding.. The potential drug side effect severity of oral anticoagulation must lead to find the "reasonable" clinical indications in term of benefice/risk ratio and what measures should be take to increase the safety of oral anticoagulation in the elderly. The comprehensive geriatric evaluation should be considered as a decision-aid tool in long-term oral anticoagulation in the frail elderly. Anticoagulation clinics, informatics'-prescription coupled with dose-adaptation decision-aid adapted to the elderly should be helpful in this research of quality. Finally, prescribers education supports must insist on the early course of therapy that is at higher risk of bleeding.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Female; Humans; Male; Middle Aged; Risk Factors; Treatment Outcome; Venous Thrombosis; Warfarin

A 12-year-old girl underwent laparoscopy-assisted splenectomy and cholecystectomy with removal of her spleen through a small Pfannenstiel incision. She had an unremarkable postoperative course but returned 16 days later because of increasing right-sided abdominal pain. The pain was constant, sharp, and stabbing without radiation. Abdominal examination showed diffuse right upper quadrant and epigastric tenderness without peritoneal irritation. Laboratory test results included white blood cell count, 14.4 x 10(9)/mm3; hemoglobin, 8.5 g/dL; platelets, 1,483,000; and normal values for lipase, amylase, aspartate transaminase, and alanine transaminase. Evaluation with ultrasonography and vessel Doppler studies showed an occlusive thrombus throughout the portal and splenic veins. The patient underwent intravenous heparin anticoagulation therapy. Her symptoms resolved completely over the next 2 days. The patient is currently receiving warfarin and anagrelide as an outpatient (international normalized ratio, 2). There were no long-term complications caused by portal vein thrombosis. This is the first reported case of portal vein thrombosis after laparoscopic splenectomy in the pediatric population.

Topics: Anemia, Hemolytic, Autoimmune; Anticoagulants; Child; Cholecystectomy, Laparoscopic; Cholelithiasis; Drug Therapy, Combination; Female; Humans; Hypersplenism; Laparoscopy; Portal Vein; Postoperative Complications; Quinazolines; Splenectomy; Splenic Vein; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Heparin; Humans; Nursing Assessment; Risk Factors; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Evidence-Based Medicine; Humans; Randomized Controlled Trials as Topic; Recurrence; Risk Factors; Thromboembolism; Time Factors; Venous Thrombosis; Warfarin

Venous thromboembolism (VTE) in patients suffering from the antiphospholipid syndrome (APS) has been reported in almost any location of the vessel tree and the risk of recurrences has been found in several studies to be more closely associated with the presence of lupus anticoagulant than with the positivity for anti-cardiolipin antibodies. The thrombophilic state of APS raises the problem of the secondary prophylaxis to avoid VTE recurrences. For APS patients with VTE, published data appear to support a longer warfarin treatment if compared with the standard management of antiphospholipid (aPL)-negative patients with VTE. The question of how long oral anticoagulant treatment should be continued for APS patients, however, remains unanswered. Concerning the intensity of anticoagulation, several authors recommend a target international normalized ratio (INR) between 3.0 and 4.0 to efficiently protect from VTE recurrences. A recent decision analysis study does support such a suggestion. On the contrary, in a few prospective studies regimens with lower target INRs appear to be effective, and some authors therefore recommend a target INR of between 2.0 and 3.0. Specific large and prospective trials are needed to address this question. Until such information becomes available, individualized treatment according to the patient's individual risk factors for both bleeding and thrombosis is the general practice.

Topics: Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Humans; Secondary Prevention; Thromboembolism; Venous Thrombosis; Warfarin

Central venous catheters (CVCs) are used in a wide variety of patients. Associated complications are thrombosis and infection. It is a matter of debate whether thromboprophylaxis is beneficial.. We performed a systematic review of 3 different patient populations to render the available information in the literature more accessible to clinical practice: patients receiving parenteral nutrition (PN), patients with cancer, and patients admitted to intensive care units.. Prophylaxis with heparin added to PN was found to give a nonsignificant reduction in the incidence of catheter-related thrombosis (pooled relative risk of randomized studies, 0.77; 95% confidence interval [CI], 0.11-5.48). In cancer patients, both low-dose warfarin and low-molecular-weight heparin significantly reduced the incidence of catheter-related thrombosis (relative risk of randomized studies, 0.25 [95% CI, 0.09-0.70] and 0.10 [95% CI, 0.01-0.71], respectively). So far, intensive care patients have hardly been studied with respect to thromboprophylaxis and the incidence of CVC thrombosis. Any effect of the type of catheter could not be established because of small numbers. There was no apparent increase in bleeding events with prophylactic anticoagulation in patients with CVCs.. In the small number of patients studied, the addition of heparin to PN did not significantly decrease the risk of catheter-related thrombosis, whereas warfarin and dalteparin did decrease the thrombosis risk in cancer patients with CVCs. There is no apparent increase in bleeding events with prophylactic anticoagulants in patients with CVCs.

Topics: Anticoagulants; Antineoplastic Agents; Catheterization, Central Venous; Critical Illness; Dalteparin; Heparin; Humans; Intensive Care Units; Neoplasms; Parenteral Nutrition; Randomized Controlled Trials as Topic; Risk Factors; Venous Thrombosis; Warfarin

The reported overall risk of deep venous thrombosis in gynaecological surgery ranges from 7 to 45%. Fatal pulmonary embolism is estimated to occur in nearly 1% of these women. Pharmaceutical interventions are one possible prophylactic measure for preventing emboli in women undergoing major gynaecological surgery. Agents include unfractionated heparin (low -dose and adjusted-dose), low-molecular-weight heparins, heparinoids and warfarin.. The objective of this review was to evaluate the effectiveness of warfarin, heparin and aspirin in preventing thromboembolism after major gynaecological surgery.. We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (searched 15 August 2003), the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library issue 2, 2003), MEDLINE (1966 to April 2003), EMBASE (1985 to April 2003), and CINAHL (1982 to April 2003). References from relevant articles were searched and authors contacted where necessary. In addition we contacted experts in the field for unpublished works.. Randomised controlled trials of heparins, warfarin or aspirin to prevent thromboembolism after major gynaecological surgery were eligible for inclusion.. Thirty-three trials were identified in the initial search. On careful inspection only eight of these met the inclusion criteria. Trials were data extracted and assessed for quality by at least two reviewers. Data were combined for meta-analysis using odds ratios for dichotomous data or weighted mean difference for continuous data. A random effects statistical model was used.. The meta-analysis of heparin versus placebo found a statistically significant decrease in the number of DVTs in both the all women group (including those with and without malignancy) (OR 0.30, 95% CI 0.12 to 0.76) and the subgroup of only women with malignancy (OR 0.30, 95% CI 0.10 to 0.89). There was no significant difference in the incidence of PE. Oral warfarin reduced DVT when compared to placebo in all women (OR 0.22, 95% CI 0.06 to 0.86) and in women with malignancy (OR 0.18, 95% CI 0.04 to 0.87). Meta-analyses of UH and LMWH showed no statistical difference in any comparison. No studies compared aspirin alone to placebo, heparin or warfarin. There was a statistically significant increase in injection site haematomas associated with heparin compared to placebo (OR 0.30, 95% CI 0.10 to 0.89).. Women, undergoing major gynaecological surgery and without contraindications to anticoagulants should be offered thromboprophylaxis. Evidence suggests that UH and LMWH are equally as effective in preventing DVT and the one trial available suggests that warfarin is as effective as UH. There is no evidence as yet to suggest that warfarin, heparin or aspirin reduce incidence of PE.

Topics: Anticoagulants; Aspirin; Female; Gynecologic Surgical Procedures; Heparin; Humans; Postoperative Complications; Pulmonary Embolism; Venous Thrombosis; Warfarin

Topics: Drug Administration Schedule; Humans; Secondary Prevention; Venous Thrombosis; Warfarin

Mesenteric vein thrombosis (MVT) is a distinct clinical cause of intestinal ischemia representing 5-15% of all ischemic events. MVT has acute, subacute, and chronic presentations and an underlying cause can be found in nearly 75% of cases. Exogenous hormones are used worldwide by millions of women for contraception and postmenopausal replacement therapy. Current preparations include oral, transdermal, and intravaginal delivery systems. The risk of venous and arterial thrombosis with oral preparations is well established, however the risk with parenteral preparations has not been fully established. The mechanisms underlying these increased risks have not been fully elucidated. We report a case of mesenteric vein thrombosis associated with intravaginal hormonal contraception. A review of the current literature reveals no prior reports of this complication of intravaginal or transdermal hormonal therapy. When taking a medical history, it is imperative for physicians to be aware of all medications, including those not taken orally.

Topics: Administration, Intravaginal; Contraceptive Agents, Female; Female; Humans; Mesenteric Veins; Middle Aged; Ultrasonography, Doppler; Venous Thrombosis; Warfarin

Adjusted doses of oral warfarin sodium or fixed doses of subcutaneous low-molecular-weight heparin (LMWH) are the standard approaches for preventing venous thromboembolism following major orthopedic surgery of the legs. In recent years, new anticoagulants have been compared with either LMWH or warfarin. The optimal timing for the first dose of LMWH prophylaxis and of the new anticoagulants is controversial. Recent clinical trials of LMWH and of newer anticoagulants have provided new information on the relationship between the timing of the first anticoagulant dose and the efficacy and safety of thromboprophylaxis after major orthopedic surgery. These data on the optimal timing of initiating prophylaxis come from limited direct randomized comparisons of different timing with the same anticoagulant, subgroup analysis of large studies with a single anticoagulant, indirect comparisons across studies in systematic reviews, and single randomized trials comparing different anticoagulants. In the direct comparison of the same anticoagulant, preoperative initiation of the same regimen of LMWH (dalteparin) increased major bleeding, without improved antithrombotic efficacy compared to the early postoperative regimen. Fondaparinux, 2.5 mg, begun 6 h postoperatively is more effective and as safe as the currently approved regimens of enoxaparin begun either 12 h preoperatively, or 12 to 24 h postoperatively, in patients undergoing major orthopedic surgery. In a subgroup analysis of several large randomized trials, fondaparinux, 2.5 mg, begun < 6 h postoperatively was associated with increased major bleeding, without improved efficacy. The results of indirect comparisons also favor the use of a 6-h postoperative starting time for the first dose, while the single randomized trials comparing different anticoagulants performed to date are not helpful in establishing an optimal time for the first dose. The aggregate clinical research evidence supports the following general conclusions about the relationship between the timing of the first anticoagulant dose and the efficacy and safety of prophylaxis: (1) preoperative initiation is not required for good efficacy and, when begun within 2 h of surgery, increases major bleeding; (2) initiation at 6 h postoperatively is effective and not associated with increased major bleeding; (3) initiation < 6 h postoperatively increases major bleeding, without improved efficacy; thus, 6 h appears to be the threshold for early postoperative

Topics: Anticoagulants; Drug Administration Schedule; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Leg; Polysaccharides; Postoperative Complications; Randomized Controlled Trials as Topic; Time Factors; Venous Thrombosis; Warfarin

Venous thromboembolism (VTE) prophylaxis is indicated while in the hospital after major surgery. There is evidence that the prevalence of asymptomatic deep-vein thrombosis, detected by routine venography after major orthopedic surgery, is lower at hospital discharge in patients who have received 10 days rather than 5 days of prophylaxis. This observation supports the current American College of Chest Physicians (ACCP) recommendation for a minimum of 7 to 10 days of prophylaxis after hip and knee replacement, even if patients are discharged from the hospital within 7 days of surgery. As risk of VTE persists for up to 3 months after surgery, patients at high risk for postoperative VTE may benefit from extended prophylaxis (eg, an additional 3 weeks after the first 7 to 10 days). Extended prophylaxis with low-molecular-weight heparin (LMWH) reduces the frequency of postdischarge VTE by approximately two thirds after hip replacement; however, the resultant absolute reduction in the frequency of fatal pulmonary embolism is small (ie, estimated at 1 per 2,500 patients). Indirect evidence suggests that, compared with LMWH, efficacy of extended prophylaxis after hip replacement is greater with fondaparinux, similar with warfarin, and less with aspirin. Extended prophylaxis is expected to be of less benefit after knee than after hip replacement. In keeping with current ACCP recommendations, at a minimum, extended prophylaxis should be used after major orthopedic surgery in patients who have additional risk factors for VTE (eg, previous VTE, cancer). If anticoagulant drug therapy is stopped after 7 to 10 days, an additional month of prophylaxis with aspirin should be considered.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Drug Administration Schedule; Fondaparinux; Hemorrhage; Heparin; Humans; Polysaccharides; Postoperative Complications; Prevalence; Radiography; Risk Factors; Time Factors; Venous Thrombosis; Warfarin

Based on the established fact that anticoagulation with warfarin is superior to antiplatelet agents in the prevention of thromboembolic events in atrial fibrillation (AF), we propose that, in contrast to atherothrombotic disorders, the risk of developing a stroke or thromboembolic event in AF is more likely to be affected by the coagulation pathway than by platelet activity. Indeed, platelet-rich thrombi may be the predominant underlying pathophysiological process in coronary artery disease patients, thus representing an entirely different prothrombotic profile to the patients with AF, where clotting factor abnormalities (and thus fibrin-rich thrombi) are more likely. Thus, we would hypothesise that warfarin is probably more likely to be more beneficial than aspirin-clopidogrel combination therapy when used in this setting. Indeed, this hypothesis would need to be tested in large randomised clinical trials.

Topics: Aspirin; Atrial Fibrillation; Clopidogrel; Humans; Platelet Aggregation Inhibitors; Risk Assessment; Stroke; Thrombolytic Therapy; Ticlopidine; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Decision Support Systems, Clinical; Drug Therapy, Combination; Heparin, Low-Molecular-Weight; Humans; Pulmonary Embolism; Thromboembolism; Thrombolytic Therapy; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Dose-Response Relationship, Drug; Drug Therapy, Combination; Heparin; Humans; International Normalized Ratio; Thrombophilia; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Decision Support Systems, Clinical; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Heparin; Heparin, Low-Molecular-Weight; Humans; Pulmonary Embolism; Randomized Controlled Trials as Topic; Treatment Outcome; Venous Thrombosis; Warfarin

Venous thromboembolism (VTE) and particularly idiopathic VTE may be paraneoplastic phenomena. The merits of screening patients with idiopathic VTE for occult cancer are still under debate, and randomized studies are required to establish its potential cost-effectiveness. Cancer and its related surgery greatly increase the risk of VTE. Thromboprophylaxis using agents such as low-molecular-weight heparin (LMWH) has proved to be safe and effective in reducing the incidence of postoperative VTE. The ENOXACAN II study has shown that prolonging the standard 1-week regimen of the LMWH enoxaparin to 4 weeks may further reduce the incidence of postoperative VTE. Enoxaparin has also shown potential benefits in the secondary prevention of VTE and the reduction of bleeding complications. Emerging data indicate that LMWH may improve survival rates in cancer patients with VTE, making this a very important area for future research.

Topics: Antineoplastic Agents; Double-Blind Method; Enoxaparin; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Meta-Analysis as Topic; Multicenter Studies as Topic; Neoplasms; Paraneoplastic Syndromes; Postoperative Complications; Prospective Studies; Randomized Controlled Trials as Topic; Risk; Thromboembolism; Thrombophilia; Treatment Outcome; Venous Thrombosis; Warfarin

Thrombosis is the most common cause of mortality in the United States, resulting in more than 2 million deaths per year. Almost an equal number of individuals are affected each year by nonfatal thrombosis, including deep vein thrombosis and nonfatal pulmonary embolism. A large proportion of thrombotic episodes can be prevented by the appropriate selection of prophylactic therapy--a clinical decision that figures greatly in numerous clinical conditions associated with an increased risk of thrombosis, including major orthopedic surgery. Orthopedic surgeons are well aware of the risks for complications inherent in total hip arthroplasty and total knee arthroplasty in particular. However, determining which protocols are optimal for thromboprophylaxis remains a matter of contention, and the choice of prophylactic therapy is a critical factor in the successful completion of any major orthopedic surgical procedure. Although there are key differences between total hip and knee arthroplasty in terms of the measures available for thromboprophylaxis and the data documenting their relative degree of effectiveness, the two procedures share many similarities in these respects as well as in their surgical protocols. By reviewing the data and practice guidelines on thromboprophylaxis in total hip and knee arthroplasty together, orthopedic surgeons can more clearly see the implications for clinical success that the choice of prophylactic therapy has on their management of these two vitally important procedures.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Heparin, Low-Molecular-Weight; Humans; Incidence; Postoperative Complications; Prevalence; Risk Factors; Syndrome; Venous Thrombosis; Warfarin

The management of patients who require temporary interruption of oral anticoagulant therapy because of surgery or other invasive procedures is a clinically important topic because of the increasing prevalence of patients who are receiving oral anticoagulants and the availability of low-molecular-weight heparins (LMWHs), which allow out-of-hospital perioperative anticoagulation. The optimal management of such patients has been hampered by the lack of well-designed prospective studies investigating the efficacy and safety of different perioperative management strategies. The two main issues that need to be considered in perioperative anticoagulant management is the patient's risk of thromboembolic event when anticoagulant therapy is interrupted and the risk of bleeding that is associated with the surgery or procedure. An assessment of these factors will determine the perioperative management approach. The objectives of this review are to focus on practical issues relating to perioperative anticoagulation and the implementation of a perioperative anticoagulation management approach that can be used in everyday clinical practice.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Blood Loss, Surgical; Female; Heart Valve Prosthesis; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Middle Aged; Perioperative Care; Postoperative Hemorrhage; Renal Insufficiency; Risk Factors; Thromboembolism; Thrombosis; Venous Thrombosis; Warfarin

The treatment and prevention of deep vein thrombosis (DVT) and pulmonary embolism (PE) in pregnant patients is challenging for several reasons. Coumarins can cause embryopathy and other adverse effects in the fetus. Although unfractionated heparin and low-molecular-weight heparins, the cornerstones of initial therapy, are safe for the fetus, they can have significant maternal side effects, including osteoporosis and thrombocytopenia. Because they must be given parenterally, long-term administration is inconvenient. Further, although low-molecular-weight heparins probably cause less maternal osteoporosis and thrombocytopenia than unfractionated heparin, the appropriate dosing regimens for prevention and treatment of thrombosis during pregnancy have not been established. In addition, there is a paucity of reliable information on the incidence of venous thromboembolism and the risk of recurrent thrombosis during pregnancy. This paper briefly reviews the areas of controversy and provides recommendations for the treatment and prophylaxis of acute deep vein thrombosis and pulmonary embolism in pregnant patients.

Topics: Anticoagulants; Delivery, Obstetric; Female; Heparin; Heparin, Low-Molecular-Weight; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Pulmonary Embolism; Safety; Thromboembolism; Vena Cava Filters; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Decision Support Systems, Clinical; Drug Administration Schedule; Drug Therapy, Combination; Heparin; Heparin, Low-Molecular-Weight; Humans; Pulmonary Embolism; Venous Thrombosis; Warfarin

Older individuals (subjects aged >65 years) largely contribute to the percentage deaths due to myocardial infarction (MI) and stroke. The incidence of venous thromboembolism (VTE) is also higher >65 years old patients. However, the risk of bleeding complications in patients on antithrombotic drugs increases with age and with clinical conditions, as cognitive/psychiatric diseases, traumas, hypertension, poor compliance with medications, common in the elderly. Thus the risk-benefit ratio of antithrombotics should be carefully evaluated in older individuals. To prevent the risk and the recurrence of ischemic stroke and MI in the older patients with stable/ unstable angina, MI, TIA/stroke or peripheral arterial disease, antiplatelet drugs are of choice. Aspirin is the most widely used antiplatelet drug. Clopidogrel is safer and more effective than aspirin in this respect. The combination of heparin and aspirin is the treatment of choice for unstable angina and non-Q wave MI, also in the elderly. Low molecular weight heparins (LMWHs) proved to be as effective as standard heparin in this indication. In the absence of contraindications, thrombolysis for treatment of acute MI may be considered in the elderly. For the treatment of acute venous thromboembolism (VTE), intravenous standard heparin, subcutaneous standard heparin or LMWHs are effective. Because of the limited risk/benefit ratio, thrombolytic agents are not recommended for treating deep vein thrombosis (DVT) in the elderly. They should be limited to young patients and to patients with massive pulmonary embolism (PE). For chronic treatment of VTE, warfarin is the treatment of choice (INR 2.0-3.0), also in the elderly. Because of hypersensitivity to oral anticoagulants, lower dosages of warfarin are needed in the old patient. As to prophylaxis of VTE in surgery, in subjects at low-moderate risk, or in medical patients, low-dose heparin or low-dose LMWHs are effective. As to prophylaxis of VTE in surgery in subjects at high risk, adjusted-dose heparin or high-dose LMWHs are recommended. Finally, as to prevention of stroke in patients older than 75 with atrial fibrillation (AF), warfarin is of choice.

Topics: Aged; Aspirin; Clopidogrel; Fibrinolytic Agents; Heparin; Heparin, Low-Molecular-Weight; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Pulmonary Embolism; Secondary Prevention; Stroke; Thromboembolism; Thrombolytic Therapy; Ticlopidine; Venous Thrombosis; Warfarin

The advanced practice nurse is uniquely qualified to act as a consultant and specialist in the field of anticoagulation at an acute care hospital. The advanced practice nurse acts at both a system level and a patient care level to improve anticoagulation with low-molecular-weight heparins, heparin, and warfarin through education, research, quality improvement initiatives, and patient care management.

Topics: Anticoagulants; Disease Management; Heparin; Humans; Nurse Practitioners; Nurse's Role; Patient Education as Topic; Risk Factors; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Arthroplasty, Replacement; Humans; Postoperative Complications; Postoperative Hemorrhage; Venous Thrombosis; Warfarin

Thrombosis and the complicating emboli that can result are important causes of illness and death. Thrombosis is of greater overall clinical importance in terms of morbidity and mortality than all of the hemorrhagic disorders combined. Agents such as heparin, low-molecular weight heparin, warfarin, aspirin, ticlopidine, clopidogrel, and tirofiban are used to prevent venous or arterial thrombosis. Patients taking these antithrombotic agents may be at risk for excessive bleeding after invasive dental procedures. The current antithrombotic agents used in medicine are reviewed, and the dental management of patients taking these agents is discussed.

Topics: Anticoagulants; Aspirin; Blood Coagulation Tests; Clopidogrel; Dental Care; Drug Interactions; Embolism; Fibrinolytic Agents; Hemostasis; Heparin; Heparin, Low-Molecular-Weight; Humans; Oral Hemorrhage; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Thrombosis; Ticlopidine; Tirofiban; Tyrosine; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Blood Coagulation; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Practice Guidelines as Topic; Pulmonary Embolism; Severity of Illness Index; Vena Cava Filters; Venous Thrombosis; Warfarin

Venous thromboembolism is a common and potentially fatal disease. If properly used, anticoagulation therapy is effective in preventing recurrence of venous thromboembolism and in improving survival. Symptomatic patients with an objective diagnosis of acute deep vein thrombosis (DVT) or pulmonary embolism (PE) should receive immediate systemic heparin anticoagulation at dosages sufficient to rapidly prolong the activated partial thromboplastin time into the laboratory-specific therapeutic range; this range corresponds to a plasma heparin concentration of 0.2 to 0.4 IU/ml (as measured by protamine sulfate titration), or 0.3 to 0.7 anti-Xa IU/ml. An oral vitamin K antagonist (e.g. warfarin) should be started within 24 hours after starting heparin; the starting dose should be the estimated patient-specific daily dose with no loading dose. Heparin and warfarin anticoagulation should be overlapped for at least 4 to 5 days and until the international normalized ratio (INR) is within the therapeutic range (2.0 to 3.0) on 2 measurements made at least 24 hours apart. The duration of warfarin anticoagulation should be individualized based on the respective risks of venous thromboembolism recurrence and anticoagulant-related bleeding. In general, warfarin should be continued for at least 3 months, and longer for patients with recurrent or idiopathic venous thromboembolism, malignant neoplasm, neurologic disease with extremity paresis, obesity, or laboratory evidence of a lupus anticoagulant/anticardiolipin antibody, homozygous carrier or combined heterozygous carrier for the factor V R506Q (Leiden) and prothrombin G20210A mutations, and possibly deficiency of either antithrombin, protein C, or protein S. Low molecular weight heparin (LMWH) is effective and well tolerated as acute therapy for patients with DVT or stable PE, and does not require laboratory monitoring or dose adjustment. Outpatient LMWH therapy is also well tolerated and cost effective for most patients with DVT, and possibly for selected patients with PE.

Topics: Acute Disease; Anticoagulants; Heparin; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Pulmonary Embolism; Recurrence; Risk Factors; Venous Thrombosis; Warfarin

Although pharmacologic prophylaxis against venous thromboembolism has become the standard of care following total hip and knee replacement, prophylaxis among patients undergoing surgery for hip fracture and other lower extremity trauma remains underutilized. Available experience consistently supports the view that low-molecular-weight heparins are more effective than unfractionated heparin for prevention of proximal deep vein thrombosis (DVT) with no additional hemorrhagic risk and more effective than oral anticoagulants for prevention of in-hospital (mostly distal) venous thrombosis at the price of a higher surgical site bleeding and wound hematoma. The choice between low-molecular-weight heparin and warfarin should be tailored to the individual patients based on the clinical assessment of postoperative thrombosis and bleeding risk as well as the prophylaxis-specific cost and convenience. Whether thromboprophylaxis should be continued for a few additional weeks after hospital discharge is controversial. The overall incidence of postoperative DVT in patients with cancer is about twice as high as that of patients free of malignancy. Accordingly, they require prophylactic measures comparable with those usually recommended for major orthopedic surgery. In this setting, dermatan sulfate shows promise. In contrast to surgical patients, prevention of venous thromboembolism is less well studied in hospitalized medical patients. In a recent controlled randomized trial, enoxaparin in high prophylactic doses was an effective and safe measure of thromboprophylaxis in ordinary bedridden patients.

Topics: Anesthesia, Conduction; Anticoagulants; Arthroplasty, Replacement, Hip; Comorbidity; Heart Diseases; Heparin, Low-Molecular-Weight; Hospitalization; Humans; Neoplasms; Postoperative Complications; Spinal Cord Injuries; Venous Thrombosis; Warfarin

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Coumarins; Drug Interactions; Food; Heart Valve Prosthesis; Humans; Myocardial Infarction; Thromboembolism; Venous Thrombosis; Warfarin

Topics: Adult; Aged; Anticoagulants; Female; Forecasting; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Postphlebitic Syndrome; Surgical Instruments; Thrombolytic Therapy; Vascular Surgical Procedures; Venous Thrombosis; Warfarin

Deep venous thrombosis (DVT) is common in total knee arthroplasty (TKA). Because of the rarity of the most serious outcomes, most randomized controlled trials lack the power to analyze these outcomes. A meta-analysis was performed for agents used in DVT prophylaxis in TKA employing a Medline literature search. Study inclusion criteria were randomized controlled trials comparing prophylactic agents in elective TKA with mandatory screening for DVT by venography. Fourteen studies (3,482 patients) met inclusion criteria. For total DVT, all agents except dextran and aspirin protected significantly better than placebo (P < .0001). For proximal DVT rates, low-molecular-weight heparin was significantly better than warfarin (P = .0002). There was a trend that aspirin was better than warfarin (P = .0106). No significant difference was found for symptomatic pulmonary embolism, fatal pulmonary embolism, major hemorrhage, or total mortality.

Topics: Aged; Arthroplasty, Replacement, Knee; Aspirin; Female; Heparin, Low-Molecular-Weight; Humans; Male; Postoperative Complications; Randomized Controlled Trials as Topic; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Blood Coagulation; Contraceptives, Oral; Female; Heparin; Hormone Replacement Therapy; Humans; Pregnancy; Pregnancy Complications, Hematologic; Risk Factors; Thrombin; Thrombophilia; Venous Thrombosis; Warfarin

Patients sustaining traumatic injuries are at high risk for the development of venous thromboembolism. The reported incidence of deep venous thrombosis in trauma patients ranges from 20 to 90%. The reported incidence of pulmonary embolism in trauma patients varies between 2.3 and 22%. The aging population and the survival of more severely injured patients may suggest an increasing risk of thromboembolism in the trauma patient population. There have been few randomized prospective studies assessing methods of thromboembolism prophylaxis in trauma patients. Controversy exists as to the optimal method of prophylaxis in this high-risk population. Contraindications arising from associated injuries often limit the potential options for prophylaxis in patients with trauma. Large prospective randomized studies are needed to determine the most effective means of prophylaxis in trauma patients, who have a wide range of both isolated and combined injuries. Future studies should also address the duration of prophylaxis because many trauma patients remain immobile for an extended time.

Topics: Aged; Anticoagulants; Clinical Trials as Topic; Diagnosis, Differential; Female; Fractures, Bone; Heparin; Heparin, Low-Molecular-Weight; Humans; Incidence; Leg; Male; Middle Aged; Risk Factors; Thromboembolism; Vena Cava Filters; Venous Thrombosis; Warfarin; Wounds and Injuries

This article focuses on deep vein thrombosis (DVT) and anticoagulant therapy. The risk factors, pathophysiology, prevention, and detection of DVT are explained. Anticoagulants such as unfractionated heparin (UFH), low molecular weight heparin (enoxaparin), and warfarin are discussed. The article also reviews nursing assessment and monitoring of patients with DVT as well as patient education on anticoagulants.

Topics: Anticoagulants; Drug Interactions; Heparin; Humans; Nursing Assessment; Risk Factors; Venous Thrombosis; Warfarin

Venous thromboembolism is the most common cause of preventable death among hospitalised patients. Systematic prophylaxis with antithrombotic agents in patients at risk for venous thromboembolism is the most effective approach to reduce morbidity and mortality. Despite this evidence, antithrombotic prophylaxis is still underused, due to the underestimation of incidence of venous thromboembolism and to the unjustified fear of bleeding complications. Both the characteristics of the individual patient and the clinical setting contribute to the definition of the risk for venous thromboembolism. Patient-related risk factors include clinical and molecular abnormalities. The grade of risk for venous thromboembolism is defined better by the clinical setting than by the patient characteristics. Prophylactic studies have been extensively carried out in surgical patients and, only more recently, in medical patients. Prophylactic methods include pharmacological agents, such as heparin, low molecular weight heparins, warfarin, and hirudin, as well as mechanical methods such as compression stockings and intermittent pneumatic compression.

Topics: Anticoagulants; Heparin; Heparin, Low-Molecular-Weight; Hirudin Therapy; Humans; Physical Therapy Modalities; Risk Factors; Venous Thrombosis; Warfarin

Venous thromboembolism is a common complication in patients with cancer. The management of deep-vein thrombosis and pulmonary embolism can be a considerable challenge in these patients. Diagnosing venous thrombosis requires objective testing, and noninvasive investigations may be less accurate in patients who have cancer than in those who do not. Treatment of acute venous thrombosis at home with low-molecular-weight heparin is an attractive option in patients with malignant disease, in whom quality of life is especially important. Comorbid conditions, warfarin resistance, difficult venous access, and a potentially high bleeding risk are some of the factors that often complicate the prolonged course of anticoagulant therapy needed in this group. In addition, the use of central venous catheters is increasing, but the optimal treatment of catheter-related thrombosis remains controversial. This article reviews the current diagnostic and treatment approaches to venous thromboembolism in patients with cancer and provides several clinical scenarios to illustrate and discuss some common management problems.

Topics: Adult; Aged; Anticoagulants; Catheterization, Central Venous; Female; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Neoplasms; Pulmonary Embolism; Venous Thrombosis; Warfarin

Although several agents have been shown to reduce the risk of thromboembolic disease, there is no clear preference for thromboembolic prophylaxis in elective total hip arthroplasty. The purpose of this study was to define the efficacy and safety of the agents that are currently used for prophylaxis against deep venous thrombosis -- namely, low-molecular-weight heparin, warfarin, aspirin, low-dose heparin, and pneumatic compression.. A Medline search identified all randomized, controlled trials, published from January 1966 to May 1998, that compared the use of one of the prophylactic agents with the use of any other agent or a placebo in patients undergoing elective total hip arthroplasty. For a study to be included in our analysis, bilateral venography had to have been performed to confirm the presence or absence of deep venous thrombosis. Fifty-two studies, in which 10,929 patients had been enrolled, met the inclusion criteria and were included in the analysis. The rates of distal, proximal, and total (distal and proximal) deep venous thrombosis; symptomatic and fatal pulmonary embolism; minor and major wound-bleeding complications; major non-wound bleeding complications; and total mortality were determined for each agent in each study. The absolute risk of each outcome was determined by dividing the number of events by the number of patients at risk. A general linear model with random effects was used to calculate the 95 percent confidence interval of risk. A crosstabs of study by outcome was performed to test homogeneity (ability to combine studies). The risk of each outcome was compared among agents and between each agent and the placebo.. With prophylaxis, the risk of total (proximal and distal) deep venous thrombosis ranged from 17.7 percent (low-molecular-weight heparin) to 31.1 percent (low-dose heparin); the risk with prophylaxis with any agent was significantly lower than the risk with the placebo (48.5 percent) (p < 0.0001). The risk of proximal deep venous thrombosis was lowest with warfarin (6.3 percent) and low-molecular-weight heparin (7.7 percent), and again the risk with any prophylactic agent was significantly lower than the risk with the placebo (25.8 percent) (p < 0.0001). Compared with the risk with the placebo (1.51 percent), only warfarin (0.16 percent), pneumatic compression (0.26 percent), and low-molecular-weight heparin (0.36 percent) were associated with a significantly lower risk of symptomatic pulmonary embolism. There were no significant differences among agents with regard to the risk of fatal pulmonary embolism or of mortality with any cause. The risk of minor wound-bleeding was significantly higher with low-molecular-weight heparin (8.9 percent) and low-dose heparin (7.6 percent) than it was with the placebo (2.2 percent) (p < 0.05). Compared with the risk with the placebo (0.28 percent), only low-dose heparin was associated with a significantly higher risk of major wound-bleeding (2.56 percent) and total major bleeding (3.46 percent) (p < 0.0001).. The best prophylactic agent in terms of both efficacy and safety was warfarin, followed by pneumatic compression, and the least effective and safe was low-dose heparin. Warfarin provided the lowest risk of both proximal deep venous thrombosis and symptomatic pulmonary embolism. However, there were no identifiable significant differences in the rates of fatal pulmonary embolism or death among the agents. Significant risks of minor and major bleeding complications were observed with greater frequency with certain prophylactic agents, particularly low-molecular-weight heparin (minor bleeding) and low-dose heparin (both major and minor bleeding).

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Aspirin; Chemoprevention; Confidence Intervals; Female; Heparin, Low-Molecular-Weight; Humans; Linear Models; Male; Middle Aged; Placebos; Platelet Aggregation Inhibitors; Postoperative Hemorrhage; Pressure; Pulmonary Embolism; Randomized Controlled Trials as Topic; Risk Factors; Safety; Survival Rate; Thromboembolism; Treatment Outcome; Venous Thrombosis; Warfarin

While the most recent trend in secondary prophylaxis after venous thromboembolism has been toward a prolonged duration, it has become obvious that individualization according to risk factors is crucial. Subgroup analyses in a long-term follow-up of a previous trial, as well as new trials on patients with idiopathic thromboembolism, have now improved our base of evidence. Many studies on the influence of biochemical factors in the risk of recurrence have also been published recently. This review should be helpful in-the individual decision on how to tailor the duration of anticoagulation.

Topics: Anticoagulants; Humans; Odds Ratio; Randomized Controlled Trials as Topic; Recurrence; Risk Factors; Thromboembolism; Venous Thrombosis; Warfarin

Deep-vein thrombosis (DVT) and pulmonary embolism are among the most common complications of heparin-induced thrombocytopenia (HIT), an antibody-mediated adverse effect of heparin that leads paradoxically to in vivo activation of platelets and the coagulation system. Inappropriate treatment of HIT-associated DVT with warfarin can cause the DVT to progress to limb gangrene: this results from impaired ability of the protein C natural anticoagulant pathway to down-regulate thrombin generation, thus leading to microvascular thrombosis and tissue necrosis. Appreciation of the importance of coagulation system activation in HIT provides a rationale for treatments that reduce thrombin generation, either via inhibiting factor Xa (danaparoid) or via inhibiting thrombin directly (lepirudin). Clinicians should know how to distinguish HIT from other thrombocytopenic disorders: for example, thrombocytopenia associated with pulmonary embolism can mimic HIT (pseudo-HIT), and acute dyspnea that can mimic acute pulmonary embolism can result from acute in vivo platelet activation in a patient with HIT antibodies who receives heparin bolus therapy (pseudo-pulmonary embolism).

Topics: Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Gangrene; Heparin; Heparitin Sulfate; Humans; Leg; Pulmonary Embolism; Thrombocytopenia; Venous Thrombosis; Warfarin

Topics: Administration, Oral; Adult; Anticoagulants; Enoxaparin; Female; Fibrinolytic Agents; Heparin; Heparin, Low-Molecular-Weight; Humans; Male; Meta-Analysis as Topic; Pregnancy; Pregnancy Complications, Cardiovascular; Randomized Controlled Trials as Topic; Risk; Thrombectomy; Thromboembolism; Thrombolytic Therapy; Time Factors; Vena Cava Filters; Venous Thrombosis; Warfarin

The critical focus in the acute management of deep vein thrombosis (DVT) continues to be the effective prevention of associated life-threatening pulmonary embolism (PE) and the achievement of survival for those in whom such emboli occur. As such, primary treatment for DVT or PE demands adequate anticoagulation with intravenous heparin followed by maintenance oral warfarin for 3 to 6 months. This centered approach successfully prevents 90% to 95% of cases of associated pulmonary embolism. However, under circumstances in which anticoagulation cannot be used, or in which it fails, there is clear indication for placement of a mechanical filter into the inferior vena cava to provide a protective barrier against the passage of clinically significant emboli from pelvic or lower extremity veins. Considerable technical ingenuity and continued evolution of materials and design have propelled the development and number of vena cava filters available for clinical use. Variable data on safety and effectiveness require physicians to match the best filter to each patient's particular situation and anatomy. However, many interventional radiologists and surgeons often base their filter selection on ease of insertion and device cost. Thus, it is paramount that physician users of these devices remember that the primary objective of vena cava filtration is to provide a safe and effective device for permanent implantation. If this objective is not met, the quality of care in the management of deep venous thrombosis or pulmonary embolism will diminish.

Topics: Anticoagulants; Biocompatible Materials; Chemoprevention; Decision Making; Equipment Design; Heparin; Humans; Pulmonary Embolism; Safety; Treatment Outcome; Vena Cava Filters; Venous Thrombosis; Warfarin

Venous thromboembolism remains an important cause of considerable morbidity and mortality. Low-molecular-weight heparin appears to be a safe and effective alternative to unfractionated heparin for inpatient treatment. In addition, we recommend considering its use in outpatient treatment in selected patients. When warfarin therapy is initiated, the starting dose should approximate the suspected maintenance dose. The optimal length of anticoagulation after an initial episode of venous thromboembolism is 6 months unless a persistent risk factor is identified. Thrombolytic therapy for hemodynamically stable patients remains controversial, primarily because of the potential for devastating complications.

Topics: Ambulatory Care; Anticoagulants; Contraindications; Heparin; Heparin, Low-Molecular-Weight; Humans; Pulmonary Embolism; Thrombolytic Therapy; Venous Thrombosis; Warfarin

Pregnancy is an important risk factor for venous thrombosis, and venous thromboembolism is a leading cause of preventable death in pregnancy. Diagnosis of venous thromboembolism is complicated in that the symptoms of dyspnea and lower extremity edema are relatively common complaints of pregnant patients. Physicians should maintain an appropriately high index of suspicion and request diagnostic imaging in a timely manner. Diagnosis of deep venous thrombosis with Doppler ultrasonography of the lower extremity poses no health risk to the fetus, but other radiographic studies pose a low radiation risk to the fetus. Because anticoagulant therapy poses a greater health risk to mother and fetus than does the radiation required for the diagnosis of pulmonary embolism, clinicians should aggressively pursue objective evidence of venous thromboembolism. Once the diagnosis is made, anticoagulation with intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin should be used prepartum followed by warfarin therapy after delivery.

Topics: Adult; Anticoagulants; Contraindications; Female; Heparin; Humans; Pregnancy; Pregnancy Complications, Hematologic; Pulmonary Embolism; Risk Factors; Venous Thrombosis; Warfarin

The past 10 years have seen dramatic changes in how we treat deep vein thrombosis (DVT). A decade ago, we would treat patients for 5 days with intravenous heparin and then start warfarin sodium therapy and continue administering both anticoagulants for another 5 to 7 days. In the early 1990s, we started warfarin therapy at the same time heparin was begun and decreased the hospital stay from 10 to 14 days to 5 to 7 days. With the development of low-molecular-weight heparin and the approval for use as outpatient treatment, patients are now spending 1 to 2 days in the hospital, and many times, they are not admitted. A case scenario (in italics) is integrated into this review to illustrate the cost-effective application of an evidence-based approach.

Topics: Ambulatory Care; Anticoagulants; Evidence-Based Medicine; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Patient Discharge; Time Factors; Venous Thrombosis; Warfarin

The clinical management of the antiphospholipid syndrome is aimed at assessing the thrombotic risk of an individual in order to undertake primary prevention for the asymptomatic subject positive for antiphospholipid antibodies or prophylaxis of major ischaemic events for the patient who has already experienced thrombosis. Lack of immunological parameters with a clear predictive value and the current concept that thrombosis is a multifactorial disease suggest that all the known acquired and genetic thrombotic risk factors should be taken into account in antiphospholipid syndrome. Low-dose aspirin and hydroxychloroquine have been proven useful in primary prevention. While convincing evidence has been provided that aspirin and hydroxychloroquine do not prevent secondary thrombosis, much debate has recently developed on the level of oral anticoagulation needed to guarantee this prevention. Main concerns are also related to duration of anticoagulation therapy, risk of bleeding, and the increased risk of thrombosis as a result of withdrawal of the anticoagulant. Low-molecular-weight heparin has recently emerged as a valid and safe alternative for those conditions that require transient interruption or withdrawal of anticoagulation. Although treatment of the catastrophic antiphospholipid syndrome is largely empirical, the therapeutic approach based on plasmapheresis associated with immunosupression or intravenous immunoglobulin seems to be the most promising. Most attention has recently been paid to the role of oxidative stress in the pathogenesis of antiphospholipid syndrome, as a correlation between lipid peroxidation and antiphospholipid antibodies has been demonstrated. Our studies showed that lipid peroxidation may contribute to the activation of the clotting system observed in antiphospholipid syndrome and that markers of both procoagulant state and increased lipid peroxidation can be modified by experimental antioxidant treatment.

Topics: Animals; Antiphospholipid Syndrome; Blood Coagulation; Heparin, Low-Molecular-Weight; Humans; Lipid Peroxidation; Protein C; Thrombosis; Venous Thrombosis; Warfarin

It is well-known that peri-operative and post-operative venous thrombosis are common. Trials in Europe have shown that extended out-of-hospital prophylaxis with a low-molecular-weight heparin reduces the rate of deep vein thrombosis in patients undergoing elective hip surgery. North American investigators of limited-outcome descriptive studies, however, have suggested that out-of-hospital prophylaxis is not necessary. To resolve this uncertainty, NAFT (North American Fragmin Trial) was conducted, the results of which are summarized in this paper. The findings of NAFT support the favourable findings of the European studies on extended prophylaxis. Furthermore, European data have shown extended out-of-hospital prophylaxis to be cost-effective. On the basis of the aggregate data, it is felt that the A2 recommendation made by the Fifth American College of Chest Physicians consensus conference for extended prophylaxis should be changed to an A1 recommendation.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Cost-Benefit Analysis; Dalteparin; Decision Making; Double-Blind Method; Drug Administration Schedule; Drug Costs; Elective Surgical Procedures; Follow-Up Studies; Hematoma; Humans; North America; Postoperative Complications; Postoperative Period; Practice Guidelines as Topic; Safety; Treatment Outcome; Venous Thrombosis; Warfarin

Post-surgical deep vein thrombosis (DVT) is often underdiagnosed by clinical assessment alone. Subclinical DVT is a major source of pulmonary embolism, which is an important cause of death, particularly following total hip replacement surgery. Results from pathophysiological studies and recently conducted, prospective double-blind venographic studies in Europe and North America suggest that, in patients undergoing total hip replacement surgery, thromboprophylaxis with a low-molecular-weight heparin should be continued for at least 5 weeks post-operatively to minimize this serious complication.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Double-Blind Method; Europe; Heparin, Low-Molecular-Weight; Humans; Leg; Multicenter Studies as Topic; North America; Outpatients; Phlebography; Postoperative Complications; Postoperative Period; Prevalence; Prospective Studies; Pulmonary Embolism; Randomized Controlled Trials as Topic; Regional Blood Flow; Risk Factors; Thromboembolism; Thromboplastin; Venous Thrombosis; Warfarin

Postoperative thromboembolic events are a major cost factor for every healthcare system. Although thromboprophylaxis carries its own costs, the application of a thromboprophylactic regimen is cost-effective in most instances, at least in high-risk patients. A regimen of general postoperative prevention of deep vein thrombosis is always more cost-effective than surveillance programmes with treatment after diagnosis, and is almost always more cost-effective than no prophylaxis. For patients with a high risk of postoperative thromboembolism, such as after orthopaedic surgery, low-molecular-weight heparins have a rather clear advantage over prophylaxis with unfractionated heparin and warfarin, also in terms of cost- effectiveness. With regard to moderate-risk patients, such as after general surgery, the economic benefits are less clear. However, since the results of economic analyses are heavily dependent on the healthcare system, and since there are methodological difficulties and uncertainties connected with the analyses, the implications are difficult -- if not impossible -- to generalize. There is an urgent need for further prospective studies, which should be performed with defined economic variables a priori and in close cooperation with health economists.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Clinical Trials as Topic; Cohort Studies; Cost of Illness; Cost-Benefit Analysis; Drug Costs; Heparin, Low-Molecular-Weight; Hospitalization; Humans; Incidence; Postoperative Complications; Randomized Controlled Trials as Topic; Research Design; Retrospective Studies; Risk; Venous Thrombosis; Warfarin

Venous thrombosis most often attacks patients who have had alterations of venous stasis, endothelial damage, and/or hypercoagulability. Diagnosis generally depends on venography or duplex doppler ultrasonography; treatment is usually started with heparin and may proceed to warfarin alone.

Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Thrombophilia; Venous Thrombosis; Warfarin

The past decade has seen many important advances in the pathogenesis, clinical and laboratory diagnosis, and management of heparin-induced thrombocytopenia (HIT), one of the most common immune-mediated adverse drug reactions. HIT is caused by IgG antibodies that recognize complexes of heparin and platelet factor 4, leading to platelet activation via platelet Fc gamma IIa receptors. Formation of procoagulant, platelet-derived microparticles, and, possibly, activation of endothelium generate thrombin in vivo. Thrombin generation helps to explain the strong association between HIT and thrombosis, including the newly recognized syndrome of warfarin-induced venous limb gangrene. This syndrome occurs when acquired protein C deficiency during warfarin treatment of HIT and deep venous thrombosis leads to the inability to regulate thrombin generation in the microvasculature. The central role of HIT antibodies in causing HIT, as well as refinements in laboratory assays to detect these antibodies, means that HIT should be considered a clinicopathologic syndrome. The diagnosis can be made confidently when one or more typical clinical events (most frequently, thrombocytopenia with or without thrombosis) occur in a patient with detectable HIT antibodies. The central role of thrombin generation in this syndrome provides a rationale for the use of anticoagulants that reduce thrombin generation (danaparoid) or inhibit thrombin (lepirudin).

Topics: Antibodies; Anticoagulants; Antithrombin III; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Fibrinolytic Agents; Gangrene; Heparin; Heparinoids; Heparitin Sulfate; Hirudin Therapy; Hirudins; Humans; Immunoglobulin G; Leg; Platelet Activation; Platelet Factor 4; Protein C Deficiency; Receptors, IgG; Recombinant Proteins; Retrospective Studies; Syndrome; Thrombin; Thrombocytopenia; Venous Thrombosis; Warfarin

A 28-year-old man was hospitalized with nausea, vomiting, abdominal pain and low-grade fever. He had a 6-month history of paroxysmal nocturnal haemoglobinuria (PNH), and laboratory data showed anaemia and liver dysfunction. An abdominal ultrasonography showed ascites and portal vein thrombosis. After receiving antithrombotic treatment, the portal vein thrombosis did not extend. Portal vein thrombosis is very rare but should be considered when we encounter liver dysfunction associated with PNH as well as hepatic vein thrombosis. Ultrasonography is very useful in detecting portal vein thrombosis and facilitating early diagnosis. Warfarin is very effective in preventing exacerbation of portal vein thrombosis in PNH.

Topics: Adult; Anticoagulants; Hemoglobinuria, Paroxysmal; Humans; Liver Function Tests; Male; Portal Vein; Tomography, X-Ray Computed; Ultrasonography; Venous Thrombosis; Warfarin

The incidence of DVT in axillo-subclavian district is rather low. Up-to-date reports show however it is progressively increasing, owing to the widespread diffusion of intravenous prosthetic devices. While the opportunities of a correct diagnosis are becoming various, particularly because of the development of echo color-Doppler and imaging techniques, there is indecision for the treatment: the question is about a medical and a surgical therapy. Neither the former nor the latter are well established. This case report is about a 61-year-old woman affected by a recurrent DVT of the subclavian and axillary veins, who never underwent operation and/or handling of the venous district. Clinical tests didn't show any well determinate cause of thrombosis. It was decided not to treat the patient surgically, so a medical therapy was undertaken. Now she is completely recovered.

Topics: Anticoagulants; Arm; Female; Follow-Up Studies; Heparin; Humans; Middle Aged; Recurrence; Retreatment; Venous Thrombosis; Warfarin

Topics: Adult; Anticoagulants; Female; Humans; Mesenteric Vascular Occlusion; Mesenteric Veins; Protein S Deficiency; Radiography; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Contraindications; Controlled Clinical Trials as Topic; Humans; Radionuclide Imaging; Randomized Controlled Trials as Topic; Risk Factors; Thromboembolism; Thrombophilia; Venous Thrombosis; Warfarin

The identified main causes of inherited thrombophilia are deficiencies of antithrombin, protein C and protein S, activated protein C (APC) resistance and the factor V Leiden mutation, mutant factor II, and inherited hyperhomocysteinemia. In women from symptomatic families these defects may be associated with an increased risk of venous thrombosis in pregnancy and recurrent fetal loss. Inherited thrombophilia is common and appears to be a multigene disorder. The thrombotic risk would seem to be greatest in women with antithrombin deficiency and more than one thrombophilia defect. The abnormalities that are now recognized represent only part of the genetic predisposition to thrombosis. In assessing thrombotic risk in pregnancy, acquired risk factors as well as genetic predisposition should be considered. Increasing age, obesity, immobility, and delivery by cesarean section are major risk factors. Pregnancy should be planned, and each patient should be managed on an individual basis. In pregnancy, heparin is the anticoagulant of choice, and as far as possible, treatment with warfarin should be avoided because of the risks to the fetus. When patients are on long-term treatment with warfarin, pregnancy should be avoided, and warfarin should be discontinued prior to embarking on a pregnancy or as soon as pregnancy is suspected and before 6 weeks' gestation. In women from symptomatic families with antithrombin deficiency, adjusted dose heparin throughout pregnancy is recommended and warfarin for at least 3 months post partum. In protein C and protein S deficiency, factor V Leiden, or mutant factor II, treatment can be based on personal and family history. Thromboprophylaxis in late pregnancy and post partum should be considered. Fetal loss may be increased in women with inherited thrombophilia. The risk appears greatest in women with antithrombin deficiency and women with more than one thrombophilia defect. A number of reports have claimed that prophylactic treatment with heparin during pregnancy has resulted in successful pregnancy in women with recurrent fetal death and inherited thrombophilia.

Topics: Family Health; Female; Heparin; Humans; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy Maintenance; Risk Factors; Thrombophilia; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Clinical Trials as Topic; Drug Administration Schedule; Humans; Risk Assessment; Time Factors; Venous Thrombosis; Warfarin

Venous thromboembolism is a life-threatening complication of traumatic brain injury. Consequently, knowledge of available screening, diagnostic, prophylactic, and treatment methods is critical to the management of the individual with traumatic brain injury. Venous thromboembolic risk varies among individuals, resulting in unique screening and prophylactic needs for each patient. In addition, anticoagulation, commonly employed for prophylaxis and treatment in other patient populations, may create an increased risk for intracranial hemorrhage when utilized following traumatic brain injury. The cost, sensitivity, specificity, efficacy, potential side effects, and alternatives for preventing, detecting, and treating venous thromboembolism are important considerations discussed in this article.

Topics: Acute Disease; Anticoagulants; Bandages; Brain Injuries; Heparin; Humans; Thromboembolism; Vena Cava Filters; Venous Thrombosis; Warfarin

During pregnancy and the immediate puerperium, the risk for venous thromboembolism (VTE) is substantially increased. Certain medical conditions, including inherited or acquired thrombophilias, and obstetric manipulations such as cesarean delivery further increase this risk. Consequently, acute VTE is one of the leading causes of maternal morbidity and direct mortality in the United States and other developed countries. That considered, clinicians and researchers must understand how to effectively use anticoagulant drugs during pregnancy, and must recognize areas for improvement in the knowledge of these medications. These areas are especially important, because the use of anticoagulants during pregnancy may even increase in light of recent information indicating that thrombophilia is associated with certain more common obstetrical complications.

Topics: Anticoagulants; Female; Heparin; Heparin, Low-Molecular-Weight; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Venous Thrombosis; Warfarin

When the need for surgery arises, temporary interruption of long-term anticoagulation exposes patients to additional thrombotic risk. There is no consensus as to how perioperative anticoagulation should be managed in this setting. Based on an individual assessment of risk factors for arterial or venous thromboembolism and the risk of postoperative bleeding, this review outlines an approach to the perioperative management of anticoagulation that is designed to optimize patient safety and efficient delivery of health care. The duration of interruption of oral anticoagulation is minimized by withholding four daily doses of warfarin before surgery, and by restarting warfarin the same day that surgery is performed. This will usually achieve satisfactory coagulation status intraoperatively (e.g., International Normalized Ratio of 1.5 or less) with a low risk of postoperative bleeding. Supplemental prophylaxis with therapeutic doses of heparin, usually unfractionated heparin, can be reserved for patients with the highest risk of thromboembolism. In the preoperative period, this applies to patients who have had an episode of arterial or venous thromboembolism in the preceding month. In the postoperative period, this approach is generally reserved for patients with an episode of venous thromboembolism in the preceding 3 months, and patients with an episode of arterial embolism in the preceding month who have a low risk of bleeding. Differences in the approach to management of anticoagulation before and after surgery relate to the fact that surgery is an important risk factor for venous, but not arterial, thromboembolism, and that recent surgery greatly increases the risk of anticoagulant-induced bleeding. Subcutaneous unfractionated or low-molecular-weight heparin, in doses recommended to prevent venous thromboembolism in high-risk surgical patients, should be administered to in-patients who have a lesser risk of thromboembolism until oral anticoagulation is reestablished.

Topics: Anticoagulants; Blood Loss, Surgical; Heparin; Heparin, Low-Molecular-Weight; Humans; Venous Thrombosis; Warfarin

Low-molecular-weight heparins (LMWH) are a new group of parenteral anticoagulants. They represent a major clinical advance in anticoagulation since the identification of unfractionated heparin (UFH) in 1922 and the introduction of the synthetic coumarin derivative, warfarin, in 1948. Their predictable pharmacokinetics, increased bioavailability, and longer plasma half-life allow for once- or twice-daily dosing and eliminate the need for routine laboratory monitoring. This simplified administration stands to alter the clinical practice of anticoagulation. This review high-lights recent clinical trials and focuses on studies comparing LMWH with the other two major anticoagulants: UFH and coumadin.

Topics: Anticoagulants; Cerebrovascular Disorders; Clinical Trials as Topic; Coronary Disease; Heparin; Heparin, Low-Molecular-Weight; Humans; Pulmonary Embolism; Venous Thrombosis; Warfarin

Warfarin remains the standard drug for secondary prophylaxis following venous thromboembolism, however this treatment is not ideal. In patients for whom monitoring is problematic or who have a high risk of bleeding complications, other possible solutions have been explored. Unfractionated heparin has been used to a limited extent in these situations and requires dose adjustment in order to achieve an acceptable efficacy. Low-molecular-weight heparin (LMWH) is a valuable alternative to warfarin for these patients and for thromboprophylaxis during pregnancy. In several subgroups of patients with venous thromboembolism the use of a LMWH instead of warfarin could offer specific advantages. The combination of warfarin and LMWH is warranted in patients for whom it is predicted that warfarin treatment alone may fail. The optimal dose of LMWH in long-term prophylaxis has not been evaluated in a properly designed study and the optimal duration of prophylaxis with LMWH is thought to be similar to that for warfarin.

Topics: Administration, Oral; Anticoagulants; Female; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Humans; Injections, Intravenous; Pregnancy; Randomized Controlled Trials as Topic; Venous Thrombosis; Warfarin

Topics: Abortion, Habitual; Adult; Antigens; Aspirin; Biomarkers; Enzyme-Linked Immunosorbent Assay; Female; Fetal Death; Heparin; Humans; Male; Middle Aged; Phospholipids; Pregnancy; Risk Assessment; Sensitivity and Specificity; Venous Thrombosis; Warfarin

Portal vein thrombosis (PVT) and acute variceal bleeding (AVB) are frequent complications of cirrhosis. The efficacy, safety, and timing of anticoagulant treatment in cirrhotic patients with PVT and AVB are contentious issues. We aimed to establish the safety and efficacy of initiating nadroparin calcium-warfarin sequential (NWS) anticoagulation therapy early after esophageal variceal band ligation within PVT patients having cirrhosis and AVB. Cirrhotic patients having AVB and PVT who underwent EVL were included and randomly allocated to either the NWS therapy group (1-month nadroparin calcium by subcutaneous injection following 5-month warfarin through oral administration, n = 43) or the control group (without any anticoagulation therapy, n = 43). The primary endpoint was the rate of PVT recanalization. Secondary endpoints included major bleeding events mainly referring to variceal rebleeding (5-day failure, 14-day, 4-week, 6-week, and 6-month rebleeding rates) and mortality after EVL. The overall recanalization (complete and partial) rate in the NWS therapy group was significantly higher than that in the control group (67.4% vs. 39.5%, P = 0.009). Low Child-Pugh score (P = 0.039, OR: 0.692, 95% CI 0.488-0.982), D-dimer < 2.00 ug/mL (P = 0.030, OR: 3.600, 95% CI 1.134-11.430), and NWS anticoagulation therapy (P = 0.002, OR: 4.189, 95% CI 1.660-10.568) were the predictors of PVT recanalization through univariate analysis of binary logistic regression. NWS anticoagulation therapy (P = 0.003, OR: 4.506, 95% CI 1.687-12.037) was the independent factor of recanalization through multivariate analysis. Nobody bled except for variceal rebleeding. Five-day failure and 14-day rebleeding were zero. There were no significantly different in 4-week (2.3% vs. 4.7%, P = 1.000), 6-week (4.7% vs. 9.3%, P = 0.672) and 6-month rebleeding (18.6% vs. 20.9%, P = 0.787) between the two groups. There was no mortality during six months follow-up. Low serum albumin (P = 0.011, OR: 0.844, 95% CI 0.741-0.962), high MELD score (P = 0.003, OR: 1.564, 95% CI 1.167-2.097) and Child-Pugh score (P = 0.006, OR: 1.950, 95% CI 1.206-3.155) were predictors of rebleeding by univariate analysis of binary logistic regression analysis. The Child-Pugh score (7 [6-8] vs. 6 [5-7], P = 0.003) and albumin levels (33.93 ± 5.30 vs. 37.28 ± 4.32, P = 0.002) were improved in the NWS therapy group at six months. In PVT patients with cirrhosis and AVB, starting NWS anticoagulation therapy early after EVL wa

Topics: Albumins; Anticoagulants; Esophageal and Gastric Varices; Fibrosis; Gastrointestinal Hemorrhage; Humans; Liver Cirrhosis; Nadroparin; Portal Vein; Treatment Outcome; Venous Thrombosis; Warfarin

Warfarin and rivaroxaban were the two most commonly-used anticoagulant drugs for Deep venous thrombosis (DVT). The aim of this study was to explore the effects of post-discharge pharmacist-led follow-up on drug treatment in patients with DVT in primary hospitals from a pharmacological perspective. A total of 125 patients were recruited from July 2017 to June 2019 and randomized to either a control group or an intervention group. The control group was given routine medication guidance, clinical pharmacists followed up at 3 and 6 months after discharge. The intervention group was based on the control group and was followed up weekly for 6 months after discharge. For patients taking warfarin, the percentage of time in therapeutic range (TTR) and TTR>65% were significantly higher in the intervention group (p<0.05) and they also had less frequent dose changes. For patients taking warfarin or rivaroxaban, vascular ultrasonography showed better improvement rate in the intervention group (p<0.05). Pharmacist-led follow-up showed that the medication adherence (p<0.05) were significantly improved. There were lower risks of total and minor hemorrhage events and thrombosis events in the intervention group (p<0.05). Pharmacist-led follow-up not only reduced the risk of hemorrhage and thrombosis events, but also improved adherence to anticoagulation drugs.

Topics: Aftercare; Follow-Up Studies; Hemorrhage; Hospitals; Humans; Patient Discharge; Pharmacists; Rivaroxaban; Thrombosis; Venous Thrombosis; Warfarin

The effect of different anticoagulants on recanalization after cerebral venous thrombosis has not been studied in a randomized controlled trial.. RE-SPECT CVT (ClinicalTrials.gov number: NCT02913326) was a Phase III, prospective, randomized, parallel-group, open-label, multicenter, exploratory trial with blinded endpoint adjudication. Acute cerebral venous thrombosis patients were allocated to dabigatran 150 mg twice daily, or dose-adjusted warfarin, for 24 weeks, after 5-15 days' treatment with unfractionated or low-molecular-weight heparin. A standardized magnetic resonance protocol including arterial spin labeling, three-dimensional time-of-flight venography, and three-dimensional contrast-enhanced magnetic resonance angiography was obtained at the end of the treatment period. Cerebral venous recanalization at six months was assessed by two blinded adjudicators, using the difference in a score of occluded sinuses and veins (predefined secondary efficacy endpoint) and in the modified Qureshi scale (additional endpoint), between baseline and the end of the treatment.

Topics: Anticoagulants; Cerebral Veins; Dabigatran; Humans; Prospective Studies; Sinus Thrombosis, Intracranial; Stroke; Treatment Outcome; Venous Thrombosis; Warfarin

Warfarin is an effective treatment for thromboembolic disease but has a narrow therapeutic index; optimal anticoagulation dosage can differ tremendously among individuals. We aimed to evaluate whether genotype-guided warfarin dosing is superior to routine clinical dosing for the outcomes of interest in Chinese patients.. We conducted a multicenter, randomized, single-blind, parallel-controlled trial from September 2014 to April 2017 in 15 hospitals in China. Eligible patients were ≥18 years of age, with atrial fibrillation or deep vein thrombosis without previous treatment of warfarin or a bleeding disorder. Nine follow-up visits were performed during the 12-week study period. The primary outcome measure was the percentage of time in the therapeutic range of the international normalized ratio during the first 12 weeks after starting warfarin therapy.. A total of 660 participants were enrolled and randomly assigned to a genotype-guided dosing group or a control group under standard dosing. The genotype-guided dosing group had a significantly higher percentage of time in the therapeutic range than the control group (58.8% versus 53.2% [95% CI of group difference, 1.1-10.2];. The outcomes of genotype-guided warfarin dosing were superior to those of clinical standard dosing. These findings raise the prospect of precision warfarin treatment in China. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02211326.

Topics: Aged; Anticoagulants; Asian People; Atrial Fibrillation; China; Cytochrome P-450 CYP2C9; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Genotype; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Single-Blind Method; Treatment Outcome; Venous Thrombosis; Vitamin K Epoxide Reductases; Warfarin

Anticoagulation therapy in portal vein thrombosis (PVT) in patients with cirrhosis is still a matter of debate. Therefore, the aim of this work was to evaluate the efficacy and safety of nadroparin calcium-warfarin sequential (NWS) anticoagulation therapy in cirrhotic patients and to find an optimal anticoagulation strategy.. Consecutive cirrhotic patients with PVT who have not received anticoagulation therapy were randomly divided into the NWS therapy group (1-month nadroparin calcium by subcutaneous injection followed by 5-month warfarin by oral administration) and control group (no anticoagulation therapy). Overall recanalization rate of PVT and risks of bleeding were evaluated at the sixth month.. Among 64 patients, complete or partial recanalization of PVT was observed in 20/32 NSW therapy group patients vs 11/32 control group patients (62.5% vs 34.4%, P = 0.024), with no statistically significant difference in bleeding rate. Child-Pugh score (P = 0.023), D-dimer < 2.00 μg/mL (P = 0.020), and NWS anticoagulation therapy (P = 0.004) were predictors associated with the recanalization. NWS anticoagulation therapy (P = 0.008) was an independent predicting factor of recanalization. In the NWS therapy group, the Child-Pugh score (P = 0.007) and albumin level (P = 0.004) were improved in the sixth month.. NWS anticoagulation therapy was effective and safe in PVT patients with cirrhosis and could increase the level of albumin. NWS therapy is safe and easily accepted.

Topics: Adult; Anticoagulants; Drug Administration Schedule; Female; Fibrin Fibrinogen Degradation Products; Humans; Liver Cirrhosis; Male; Middle Aged; Nadroparin; Portal Vein; Prospective Studies; Serum Albumin, Human; Severity of Illness Index; Tomography, X-Ray Computed; Treatment Outcome; Venous Thrombosis; Warfarin

Patients with cerebral venous thrombosis (CVT) are at risk of recurrent venous thrombotic events (VTEs). Non-vitamin K oral anticoagulants have not been evaluated in randomized controlled trials in CVT.. To compare the efficacy and safety of dabigatran etexilate with those of dose-adjusted warfarin in preventing recurrent VTEs in patients who have experienced a CVT.. RE-SPECT CVT is an exploratory, prospective, randomized (1:1), parallel-group, open-label, multicenter clinical trial with blinded end-point adjudication (PROBE design). It was performed from December 21, 2016, to June 22, 2018, with a follow-up of 25 weeks, at 51 tertiary sites in 9 countries (France, Germany, India, Italy, the Netherlands, Poland, Portugal, Russia, and Spain). Adult consecutive patients with acute CVT, who were stable after 5 to 15 days of treatment with parenteral heparin, were screened for eligibility. Patients with CVT associated with central nervous system infection or major trauma were excluded, but those with intracranial hemorrhage from index CVT were allowed to participate. After exclusions, 120 patients were randomized. Data were analyzed following the intention-to-treat approach.. Dabigatran, 150 mg twice daily, or dose-adjusted warfarin for a treatment period of 24 weeks.. Primary outcome was a composite of patients with a new VTE (recurrent CVT, deep vein thrombosis of any limb, pulmonary embolism, and splanchnic vein thrombosis) or major bleeding during the study period. Secondary outcomes were cerebral venous recanalization and clinically relevant non-major bleeding events.. In total, 120 patients with CVT were randomized to the 2 treatment groups (60 to dabigatran and 60 to dose-adjusted warfarin). Of the randomized patients, the mean (SD) age was 45.2 (13.8) years, and 66 (55.0%) were women. The mean (SD) duration of exposure was 22.3 (6.16) weeks for the dabigatran group and 23.0 (5.20) weeks for the warfarin group. No recurrent VTEs were observed. One (1.7%; 95% CI, 0.0-8.9) major bleeding event (intestinal) was recorded in the dabigatran group, and 2 (3.3%; 95% CI, 0.4-11.5) (intracranial) in the warfarin group. One additional patient (1.7; 95% CI, 0.0-8.9) in the warfarin group experienced a clinically relevant non-major bleeding event. Recanalization occurred in 33 patients in the dabigatran group (60.0%; 95% CI, 45.9-73.0) and in 35 patients in the warfarin group (67.3%; 95% CI, 52.9-79.7).. This trial found that patients who had CVT anticoagulated with either dabigatran or warfarin had low risk of recurrent VTEs, and the risk of bleeding was similar with both medications, suggesting that both dabigatran and warfarin may be safe and effective for preventing recurrent VTEs in patients with CVT.. ClinicalTrials.gov identifier: NCT02913326.

Topics: Adult; Aged; Anticoagulants; Antithrombins; Dabigatran; Female; Follow-Up Studies; Hemorrhage; Humans; Intracranial Thrombosis; Male; Middle Aged; Prospective Studies; Single-Blind Method; Treatment Outcome; Venous Thrombosis; Warfarin

Anticoagulation therapy is the main line of treatment for acute portal vein thrombosis (PVT) in the absence of cirrhosis. However, the use of this therapy in cirrhotic PVT is still with doubtful evidence. We aimed to evaluate the efficacy and safety of rivaroxaban compared to warfarin for the management of acute non-neoplastic PVT in Hepatitis C virus (HCV)-related compensated cirrhosis.. Out of 578 patients with chronic HCV infection, 80 patients with acute PVT who had undergone splenectomy due to hypersplenism and 4 patients with acute PVT due to portal pyemia were selected. The patients were randomly assigned (1:1) to the study group (n = 40), in which the patients received rivaroxaban 10 mg/12 h, or the control group (n = 40), in which the patients received warfarin.. In the rivaroxaban group, the resolution of PVT was achieved in 34 patients (85%) within 2.6 ± 0.4 months and delayed, partial recanalization after 6.7 ± 1.2 months (n = 6.15%). Complications such as major bleeding, abnormal liver functions, death, or recurrence did not occur during treatment, and patients in this group showed improved short-term survival rate (20.4 ± 2.2 months) compared to the survival rate in the control group (10.6 ± 1.8 months) in which warfarin achieved complete resolution in 45% of patients. Complications such as severe upper GI tract bleeding (43.3%), hepatic decompensation (22.5%), progression to mesenteric ischemia (12.5%), recurrence (10%), and death (20%) were observed in the control group. The duration until complete resolution of thrombus correlated with age, the extent of the thrombus, creatinine level, and MELD score. The recurrence after complete resolution of thrombus correlated with age, the extent of the thrombus, thrombogenic gene polymorphism, and the use of warfarin.. Rivaroxaban was effective and safe in acute HCV-related non-neoplastic PVT with improved short-term survival rate; ClinicalTrials.gov Identifier: NCT03201367.

Topics: Adult; Anticoagulants; Blood Coagulation; Computed Tomography Angiography; Egypt; Factor Xa Inhibitors; Female; Hemorrhage; Hepatitis C, Chronic; Humans; Liver Cirrhosis; Male; Middle Aged; Phlebography; Portal Vein; Recurrence; Rivaroxaban; Time Factors; Treatment Outcome; Ultrasonography, Doppler, Color; Venous Thrombosis; Warfarin

To evaluate the international normalized ratio (INR) monitoring patterns in patients with deep vein thrombosis.. Of 32,012 patients with ≥1 outpatient INR measurement and 42,582 patients with confirmed deep vein thrombosis diagnosis registered to our hospital between 1 January 2010 and 31 December 2013, 6720 records were identified to have both deep vein thrombosis and international normalized ratio measurement, and 4.377 out of 6.720 single patient records were determined to be statistically analyzable.. Median INR measurement frequency was 6.47 times/year and patients had INR levels of 2-3 in 34.3% of follow-up time. Having ≥70% vs. <70% of follow-up time within therapeutic range was associated with lower hospital admission frequency (9.7 vs. 10.3 times/year).. Our study revealed only one-third of the follow-up time to be spent within therapeutic INR, association of INR therapeutic range with lesser number of hospital admissions and INR monitoring frequency of 6.47 times/year despite lack of stable INR control in most of the deep vein thrombosis patients.

Topics: Administration, Oral; Adult; Aged; Databases, Factual; Drug Monitoring; Female; Follow-Up Studies; Humans; International Normalized Ratio; Male; Middle Aged; Venous Thrombosis; Warfarin

The optimal duration of anticoagulation after a first episode of unprovoked deep-vein thrombosis is uncertain. We aimed to assess the benefits and risks of an additional 18 months of treatment with warfarin

Topics: Administration, Oral; Aged; Anticoagulants; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prognosis; Time Factors; Venous Thrombosis; Warfarin; Withholding Treatment

Portal vein system thrombosis (PVST) is a common, potentially life-threatening complication after splenectomy. The optimal recognized anticoagulation drugs for preventing PVST in cirrhotic patients after splenectomy remain unclear. The aim of this study is to evaluate the safety and efficacy of warfarin in preventing PVST after laparoscopic splenectomy and azygoportal disconnection (LSD).. In this randomized controlled single-center study, 80 cirrhotic patients who underwent LSD were randomly assigned to 2 years of treatment with either warfarin (n = 40) or aspirin (n = 40). The primary outcome was prevention of PVST. Sonographers and radiologists who assessed outcomes were blinded to group assignments. Intention-to-treat analysis was performed.. During the first year, excluding two patients withdrawing from the study, 15 of the 39 warfarin-treated patients (38.5%) and five of the 39 aspirin-treated patients (12.8%) did not develop PVST (P = 0.010). The incidence of PVST in the first 2 postoperative years was significantly lower in the warfarin group than in the aspirin group (F = 7.360, P = 0.008). The warfarin group in paired within-group comparisons had significantly greater improvements in total bilirubin and albumin levels at baseline versus at 6 months postoperatively and in creatinine levels at baseline versus at 12, 18, and 24 months postoperatively respectively (all P < 0.05). In contrast, those paired comparisons of the aspirin group showed no significant differences (all P > 0.05).. Warfarin therapy was safe and effective and significantly reduced the risk of PVST after LSD, compared with aspirin treatment. Warfarin treatment was associated with better liver function protection and renal function improvement than aspirin treatment.

Topics: Aged; Aged, 80 and over; Aspirin; Female; Humans; Incidence; Laparoscopy; Liver Cirrhosis; Male; Middle Aged; Portal Vein; Postoperative Complications; Splenectomy; Venous Thrombosis; Warfarin

In this article, we report the outcomes of patients with deep venous thrombosis in the lower limbs treated with the oral anticoagulant rivaroxaban or warfarin, focusing on the recanalization rate (measured with duplex ultrasound) and the incidence of postthrombotic syndrome.. This was a prospective, consecutive, randomized, blind cohort study of patients admitted with deep venous thrombosis to the Division of Vascular and Endovascular Surgery, Hospital do Servidor Público Estadual, São Paulo, Brazil, between March 2016 and July 2018. The patients were randomized into 2 groups and treated with oral anticoagulation for 6 months: either rivaroxaban (group 1) or warfarin (group 2). The study was registered at clinicaltrials.gov under NCT 02704598.. Eighty-eight patients with deep venous thrombosis were admitted to the Vascular Surgery Department and randomized into the 2 groups. The follow-up time was 360 days. Analyses were performed at 180 and 360 days. Four patients were excluded from the study during follow-up because of a diagnosis of ovarian cancer (1 patient), head and neck cancer (1 patient), lung cancer (1 patient), and stomach cancer (1 patient). Therefore, 84 patients were evaluated: 46 patients in group 1 and 38 in group 2. The incidence of postthrombotic syndrome was 17.9% (15 cases) in the total cohort, but was significantly higher in group 2 (11 cases, 28.9%) than in group 1 (4 cases, 8.7%; P < .001; odds ratio, 4.278). The rate of total venous recanalization at 360 days was 40.5% (34 patients) in the total cohort, but was significantly higher in group 1 (35 patients, 76.1%) than in group 2 (5 patients, 13.2%; P < .001). The incidence of partial venous recanalization was 46.4% and was significantly higher in group 2 (28 patients, 73.7%) than in group 1 (11 patients, 23.9%; P = .016). Five patients in the total cohort (6%) showed no venous recanalization, all of them in group 2 (P = .016).. In this study, patients who received oral rivaroxaban displayed a lower incidence of postthrombotic syndrome and a better total vein recanalization rate after 6 and 12 months than patients who received warfarin.

Topics: Administration, Oral; Anticoagulants; Brazil; Female; Follow-Up Studies; Humans; Incidence; Lower Extremity; Male; Middle Aged; Postthrombotic Syndrome; Prospective Studies; Rivaroxaban; Treatment Outcome; Ultrasonography, Doppler, Duplex; Vascular Patency; Venous Thrombosis; Warfarin

Individuals with deep vein thrombosis (DVT) have an increased risk of pulmonary embolism (PE), death, and long-term thrombotic complications.. To evaluate the efficacy and safety of bemiparin once daily versus enoxaparin twice daily in the treatment of acute DVT, and to establish therapeutic non-inferiority of bemiparin.. This multicenter, randomized, open-label, active-controlled phase III clinical trial enrolled patients with acute proximal DVT confirmed by complete compression ultrasound (CCUS). Patients received bemiparin once daily or enoxaparin twice daily subcutaneously for 7 days, in combination with warfarin 5 mg/day. Assessment of thrombotic burden was blinded and used CCUS recordings. The primary efficacy endpoint was the percentage of patients with an improvement in thrombotic burden at day 83 (end of follow-up); the secondary efficacy endpoint was the incidence of symptomatic recurrent DVT and PE. Safety endpoints included treatment-emergent adverse events.. Three-hundred and twelve patients were enrolled (~ 62% male; mean age 55.2 years). At least one DVT risk factor was present in 26.1% and 28.7% of the bemiparin and enoxaparin groups, respectively. The proportion of patients who had an improvement in thrombotic burden was similar for bemiparin (78.2%) and enoxaparin [80.8%; difference - 2.66 (97.5% CI - 12.39; ∞)], as was mean change in thrombus score (- 8.8 and - 8.6, respectively). There were no cases of recurrent DVT, and one case of non-fatal symptomatic PE in each treatment group. No major bleeding was reported, and there was no difference in the incidence of non-major bleeding.. The efficacy of bemiparin administered once daily is non-inferior to that of enoxaparin administered twice daily with a similar safety profile. CLINICALTRIALS.. NCT01880216.

Topics: Acute Disease; Adult; Aged; Anticoagulants; Drug Administration Schedule; Drug Therapy, Combination; Enoxaparin; Female; Heparin, Low-Molecular-Weight; Humans; Injections, Subcutaneous; Male; Middle Aged; Venous Thrombosis; Warfarin

Rationale To prevent recurrent venous thrombotic events after acute cerebral venous or dural sinus thrombosis, guidelines recommend long-term oral anticoagulation with vitamin K antagonists. Non-vitamin K oral anticoagulant experience in cerebral venous or dural sinus thrombosis is limited to case reports and series. Aim To compare dabigatran with dose-adjusted warfarin in patients with cerebral venous or dural sinus thrombosis for the prevention of recurrent venous thrombotic event. Sample size One hundred and twenty patients. Methods and design This study is a phase III, prospective, randomized, parallel-group, open-label, multicenter, exploratory trial with blinded endpoint adjudication. Patients with acute cerebral venous or dural sinus thrombosis after 5-15 days of treatment with parenteral heparin are randomized to either dabigatran etexilate 150 mg twice daily or dose-adjusted (international normalized ratio 2-3) warfarin (≤24 weeks). Study outcome The primary endpoint is a composite of patients with new venous thrombotic event (recurring cerebral venous or dural sinus thrombosis, deep venous thrombosis of any limb, pulmonary embolism, and major bleeding (International Society on Thrombosis and Hemostasis definition)) during the treatment period. Statistics will be descriptive (number and frequencies). Study timelines Inclusion started in December 2016. Final results are expected by the end of 2018. Discussion This exploratory trial is the first to compare vitamin K with non-vitamin K antagonists in cerebral venous or dural sinus thrombosis. It will provide evidence to guide physicians and patients in choosing oral anticoagulants to prevent venous thrombotic event after acute cerebral venous or dural sinus thrombosis. ClinicalTrials.gov number: NCT02913326.

Topics: Adult; Aged; Anticoagulants; Cerebral Veins; Clinical Trials, Phase III as Topic; Dabigatran; Dura Mater; Female; Humans; Male; Middle Aged; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Venous Thrombosis; Warfarin; Young Adult

Sudden death in patients with severe motor and intellectual disabilities (SMID) is sometimes caused in part by pulmonary thromboembolism (PTE), and deep venous thrombosis (DVT) has drawn attention as a possible embolic source. Warfarin, which is a conventional therapeutic agent, is not easy to control appropriately, and daily management can be especially difficult in SMID patients. On the other hand, edoxaban tosilate hydrate, which has been newly approved for insurance coverage for the treatment of DVT, is not listed in the Guidelines for the Diagnosis, Treatment and Prevention of Pulmonary Thromboembolism and Deep Vein Thrombosis (DVT-PTE guidelines). The aim of this study is to evaluate the efficacy and safety of anticoagulation therapy (warfarin vs. edoxaban) in DVT treatment in SMID patients by means of an open-label, randomized controlled trial. The primary endpoint is the incidence of hemorrhagic events during 12 months of follow up.

Topics: Anticoagulants; Factor Xa Inhibitors; Hemorrhage; Humans; Intellectual Disability; Intelligence; Japan; Motor Activity; Motor Disorders; Multicenter Studies as Topic; Persons with Mental Disabilities; Pyridines; Randomized Controlled Trials as Topic; Thiazoles; Time Factors; Treatment Outcome; Venous Thrombosis; Warfarin

Warfarin use accounts for more medication-related emergency department visits among older patients than any other drug. Whether genotype-guided warfarin dosing can prevent these adverse events is unknown.. To determine whether genotype-guided dosing improves the safety of warfarin initiation.. The randomized clinical Genetic Informatics Trial (GIFT) of Warfarin to Prevent Deep Vein Thrombosis included patients aged 65 years or older initiating warfarin for elective hip or knee arthroplasty and was conducted at 6 US medical centers. Enrollment began in April 2011 and follow-up concluded in October 2016.. Patients were genotyped for the following polymorphisms: VKORC1-1639G>A, CYP2C9*2, CYP2C9*3, and CYP4F2 V433M. In a 2 × 2 factorial design, patients were randomized to genotype-guided (n = 831) or clinically guided (n = 819) warfarin dosing on days 1 through 11 of therapy and to a target international normalized ratio (INR) of either 1.8 or 2.5. The recommended doses of warfarin were open label, but the patients and clinicians were blinded to study group assignment.. The primary end point was the composite of major bleeding, INR of 4 or greater, venous thromboembolism, or death. Patients underwent a screening lower-extremity duplex ultrasound approximately 1 month after arthroplasty.. Among 1650 randomized patients (mean age, 72.1 years [SD, 5.4 years]; 63.6% women; 91.0% white), 1597 (96.8%) received at least 1 dose of warfarin therapy and completed the trial (n = 808 in genotype-guided group vs n = 789 in clinically guided group). A total of 87 patients (10.8%) in the genotype-guided group vs 116 patients (14.7%) in the clinically guided warfarin dosing group met at least 1 of the end points (absolute difference, 3.9% [95% CI, 0.7%-7.2%], P = .02; relative rate [RR], 0.73 [95% CI, 0.56-0.95]). The numbers of individual events in the genotype-guided group vs the clinically guided group were 2 vs 8 for major bleeding (RR, 0.24; 95% CI, 0.05-1.15), 56 vs 77 for INR of 4 or greater (RR, 0.71; 95% CI, 0.51-0.99), 33 vs 38 for venous thromboembolism (RR, 0.85; 95% CI, 0.54-1.34), and there were no deaths.. Among patients undergoing elective hip or knee arthroplasty and treated with perioperative warfarin, genotype-guided warfarin dosing, compared with clinically guided dosing, reduced the combined risk of major bleeding, INR of 4 or greater, venous thromboembolism, or death. Further research is needed to determine the cost-effectiveness of personalized warfarin dosing.. clinicaltrials.gov Identifier: NCT01006733.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Drug Interactions; Elective Surgical Procedures; Genotype; Hemorrhage; Humans; International Normalized Ratio; Kaplan-Meier Estimate; Pharmacogenomic Testing; Venous Thrombosis; Warfarin

Purposes of the study To evaluate the benefit of stenting the iliac vein in patients with residual iliac vein stenosis treated with catheter-directed thrombolysis for acute iliofemoral deep venous thrombosis. Procedures In this randomized prospective study, patients with a first-time acute lower extremity deep venous thrombosis that had persisted <14 days were treated with catheter-directed thrombolysis. After catheter-directed thrombolysis, patients with >50% residual iliac vein stenosis were randomly divided into two groups: catheter-directed thrombolysis + Stent Group and catheter-directed thrombolysis Alone Group. Patients received urokinase thrombolysis and low-molecular-weight heparin/oral warfarin during the hospitalization period and were administrated oral warfarin after discharge. Cumulative deep vein patency, the Clinical Etiology Anatomic Pathophysiologic classification system, the Venous Clinical Severity Score and the Chronic Venous Insufficiency Questionnaire score were evaluated. Findings The cumulative deep vein patency rate was 74.07% in the catheter-directed thrombolysis + Stent Group and 46.59% in the catheter-directed thrombolysis Alone Group. The mean postoperative Clinical Etiology Anatomic Pathophysiologic classification and Venous Clinical Severity Score was significantly lower in the catheter-directed thrombolysis + Stent Group than in the catheter-directed thrombolysis Alone Group. The mean postoperative Chronic Venous Insufficiency Questionnaire score was significantly higher in the catheter-directed thrombolysis + Stent Group than the catheter-directed thrombolysis Alone Group. Conclusions Placement of an iliac vein stent in patients with residual iliac vein stenosis after catheter-directed thrombolysis for acute lower extremity deep venous thrombosis increases iliac vein patency and improves clinical symptoms and health-related quality of life at mid-term follow-up compared to patients treated with catheter-directed thrombolysis alone.

Topics: Administration, Oral; Catheterization, Peripheral; Female; Heparin; Humans; Lower Extremity; Male; Mechanical Thrombolysis; Middle Aged; Prospective Studies; Stents; Urokinase-Type Plasminogen Activator; Venous Thrombosis; Warfarin

The purpose of this article was to review the current literature pertaining to the use of mobile compression devices (MCDs) for venous thromboembolism (VTE) following total joint arthroplasty (TJA), and to discuss the results of data from our institution.. Previous studies have illustrated higher rates of post-operative wound complications, re-operation and re-admission with the use of more aggressive anticoagulation regimens, such as warfarin and factor Xa inhibitors. This highlights the importance of the safety, as well as efficacy, of the chemoprophylactic regimen.. Studies have shown a symptomatic VTE rate of 0.92% with use of MCDs for prophylaxis, which is comparable with rates seen with more aggressive anticoagulation protocols. A prior prospective study found that use of a pre-operative risk stratification protocol based on personal history of deep vein thrombosis, family history of VTE, active cancer, or a hypercoaguable state allowed for the avoidance of aggressive prophylactic anticoagulation in over 70% of patients while maintaining a low incidence of symptomatic VTE.. Further investigation is needed into the role of aspirin in VTE prophylaxis as well as the efficacy of MCDs as stand-alone prophylactic treatment. Cite this article: Bone Joint J 2017;99-B(1 Supple A):8-13.

Topics: Adult; Aged; Ambulatory Care; Anticoagulants; Arthroplasty, Replacement; Aspirin; Combined Modality Therapy; Humans; Intermittent Pneumatic Compression Devices; Middle Aged; Postoperative Care; Postoperative Hemorrhage; Risk Assessment; Venous Thromboembolism; Venous Thrombosis; Warfarin; Young Adult

To investigate the feasibility, effectiveness, and complications of catheter-directed thrombolysis (CDT) using three different approaches for acute lower-extremity deep venous thrombosis (DVT).. A total of 106 patients with acute DVT were enrolled in this study. Forty-one patients received CDT through the small saphenous vein (Group A), 35 through the great saphenous vein (Group B), and 30 through the popliteal vein (Group C). Iliac vein balloon dilation and stenting was performed in 65 cases.. The vascular approach route was not statistically related to limb edema reduction rates (Groups A, B, and C: 82.3 ± 7.6% vs. 81.6 ± 6.0% vs. 83.9 ± 6.1%), nor to thrombolysis rates (63.5 ± 7.7% vs. 66.9 ± 8.4% vs. 66.1 ± 2.7%). The procedure was significantly shorter for Groups B and C. No significant difference was found between Groups B and C. Most complications occurred in Group A. The complication rate in Group B was the lowest. Eighty-eight patients were followed up for 7-24 months. Of these, 78 were pain-free and without limb edema; six showed rethrombosis.. CDT is an effective method to manage acute DVT. Of the three routes tested, the small saphenous vein route was associated with more frequent complications. Great saphenous vein catheterization was more effective because of its lower complication rate.

Topics: Adolescent; Adult; Aged; Anticoagulants; Catheterization, Peripheral; China; Female; Fibrinolytic Agents; Follow-Up Studies; Humans; Iliac Vein; Lower Extremity; Male; Middle Aged; Operative Time; Popliteal Vein; Postoperative Complications; Saphenous Vein; Stents; Thrombolytic Therapy; Venous Thrombosis; Warfarin; Young Adult

The American College of Chest Physicians recommends anticoagulant therapy for at least 3 months in children hospitalized for venous thromboembolism. The objectives of the study were to evaluate the medication utilization patterns and predictors of adherence to anticoagulant therapy in pediatric population.. Texas Medicaid medical and prescription claims from September 1, 2007 to December 12, 2012 were extracted for children (<18 years) hospitalized for pulmonary embolism (PE) or deep vein thrombosis (DVT). The index date was defined as the date of the first prescription of an anticoagulant given within 14 days of discharge. Proportion of days covered (≥80% vs <80%) was used to assess adherence to anticoagulants while controlling for demographics, cause of hospitalization, history of nonsteroidal anti-inflammatory drug use, anticoagulant use, malignancy, drug type, and Charlson comorbidity index (CCI).. The patients (n = 60) had a mean (± standard deviation [SD]) age of 14.2 (±4.8) years, were primarily female (56.7%), African American (55.0%), enoxaparin users (58.3%), and had a mean (±SD) CCI of 18.3 (±37.7). The mean (±SD) adherence rates for warfarin and enoxaparin were 85.5% (±22.7%) and 78.7% (±27.8%), respectively. Overall, 66.7% were adherent (≥80%) to anticoagulant therapy. Logistic regression showed that increasing age was significantly associated with adherence to anticoagulant therapy, after controlling for other covariates (odds ratio = 1.5, 95% confidence interval = 1.13-1.85).. Nearly one-third of the pediatric patients on anticoagulant therapy after discharge from PE or DVT were still nonadherent. Further research is needed to highlight the factors responsible for nonadherence in pediatric patients.

Topics: Adolescent; Anticoagulants; Child; Enoxaparin; Female; Hospitalization; Humans; Male; Medicaid; Medication Adherence; Pulmonary Embolism; Retrospective Studies; Texas; United States; Venous Thrombosis; Warfarin

Acute venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is traditionally managed with a short course of parenteral anticoagulation followed by 3-6 months of a vitamin-K antagonist. Non-vitamin K oral anticoagulants (NOACs) do not require routine monitoring and dose adjustment, thus potentially provide an alternative treatment option.. Because of the lack of head-to-head clinical studies, an indirect comparison was conducted of dabigatran etexilate and rivaroxaban based on the respective phase III clinical trial. The derived relative safety and efficacy estimates were used to evaluate the cost-utility of dabigatran compared with rivaroxaban in the treatment and secondary prevention of VTE. The results of the indirect comparison showed no significant difference between dabigatran and rivaroxaban in avoiding recurrent VTE following index PE, index DVT, or DVT/PE combined, in treatment and extended anticoagulation. Dabigatran has significantly less major or clinically relevant bleeds (MCRBE) compared to rivaroxaban in treatment after index DVT and treatment after DVT or PE combined, but was not significantly different from rivaroxaban after index PE or in extended anticoagulation. In cost-utility deterministic analyses, dabigatran was projected dominant in all analyzed settings, given its marginally lower total cost and marginally higher QALYs gained compared to rivaroxaban. Probabilistic analyses results showed a high likelihood of dabigatran being considered good value for money in the UK, in treatment and in secondary prevention of VTE.. The cost-effectiveness evaluations showed that dabigatran can be considered the dominant treatment strategy compared to rivaroxaban in the patients' sub-groups considered, given the projected marginally higher clinical benefits and lower treatment costs.

Topics: Anticoagulants; Cost-Benefit Analysis; Dabigatran; Double-Blind Method; Female; Health Services; Hemorrhage; Humans; Male; Middle Aged; Models, Econometric; Pulmonary Embolism; Quality-Adjusted Life Years; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis; Warfarin

Portal vein system thrombosis (PVST) is a frequent and potentially life-threatening complication after laparoscopic splenectomy and azygoportal disconnection (LSD) in patients with cirrhotic portal hypertension. The objective of this study was to investigate the safety and effectiveness of warfarin with a target international normalized ratio (INR) of 2.0-2.5 for the prevention of PVST after LSD. Hitherto, this is the first study to assess the use of warfarin in this field.. We retrospectively analyzed a database of 73 consecutive patients who underwent LSD from January 2013 to September 2014. Patients were categorized into the warfarin group (34 patients) and the aspirin group (39 patients). The INR and incidence of PSVT were monitored for 90 days.. Compared with the aspirin group, the warfarin group had a lower incidence of PVST on postoperative day (POD) 30 [17/34 (50.0%) versus 29/39 (74.4%); P = .032] and POD 90 [8/34 (23.5%) versus 30/39 (76.9%); P < .0001] and main portal vein thrombosis (MPVT) on POD 90 [3 (8.8%) versus 13 (33.3%); P = .012]. From POD 30 to 90, the warfarin group achieved more complete recanalization of PVST [9/17 (52.9%) versus 3/29 (10.3%), P = .005] and MPVT [9/12 (75.0%) versus 3/12 (25.0%), P = .039]. Multiple logistic regression analysis revealed that warfarin was an independent protective factor for PVST at POD 90 (relative risk, 0.027; 95% confidence interval, 0.004-0.168; P < .001). No patients developed bleeding complications.. Anticoagulation therapy with warfarin is safe and effective for the prevention of PVST in cirrhotic patients with portal hypertension after LSD.

Topics: Adolescent; Adult; Aged; Anticoagulants; Aspirin; Azygos Vein; Female; Heparin, Low-Molecular-Weight; Humans; Liver Cirrhosis; Male; Middle Aged; Portal Vein; Postoperative Complications; Retrospective Studies; Splenectomy; Treatment Outcome; Venous Thrombosis; Warfarin; Young Adult

The feasibility of magnetic resonance venography (MRV) for measuring change in thrombus volume with a novel anticoagulation regimen versus standard anticoagulation in patients with symptomatic deep vein thrombosis (DVT) has not been assessed. Our aim was to study the feasibility of MRV to measure change in thrombus volume in patients with acute symptomatic objectively confirmed proximal DVT in an open-label multicenter trial (edoxaban Thrombus Reduction Imaging Study, eTRIS). We randomized patients in a 2:1 allocation ratio to edoxaban 90 mg/day for 10 days followed by 60 mg/day versus parenteral anticoagulation bridging to warfarin for 3 months. The primary efficacy outcome was a surrogate end point of the relative change in MRV-quantified thrombus volume from baseline to Day 14-21. A total of 85 eligible patients from 26 study sites were randomized to edoxaban monotherapy (n=56) versus parenteral anticoagulation as a 'bridge' to warfarin (n=29). The mean relative change in MRV-quantified thrombus volume from baseline to Day 14-21 was similar in patients treated with edoxaban and parenteral anticoagulation as a 'bridge' to warfarin (-50.1% vs -58.9%; 95% confidence interval of treatment difference, -12.7%, 30.2%). However, thrombus extension was observed in eight patients in the edoxaban monotherapy group and in none in the warfarin group. Rates of recurrent venous thromboembolism (3.6% vs 3.6%, p=0.45) and clinically relevant non-major bleeding (5.4% vs 7.1%, p=0.34) were also similar. No major bleeds occurred in either on-treatment group during the study period. In conclusion, MRV can assess change in thrombus volume in patients with acute DVT randomized to two different anticoagulant regimens.ClinicalTrials.gov IDENTIFIER NCT01662908: INVESTIGATIONAL NEW DRUG IND APPLICATION EDOXABAN IND # 63266.

Topics: Administration, Intravenous; Administration, Oral; Adult; Aged; Anticoagulants; Blood Coagulation; Drug Therapy, Combination; Factor Xa Inhibitors; Feasibility Studies; Female; Heparin; Humans; International Normalized Ratio; Magnetic Resonance Angiography; Male; Middle Aged; Phlebography; Predictive Value of Tests; Pyridines; Thiazoles; Time Factors; Treatment Outcome; United States; Venous Thrombosis; Warfarin

Edoxaban exposure-response relationships from the phase III study evaluating edoxaban for prevention and treatment of venous thromboembolism (VTE) in patients with acute deep vein thrombosis (DVT) and/or pulmonary embolism (PE) were assessed by parametric time-to-event analysis. Statistical significant exposure-response relationships were recurrent VTE with hazard ratio (HR) based on average edoxaban concentration at steady state (Cav) (HRCav) = 0.98 (i.e., change in the HR with every 1 ng/mL increase of Cav); the composite of recurrent DVT and nonfatal PE with HRCav = 0.99; and the composite of recurrent DVT, nonfatal PE, and all-cause mortality HRCav = 0.98, and all death using maximal edoxaban concentration (Cmax) with HR (Cmax) = 0.99. No statistical significant exposure-response relationships were found for clinically relevant bleeding or major adverse cardiovascular event. Results support the recommendation of once-daily edoxaban 60 mg, and a reduced 30 mg dose in patients with moderate renal impairment, body weight ≤60 kg, or use of P-glycoprotein inhibitors verapamil or quinidine.

Topics: Aged; Double-Blind Method; Drug Dosage Calculations; Factor Xa Inhibitors; Female; Humans; Male; Pulmonary Embolism; Pyridines; Risk Assessment; Thiazoles; Venous Thrombosis; Warfarin

Dabigatran was non-inferior to warfarin for prevention of recurrent venous thromboembolism (VTE), and dabigatran had a lower rate of bleeding compared with warfarin in two large-scale randomised trials, RE-COVER and RE-COVER II. In this study, we investigate the efficacy and safety of dabigatran versus warfarin according to the index event that qualified the patient for enrollment, either symptomatic pulmonary embolism (PE) with or without deep-vein thrombosis (DVT), or DVT alone. We then analyse the anticoagulant effect of dabigatran vs warfarin on patients enrolled with PE. The pooled dataset for the efficacy analysis consisted of 2553 and 2554 patients who were randomised to dabigatran and warfarin, respectively. Recurrent VTE/VTE-related death during the study period and additional 30-day follow-up occurred in 2.7 % of all patients on dabigatran and in 2.4 % on warfarin (hazard ratio [HR] 1.09 [95 % confidence interval 0.77, 1.54]). In patients with PE as their index event, recurrent VTE/VTE-related death occurred in 2.9 % vs 3.1 % of patients (HR 0.93 [0.53, 1.64]). There were significantly fewer major bleeding events in patients treated with dabigatran than with warfarin (HR 0.60 [0.36, 0.99]). The pattern was similar both in patients with PE and in those with DVT alone as the index event. These analyses of the pooled dataset from the RE-COVER and RE-COVER II trials indicate that dabigatran is as effective as warfarin in preventing recurrent VTE, regardless of whether patients present with symptomatic PE (with or without DVT) or with symptomatic DVT alone. Dabigatran was also associated with a lower risk of bleeding than warfarin, regardless of the index event.

Topics: Adult; Aged; Anticoagulants; Dabigatran; Female; Humans; Male; Middle Aged; Pulmonary Embolism; Venous Thromboembolism; Venous Thrombosis; Warfarin

Warfarin-dosing algorithms combine clinical factors and dosing history with the current international normalized ratio (INR) to estimate the therapeutic warfarin dose. Unfortunately, these approaches can result in an overdose if the INR is spuriously low. Our goal was to develop an alert mechanism based on prior INRs in addition to the current INR. Using data from the Genetics InFormatics Trial (GIFT) of Warfarin to Prevent DVT, we analyzed warfarin dose estimates for days 3 through 11 that were ≥10 % higher than an average of the previous two dose estimates. We fit a stepwise mixed model to current and prior dose estimates, and subsequently compared the root-mean-square-error (RMSE) in predicting the final therapeutic dose using the GIFT algorithm versus the mixed model. From 861 dosing records (obtain from 556 patients), 646 dosing records (75 %) were randomly selected for the derivation cohort and 215 dosing records (25 %) for the validation cohort. Using one prior dose estimate improved the accuracy of the warfarin dose estimate. Compared to a dose estimate based on current INR (GIFT algorithm), the mixed model reduced the RMSE in the derivation cohort by 0.0015 mg/day (RMSE 0.2079 vs. 0.2094; p = 0.039). In the validation cohort, the RMSE reduction was not significant. A mixed model of dose estimates based on the current and most recent INRs shows potential to improve the safety of warfarin dosing. Clinicians should be cautious about aggressively escalating the warfarin dose after an INR that is lower than expected.

Topics: Aged; Algorithms; Female; Humans; International Normalized Ratio; Male; Models, Cardiovascular; Venous Thrombosis; Warfarin

In Japan, the standard of care for the treatment of pulmonary embolism (PE) and/or deep vein thrombosis (DVT) consists of intravenous unfractionated heparin (UFH) followed by warfarin, which was recently compared with rivaroxaban, an oral factor Xa inhibitor, in randomized trials.. To examine the length of hospital stay in patients with PE and/or DVT receiving rivaroxaban compared to Japanese standard therapy in the Japanese (J)-EINSTEIN PE and DVT program.. Open-label, randomized clinical trials that compared 3, 6, or 12 months of rivaroxaban with UFH and warfarin in patients with acute, confirmed symptomatic proximal PE and/or DVT. Decisions regarding hospital admission and/or discharge were left to the clinical judgment of attending physicians. Analyses were conducted in the intention-to-treat (ITT) population.. In the ITT population (N = 97), overall patient characteristics were similar in both treatment arms. The median length of stay in rivaroxaban patients was 10.0 days (interquartile range [IQR] 6.0 to 15.0 days) while it was 15.0 days (IQR 9.0 to 22.0) for patients on standard therapy (p = 0.016). All of the four DVT patients who were not hospitalized for the index event were in the rivaroxaban arm.. Our results suggest that treatment with rivaroxaban may significantly reduce the length of hospital stay in patients hospitalized for PE and/or DVT compared with the current standard of care in Japan, thereby reducing the burden on patients and the healthcare system. The limitations of our study include small sample size and the generalizability of the findings to the real-world setting. Further research is warranted to identify PE and/or DVT patients in Japanese clinical practice who may potentially be managed as outpatients.. Clinicaltrials.gov: NCT01516814 and NCT01516840.

Topics: Aged; Aged, 80 and over; Anticoagulants; Asian People; Female; Heparin; Humans; Japan; Length of Stay; Male; Middle Aged; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis; Warfarin

Anticoagulation is recommended as standard of care for venous thromboembolism (VTE) (pulmonary embolism [PE]/deep vein thrombosis [DVT]), for which unfractionated heparin (UFH) and warfarin are used in Japan. In the multi-regional AMPLIFY study, a fixed-dose regimen of apixaban alone was non-inferior to conventional therapy for treatment of PE/DVT and was associated with significantly fewer bleeding events.. Japan phase 3 study (AMPLIFY-J), randomized, active-controlled, open-label study in Japanese subjects with acute PE/DVT, was designed based on AMPLIFY. Key objectives were to investigate safety and efficacy of apixaban in symptomatic PE/DVT subjects during 24-week treatment. UFH/warfarin was used as control treatment. Apixaban was initiated at 10 mg twice daily for 7 days, followed by 5 mg twice daily for 23 weeks. All endpoints and imaging for thrombotic burden were assessed by an event adjudication committee. Eighty subjects were randomized, 33 subjects (41.3%) were aged <65 years. Proportion of major/clinically relevant non-major bleeding was lower in apixaban (7.5%) compared with well-controlled UFH/warfarin (28.2%; median TTR, 70.4%). [corrected]. Recurrent VTE occurred in no subjects in apixaban and in 1 subject in UFH/warfarin. Thrombotic burden results were similar in both groups. Proportions of subjects with adverse events was generally similar in both groups.. Apixaban was well-tolerated and had a favorable safety profile. No clinically important efficacy difference compared with UFH/warfarin was observed.

Topics: Aged; Aged, 80 and over; Anticoagulants; Factor Xa Inhibitors; Female; Hemorrhage; Heparin; Humans; International Normalized Ratio; Japan; Male; Middle Aged; Pulmonary Embolism; Pyrazoles; Pyridones; Recurrence; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis; Warfarin

Direct oral anticoagulants have been evaluated for their efficacy and safety in the treatment of venous thromboembolism (VTE), which comprises deep vein thrombosis and pulmonary embolism. The randomized, double-blind Hokusai-VTE trial demonstrated that 60 mg of edoxaban once daily following initial heparin treatment is non-inferior to heparin overlapped with and followed by warfarin for the treatment of VTE, and is associated with significantly fewer bleeding events.. To assess the efficacy and safety of edoxaban versus warfarin among East Asian patients enrolled in the Hokusai-VTE trial.. The Hokusai-VTE trial enrolled 8292 patients from 439 centers worldwide, including 1109 patients from Japan, China, Korea, and Taiwan. The primary efficacy and safety outcomes were symptomatic recurrent VTE and clinically relevant bleeding, respectively.. In the overall East Asian population, the primary efficacy outcome of symptomatic recurrent VTE occurred in 16 of 563 (2.8%) patients in the edoxaban group versus 24 of 538 (4.5%) patients in the warfarin group (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.34-1.19; P = 0.1601). The primary safety outcome of clinically relevant bleeding occurred in 56 of 563 (9.9%) patients in the edoxaban group versus 93 of 538 (17.3%) patients in the warfarin group (HR 0.56; 95% CI 0.40-0.78; P < 0.001).. Edoxaban is an effective and safer alternative to warfarin in East Asian patients with acute VTE who require anticoagulant therapy, consistent with overall study findings from the Hokusai-VTE trial.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Asia, Eastern; Asian People; Double-Blind Method; Factor Xa Inhibitors; Female; Follow-Up Studies; Hemorrhage; Humans; Male; Middle Aged; Pulmonary Embolism; Pyridines; Recurrence; Therapeutic Equivalency; Thiazoles; Venous Thromboembolism; Venous Thrombosis; Vitamin K; Warfarin; Young Adult

This is a retrospective cohort study of adults with a primary diagnosis of deep venous thrombosis (DVT) unaccompanied by pulmonary embolism (PE), seen in 4 emergency departments in 2013 and part of 2014. The purpose was to assess the prevalence of home treatment of DVT in the present era of new oral anticoagulants. Among 96 patients with DVT and no PE, 85 (88.5%) were hospitalized and 11 (11.5%) were discharged to home. Most of the patients discharged to home received low-molecular-weight heparin, 9 (81.8%) of 11. None were prescribed new oral anticoagulants. Early discharge in ≤2 days occurred 28 (32.9%) of 85 patients. Most (64.3%) received enoxaparin and/or warfarin at early discharge. Rivaroxaban was prescribed in 7 (25.0%) of those discharged in ≤2 days. We conclude that in some emergency departments, patients with DVT are uncommonly discharged to home even though new oral anticoagulants are available.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Enoxaparin; Female; Humans; Male; Middle Aged; Retrospective Studies; Rivaroxaban; Venous Thrombosis; Warfarin

Low-molecular-weight heparin is recommended over warfarin for the treatment of acute venous thromboembolism (VTE) in patients with active cancer largely based on results of a single, large trial.. To study the efficacy and safety of tinzaparin vs warfarin for treatment of acute, symptomatic VTE in patients with active cancer.. A randomized, open-label study with blinded central adjudication of study outcomes enrolled patients in 164 centers in Asia, Africa, Europe, and North, Central, and South America between August 2010 and November 2013. Adult patients with active cancer (defined as histologic diagnosis of cancer and receiving anticancer therapy or diagnosed with, or received such therapy, within the previous 6 months) and objectively documented proximal deep vein thrombosis (DVT) or pulmonary embolism, with a life expectancy greater than 6 months and without contraindications for anticoagulation, were followed up for 180 days and for 30 days after the last study medication dose for collection of safety data.. Tinzaparin (175 IU/kg) once daily for 6 months vs conventional therapy with tinzaparin (175 IU/kg) once daily for 5 to 10 days followed by warfarin at a dose adjusted to maintain the international normalized ratio within the therapeutic range (2.0-3.0) for 6 months.. Primary efficacy outcome was a composite of centrally adjudicated recurrent DVT, fatal or nonfatal pulmonary embolism, and incidental VTE. Safety outcomes included major bleeding, clinically relevant nonmajor bleeding, and overall mortality.. Nine hundred patients were randomized and included in intention-to-treat efficacy and safety analyses. Recurrent VTE occurred in 31 of 449 patients treated with tinzaparin and 45 of 451 patients treated with warfarin (6-month cumulative incidence, 7.2% for tinzaparin vs 10.5% for warfarin; hazard ratio [HR], 0.65 [95% CI, 0.41-1.03]; P = .07). There were no differences in major bleeding (12 patients for tinzaparin vs 11 patients for warfarin; HR, 0.89 [95% CI, 0.40-1.99]; P = .77) or overall mortality (150 patients for tinzaparin vs 138 patients for warfarin; HR, 1.08 [95% CI, 0.85-1.36]; P = .54). A significant reduction in clinically relevant nonmajor bleeding was observed with tinzaparin (49 of 449 patients for tinzaparin vs 69 of 451 patients for warfarin; HR, 0.58 [95% CI, 0.40-0.84]; P = .004).. Among patients with active cancer and acute symptomatic VTE, the use of full-dose tinzaparin (175 IU/kg) daily compared with warfarin for 6 months did not significantly reduce the composite measure of recurrent VTE and was not associated with reductions in overall mortality or major bleeding, but was associated with a lower rate of clinically relevant nonmajor bleeding. Further studies are needed to assess whether the efficacy outcomes would be different in patients at higher risk of recurrent VTE.. clinicaltrials.gov Identifier: NCT01130025.

Topics: Aged; Anticoagulants; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Male; Middle Aged; Neoplasms; Pulmonary Embolism; Recurrence; Survival Analysis; Tinzaparin; Venous Thromboembolism; Venous Thrombosis; Warfarin

To investigate the correlations between three vascular endothelial growth factor 2 (VEGFR2) gene polymorphisms, +1192C>T, +1719T>A, and -604T>C, and deep venous thrombosis (DVT) in Chinese Han population.. We conducted a case-control study, between September 2009 and September 2012, in a Chinese Han population with onset of lower extremity DVT. A total of 135 patients were enrolled in the case group and 156 healthy individuals in the control group. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the genotype and allele frequencies of the VEGFR2 gene polymorphisms +1192C>T, +1719T>A, and -604T>C. Haplotype analyses were conducted with SHEsis program. Logistic regression was used to detect the risk factors of DVT. Outpatient review and telephone follow-up were conducted to analyze the long-term treatment of DVT patients.. The allele and genotype frequencies of -604T>C VEGFR2 polymorphism exhibited significant differences between the case and control groups (both p < 0.05). Haplotype analyses showed remarkable differences between the case and control groups in the distribution frequency of TAC and CTT haplotypes in the VEGFR2 gene (both p < 0.05). Logistic regression analysis showed independent correlation between the incidence of DVT and TAC haplotype in the VEGFR2 gene (p < 0.05). In addition, the TAC haplotype may be a risk factor for DVT treatment failure.. Our findings suggest that the VEGFR2 gene -604T>C polymorphism and TAC haplotype are associated with DVT, and the TAC haplotype might affect the efficacy of long-term treatment of DVT patients.

Topics: Adult; Aged; Asian People; China; Female; Follow-Up Studies; Haplotypes; Humans; Male; Middle Aged; Polymorphism, Restriction Fragment Length; Risk Factors; Treatment Failure; Vascular Endothelial Growth Factor Receptor-2; Venous Thrombosis; Warfarin

In the Apixaban for the Initial Management of Pulmonary Embolism and Deep-Vein Thrombosis as First-Line Therapy (AMPLIFY) trial, apixaban was noninferior to enoxaparin/warfarin in preventing recurrent symptomatic venous thromboembolism (VTE) or venous thromboembolism-related death, with significantly less bleeding. This analysis evaluated the effects of apixaban versus enoxaparin/warfarin on all-cause hospitalizations during AMPLIFY.. Of the 5365 patients included, 2676 received apixaban and 2689 received enoxaparin/warfarin. All-cause hospitalizations during the treatment period after the index event were captured using dedicated case report forms. Outcomes included all-cause hospitalizations and time from randomization to first hospitalization. Patients were censored at death, loss to follow-up, or end of study, whichever came first. Treatment effects were assessed using Cox proportional hazards regression models. During the treatment period after the index event, 343 patients were hospitalized at least once: 153 (5.72%) in the apixaban group and 190 (7.07%) in the enoxaparin/warfarin group. Compared with enoxaparin/warfarin, apixaban significantly reduced all-cause hospitalizations (hazard ratio 0.804, 95% CI=0.650-0.995, P=0.045). All-cause hospitalization rates within the first 30 days after the index event were 2.28% and 3.35% in the apixaban and enoxaparin/warfarin groups, respectively (hazard ratio 0.676, 95% CI=0.488-0.935, P=0.018). For all patients, the average per-patient estimated mean length of hospital stay was also shorter with apixaban than enoxaparin/warfarin (0.57 days versus 1.01 days, P<0.0001).. Apixaban significantly reduced all-cause hospitalizations versus enoxaparin/warfarin, and shortened the length of hospital stay in patients with acute venous thromboembolism.. URL: https://Clinicaltrials.Gov/. Unique identifier: NCT00643201.

Topics: Aged; Anticoagulants; Double-Blind Method; Drug Therapy, Combination; Enoxaparin; Factor Xa Inhibitors; Female; Hospitalization; Humans; Length of Stay; Male; Middle Aged; Proportional Hazards Models; Pulmonary Embolism; Pyrazoles; Pyridones; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis; Warfarin

To evaluate the safety of uninterrupted rivaroxaban, a novel oral anticoagulant that directly inhibits factor Xa, and a vitamin K antagonist (VKA) in eligible adult patients with nonvalvular AF (NVAF) who are scheduled for a catheter ablation.. This is a prospective, randomized, open-label, active-controlled, global multicenter safety study of up to 250 randomized patients. Eligible patients with paroxysmal or persistent NVAF, a left ventricular ejection fraction >40 %, and a creatinine clearance >50 mL/min will be randomized 1:1 to rivaroxaban 20 mg orally once daily or to dose-adjusted oral VKA (recommended international normalized ratio (INR) 2.0-3.0) and stabilized on anticoagulation therapy for 1-7 days (if no intracardiac thrombus on transesophageal echocardiogram (TEE) immediately prerandomization/post-randomization or if 3 weeks of sufficient anticoagulation is documented) or for 4-5 weeks (if no TEE, no documented 3 weeks of sufficient anticoagulation, or by patient choice). During catheter ablation, heparin will be administered (ACT-targeted range = 300-400 s) after catheter ablation, and VKA will be managed per usual care. The next dose of rivaroxaban will be provided at least 6 h after establishment of hemostasis. The primary endpoint will be the incidence of post-procedure major bleeding events observed during the first 30 ± 5 days post-ablation. Secondary endpoints will include post-procedure thromboembolic events, additional bleeding, time-to-event, and medication adherence.. This study is intended to provide information about the safety characteristics of rivaroxaban in patients with NVAF undergoing catheter ablation.

Topics: Adult; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Morpholines; Patient Safety; Postoperative Care; Preoperative Care; Prospective Studies; Pulmonary Embolism; Rivaroxaban; Statistics, Nonparametric; Survival Rate; Thiophenes; Treatment Outcome; Venous Thrombosis; Vitamin K; Warfarin

Decreased antithrombin III (ATIII) activity and large splenic vein diameter (SVD) are risk factors for portal vein thrombosis (PVT) after splenectomy in liver cirrhosis with portal hypertension. Antithrombin III concentrates can prevent PVT. This study was designed to stratify risks for PVT after splenectomy in cirrhotic patients and to develop prophylactic protocols for PVT.. In 53 patients (testing cohort), the cutoff level of preoperative ATIII activity (≤60%) was evaluated for administration of ATIII concentrates. Antithrombin III activity and SVD were re-evaluated as criteria for prophylaxis of PVT. In 57 patients (validation cohort), the risk stratification of PVT and prophylactic protocols were validated.. In the testing cohort, 10 (19%) of 53 patients had PVT. Risk level of PVT was stratified and prophylactic protocols were developed. Patients at low risk (ATIII activity ≥70% and SVD <10 mm) were not treated; those at high risk (ATIII activity <70% or SVD ≥10 mm) received ATIII concentrates (1,500 U/day) for 3 days; and those at highest risk (SVD ≥15 mm) received ATIII concentrates for 3 days, followed by danaparoid sodium (2,500 U/day) for 14 days and warfarin. In the validation cohort, 0 of 14 low-risk and 2 of 32 high-risk patients had PVT. Although 8 of 11 patients at highest risk had temporary PVT, it disappeared within 3 months postoperatively. Finally, only 2 (3.5%) of 57 patients had PVT.. Risk stratification of PVT after splenectomy and prophylaxis with ATIII concentrates and danaparoid sodium dramatically reduced the incidence of PVT.

Topics: Adult; Aged; Anticoagulants; Antithrombin III; Chondroitin Sulfates; Clinical Protocols; Decision Support Techniques; Dermatan Sulfate; Drug Therapy, Combination; Female; Fibrinolytic Agents; Heparitin Sulfate; Humans; Hypertension, Portal; Laparoscopy; Liver Cirrhosis; Male; Middle Aged; Portal Vein; Postoperative Complications; Prospective Studies; Risk Assessment; Risk Factors; ROC Curve; Splenectomy; Venous Thrombosis; Warfarin

Portal-vein thrombosis (PVT) develops in 10-25% of cirrhotic patients and may aggravate portal hypertension. There are few data regarding the effects of anticoagulation on nonmalignant PVT in liver cirrhosis. The aim of this study was to elucidate the safety, efficacy, and predictors of response to anticoagulation therapy in cirrhotic patients.. Patients with liver cirrhosis and nonmalignant PVT were identified by a hospital electronic medical record system (called BESTCARE). Patients with malignant PVT, Budd-Chiari syndrome, underlying primary hematologic disorders, or preexisting extrahepatic thrombosis were excluded from the analysis. Patients were divided into two groups (treatment and nontreatment), and propensity score matching analysis was performed to identify control patients. The sizes of the thrombus and spleen were evaluated using multidetector computed tomography.. Twenty-eight patients were enrolled in this study between 2003 and 2014: 14 patients who received warfarin for nonmalignant PVT and 14 patients who received no anticoagulation. After 112 days of treatment, 11 patients exhibited significantly higher response rates (complete in 6 and partial in 5) compared to the control patients, with decreases in thrombus size of >30%. Compared to nonresponders, the 11 responders were older, and had a thinner spleen and fewer episodes of previous endoscopic variceal ligations, whereas pretreatment liver function and changes in prothrombin time after anticoagulation did not differ significantly between the two groups. Two patients died after warfarin therapy, but the causes of death were not related to anticoagulation.. Warfarin can be safely administered to cirrhotic patients with nonmalignant PVT. The presence of preexisting portal hypertension is a predictor of nonresponse to anticoagulation.

Topics: Aged; Anticoagulants; Female; Humans; Liver Cirrhosis; Male; Middle Aged; Portal Vein; Propensity Score; Severity of Illness Index; Tomography, X-Ray Computed; Venous Thrombosis; Warfarin

Patients with iliac deep vein thrombosis (DVT) have a poor prognosis and high incidence of postthrombotic syndrome (PTS). We evaluated the effect of low-molecular-weight heparin (LMWH; tinzaparin) versus usual care (tinzaparin plus warfarin for ≥12 weeks at home) in the development of PTS according to DVT location (iliac/noniliac) by retrospective analysis of the Home-LITE cohort (480 patients with proximal DVT). Patients with iliac DVT had an overall odds ratio of 0.53 (95% confidence interval [CI] 0.33, 0.83; P = .0079) for PTS (including ulcer data) in favor of tinzaparin. Patients with noniliac DVT had a similar odds ratio (0.79 [95% CI 0.67, 0.93], P = .0046) to that reported in the overall Home-LITE population (0.76 [95% CI 0.66, 0.89], P = .0004; including ulcer data), both in favor of tinzaparin. Long-term LMWH may be a suitable alternative for the prevention of PTS in patients with iliac DVT who are unlikely to undergo invasive thrombolysis.

Topics: Cohort Studies; Drug Administration Schedule; Female; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Incidence; Male; Postthrombotic Syndrome; Prognosis; Retrospective Studies; Tinzaparin; Venous Thrombosis; Warfarin

Whether an anticoagulant prophylaxis is needed for patients with cancer with a central venous catheter is a highly controversial subject. We designed a study to compare different prophylactic strategies over 3 months of treatment.. We performed a phase III prospective, open-label randomized trial. After the insertion of a central venous access device, consecutive patients with planned chemotherapy for cancer were randomized to no anticoagulant prophylaxis, low molecular weight heparin [low molecular weight heparin (LMWH); with isocoagulation doses], or warfarin 1 mg/day. Treatments were given over the first 3 months. Doppler ultrasound and venographies were performed on days 1 and 90, respectively, or sooner in case of clinical presumption of thrombosis.. A total of 420 patients were randomized, and 407 were evaluable. Forty-two catheter-related deep vein thrombosis (DVT) occurred (10.3 %), 20 in those with no anticoagulation, 8 in those receiving warfarin, and 14 in those receiving LMWH. Nine additional non-related catheter deep vein thrombosis (CDVT) occurred. Anticoagulation significantly reduced the incidence of catheter-related DVT (p = 0.035) and catheter non-related DVT (p = 0.007), with no difference between warfarin and LMWH. Safety was good (3.4 % of attributable events) but compliance with randomized prophylaxis was lower than expected.. Prophylaxis showed a benefit regarding catheter-related and non-catheter-related DVT with no increase in serious side effects.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Antineoplastic Agents; Central Venous Catheters; Female; France; Heparin, Low-Molecular-Weight; Humans; Incidence; Intention to Treat Analysis; Lost to Follow-Up; Male; Medication Adherence; Middle Aged; Neoplasms; Severity of Illness Index; Upper Extremity Deep Vein Thrombosis; Venous Thrombosis; Warfarin; Young Adult

The time in target International Normalized Ratio (INR) range (TIR) is used to assess the control and intensity of oral anticoagulation, but it does not measure variation in the INR.. The value of assessing INR variability by use of the variance growth rate (VGR) as a predictor of events was investigated in patients treated with warfarin.. Three different methods of VGR determination (A, B1, and B2) together with the TIR were studied. Method A measures both INR variability and control, but methods B1 and B2 measure variability only. The VGR and TIR were determined over three time periods: overall follow-up to an event, and 6 months and 3 months before an event.. Six hundred and sixty-one control patients were matched to 158 cases (bleeding, thromboembolism, or death). With all VGR methods, the risk of an event was greater in unstable patients at 6 months before an event than in stable patients. Method A demonstrated the greatest risk 3 months before an event in the unstable VGR group as compared with the stable group (odds ratio 3.3, 95% confidence interval 1.9-5.7, P < 0.005). The risk of an event was 1.9 times greater in patients with a low TIR (< 39%) than in those with a high TIR (> 80%) in the 3-month period (P = 0.02). Risk of bleeding was significantly greater in the 3-month period in patients with unstable VGR, with the greatest risk found with method B2 (P < 0.01).. Patients with unstable anticoagulation have a significantly increased risk of 'clinical events' at 3 and 6 months before an event. The VGR can be incorporated into computer-dosage programs, and may offer additional safety when oral anticoagulation is monitored.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Calibration; Case-Control Studies; Drug Administration Schedule; Female; Fibrinolytic Agents; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Odds Ratio; Pulmonary Embolism; Regression Analysis; Risk; Time Factors; Venous Thrombosis; Warfarin

The risk of venous thromboembolism (VTE) is higher after the total hip or knee replacement surgery than after almost any other surgical procedure; warfarin sodium is commonly prescribed to reduce this peri-operative risk. Warfarin has a narrow therapeutic window with high inter-individual dose variability and can cause hemorrhage. The genetics-informatics trial (GIFT) of warfarin to prevent deep vein thrombosis (DVT) is a 2 × 2 factorial-design, randomized controlled trial designed to compare the safety and effectiveness of warfarin-dosing strategies. GIFT will answer two questions: (1) does pharmacogenetic (PGx) dosing reduce the rate of adverse events in orthopedic patients; and (2) is a lower target international normalized ratio (INR) non-inferior to a higher target INR in orthopedic participants? The composite primary endpoint of the trial is symptomatic and asymptomatic VTE (identified on screening ultrasonography), major hemorrhage, INR ≥ 4, and death.

Topics: Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP2C9; Dose-Response Relationship, Drug; Genotype; Humans; Mixed Function Oxygenases; Postoperative Period; Venous Thrombosis; Vitamin K Epoxide Reductases; Warfarin

Cerebral vein thrombosis (CVT) is a potentially fatal disorder for which treatment guidelines are scanty. To assess the short- and long-term benefit of anticoagulant therapy, we performed a prospective cohort study on CVT patients.. Forty-four consecutive CVT patients received conventional anticoagulation with heparin followed by warfarin for at least 3 months. Patients presenting with symptoms suggestive of pulmonary embolism (PE) underwent confirmatory objective tests. Acquired or inherited risk factors for thrombosis were investigated in all patients. Thrombotic and hemorrhagic events occurring during treatment, and the long-term outcome using the modified Rankin Scale (mRS) were recorded.. Congenital and/or acquired conditions predisposing to thrombosis were detected in 37 patients (84.1%), with a high prevalence of oral contraceptive use (66.7% of females) and thrombophilia (31.8%); more than one risk factor was seen in 31.8% of cases. At referral, six patients (13.6%) presented with symptoms of PE, which was confirmed in all. During the initial treatment period, two patients (4.5%) developed symptomatic progression of CVT, which was fatal in 1, and 2 (4.5%) developed major bleeding complications. A favorable outcome (mRS 0-2) at 6-12 months was recorded in 37 of the 43 patients who survived the acute phase (86%).. The outcome of CVT patients managed with conventional anticoagulation who survive the initial phase is favorable in the vast majority. The prevalence of concomitant PE is considerably high, supporting the need of anticoagulant therapy.

Topics: Adult; Aged; Anticoagulants; Causality; Cerebral Veins; Female; Hemorrhage; Heparin; Humans; Male; Middle Aged; Prospective Studies; Time Factors; Venous Thrombosis; Warfarin

Therapy with Vitamin K antagonists (VKA) effectively reduces the thrombosis risk in many clinical conditions. Genetic variants of vitamin K epoxide reductase (VKORC-1) are associated with increased VKA effect and bleeding risk. It is unknown whether these variants could also affect the long-term outcome in patients with high-dosage oral anticoagulation and/or more difficult adherence to the therapeutic INR range. Hundred and twenty-four patients with mechanical heart valve replacement assuming VKA were genotyped for VKORC-1 -1639G>A (Rs9923231) polymorphism. Hemorrhage, venous thrombosis and atherothrombotic events were retrospectively assessed for a 6-year period. Furthermore, stability of their INR in relationship with the VKORC-1 genotype was investigated day-by-day for 3 months. No differences were observed in hemorrhage and venous thrombosis events according to rs 9923231. GG genotype carriers (n = 41) had no atherothrombotic events, while 4 strokes, 4 TIA and 3 AMI were diagnosed in A carriers (n = 83; P = 0.0008). During the daily observation period, A allele carriers had lower VKA requirements (4.7, 3.7, 2.2 mg/day for GG/GA/AA genotype respectively; P = 0.00001), higher mean INR (2.7, 2.8, 2.9; P = 0.05) and a higher number of examinations above the therapeutic range than GG carriers (17 % vs. 0 % in GG genotype, P = 0.036). Conversely, patients with GG genotype had a more stable dosage of VKA (P = 0.006) and a higher percentage of examinations under the therapeutic range (51, 43 and 36 % in GG, GA and AA genotype, respectively, P = 0.040). In patients with high dosage VKA, VKORC-1 polymorphism is associated to a different warfarin dosage, anticoagulation level, time spent outside the therapeutic range and, in the long-term, a different incidence of atherothrombotic events.

Topics: Administration, Oral; Aged; Anticoagulants; Female; Follow-Up Studies; Heart Valve Prosthesis; Hemorrhage; Humans; Male; Middle Aged; Mixed Function Oxygenases; Myocardial Infarction; Polymorphism, Genetic; Retrospective Studies; Stroke; Time Factors; Venous Thrombosis; Vitamin K; Vitamin K Epoxide Reductases; Warfarin

Factor Xa (FXa) is a key serine protease in the coagulation cascade and a promising target for a new antithrombotic agent. Edoxaban is an oral, selective and direct FXa inhibitor. The objective of this study was to compare the antithrombotic and haemorrhagic effects of edoxaban with clinically available anticoagulants, warfarin and enoxaparin, in rat models of thrombosis and haemorrhage.. Rats were treated with single oral administration of edoxaban, repeated oral dosing of warfarin for 4 days and single subcutaneous administration of enoxaparin before thrombosis or haemorrhage induction. Thrombosis was induced by the insertion of a platinum wire into the inferior vena cava for 60 min. Tail template bleeding time was measured after making an incision on the tail.. Edoxaban at 0.3, 1 and 3mg/kg exerted dose-dependent and significant inhibition of venous thrombus formation. The 50% thrombus inhibition dose (ED(50)) was 1.9 mg/kg. At supra-therapeutic doses (10 and 20mg/kg), edoxaban significantly but moderately (less than 2-fold) prolonged bleeding time. Warfarin and enoxaparin also dose-dependently inhibited venous thrombosis and prolonged bleeding time. The ED(50) values of warfarin and enoxaparin were 0.12 mg/kg and 500 IU/kg, and the 2-fold bleeding time prolongation doses (BT2) were 0.16 mg/kg and 1700 IU/kg, respectively. The safety margin (ratio of BT2 to ED(50)) of edoxaban (>10.5) was greater than those of warfarin (1.3) and enoxaparin (3.4).. Edoxaban inhibited venous thrombosis comparably to warfarin and enoxaparin, and the attendant bleeding risk of edoxaban was lower than that of warfarin and enoxaparin in rats.

Topics: Administration, Oral; Animals; Anticoagulants; Enoxaparin; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Hemostatics; Male; Pyridines; Rats; Rats, Wistar; Thiazoles; Treatment Outcome; Venous Thrombosis; Warfarin

We performed a randomised pilot trial of PerMIT, a novel decision support tool for genotype-based warfarin initiation and maintenance dosing, to assess its efficacy for improving warfarin management. We prospectively studied 26 subjects to compare PerMIT-guided management with routine anticoagulation service management. CYP2C9 and VKORC1 genotype results for 13 subjects randomly assigned to the PerMIT arm were recorded within 24 hours of enrolment. To aid in INR interpretation, PerMIT calculates estimated loading and maintenance doses based on a patient's genetic and clinical characteristics and displays calculated S-warfarin plasma concentrations based on planned or administered dosages. In comparison to control subjects, patients in the PerMIT study arm demonstrated a 3.6-day decrease in the time to reach a stabilised INR within the target therapeutic range (4.7 vs. 8.3 days, p = 0.015); a 12.8% increase in time spent within the therapeutic interval over the first 25 days of therapy (64.3% vs. 55.3%, p = 0.180); and a 32.9% decrease in the frequency of warfarin dose adjustments per INR measurement (38.3% vs. 57.1%, p = 0.007). Serial measurements of plasma S-warfarin concentrations were also obtained to prospectively evaluate the accuracy of the pharmacokinetic model during induction therapy. The PerMIT S-warfarin plasma concentration model estimated 62.8% of concentrations within 0.15 mg/l. These pilot data suggest that the PerMIT method and its incorporation of genotype/phenotype information may help practitioners increase the safety, efficacy, and efficiency of warfarin therapeutic management.

Topics: Adult; Aged; Aged, 80 and over; Alleles; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Atrial Fibrillation; Cytochrome P-450 CYP2C9; Decision Support Techniques; Disease Management; Drug Monitoring; Female; Genotype; Humans; International Normalized Ratio; Male; Metabolic Clearance Rate; Middle Aged; Mixed Function Oxygenases; Pilot Projects; Prospective Studies; Software; Stroke; Thrombophilia; Venous Thrombosis; Vitamin K Epoxide Reductases; Warfarin; Young Adult

The efficacy and safety of enoxaparin in outpatient treatment of deep vein thrombosis have been well studied. The present study aimed to compare the efficacy of a 10-mg loading dose of warfarin with 5 mg of the drug and enoxaparin in achieving the international normalized ratio (INR) range.. This randomized clinical trial was performed in the emergency department (ED) of our study. International normalized ratio was checked daily for 7 days and on the 14th day. Based on the patient's INR on the third day, the doses were adjusted. Patients received enoxaparin (1.5 mg/kg per day) simultaneously until the therapeutic range of INR was achieved for 2 consecutive days.. The side effects were compatible in both groups. There was a significant difference in the INR rates of the 2 groups recorded on the third, fourth, and seventh days.. The 10-mg loading dose of warfarin induces the therapeutic range of INR earlier than the 5-mg dose without causing any significant difference in the side effects. More cases in the 10-mg group had INR levels higher than 3; the very dose, therefore, is recommended as the loading dose in cases of outpatients with deep vein thrombosis referring to the ED. Tight control of INR, after the third day of treatment, is also recommended in these cases.

Topics: Anticoagulants; Double-Blind Method; Drug Therapy, Combination; Enoxaparin; Female; Humans; Male; Middle Aged; Treatment Outcome; Venous Thrombosis; Warfarin

Unfractionated heparin (UFH) is the standard drug for the initial treatment of pulmonary embolism (PE) and deep vein thrombosis (DVT) in Japan, whereas fondaparinux is the standard drug in Europe and the United States. Here, we examine the efficacy and safety of fondaparinux in Japanese patients.. In 2 randomized, open-label, multicenter studies, 80 Japanese patients with acute PE or DVT received either subcutaneous fondaparinux or intravenous UFH as a non-comparative reference, in a 3:1 ratio, for 5-10 days. Concomitant warfarin therapy was continued until Day 90. Multidetector-row computed tomography-based assessment showed that 57.9% and 45.9% of the patients with acute PE and acute proximal DVT had proximal DVT and PE as a complication, respectively. There was no recurrence of symptomatic venous thromboembolism. In the fondaparinux group, the respective improvement rates at the end of the initial treatment and follow-up periods were 71.4% and 86.8% for 42 patients with PE, and 57.8% and 83.3% for 46 patients with DVT; similar results were noted in the UFH group. One patient in the fondaparinux group experienced major bleeding during the initial treatment, but no such episode in the UFH group.. Once-daily, subcutaneous fondaparinux is as effective and safe without monitoring as adjusted-dose intravenous UFH for the initial treatment of acute PE and DVT in Japanese patients.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Anticoagulants; Asian People; Contrast Media; Female; Fondaparinux; Hemorrhage; Heparin; Humans; Infusions, Intravenous; Injections, Subcutaneous; Japan; Male; Middle Aged; Polysaccharides; Predictive Value of Tests; Pulmonary Embolism; Recurrence; Risk Assessment; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Venous Thrombosis; Warfarin; Young Adult

The object of this work was to determine the efficacy of a low range International Normalized Ratio (INR) between 1.5 and 1.9, in preventing recurrent venous thrombosis and the hemorrhagic manifestations that can complicate anticoagulation with warfarin. Thirty nine patients, 10 to 78 years of age were studied between January 2006 and November 2009. All of them had been treated with warfarin, for at least 6 months, due to deep venous thrombosis or pulmonary embolism. The subjects were separated, at random, into two groups. In group A (20 patients), the doses of warfarin were adjusted until the INR was stabilized between 1.5 and 1.9; in group B, the INR was maintained between 2 and 3. The coagulant activities of plasma factors II, VII, IX and X were determined in a week and between the fourth and fifth weeks, after stabilization of the INR. Plasma activities of the coagulation factors assayed were abnormally low in both groups, in the two opportunities they were determined, although significantly lower in group B (p<0.05). No thromboembolic episodes occurred during the study, in any of the patients. One of the patients from group A and four from group B, presented minor hemorrhagic manifestations (p N.S.) The above results suggest that a range on INR lower that 2, could be sufficient to prevent recurrent thrombotic episodes while diminishing the frequency of hemorrhagic complications associated with the use of warfarin. However, it is necessary to continue incorporating more individuals in the study to obtain greater certainty in the analysis of these results.

Topics: Adolescent; Adult; Aged; Anticoagulants; Blood Coagulation Factors; Child; Dose-Response Relationship, Drug; Drug Monitoring; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Pulmonary Embolism; Recurrence; Venous Thrombosis; Warfarin; Young Adult

The safest duration of anticoagulation after idiopathic deep vein thrombosis (DVT) is unknown. We conducted a prospective study to assess the optimal duration of vitamin K antagonist (VKA) therapy considering the risk of recurrence of thrombosis according to residual vein thrombosis (RVT). Patients with a first unprovoked DVT were evaluated for the presence of RVT after 3 months of VKA administration; those without RVT suspended VKA, while those with RVT continued oral anticoagulation for up to 2 years. Recurrent thrombosis and/or bleeding events were recorded during treatment (RVT group) and 1 year after VKA withdrawal (both groups). Among 409 patients evaluated for unprovoked DVT, 33.2% (136 of 409 patients) did not have RVT and VKA was stopped. The remaining 273 (66.8%) patients with RVT received anticoagulants for an additional 21 months; during this period of treatment, recurrent venous thromboembolism and major bleeding occurred in 4.7% and 1.1% of patients, respectively. After VKA suspension, the rates of recurrent thrombotic events were 1.4% and 10.4% in the no-RVT and RVT groups, respectively (relative risk = 7.4; 95% confidence interval = 4.9-9.9). These results indicate that in patients without RVT, a short period of treatment with a VKA is sufficient; in those with persistent RVT, treatment extended to 2 years substantially reduces, but does not eliminate, the risk of recurrent thrombosis.

Topics: Acenocoumarol; Adult; Aged; Anticoagulants; Drug Administration Schedule; Female; Hemorrhage; Humans; Lower Extremity; Male; Middle Aged; Prospective Studies; Recurrence; Risk Factors; Ultrasonography; Venous Thromboembolism; Venous Thrombosis; Vitamin K; Warfarin

To compare effects of prolongation of the treatment with therapeutic doses of enoxaparin to 1 month on recanalization of occlusively thrombosed deep veins (OTDV) of the limbs with results of standard therapy with unfractionated heparin (UFH). Both treatments were followed by warfarin administration.. Thirty patients were selected from 111 patients with a history of deep vein thrombosis (DVT) and/or pulmonary artery embolism according to the following criteria: the presence of occlusive thrombosis of one deep vein minimum; the absence of DVT for 12 months of follow-up. Patients of group 1 (n = 15) received standard therapy (UFH for at least 5 days) with switch to warfarin. Patients of group 2 (n = 15) received therapeutic doses of enoxaparin (1 mg/kg each 12 hours) for 30 days minimum with switch to warfarin. Follow-up was 12 months. Ultrasonic duplex angioscanning of the limbs was made at baseline, 1, 3, 6 and 12 months after treatment start.. After follow-up month 1, 3 and 6 number of patients with occlusive DVT was significantly less in group 2. All the patients given enoxaparin achieved recanalization of OTDV within 3 months of treatment. OTDV recanalization was not achieved in 20% patients of group 1 even 12 months after treatment start.. Prolongation of enoxaparin treatment to 1 month followed by warfarin treatment is superior to standard UFH treatment followed by warfarin in providing recanalization of OTDV within 3 months of treatment. Moreover, this treatment predicts persistence of recanalization within 12 months of anticoagulant therapy.

Topics: Anticoagulants; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Enoxaparin; Female; Humans; Male; Middle Aged; Pulmonary Embolism; Treatment Outcome; Venous Thrombosis; Warfarin

To study effects of thrombin-activated fibrinolysis inhibitor (TAFI) on efficacy and safety of long-term anti-coagulant treatment in patients with venous thromboembolic complications (VTEC).. A total of 111 patients with a history of an episode of deep vein thrombosis (DVT) and/or pulmonary artery thromboembolism (PATE) entered the study. All the patients received unfractionated or low-molecular heparin for at least 5 days than switch on warfarin (target values of INR 2.0-3.0). Baseline blood levels of TAFI were measured. The patients were followed up for 18 months. Recurrent (DVT/TAFI and hemorrhagic complications (HC) were endpoints. Also, frequency of complete lysis of deep vein thrombi was assessed after 12 months of treatment.. A TAFI level varied from 50 to 217% (median 106%, interquartile rage 90-133%). TAFI concentration positively correlated with fibrinogen and thromb size. The patients were divided into two groups depending on TAFI content: group 1 patients had low TAFI (under 25th percentile; < 90%); patients of group 2 had high TAFI (above 25th percentile; > 90%). Group 1 patients were characterized by less stable anticoagulation. This association did not depend on genetic characteristics which determine sensitivity to warfarin (CYP2C9 and VKORC1). Low TAFI was associated with reduced risk of DVT for 18 months and higher probability of complete lysis of the thrombi after 12 months of anticoagulant therapy compared to VTEC patients with high TAFI. No differences were found by TAFI level in patients with HC and without HC, but in HC patients low TAFI was associated with spontaneous hemorrhages and bleeding in therapeutic INR values.. The results of this pilot study evidence that a TAFI level can be one of the factors influencing efficacy and safety of long-term anticoagulant therapy in patients with VTEC on warfarin treatment.

Topics: Adolescent; Adult; Aged; Anticoagulants; Carboxypeptidase B2; Dose-Response Relationship, Drug; Female; Hemorrhage; Humans; Male; Middle Aged; Multivariate Analysis; Pilot Projects; Prospective Studies; Pulmonary Embolism; Regression Analysis; Risk; Time Factors; Venous Thrombosis; Warfarin; Young Adult

The aim of this project was to determine whether a tailored multifaceted intervention aimed at site-specific barriers is more effective than audit feedback alone for improving adherence to inhospital stroke performance measures (PMs): door to needle time of less than 1 hour for tissue plasminogen activator, dysphagia screening, deep venous thrombosis prophylaxis, and warfarin treatment for atrial fibrillation.. Hospitals were paired on baseline adherence to dysphagia screening and quality improvement infrastructure and randomized to receive audit feedback alone (n=7) versus audit feedback plus site-specific interventions (n=6). Data were collected on all admitted patients with stroke seen in the neurology department before and after a 6-month implementation period. The primary end point was the difference in postintervention adherence rates for each PM, except tissue plasminogen activator because of low sample size.. Data were collected on 2071 preintervention patients and 1240 postintervention patients. Targeted site-specific interventions, such as standing orders and standardized dysphagia screens, were imperfectly implemented during the 6-month intervention period. For atrial fibrillation, the intervention group had an 11% higher postintervention adherence rate beyond that of the control group (98% v 87%, P < .005). No other statistically significant changes in PM adherence were observed.. Implementation of site-specific interventions for quality improvement of specific measures in stroke was difficult to achieve in a 6-month time frame and led to improved adherence for only one of 3 PMs. Studies with a longer intervention period and more sites are required to determine whether tailored interventions can enhance stroke improvement.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Combined Modality Therapy; Commission on Professional and Hospital Activities; Deglutition Disorders; Emergency Medical Services; Emergency Service, Hospital; Feedback; Female; Guideline Adherence; Humans; Intensive Care Units; Male; Mass Screening; Quality Assurance, Health Care; Quality of Health Care; Stroke; Tissue Plasminogen Activator; Venous Thrombosis; Warfarin

We compared the efficacy and safety of percutaneous endovenous intervention (PEVI) plus anticoagulation with anticoagulation alone in the reduction of venous thromboembolism (VTE) and post-thrombotic syndrome (PTS) in acute proximal deep venous thrombosis (DVT).. Recurrent VTE and PTS are common complications of DVT. There are no randomized trials investigating the efficacy of PEVI in the reduction of the above complications.. Patients with symptomatic proximal DVT were randomized to receive PEVI plus anticoagulation or anticoagulation alone. Anticoagulation consisted of intravenous unfractionated heparin or subcutaneous low-molecular weight heparin plus warfarin. PEVI consisted of one or more of a combination of thrombectomy, balloon venoplasty, stenting, or local low-dose thrombolytic therapy.. At 6 months follow-up, recurrent VTE developed in 2 of 88 patients of the PEVI plus anticoagulation group versus 12 of 81of the anticoagulation-alone group (2.3% vs. 14.8%, P = 0.003). PTS developed in 3 of 88 patients of the PEVI plus anticoagulation Group and 22 of 81 of the anticoagulation-alone group (3.4% vs. 27.2%, P < 0.001).. In patients with symptomatic proximal DVT, PEVI plus anticoagulation may be superior to anticoagulation-alone in the reduction of VTE and PTS at 6 months.

Topics: Aged; Anticoagulants; Arizona; Disease-Free Survival; Drug Therapy, Combination; Endovascular Procedures; Female; Heparin; Heparin, Low-Molecular-Weight; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Phlebography; Postthrombotic Syndrome; Recurrence; Stents; Suction; Thrombectomy; Thrombolytic Therapy; Time Factors; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis; Warfarin

The present study was designed to evaluate the long-term efficacy and safety of once-daily enoxaparin plus warfarin for the outpatient ambulatory treatment of lower-limb deep venous thrombosis (DVT).. A total of 246 patients, comprising 128 men (mean age, 54.28±16.48 years) and 118 women (mean age, 50.11±16.47 years) with symptomatic lower extremity DVT, were included in this open-label, single-arm, multicenter, phase IV clinical trial conducted at 14 centers in Turkey. All patients were administered subcutaneous enoxaparin (1.5 mg/kg, once-daily) until international normalized ratio (INR) levels reached to 2 to 3, followed by oral warfarin (5 mg/d) for at least 3 months and elastic compression stockings (30-40 mm Hg). Clinical signs (leg circumference), symptoms (edema, pain, tenderness), recanalization rates upon duplex ultrasound examination, laboratory findings (D-dimer and INR levels), and postthrombotic syndrome status with CEAP classification were the efficacy parameters evaluated every 3 months during 18 months of follow-up. Safety end points included minor and major bleeding as well as serious adverse events.. Ambulatory treatment with enoxaparin plus warfarin significantly reduced physical symptoms, including tenderness, edema, pain (P<.001), and the circumference of the affected leg (P<.001). The leg circumference difference in almost all patients was <1.5 cm at the end of 18 months (P<.001). Recanalization rates for occluded iliofemoral vein were 76.1% at 3 months and 86.5% at 18 months (P<.001). An early and significant decrease obtained in D-dimer levels on day 10 continued to decline significantly until month 6 and remained unchanged afterwards (P<.001). Of four patients diagnosed with major bleeding during oral anticoagulant use, three recovered with conservative treatment (reduction in hemoglobin levels in 2 developed at visit 2 [day 10] and intracranial bleeding in 1 developed at visit 3 [day 30]), and one patient required a hysterectomy after menorrhagia developed at visit 7 (month 18). Two of the 65 (9.9%) adverse events documented were serious adverse events, but none of the serious adverse events leading to death were related to the study medications.. Ambulatory treatment with enoxaparin plus warfarin seems to be effective in symptomatic healing and in clinical improvement by reducing thrombus formation and organization at all levels of lower extremity venous system with DVT, without a significant major bleeding risk. Therefore, the results of our conventional conservative treatment are in line with 1A level evidence reported in the recent American College of Chest Physicians guideline.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Ambulatory Care; Anticoagulants; Blood Coagulation; Chi-Square Distribution; Compression Bandages; Drug Administration Schedule; Drug Therapy, Combination; Enoxaparin; Female; Fibrin Fibrinogen Degradation Products; Fibrinolytic Agents; Hemorrhage; Humans; Injections, Subcutaneous; International Normalized Ratio; Lower Extremity; Male; Middle Aged; Outpatients; Prospective Studies; Risk Assessment; Time Factors; Treatment Outcome; Turkey; Ultrasonography, Doppler, Duplex; Venous Thrombosis; Warfarin; Young Adult

Rivaroxaban, an oral factor Xa inhibitor, may provide a simple, fixed-dose regimen for treating acute deep-vein thrombosis (DVT) and for continued treatment, without the need for laboratory monitoring.. We conducted an open-label, randomized, event-driven, noninferiority study that compared oral rivaroxaban alone (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with subcutaneous enoxaparin followed by a vitamin K antagonist (either warfarin or acenocoumarol) for 3, 6, or 12 months in patients with acute, symptomatic DVT. In parallel, we carried out a double-blind, randomized, event-driven superiority study that compared rivaroxaban alone (20 mg once daily) with placebo for an additional 6 or 12 months in patients who had completed 6 to 12 months of treatment for venous thromboembolism. The primary efficacy outcome for both studies was recurrent venous thromboembolism. The principal safety outcome was major bleeding or clinically relevant nonmajor bleeding in the initial-treatment study and major bleeding in the continued-treatment study.. The study of rivaroxaban for acute DVT included 3449 patients: 1731 given rivaroxaban and 1718 given enoxaparin plus a vitamin K antagonist. Rivaroxaban had noninferior efficacy with respect to the primary outcome (36 events [2.1%], vs. 51 events with enoxaparin-vitamin K antagonist [3.0%]; hazard ratio, 0.68; 95% confidence interval [CI], 0.44 to 1.04; P<0.001). The principal safety outcome occurred in 8.1% of the patients in each group. In the continued-treatment study, which included 602 patients in the rivaroxaban group and 594 in the placebo group, rivaroxaban had superior efficacy (8 events [1.3%], vs. 42 with placebo [7.1%]; hazard ratio, 0.18; 95% CI, 0.09 to 0.39; P<0.001). Four patients in the rivaroxaban group had nonfatal major bleeding (0.7%), versus none in the placebo group (P=0.11).. Rivaroxaban offers a simple, single-drug approach to the short-term and continued treatment of venous thrombosis that may improve the benefit-to-risk profile of anticoagulation. (Funded by Bayer Schering Pharma and Ortho-McNeil; ClinicalTrials.gov numbers, NCT00440193 and NCT00439725.).

Topics: Acenocoumarol; Acute Disease; Administration, Oral; Aged; Anticoagulants; Double-Blind Method; Enoxaparin; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Injections, Subcutaneous; Intention to Treat Analysis; Kaplan-Meier Estimate; Male; Middle Aged; Morpholines; Pulmonary Embolism; Rivaroxaban; Thiophenes; Venous Thromboembolism; Venous Thrombosis; Vitamin K; Warfarin

The role and dose of anticoagulants in thromboprophylaxis for patients with cancer receiving chemotherapy through central venous catheters (CVCs) is controversial. We therefore assessed whether warfarin reduces catheter-related thrombosis compared with no warfarin and whether the dose of warfarin determines the thromboprophylactic effect.. In 68 clinical centres in the UK, we randomly assigned 1590 patients aged at least 16 years with cancer who were receiving chemotherapy through CVCs to no warfarin, fixed-dose warfarin 1 mg per day, or dose-adjusted warfarin per day to maintain an international normalised ratio between 1.5 and 2.0. Clinicians who were certain of the benefit of warfarin randomly assigned patients to fixed-dose or dose-adjusted warfarin groups. The primary outcome was the rate of radiologically proven, symptomatic catheter-related thrombosis. Analysis was by intention to treat. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN 50312145.. Compared with no warfarin (n=404), warfarin (n=408; 324 [79%] on fixed-dose and 84 [21%] on dose-adjusted) did not reduce the rate of catheter-related thromboses (24 [6%] vs 24 [6%]; relative risk 0.99, 95% CI 0.57-1.72, p=0.98). However, compared with fixed-dose warfarin (n=471), dose-adjusted warfarin (n=473) was superior in the prevention of catheter-related thromboses (13 [3%] vs 34 [7%]; 0.38, 0.20-0.71, p=0.002). Major bleeding events were rare; an excess was noted with warfarin compared with no warfarin (7 vs 1, p=0.07) and with dose-adjusted warfarin compared with fixed-dose warfarin (16 vs 7, p=0.09). A combined endpoint of thromboses and major bleeding showed no difference between comparisons. We did not note a survival benefit in either comparison.. The findings show that prophylactic warfarin compared with no warfarin is not associated with a reduction in symptomatic catheter-related or other thromboses in patients with cancer and therefore we should consider newer treatments.. Medical Research Council and Cancer Research UK.

Topics: Aged; Anticoagulants; Antineoplastic Agents; Catheterization, Central Venous; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Meta-Analysis as Topic; Middle Aged; Neoplasms; Venous Thrombosis; Warfarin

The incidence of venous lesions following transvenous cardiac device implantation is high. Previous implantation of temporary leads ipsilateral to the permanent devices, and a depressed left ventricular ejection fraction have been associated with an increased risk of venous lesions, though the effects of preventive strategies remain controversial. This randomized trial examined the effects of warfarin in the prevention of these complications in high-risk patients.. Between February 2004 and September 2007, we studied 101 adults who underwent a first cardiac device implantation, and who had a left ventricular ejection fraction < or =0.40, or a temporary pacing system ipsilateral to the permanent implant, or both. After device implantation, the patients were randomly assigned to warfarin to a target international normalized ratio of 2.0-3.5, or to placebo. Clinical and laboratory evaluations were performed regularly up to 6 months postimplant. Venous lesions were detected at 6 months by digital subtraction venography.. Venous obstructions of various degrees were observed in 46 of the 92 patients (50.0%) who underwent venography. The frequency of venous obstructions was 60.4% in the placebo, versus 38.6% in the warfarin group (P = 0.018), corresponding to an absolute risk reduction of 22% (relative risk = 0.63; 95% confidence interval = 0.013-0.42).. Warfarin prophylaxis lowered the frequency of venous lesions after transvenous devices implantation in high-risk patients.

Topics: Anticoagulants; Cardiac Pacing, Artificial; Comorbidity; Defibrillators, Implantable; Electrodes; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Pacemaker, Artificial; Phlebography; Risk Factors; Treatment Outcome; Venous Thrombosis; Warfarin

Home-LITE compared long-term treatment at home with tinzaparin or usual care in terms of efficacy, safety, patients' treatment satisfaction, incidence of post-thrombotic syndrome, and associated venous leg ulcers.. This multicenter, randomized, controlled trial enrolled 480 patients with documented, acute, proximal deep vein thrombosis. Patients received tinzaparin 175 IU/kg subcutaneously once daily for 12 weeks, or tinzaparin for >or=5 days plus oral warfarin, commenced on day 1, international normalized ratio-adjusted, and continued for >or=12 weeks ("usual care"). Patients received 1 in-clinic injection, then home treatment.. The rate of recurrent venous thromboembolism at 12 weeks was 3.3% in both groups (absolute difference 0%; 95% confidence interval -3.2-3.2), and at 1 year was 10.4%/8.3% in the tinzaparin/usual-care groups, respectively (difference 2.1%; 95% confidence interval -3.1-7.3). There were no between-group differences in deaths at 12 weeks or 1 year, or bleeding at 12 weeks. Patients in the tinzaparin group expressed significantly greater treatment satisfaction (P = .0024), particularly regarding freedom from the inconvenience of blood monitoring; were less likely to report signs/symptoms of post-thrombotic syndrome (individual odds ratios 0.66 to 0.91, overall odds ratio 0.77, P = .001); and reported fewer leg ulcers at 12 weeks: 1 (0.5%) versus 8 (4.1%) (P = .02) with usual care.. Long-term home treatment with tinzaparin or usual care resulted in similar rates of recurrent venous thromboembolism, death, and bleeding. The significantly lower incidence of post-thrombotic syndrome and leg ulcers observed in the tinzaparin group is a potentially important benefit and deserves further study.

Topics: Administration, Oral; Female; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Home Care Services; Humans; Injections, Subcutaneous; Male; Middle Aged; Patient Satisfaction; Postthrombotic Syndrome; Recurrence; Tinzaparin; Venous Thromboembolism; Venous Thrombosis; Warfarin

The aim of the study was to assess the regression rate of persistent echogenic masses in patients with idiopathic deep venous thrombosis (DVT) who were after initial 6 months randomized to long-term anticoagulation treatment or to discontinuation of anticoagulation.. We followed 168 patients with idiopathic DVT for two years since diagnosis. After 6 months of standard therapy (heparin/LMWH, warfarin with target INR 2-3) we randomized patients with persistent echogenic masses of over 20% of venous diameter to either discontinuation of warfarin or to continuation of warfarin for another 6 months. We evaluated the size of thrombotic masses with duplex ultrasound.. After 6 months of standard therapy complete regression was observed in 69 patients while in 99 patients echogenic masses persisted, with 71 patients maintaining an obstruction of at least 20% of venous cross-sectional area. 52 patients were randomized. 27 patients continued warfarin therapy and in 25 patients warfarin was discontinued. After discontinuation of warfarin a further trend to regression was seen in both groups. A significant difference in regression of thrombotic masses between the 6th and 12th month of follow up was seen in patients continuing to receive warfarin, both within the popliteal vein (2.81 +/- 1.56 vs. 2.10 +/- 1.67 mm, p < 0.05) and the femoral vein (3.95 +/- 2.74 vs. 2.30 +/- 1.34 mm, p < 0.05).. After 6 months of DVT treatment persistent echogenic masses can be found in almost two thirds of patients. Even after discontinuation of anticoagulation treatment echogenic masses further regress. However, the rate of regression in patients with deep venous thrombosis between the 6th and 12th month was greater in patients randomized to continue warfarin during this period than in patients without anticoagulation.

Topics: Aged; Anticoagulants; Blood Coagulation; Drug Administration Schedule; Female; Femoral Vein; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Male; Middle Aged; Popliteal Vein; Recurrence; Severity of Illness Index; Time Factors; Treatment Outcome; Ultrasonography, Doppler, Duplex; Venous Thrombosis; Warfarin

The aim of trial is to observe the Chinese bleeding frequency and frequency of recurrent VTE in different international normalized ratio (INR) range of warfarin for venous thromboembolism (VTE) including deep venous thrombosis (DVT) and pulmonary embolism (PE), and to search optimal INR range.. We conducted a randomized, double-blind cohort trial, in which 180 patients were assigned to apply warfarin in a target INR of 1.50 to 1.99 (group A), a target INR of 2.00 to 2.50 (group B) or a target of INR of 2.51 to 3.00 (group C). Every group had respectively 60 patients. After they had completed warfarin therapy to be stability kept with those target INR range for two or more weeks, this study would be begun to observe the bleeding frequency and frequency of recurrent VTE.. There was significant difference in recurrent VTE frequency between Group A (8.3%) and BC (1.7%, P = 0.042). The minor bleeding frequency of Group A, B and C is respectively 8.3%, 18.3% and 6.7% (P = 0.089). The moderate bleeding frequency of Group A and BC is respectively 3.3% and 7.5% (P = 0.341), and large bleeding frequency of them is respectively 0% and 3.3% (P = 0.303). To patients whose age above 62 year, major bleeding episode occurred respectively in 1 patient assigned to INR of 1.5-2.5 and in three patients assigned to Group C (hazard ratio, 12. 600; 95 percent confidence interval, 1.183-134.238).. Warfarin therapy in INR of 2.0-3.0 is more effective than INR of 1.5-1.99 for the long-term prevention of recurrent VTE. And warfarin regimen in INR of 2.0-3.0 does not increase the risk of major bleeding either. So to general Chinese, INR ought to be recommended in 2.0-3.0. To patients whose age above 62 year, INR ought to be recommended between 2.0 to 2.5.

Topics: Adolescent; Adult; Aged; Anticoagulants; Double-Blind Method; Humans; Middle Aged; Secondary Prevention; Venous Thromboembolism; Venous Thrombosis; Warfarin; Young Adult

Warfarin is commonly used for management of deep vein thrombosis (DVT) and pulmonary embolism (PE), controlling therapy by means of the International Normalized Ratio (INR).. To identify differences in INR results between patients with thromboembolic and haemorrhagic complications and controls.. Two nested case-control studies from within a controlled trial of the duration of warfarin therapy (47 thrombotic and 16 haemorrhagic complications).. Patients whose thromboembolism failed to resolve during treatment or recurred during or after treatment had non-significantly lower INR levels than matched controls (geometric mean 2.2 versus 2.3, p = 0.12). Patients with haemorrhage also had not statistically significant lower INR levels than their matched controls (2.1 versus 2.3, p = 0.22). The variability of INR levels was similar in both case groups and controls. The mean percentage of INR levels in the therapeutic range 2 - 3 was almost identical in thrombotic cases and controls (56.5% versus 56.1%). Compared to the haemorrhagic group, better control was achieved in controls (61.5% versus 43.0%, p=0.01), but controls had slightly more INR values above the therapeutic range (12.1% versus 10.5%, p = 0.74) whilst haemorrhagic cases had more INR values below the therapeutic range (46.6% versus 26.4%, p = 0.03).. In this study, higher INR levels were not associated with haemorrhage suggesting that, for patients being treated for DVT/PE, a modest increase in the target therapeutic range could be considered.

Topics: Adolescent; Adult; Aged; Anticoagulants; Case-Control Studies; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Pulmonary Embolism; Secondary Prevention; Treatment Outcome; Venous Thrombosis; Warfarin; Young Adult

Long-term oral anticoagulation treatment is associated with potential morbidity. Insufficient patient education is linked to poorly controlled anticoagulation. However the impact of a specific educational program on anticoagulation related morbidity remains unknown.. To evaluate the effect of an oral anticoagulation patient education program in reducing both hemorrhagic and recurrent thrombotic complications.. We conducted a prospective, multicenter open randomized study, comparing an interventional group who received a specific oral anticoagulation treatment educational program with a control group. Eligible patients were older than 18 and diagnosed as having deep vein thrombosis or pulmonary embolism requiring therapy with a vitamin K antagonist for 3 months or more. Our primary outcome was the occurrence of hemorrhagic or thromboembolic events.. During the 3-month follow-up the main outcome criteria were observed 20 times (6.6% of patients), 5 (3.1%) in the experimental and 15 (10.6%) in the control group. Consequently, in multivariate analysis, the cumulative risk reduction in the experimental group was statistically significant (OR 0.25, 95% CI 0.1-0.7, p < 0.01).. Patient education using an educational program reduced VKA-related adverse event rates.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Female; Hemorrhage; Humans; Male; Medication Errors; Middle Aged; Patient Education as Topic; Pulmonary Embolism; Venous Thrombosis; Warfarin

Previous reparative valvular surgical options directed at reconstructing damaged common femoral vein (CFV) valves associated with pathological chronic venous insufficiency (CVI) have not succeeded in reliably managing CVI. In consequence, venous valvuloplasty is rare and most patients are managed conservatively. As a result, monocusp surgery was identified as an optional surgical solution for this large underserved patient group.. Ulcer patients appear at wound clinics and often experience disappointing results. Monocusp valves were constructed utilizing viable vein wall in 14 operations on 11 patients. These patients were observed for four years to see if such an autogenous vein wall valve might control aggressive symptomatic CVI when faced with unusable valves.. Long-term follow-up showed that the monocusp valves remained competent at four years. Symptomatic failures have not appeared at this time. Pain, swelling, ulcers and leg congestion were reliably reversed. VEnous INsufficiency Epidemiologic and Economic Study (VEINES) classification (see Abenhaim L, Krux X, VIENES Study collaborators. Angiology 1997;48:59 and Kurz X, Kahn SR, Abenhaim L, et al. Int Angiol 1999;18:83-102) improved over four years from 2.7 +/- 0.9 to 0 (P < 0.001); CEAP classifications (see Kistner RL, Eklof B, Masuda EM. Mayo Clin Proc 1996;71:338-45) improved from grade 4-6 to 0-1 (CEAP is not generally a postoperative grading system, but it can be used to develop some form of qualitative analyses as to intervention effectiveness, i.e. what existed preoperatively no longer exists postoperatively. Its postsurgery use is limited by (C5) classification - history of ulcer, which by definition cannot go below that with a history of ulcer even if the ulcer has been cured). Mean venous reflux scores decreased from 3.8 +/- 0.4 to 0.3 +/- 0.5 (P < 0.001).. Monocusp implantation reliably resolved patient symptoms when unusable CFV valves were encountered. Postoperative CFV reflux is usually undetectable. The monocusp valve exhibits minimal thrombogenicity related to its viability with attendant antithrombotic hormone production capacity and has markedly improved the patient's quality of life. Full thickness monocusp surgery could become widespread with the difficult dysplastic/aplastic CVI patient subset because of its simplicity, repeatability, durability, low complication rate, effectiveness, persistent availability and viability providing nitric oxide synthase and thymomodulin hormone production capacity. The full thickness of vein wall has distinct advantages over other partial thickness valve creation methods because of its long-term vitality. Postoperative coumadin is recommended for six months to minimize risks of deep vein thrombosis and/or pulmonary embolism.

Topics: Anticoagulants; Chronic Disease; Feasibility Studies; Femoral Vein; Humans; Pulmonary Embolism; Quality of Life; Severity of Illness Index; Surgical Flaps; Suture Techniques; Time Factors; Treatment Outcome; Ultrasonography, Doppler, Duplex; Vascular Surgical Procedures; Venous Insufficiency; Venous Thrombosis; Warfarin

To meet growing demand for oral anticoagulation worldwide there has been increased dependence on computer-assistance in dosage although the safety and effectiveness of any of the individual computer-assisted dosage programs has not previously been established. This randomised multicentre clinical end-point study assessed a new version of the PARMA 5 program. It compared PARMA 5 safety and effectiveness with manual dosage by experienced medical staff at 19 centres with a known interest in oral anticoagulation. Target recruitment was 8000 patient-years, randomised to medical staff or PARMA-5 assisted dosage. Safety and effectiveness of the PARMA 5 program was compared with manual dosage. A total of 10,421 patients were recruited (15,369 patient-years) in the 5-year study. International normalised ratio (INR) tests numbered 167,791 with manual and 160,078 with PARMA 5 dosage. With parma 5 there was overall a non-significant reduction in clinical events but in the 2542 patients with deep vein thrombosis/pulmonary embolism, clinical events were significantly reduced (P = 0.005). Success in achieving 'time in target INR range' was also significantly greater with PARMA 5 compared with the dosage by experienced medical staff. This study demonstrated the safety and effectiveness of PARMA 5-assisted dosage.

Topics: Acenocoumarol; Administration, Oral; Adult; Aged; Aged, 80 and over; Algorithms; Anticoagulants; Drug Therapy, Computer-Assisted; Female; Follow-Up Studies; Humans; International Normalized Ratio; Male; Middle Aged; Phenprocoumon; Pulmonary Embolism; Software; Software Design; Treatment Outcome; Venous Thrombosis; Warfarin

Heparin-induced thrombocytopenia (HIT) is a life-threatening immune response to heparin that is associated with a high risk of thromboembolic complications. We prospectively treated seven subjects with acute HIT with fondaparinux and compared the results to a similar historical control population from the same hospital. Six of the seven fondaparinux-treated subjects were transitioned to warfarin, beginning after platelet count recovery occurred. Ten historical controls were treated with a direct thrombin inhibitor (DTI), eight of which were transitioned to warfarin. The primary study outcome was platelet count recovery which was defined as an increase from baseline by at least 30% of nadir to greater than 100,000/mm(3) by day seven. Seven subjects were prospectively treated with fondaparinux for a median of eight days. Six of the seven had HIT with thrombosis at the time of enrollment. All fondaparinux treated subjects had a complete platelet count recovery, and none experienced a new thromboembolic complication, major bleeding or death by week four. One subject underwent limb amputation. Ten historical controls were treated with a DTI for a median duration of eleven days. Platelet count recovery occurred in eight of the ten historical controls. No new thromboembolic complications or major bleeds occurred but limb gangrene occurred in four controls. The development of limb gangrene in the historical controls may have been a result of delayed recognition of HIT and/or inappropriately early institution of warfarin in the historical controls. This pilot study suggests that fondaparinux may be useful in patients with acute HIT.

Topics: Acute Disease; Aged; Anticoagulants; Blood Coagulation; Case-Control Studies; Factor Xa Inhibitors; Feasibility Studies; Female; Fondaparinux; Hemorrhage; Heparin; Humans; International Normalized Ratio; Male; Pilot Projects; Platelet Count; Polysaccharides; Prospective Studies; Thrombocytopenia; Time Factors; Treatment Outcome; Venous Thrombosis; Warfarin

Recent guidelines do not recommend antithrombotic prophylaxis (AP) to prevent catheter-related thrombosis in cancer patients with a central line.. This study assessed the management of central lines in cancer patients, current attitude towards AP, catheter-related and systemic venous thromboses, and survival.. Of 1410 patients enrolled, 1390 were seen at least once in the 6-month median follow-up. Continuous AP, mainly low-dose warfarin, was given to 451 (32.4%); they were older, with a more frequent history of venous thromboembolism (VTE), and more advanced cancer. There was no difference in catheter-related thrombosis in patients given AP or not (2.8% and 2.2%, odds ratio 1.29, 95% confidence interval 0.64-2.6). The median time to first catheter-related complication was 120 days. Systemic VTE including deep and superficial thromboses and pulmonary embolism, were less frequent with AP (4% versus 8.2%, P = 0.005). Mortality was also lower (25% versus 44%, P = 0.0001). Multiple logistic regression analysis found only advanced cancer and no AP significantly associated with mortality. No major bleeding was recorded with AP.. Current AP schedules do not appear to prevent catheter-related thrombosis. Systemic VTE and mortality, however, appeared lower after prophylaxis.

Topics: Catheterization, Central Venous; Catheters, Indwelling; Female; Fibrinolytic Agents; Humans; Italy; Kaplan-Meier Estimate; Logistic Models; Male; Middle Aged; Neoplasms; Odds Ratio; Prospective Studies; Pulmonary Embolism; Risk Assessment; Time Factors; Treatment Outcome; Venous Thrombosis; Warfarin

A substantial clinical need exists for an alternate to vitamin K antagonists for treating deep vein thrombosis in many patients. Long-term low-molecular-weight heparin (LMWH), body-weight adjusted, avoids anticoagulant monitoring and may be associated with less bleeding. We evaluated the effectiveness and safety of long-term LMWH compared with vitamin K antagonist therapy in a broad spectrum of patients with proximal vein thrombosis.. We performed a multicenter, randomized, open-label clinical trial using objective outcome measures comparing therapy for 3 months. Outcomes were assessed at 3 and 12 months.. Of 737 patients, 18 of 369 receiving tinzaparin (4.9%) had recurrent venous thromboembolism at 3 months compared with 21 of 368 (5.7%) receiving usual care (absolute difference, -0.8%, 95% confidence interval -4.1-2.4). Hemorrhagic complications occurred less frequently in the LMWH group largely because of less minor bleeding: 48 of 369 patients (13.0%) versus 73 of 368 patients (19.8%) receiving usual-care anticoagulation (absolute difference -6.8%; P = .011; risk ratio = 0.66). New major bleeding events ceased early (by day 23, P = .034) for patients receiving LMWH but persisted throughout the study treatment interval for patients receiving vitamin K antagonist therapy. No mortality advantage was shown for LMWH.. Our study shows that LMWH is similar in effectiveness to the usual-care vitamin K antagonist treatment for preventing recurrent venous thromboembolism in a broad spectrum of patients. It causes less harm and enhances the clinicians' therapeutic options for patients with proximal deep vein thrombosis. Our findings reported here suggest the possibility of a broader role for long-term LMWH in selected patients.

Topics: Anticoagulants; Cause of Death; Female; Fibrinolytic Agents; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Recurrence; Self Administration; Tinzaparin; Treatment Outcome; Venous Thrombosis; Vitamin K; Warfarin

The purpose of this study is to address the safety and efficacy of a warfarin dosing nomogram. Patients undergoing hip or knee arthroplasty were randomized to warfarin dosed by nomogram (n = 106) or by house staff (n = 110) during their hospital stay. The average daily dose of warfarin was 4.14 mg for the nomogram group and 4.18 mg for the house staff group. On postoperative day 4, the average international normalized ratio was 1.55 in the nomogram group compared with 1.59 in the house staff group. On postoperative day 4, 19.1% of the patients in the nomogram group had a therapeutic international normalized ratio, compared with 14.7% in the house staff group. There were no differences in bleeding or thrombotic complications in the 2 groups. This nomogram appears to be both safe and effective.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Female; Humans; International Normalized Ratio; Internship and Residency; Male; Postoperative Complications; Statistics, Nonparametric; Venous Thrombosis; Warfarin

To determine the optimum duration of oral anticoagulant therapy after an episode of deep vein thrombosis or pulmonary embolism, or both.. Multicentre, prospective, randomised study with follow-up for one year.. 46 hospitals in United Kingdom.. Patients aged > or =18 with deep vein thrombosis or pulmonary embolism, or both.. Three (n=369) or six months (n=380) of anticoagulation with heparin for five days accompanied and followed by warfarin, with a target international normalised ratio of 2.0-3.5.. Death from deep vein thrombosis or pulmonary embolism; failure to resolve, extension, recurrence of during treatment; recurrence after treatment; and major haemorrhage during treatment.. In the patients allocated to three months' treatment two died from deep vein thrombosis or pulmonary embolism during or after treatment, compared with three in the six month group. During treatment deep vein thrombosis or pulmonary embolism failed to resolve, extended, or recurred in six patients in the three month group without fatal consequences, compared with 10 in the six month group. After treatment there were 23 non-fatal recurrences in the three month group and 16 in the six month group. Fatal and non-fatal deep vein thrombosis or pulmonary embolism during treatment, and after treatment thus occurred in 31(8%) of those who had received three months' anticoagulation compared with 29 (8%) of those who had received six months' (P=0.80, 95% confidence interval for difference -3.1% to 4.7%). There were no fatal haemorrhages during treatment but there were eight major haemorrhages in those treated for six months and none in those treated for three months (P=0.008, -3.5% to -0.7%). Thus 31 (8%) of the patients receiving three months' anticoagulation experienced adverse outcomes as a result of deep vein thrombosis or pulmonary embolism or its treatment compared with 35 (9%) of those receiving six months' (P=0.79, -4.9% to 3.2%).. For patients in the UK with deep vein thrombosis or pulmonary embolism and no known risk factors for recurrence, there seems to be little, if any, advantage in increasing the duration of anticoagulation from three to six months. Any possible advantage would be small and would need to be judged against the increased risk of haemorrhage associated with the longer duration of treatment with warfarin.. Clinical Trials NCT00365950 [ClinicalTrials.gov].

Topics: Adult; Aged; Anticoagulants; Drug Administration Schedule; Drug Therapy, Combination; Female; Heparin; Humans; Male; Middle Aged; Prospective Studies; Pulmonary Embolism; Recurrence; Treatment Outcome; Venous Thrombosis; Warfarin

The aim of this study was to evaluate the dynamics of the recanalization process (spontaneous fibrinolysis) in completely occlusive deep venous thrombosis (DVT) using duplex ultrasound examination and to investigate the influence of different factors on the evolution of thrombus regression.. This longitudinal prospective study was done with 74 consecutive patients with completely occlusive acute multilevel DVT, confirmed by echo duplex scan after 1, 3, 6, and 12 months. At each re-evaluation, the degree and the type of recanalization were determined. Efficacy of tinzaparin (175 IU/kg, s.c., q.d. for 7-14 days) and continued with warfarin (12 months at INR 2-3) as well as patients' compliance with compressive elastic hosiery wearing were carefully followed. Relationship between the degree and pattern of recanalization and patients' age, gender, as well as thrombosis etiology and location were determined.. Sixty-four patients completed the study. The mean recanalization rate was 39.7% at 1, 64.8% at 3, 82% at 6, and 90.3% at 12 months. Marginal recanalization was more frequently observed, but recanalization pattern was changing during follow-up.. In the case of efficient anticoagulant and compressive therapy, the spontaneous recanalization process of DVT is important from the very first month of evolution, but an almost complete re-permeabilization is observed only after 12 months of treatment. The unilocular, marginal pattern of thrombus lysis is often observed and has better evolution than the multilocular cavernous one. The dynamics of recanalization are characterized by distal-to-proximal extension and in the first 6 months are significantly influenced by patient's gender and thrombosis etiology.

Topics: Adult; Aged; Anticoagulants; Female; Fibrinolysis; Fibrinolytic Agents; Follow-Up Studies; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Patient Compliance; Prospective Studies; Sex Factors; Stockings, Compression; Time Factors; Tinzaparin; Treatment Outcome; Ultrasonography, Doppler, Color; Venous Thrombosis; Warfarin

Recurrent thromboembolic events may occur after termination of anticoagulant therapy for acute venous thromboembolism (VTE) using oral direct thrombin inhibitor ximelagatran.. Patients with VTE recruited at the German study centres were followed-up for an additional 18 months, treated initially with 2x36 mg ximelagatran daily or with enoxaparin/warfarin over 6 months (THRIVE Treatment study) and 2x24 mg ximelagatran daily or placebo over 18 months (THRIVE III study). Recurrent VTE and the combined outcome events consisting of recurrent VTE, other thrombotic complication, major bleeding and mortality were analysed.. In the THRIVE Treatment study, no patient suffered from a recurrent VTE, but 1 patient randomised to enoxaparin/warfarin experienced major bleeding. During follow-up, 4/32 and 3/32 patients initially randomised to ximelagatran and enoxaparin/warfarin developed recurrent VTE (p=0.7024). No major bleed occurred. One patient in each group died. The incidences of the combined outcome events were not different (p=0.9326). In the THRIVE III study, 0/9 versus 5/14 patients randomised to ximelagatran and placebo developed recurrent VTE including 1 fatal pulmonary embolism (p=0.0501). During follow-up, 3/9 and no patients initially randomised to ximelagatran and placebo developed recurrent VTE. One and 3 other outcome events occurred in patients initially randomised to ximelagatran or placebo. During follow-up, recurrent VTE (p=0.6893) and combined outcome events (p=0.3642) were not different between the groups.. The results of the follow-up studies suggest that thromboembolic events may re-occur in patients with acute VTE after termination of treatment with both vitamin K-antagonists and ximelagatran.

Topics: Administration, Oral; Anticoagulants; Arteries; Azetidines; Benzylamines; Drug Therapy, Combination; Enoxaparin; Follow-Up Studies; Germany; Hemorrhage; Humans; Incidence; International Normalized Ratio; Muscle, Skeletal; Prospective Studies; Recurrence; Retinal Vein Occlusion; Time Factors; Venous Thrombosis; Warfarin

The influence of the duration of anticoagulant therapy after venous thromboembolism (VTE) on the long-term morbidity and mortality is unclear.. To investigate the long-term sequelae of VTE in patients randomized to different duration of secondary prophylaxis.. In a multicenter trial comparing secondary prophylaxis with vitamin K antagonists for 6 weeks or 6 months, we extended the originally planned 2 years follow-up to 10 years. The patients had annual visits and at the last visit clinical assessment of the post-thrombotic syndrome (PTS) was performed. Recurrent thromboembolism was adjudicated by a radiologist, blinded to treatment allocation. Causes of death were obtained from the Swedish Death Registry.. Of the 897 patients randomized, 545 could be evaluated at the 10 years follow-up. The probability of developing severe PTS was 6% and any sign of PTS was seen in 56.3% of the evaluated patients. In multivariate analysis, old age and signs of impaired circulation at discharge from the hospital were independent risk factors at baseline for development of PTS after 10 years. Recurrent thromboembolism occurred in 29.1% of the patients with a higher rate among males, older patients, those with permanent triggering risk factor - especially with venous insufficiency at baseline - signs of impaired venous circulation at discharge, proximal deep vein thrombosis, or pulmonary embolism. Death occurred in 28.5%, which was a higher mortality than expected with a standardized incidence ratio (SIR) of 1.43 (95% CI 1.28-1.58), mainly because of a higher mortality than expected from cancer (SIR 1.83; 95% CI 1.44-2.23) or from myocardial infarction or stroke (SIR 1.28; 95% CI 1.00-1.56). The duration of anticoagulation did not have a statistically significant effect on any of the long-term outcomes.. The morbidity and mortality during 10 years after the first episode of VTE is high and not reduced by extension of secondary prophylaxis from 6 weeks to 6 months. A strategy to reduce recurrence of VTE as well as mortality from arterial disease is needed.

Topics: Aged; Anticoagulants; Female; Humans; Male; Middle Aged; Postphlebitic Syndrome; Recurrence; Risk Factors; Thromboembolism; Time Factors; Venous Thrombosis; Vitamin K; Warfarin

Elevated plasma D-dimer and factor VIII coagulant activity (FVIIIc) may be associated with the risk of recurrent venous thromboembolism (VTE).. To evaluate D-dimer and FVIIIc as risk factors for recurrent VTE and assess the efficacy of extended low-intensity warfarin (target International Normalized Ratio 1.5-2.0) in preventing recurrence by biomarker level.. In the Prevention of Recurrent Venous Thromboembolism trial, 508 idiopathic VTE patients treated for > or = 3 months with full-intensity warfarin, and who had stopped warfarin for 7 weeks on average, were randomized to low-intensity warfarin or placebo and followed for 2.1 years for recurrent VTE. Prerandomization blood samples were analysed for D-dimer and FVIIIc.. One-third of participants had elevated baseline D-dimer (> or = 500 ng mL(-1)) and one-fourth, elevated FVIIIc (> or = 150 IU dL(-1)). Adjusting for other risk factors, the hazard ratios (HRs) for recurrent VTE with elevated D-dimer or FVIIIc were 2.0 [95% confidence interval (CI) 1.2-3.4] and 1.5 (95% CI 0.8-2.8), respectively. The association of elevated D-dimer with recurrence was larger among patients with one prior VTE (HR 3.2, 95% CI 1.3-8.0) than in patients with more than one event (HR 1.4, 95% CI 0.7-2.2). For patients with one prior VTE on placebo, the annual recurrence incidence was 10.9% with elevated D-dimer and 2.9% with normal values. Low-intensity warfarin was equally effective in recurrence risk reduction in those with normal or elevated biomarkers.. Among patients with idiopathic VTE, measurement of D-dimer, but not FVIIIc, might be useful for risk stratification. The efficacy of extended low-intensity warfarin therapy did not vary by biomarker level.

Topics: Adult; Aged; Anticoagulants; Biomarkers; Double-Blind Method; Drug Administration Schedule; Factor VIII; Female; Fibrin Fibrinogen Degradation Products; Humans; Male; Middle Aged; Risk Factors; Secondary Prevention; Thromboembolism; Venous Thrombosis; Warfarin

In some but not all studies, men with venous thrombosis had a higher risk of recurrence than women. Information on women with initial hormone-related thrombosis is scant.. We assessed the incidence of recurrent thrombosis by gender, and among women using exogenous hormones or pregnant/postpartum at the time of index thrombosis.. A total of 508 men and women with one or more previous venous thrombosis episodes were observed while participating in a randomized trial of low-intensity warfarin or placebo for 2.1 years. Index thrombosis events during treatment with postmenopausal hormones, oral contraceptives, or during pregnancy, or the puerperium were considered to be hormone-related events.. Among 268 men the 3-year probability of recurrent thrombosis was 18.4% (95% confidence intervals; CI 12.3-24.4). Among 109 women without hormone-related thrombosis, the rate was 15.0% (95% CI 6.3-23.8). Among 129 women with hormone-related thrombosis, the rate was 5.0% (95% CI 1.1-8.9). Adjusting for other risk factors and treatment assignment, women had a 39% lower thrombosis recurrence risk than men: hazard ratio (HR) 0.61 (95% CI 0.34-1.08). Women with hormone-related thrombosis had a 58% lower risk than men: HR 0.42 (95% CI 0.19-0.97); and a 46% lower recurrence risk than other women; HR 0.54 (95% CI 0.19-1.54). Women without hormone-related index events had a recurrence rate similar to men; HR 0.83 (95% CI 0.42-1.66).. In this trial population, women had a lower risk of recurrent venous thrombosis than men. This difference was explained by a low risk of recurrence among women with hormone-related index thrombosis.

Topics: Aged; Anticoagulants; Female; Hormones; Humans; International Normalized Ratio; Male; Middle Aged; Models, Statistical; Placebos; Recurrence; Risk; Risk Factors; Sex Factors; Thromboembolism; Venous Thrombosis; Warfarin

Central venous lines (CVLs) are essential in the care of children with malignancies, but are associated with venous thromboembolism (VTE) and infections. Effective and safe prophylactic approaches are deficient.. To perform a study of adjusted low-dose warfarin for the prevention of CVL-related VTE in children with malignancies.. Children with newly diagnosed cancer, a CVL in a jugular vein and an expected treatment period of over 6 mo were eligible for the study. Participants were randomized to low-dose warfarin, with intended international normalized ratio (INR) 1.3-1.9, or to a control group. Primary outcome was VTE in a jugular vein diagnosed by ultrasonography at 1, 3 and 6 mo after inclusion. Secondary outcome was CVL-related infections, mainly measured as days on antibiotics or positive blood cultures.. The study enrolled 73 children, and 62 completed it fully. Asymptomatic CVL-related VTE was frequent (42%), but often transient. Regardless of severity, timing and duration, CVL-related VTE was equally frequent among children on warfarin as compared to controls (p=0.44). Low-dose warfarin (p=0.59) or jugular CVL-related VTE (p=0.91) did not have any impact on days on antibiotics, but we observed a tendency towards an association between CVL-related VTE and positive blood cultures (p=0.15).. Our randomized study of low-dose oral anticoagulation for the prevention of CVL-related asymptomatic VTE in children with cancer did not show any benefit of warfarin adjusted to maintain INR between 1.3 and 1.9.

Topics: Anticoagulants; Catheterization, Central Venous; Catheters, Indwelling; Child; Child, Preschool; Female; Humans; Jugular Veins; Male; Neoplasms; Venous Thrombosis; Warfarin

The optimal duration of oral anticoagulation in patients with idiopathic venous thromboembolism is uncertain. Testing of D-dimer levels may play a role in the assessment of the need for prolonged anticoagulation.. We performed D-dimer testing 1 month after the discontinuation of anticoagulation in patients with a first unprovoked proximal deep-vein thrombosis or pulmonary embolism who had received a vitamin K antagonist for at least 3 months. Patients with a normal D-dimer level did not resume anticoagulation, whereas those with an abnormal D-dimer level were randomly assigned either to resume or to discontinue treatment. The study outcome was the composite of recurrent venous thromboembolism and major bleeding during an average follow-up of 1.4 years.. The D-dimer assay was abnormal in 223 of 608 patients (36.7%). A total of 18 events occurred among the 120 patients who stopped anticoagulation (15.0%), as compared with 3 events among the 103 patients who resumed anticoagulation (2.9%), for an adjusted hazard ratio of 4.26 (95% confidence interval [CI], 1.23 to 14.6; P=0.02). Thromboembolism recurred in 24 of 385 patients with a normal D-dimer level (6.2%). Among patients who stopped anticoagulation, the adjusted hazard ratio for recurrent thromboembolism among those with an abnormal D-dimer level, as compared with those with a normal D-dimer level, was 2.27 (95% CI, 1.15 to 4.46; P=0.02).. Patients with an abnormal D-dimer level 1 month after the discontinuation of anticoagulation have a significant incidence of recurrent venous thromboembolism, which is reduced by the resumption of anticoagulation. The optimal course of anticoagulation in patients with a normal D-dimer level has not been clearly established. (ClinicalTrials.gov number, NCT00264277 [ClinicalTrials.gov].).

Topics: Acenocoumarol; Adult; Aged; Aged, 80 and over; Anticoagulants; Antiphospholipid Syndrome; Antithrombins; Drug Administration Schedule; Fibrin Fibrinogen Degradation Products; Follow-Up Studies; Hemorrhage; Humans; Middle Aged; Proportional Hazards Models; Prospective Studies; Pulmonary Embolism; Recurrence; Survival Analysis; Ultrasonography; Venous Thrombosis; Vitamin K; Warfarin

Venous thromboemobolism (VTE) is an important complication of thalidomide therapy especially when it is combined with steroids or chemotherapy. Currently there is no consensus on the most appropriate prophylactic approach. We prospectively investigated the use of low-dose warfarin sodium in prevention of thalidomide-associated VTE in patients receiving thalidomide-based combination therapies. Patients with multiple myeloma or chronic lymphocytic leukemia who were treated on thalidomide based-combination therapies were treated on low-dose warfarin (1 or 2 mg) continuously through the duration of their therapy. Among the 68 patients enrolled, four developed an episode of VTE, an overall incidence of 5.9% (odds = 0.063). Median duration of thalidomide therapy was 4 months. Low-does warfarin decreases the incidence of VTE compared to historical control and is an effective mechanism of prevention of VTE in thalidomide-based chemotherapy regimens.

Topics: Aged; Dose-Response Relationship, Drug; Female; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Multiple Myeloma; Thalidomide; Venous Thrombosis; Warfarin

Ximelagatran, an oral direct thrombin inhibitor with a rapid onset of action and predictable antithrombotic effect, has the potential to be a simple therapeutic alternative to current standard treatment of acute venous thromboembolism.. To compare the efficacy and safety of ximelagatran with standard enoxaparin/warfarin treatment for the prevention of recurrent venous thromboembolism.. Randomized, double-blind, noninferiority trial (Thrombin Inhibitor in Venous Thromboembolism [THRIVE] Treatment Study) of 2489 patients with acute deep vein thrombosis, of whom approximately one third had concomitant pulmonary embolism. The study was conducted at 279 centers in 28 countries from September 2000 through December 2002.. Patients were randomized to receive 6 months of treatment with either oral ximelagatran, 36 mg twice daily, or subcutaneous enoxaparin, 1 mg/kg twice daily, for 5 to 20 days followed by warfarin adjusted to maintain an international normalized ratio of 2.0 to 3.0.. Recurrent venous thromboembolism, bleeding, and mortality.. Venous thromboembolism recurred in 26 of the 1240 patients assigned to receive ximelagatran (estimated cumulative risk, 2.1%) and in 24 of the 1249 patients assigned to receive enoxaparin/warfarin (2.0%). The absolute difference between ximelagatran and enoxaparin/warfarin was 0.2% (95% confidence interval [CI], -1.0% to 1.3%). This met the prespecified criterion for noninferiority. Corresponding values for major bleeding were 1.3% and 2.2% (difference, -1.0%; 95% CI, -2.1% to 0.1%), and for mortality were 2.3% and 3.4% (difference, -1.1%; 95% CI, -2.4% to 0.2%). Alanine aminotransferase levels increased to more than 3 times the upper limit of normal in 119 patients (9.6%) and 25 patients (2.0%) receiving ximelagatran and enoxaparin/warfarin, respectively. Increased enzyme levels were mainly asymptomatic. Retrospective analysis of locally reported adverse events showed a higher rate of serious coronary events with ximelagatran (10/1240 patients) compared with enoxaparin/warfarin (1/1249 patients).. Oral ximelagatran administered in a fixed dose without coagulation monitoring, was as effective as enoxaparin/warfarin for treatment of deep vein thrombosis with or without pulmonary embolism and showed similar, low rates of bleeding. Increased levels of liver enzymes in 9.6% of ximelagatran-treated patients require regular monitoring; the mechanism requires further evaluation. Prospective assessment of coronary events in future studies is warranted.

Topics: Adult; Aged; Aged, 80 and over; Alanine Transaminase; Anticoagulants; Azetidines; Benzylamines; Double-Blind Method; Drug Therapy, Combination; Female; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Prodrugs; Pulmonary Embolism; Recurrence; Treatment Outcome; Venous Thrombosis; Warfarin

The post-thrombotic syndrome is a chronic, poorly understood complication of deep venous thrombosis (DVT).. To evaluate predictors of the post-thrombotic syndrome, including intensity of long-term anticoagulation, and to assess the impact of the post-thrombotic syndrome on quality of life.. The setting was 13 Canadian hospitals and one US hospital. One hundred and forty-five patients with an unprovoked episode of proximal DVT who were initially treated with 3 months of conventional-intensity warfarin [target International Normalized Ratio (INR) of 2.5] then participated in a trial comparing two intensities of long-term warfarin therapy (target INR 2.5 vs. INR 1.7). Post-thrombotic syndrome was assessed at the end of the trial using a validated clinical scale. Generic and venous disease-specific quality of life was compared in patients with and without the post-thrombotic syndrome. Multivariable regression analyses were performed to identify predictors of the post-thrombotic syndrome and of its severity.. After an average follow-up of 2.2 years, the prevalence of post-thrombotic syndrome was 37% and of severe post-thrombotic syndrome was 4%. Quality of life was worse in patients with the post-thrombotic syndrome compared with patients who did not have it. The presence of factor (F)V Leiden or the prothrombin gene mutation was an independent predictor of both a lower risk (P = 0.006) and reduced severity (P = 0.045) of the post-thrombotic syndrome. Intensity of anticoagulation did not influence the risk of developing the post-thrombotic syndrome.. The post-thrombotic syndrome is a frequent and burdensome complication of proximal DVT, even among patients maintained on long-term oral anticoagulation. While the presence of FV Leiden or prothrombin gene mutation appears to be associated with a reduced risk of post-thrombotic syndrome, this finding requires further evaluation in prospective studies.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Canada; Factor V; Female; Humans; International Normalized Ratio; Male; Middle Aged; Multivariate Analysis; Mutation; Postphlebitic Syndrome; Prevalence; Prothrombin; Quality of Life; Risk; Time Factors; United States; Venous Thrombosis; Warfarin

In this multicenter, randomized, placebo-controlled clinical trial, we studied whether warfarin 1 mg daily reduces the incidence of symptomatic central venous catheter (CVC) -associated thrombosis in patients with cancer.. Two hundred fifty-five patients with cancer who required a CVC for at least 7 days were randomly assigned to receive warfarin 1 mg or placebo.. There were 11 (4.3%) symptomatic CVC-associated thromboses among 255 patients, with no difference in the incidence of symptomatic CVC-associated thrombosis between patients taking warfarin 1 mg daily (six of 130 patients; 4.6%) and patients taking placebo (five of 125 patients; 4.0%; hazard ratio, 1.20; 95% CI, 0.37 to 3.94). Warfarin had no effect on CVC life span (84 days v 63 days in control and warfarin groups, respectively; 95% confidence limit, -16 to 55 days; P = .09), and it did not affect the number of premature CVC removals (23.2% v 25.4% in control and warfarin groups, respectively; 95% confidence limit of difference -8.34 to 12.71; P = .68) or the frequency of major bleeding episodes (2% v 0% in control and warfarin groups, respectively; P = .5, Fisher's exact test).. Symptomatic CVC-associated thrombosis in patients with cancer, although significant, is less common than previously reported. In this study, the administration of warfarin 1 mg daily did not reduce the incidence of symptomatic CVC-associated thrombosis in patients with cancer. However, the low rate of symptomatic CVC-associated thrombosis means that a much larger trial is required to address this issue definitively.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Catheterization, Central Venous; Catheters, Indwelling; Double-Blind Method; Female; Humans; Male; Middle Aged; Neoplasms; Placebos; Radiography; Treatment Outcome; Venous Thrombosis; Warfarin

Some patients develop fatigue while taking warfarin, but causality is uncertain.. To assess whether warfarin use is associated with fatigue.. This investigation was a substudy of a randomized double-blind trial in 13 outpatient thromboembolism clinics. Subjects who had received one month of open-label warfarin therapy for venous thromboembolism due to a transient risk factor were randomly assigned to receive warfarin or placebo for 2 months and followed for another 9 months after stopping the study drug. Fatigue was measured using a Likert scale, and change of fatigue was measured by the patient's global rating.. In 87 subjects, the overall ratings of fatigue were 0.1 unit lower (95% CI 0.6 units lower to 0.4 units higher) while taking warfarin. Global rating for change in fatigue intensity showed no increase of fatigue with warfarin use.. The short-term use of warfarin was not associated with symptoms of fatigue.

Topics: Analysis of Variance; Double-Blind Method; Fatigue; Female; Humans; Male; Middle Aged; Venous Thrombosis; Warfarin

Warfarin dosing with a target international normalized ratio (INR) range of 1.5-2.5 has not been reported as adequate for venous thromboembolism (VTE) prophylaxis after total knee (TKR) and total hip replacement (THR) surgery.. To evaluate the rate of symptomatic VTE after TKR and THR surgery using a low-dose (INR 1.5-2.5) warfarin protocol started the evening before surgery compared with a literature cohort treated with enoxaparin.. TKR/THR patients treated with a 21-day low-dose warfarin protocol were followed via a consecutive observational design. Main outcome measures were symptomatic VTE and pulmonary embolism (PE), with major bleeds and death as secondary outcomes. Low-dose warfarin was compared with a literature cohort of patients treated with enoxaparin who received enoxaparin for a similar length of time and was evaluated for the same outcomes. Cohort event rates were derived as a weighted average using the DerSimonian model.. VTE, PE, bleeds, and deaths in the low-dose warfarin group were 8 (1.04%), 4 (0.52%), 8 (1.04%), and 4 (0.52%), respectively. The cohort weighted average values were 35 (1.33%), 19 (0.72%), 65 (2.46%), and 18 (0.67%), respectively. Odds ratios for low-dose warfarin for VTE, PE, and VTE plus PE were 0.778 (95% CI 0.36 to 1.68), 0.717 (0.24 to 2.11), and 0.754 (0.41 to 1.42), respectively, all nonsignificant. Odds ratios for bleeds and death were 0.420 (0.20 to 0.87; p = 0.02) and 0.756 (0.26 to 2.24; NS), respectively.. For this evaluation, low-dose warfarin was comparable to the enoxaparin cohort for development of VTE, PE, and VTE+PE. Incidences of bleeds in the enoxaparin cohort were significantly higher than in patients receiving low-dose warfarin.

Topics: Angiography; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Cohort Studies; Dose-Response Relationship, Drug; Enoxaparin; Female; Hemorrhage; Hospital Mortality; Humans; International Normalized Ratio; Male; Odds Ratio; Orthopedics; Phlebography; Postoperative Complications; Prospective Studies; Pulmonary Embolism; Thromboembolism; Treatment Outcome; Venous Thrombosis; Warfarin

To determine whether computer-aided dosing of warfarin is superior to physician dosing to maintain a patient in a rehabilitation hospital within a target international normalized ratio goal.. Randomized, double-blinded, clinical trial in an inpatient rehabilitation hospital. A total of 30 consecutive patients admitted receiving warfarin were randomized to either clinician dosing or computer-aided warfarin dosing for the duration of their hospitalization. The main outcome measures included the percentage of days in a therapeutic anticoagulation range and the number of blood draws. Exclusion criteria included short length of stay (n=110, 39%) and a physician declared international normalized ratio target range of <2.0 (n=67, 23%). A total of 73 patients were excluded because of heme-positive stools at admission, recent gastrointestinal bleed, early discharge or consent refusal. Dawn AC software was used to determine warfarin dosage and frequency of blood draws to maintain a target international normalized ratio of 2.0-3.0 for the computer-dosed group (n=14). Several physicians recommended warfarin dosages for the second group (n=16). Two were dropped from the computer model secondary to lost data files for these two patients.. Computer-aided dosing of warfarin resulted in 61.7% of days within the therapeutic range (international normalized ratio, 2-3), whereas clinician dosing resulted in only 44.1%. There were no significant differences in the number of blood draws or demographic variables between the two groups.. Computers were significantly better at maintaining patients within a therapeutic international normalized ratio range than physicians. There were no significant differences in the number of recommended blood draws.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Boston; Double-Blind Method; Drug Monitoring; Drug Therapy, Computer-Assisted; Female; Humans; International Normalized Ratio; Length of Stay; Male; New York; Outcome and Process Assessment, Health Care; Rehabilitation Centers; Stroke; Vascular Diseases; Venous Thrombosis; Warfarin

Outpatient treatment of deep vein thrombosis (DVT) has become a common practice in uncomplicated patients. Few data are still present in patients with comorbidity (such as cancer) or concomitant symptomatic pulmonary embolism. Cancer patients with DVT are often excluded from home treatment because they have a higher risk of both bleeding and recurrent DVT. We tested the feasibility and safety of the Home Treatment (HT) program for acute DVT a PE in cancer patients. Patients were treated as outpatients unless they required admission for other medical problems, were actively bleeding or had pain that requires parenteral narcotics. Outpatient treatment was with low molecular weight heparin (LMWH) followed by warfarin or with LMWH alone. An educational program for patients was implemented. Two-hundred and seven patients with cancer were evaluated, 36 (17.4%) of whom had metastatic disease. Treatment with LMWH and warfarin was prescribed to 106 (51.2%) and LMWH alone to 102 (48.8%). One hundred and twenty-seven patients (61.3%) were entirely treated at home. There were no differences between patients treated at home and hospitalized patients with regard to gender, mean age, site of cancer, presence of metastases, and treatment. After 6 months, recurrent thrombo-embolism occurred in 8.7% of patients treated at home and in 5.6% of hospitalized patients (P=0.58); major bleeding in 2.0% and 1.5%, respectively (P=0.06). Twenty-seven patients (33%) in the hospitalized, and 33 (26%) in the home-treatment group, died after a follow-up of 6 months. These results indicate that, regarding cancer patients with acute DVT and/or PE, there is no difference between hospitalised and home-treated patients in terms of major outcomes.

Topics: Adult; Aged; Aged, 80 and over; Feasibility Studies; Female; Follow-Up Studies; Heparin, Low-Molecular-Weight; Home Care Services; Home Nursing; Hospitalization; Humans; Male; Middle Aged; Neoplasms; Patient Compliance; Patient Education as Topic; Pulmonary Embolism; Recurrence; Self Administration; Venous Thrombosis; Warfarin

Warfarin, which requires coagulation monitoring, is associated with relatively high rates of thromboembolism despite providing adequate prophylaxis. This study compared an oral direct thrombin inhibitor, ximelagatran, with warfarin in order to evaluate the safety and efficacy of the medication for the prevention of venous thromboembolism in patients undergoing total knee arthroplasty.. Following surgery, patients were randomly assigned to fixed-dose oral ximelagatran (36 mg twice daily) or warfarin (target international normalized ratio, 2.5), both administered for seven to twelve days in a double-blind, double-dummy design. Warfarin was initiated on the evening of the day of surgery, and ximelagatran, on the morning after surgery. The primary efficacy end point was the incidence of asymptomatic deep-vein thrombosis determined by bilateral venography, objectively confirmed symptomatic deep-vein thrombosis or pulmonary embolism, and death from all causes during treatment.. Adequate venograms or confirmed symptomatic events (efficacy population) were obtained for 1949 patients. Venous thromboembolism and death from all causes occurred in 22.5% (221) of 982 ximelagatran-treated patients and in 31.9% (308) of 967 warfarin-treated patients (p < 0.001). Proximal deep-vein thrombosis and pulmonary embolism were observed in 3.1% (thirty) and 0.2%, respectively, of the patients in the ximelagatran group and in 3.4% (thirty-three) and 0.4%, respectively, of the patients in the warfarin group. The six deaths from all causes included 0.3% (four) of the ximelagatran-treated patients and 0.2% (two) of the warfarin-treated patients. Major bleeding was noted in 1% (twelve) of the ximelagatran-treated patients and in 0.4% (five) of the warfarin-treated patients (p = 0.09).. Oral ximelagatran (36 mg twice daily), administered without coagulation monitoring or dose adjustment and started the day after total knee arthroplasty, demonstrates superior efficacy compared with warfarin prophylaxis, with no wound complications and no significant difference with respect to bleeding events, although the rate of major bleeding events was greater with ximelagatran than with warfarin.. Therapeutic Level I.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Knee; Azetidines; Benzylamines; Double-Blind Method; Female; Humans; Male; Middle Aged; Prospective Studies; Pulmonary Embolism; Treatment Outcome; Venous Thrombosis; Warfarin

Venous thromboembolic disease remains the most common reason for readmission after total hip arthroplasty. Prospective analysis of screening contrast venography was done from 1984 to 2003 in 1972 patients having elective total hip arthroplasty. Patients with deep venous thrombosis or pulmonary embolism received warfarin therapy; those with negative venograms received no further anticoagulation. From 1984 to 1992, patients not completing venography were discharged without warfarin; since 1993, patients without venography received warfarin for 6 weeks. Readmission for deep venous thrombosis, pulmonary embolism, or bleeding was tracked for 6 months. Venograms were completed in 1032 patients; 175 (16.9%) had deep venous thrombosis. Deep venous thrombosis was reduced by a clinical pathway that included continuous epidural anesthesia (14.2% versus 22.5%). The overall readmission rate for venous thromboembolic disease was 1.62%, including 14 pulmonary emboli (three fatal) and 18 femoral deep venous thrombosis. Readmission occurred in 0.27% (1 of 360) patients on continued warfarin, compared with 2.2% (19 of 880) with negative venograms discharged without further anticoagulation. Three patients (0.15%) suffered fatal pulmonary emboli; all had negative venograms and received no outpatient prophylaxis. Extended outpatient warfarin therapy provided effective protection against venous thromboembolic disease readmission. Surveillance venography was a poor predictor of need for continued prophylaxis; all patients should have extended anticoagulation after total hip arthroplasty.. Therapeutic study, Level I-1 (high-quality randomized trial with statistically significant difference or no statistically significant difference but narrow confidence intervals). See the Guidelines for Authors for a complete description of levels of evidence.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Hemorrhage; Humans; Patient Readmission; Phlebography; Postoperative Complications; Predictive Value of Tests; Prevalence; Pulmonary Embolism; Risk Factors; Venous Thrombosis; Warfarin

Topics: Adult; Aged; Ambulatory Care; Anticoagulants; Enoxaparin; Female; Humans; Male; Middle Aged; Pulmonary Embolism; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Catheterization, Central Venous; Humans; Nadroparin; Neoplasms; Pilot Projects; Prospective Studies; Venous Thrombosis; Warfarin

Tinzaparin at two dosages, 175 anti-Xa U/kg subcutaneously administered for 7 days, followed by warfarin, and 175 anti-Xa U/kg subcutaneously given for 90 days was compared with continuous intravenous unfractionated heparin (UFH) for 5 days, followed by warfarin for 3 months, were tested in the treatment of patients with proximal deep vein thrombosis. Several laboratory assays were used to monitor the effects of tinzaparin and UFH. The tinzaparin only study arm produced a 4- to 6-second prolongation of the activated partial thromboplastin time (aPTT). However, in the anti-Xa chromogenic assay and the Heptest assays, there was a prolongation after the administration of all three agents. In the two groups treated for 7 days, the anti-Xa and Heptest values returned to baseline after cessation of therapy. In the patients treated with tinzaparin for 90 days, the anti-Xa and Heptest remained elevated throughout the treatment period. The anti-IIa (anti-thrombin) results were considerably lower values in the tinzaparin-treated groups. Tissue factor pathway inhibitor (TFPI) antigen levels were elevated 2- to 2.5-fold in all three groups. In addition, the thrombin/antithrombin (TAT) complexes were also measured. After treatment, the TAT levels decreased over time. Tinzaparin was more effective in decreasing these levels. These results suggest that both Heptest and anti-Xa assays can be used to monitor patients receiving tinzaparin. TAT may be a useful test in monitoring the resolution of the clots. However, additional clinical validation is required to demonstrate the relevance of these parameters with the clinical outcome.

Topics: Biomarkers; Drug Administration Schedule; Drug Monitoring; Factor Xa Inhibitors; Heparin; Heparin, Low-Molecular-Weight; Humans; Lipoproteins; Partial Thromboplastin Time; Prothrombin; Time; Tinzaparin; Venous Thrombosis; Warfarin

The risk of recurrence is lower after treatment of an episode of venous thromboembolism associated with a transient risk factor, such as recent surgery, than after an episode associated with a permanent, or no, risk factor. Retrospective analyses suggest that 1 month of anticoagulation is adequate for patients whose venous thromboembolic event was provoked by a transient risk factor.. In this double-blind study, patients who had completed 1 month of anticoagulant therapy for a first episode of venous thromboembolism provoked by a transient risk factor were randomly assigned to continue warfarin or to placebo for an additional 2 months. Our goal was to determine if the duration of treatment could be reduced without increasing the rate of recurrent venous thromboembolism during 11 months of follow-up.. Of 84 patients assigned to placebo, five (6.0%) had recurrent venous thromboembolism, compared with three of 81 (3.7%) assigned to warfarin, resulting in an absolute risk difference of 2.3%[95% confidence interval (CI) - 5.2, 10.0]. The incidence of recurrent venous thromboembolism after discontinuation of warfarin was 6.8% per patient-year in those who received warfarin for 1 month and 3.2% per patient-year in those who received warfarin for 3 months (rate difference of 3.6% per patient-year; 95% CI - 3.8, 11.0). There were no major bleeds in either group.. Duration of anticoagulant therapy for venous thromboembolism provoked by a transient risk factor should not be reduced from 3 months to 1 month as this is likely to increase recurrent venous thromboembolism without achieving a clinically important decrease in bleeding.

Topics: Adult; Aged; Antibodies, Antiphospholipid; Anticoagulants; Double-Blind Method; Drug Administration Schedule; Female; Hemorrhage; Humans; Male; Middle Aged; Point Mutation; Prothrombin; Receptors, Cell Surface; Risk Factors; Secondary Prevention; Thromboembolism; Time Factors; Venous Thrombosis; Warfarin

The period of anticoagulation of a first episode of idiopathic venous thromboembolism has been 6 months. It is unclear if such patients would benefit from longer treatment, as there appears to be an increased risk of recurrence after anticoagulation is stopped.. In a randomized prospective study of 64 patients admitted to King Hussein Medical city, Amman, Jordan, who developed a first episode of venous thromboembolism, 32 patients were given warfarin for 24-months, while 32 patients stopped anticoagulation after completion of 6-months of therapy. Our goal was to determine the effects of extended anticoagulation on rates of recurrence of symptomatic venous thromboembolism and bleeding. The patients were followed for 12-months after stopping anticoagulation.. After 24-months, 7 of the 32 patients (21%) who had standard anticoagulation for 6-months had a recurrent episode of thromboembolism compared to one of the 32 patients who received anticoagulation for 24 months (3%). Extended warfarin therapy for 24-months has resulted in an absolute risk reduction of 0.1% (p<0.05). This translates into 8 patients having to be treated for 24-months to avoid one recurrence without increasing the risk of major bleeding. Two patients in each group (6%) had major nonfatal bleeding, all 4 bleeding episodes occurring within the first 3-months of anticoagulation. After 36-months of follow up, the recurrence rate of extended warfarin therapy was only 3 patients (9%), which is a 43% relative reduction in recurrence of thromboembolism compared to standard therapy for 6-months.. Patients with first episodes of idiopathic venous thromboembolism have an increased risk of recurrent venous thromboembolism and should be treated with oral anticoagulants for longer than 6-months, probably 24-months.

Topics: Administration, Oral; Adult; Anticoagulants; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Long-Term Care; Male; Middle Aged; Prospective Studies; Pulmonary Embolism; Risk Factors; Secondary Prevention; Venous Thrombosis; Warfarin

Self-management (SM) of warfarin by patients is an attractive strategy, particularly if it improves anticoagulation control and can be done safely under minimal physician supervision.. To compare the effect of SM with physician-management (PM) on the maintenance of therapeutic anticoagulation.. A randomized, open-label eight-month trial was performed. Patients 18 years of age and older were eligible if they were receiving warfarin for at least one month before enrolment and required anticoagulation for at least one year to a target international normalized ratio (INR) of 2.0 to 3.0 or 2.5 to 3.5. Exclusion criteria were a known hypercoaguable disorder, mental incompetence, a language barrier or an inability to attend training sessions. Patients randomly assigned to SM tested their INR using a point-of-care device (Pro Time Microcogulation System, International Technidyne Corporation, USA) and adjusted their warfarin doses using a nomogram. Patients randomly assigned to PM received usual care from their general practitioner. The primary outcome was to demonstrate 20% improvement in anticoagulation control by SM.. One hundred forty patients were randomly assigned (70 per group). Thirteen patients dropped out of SM early due to an inability to self-manage. Based on intention-to-treat analysis, there was no difference in the proportion of INR in range (SM 64.8% versus PM 58.7%, P=0.23) or time in target range (SM 71.8% versus PM 63.2%, P=0.14). Patients managing their own therapy spent less time below the therapeutic range (15.0% versus 27.3%, P=0.04). There were three major complications of thrombosis or bleeding, all occurring in the PM arm. All patients who completed SM preferred to continue with that strategy.. SM was not significantly better than PM in maintaining therapeutic anticoagulation. SM was feasible and appeared safe in the present study population.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Monitoring; Family Practice; Female; Humans; Male; Middle Aged; Patient Compliance; Prognosis; Self Administration; Severity of Illness Index; Treatment Outcome; Venous Thrombosis; Warfarin

Standard therapy to prevent recurrent venous thromboembolism includes 3 to 12 months of treatment with full-dose warfarin with a target international normalized ratio (INR) between 2.0 and 3.0. However, for long-term management, no therapeutic agent has shown an acceptable benefit-to-risk ratio.. Patients with idiopathic venous thromboembolism who had received full-dose anticoagulation therapy for a median of 6.5 months were randomly assigned to placebo or low-intensity warfarin (target INR, 1.5 to 2.0). Participants were followed for recurrent venous thromboembolism, major hemorrhage, and death.. The trial was terminated early after 508 patients had undergone randomization and had been followed for up to 4.3 years (mean, 2.1). Of 253 patients assigned to placebo, 37 had recurrent venous thromboembolism (7.2 per 100 person-years), as compared with 14 of 255 patients assigned to low-intensity warfarin (2.6 per 100 person-years), a risk reduction of 64 percent (hazard ratio, 0.36 [95 percent confidence interval, 0.19 to 0.67]; P<0.001). Risk reductions were similar for all subgroups, including those with and those without inherited thrombophilia. Major hemorrhage occurred in two patients assigned to placebo and five assigned to low-intensity warfarin (P=0.25). Eight patients in the placebo group and four in the group assigned to low-intensity warfarin died (P=0.26). Low-intensity warfarin was thus associated with a 48 percent reduction in the composite end point of recurrent venous thromboembolism, major hemorrhage, or death. According to per-protocol and as-treated analyses, the reduction in the risk of recurrent venous thromboembolism was between 76 and 81 percent.. Long-term, low-intensity warfarin therapy is a highly effective method of preventing recurrent venous thromboembolism.

Topics: Aged; Anticoagulants; Double-Blind Method; Drug Administration Schedule; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Pulmonary Embolism; Risk; Secondary Prevention; Stroke; Thromboembolism; Venous Thrombosis; Warfarin

To investigate recanalisation in the first 12 months after cerebral venous thrombosis.. 33 consecutive patients presenting with cerebral venous thrombosis were enrolled in the study. Diagnosis was made by magnetic resonance imaging (MRI) and magnetic resonance venography (MRV) or catheter angiography. Patients were initially treated with intravenous heparin. Warfarin was given for at least four months. Cerebral MRI and MRV were done at four months and repeated after 12 months if venous thrombosis persisted. Outcome was evaluated by the Rankin scale at 12 months.. Outcome at 12 months was good, with a median modified Rankin scale score of 0 (range 0 to 2); 27 patients (82%) had no residual deficits. No patient suffered recurrent cerebral venous thrombosis, deep vein thrombosis, or pulmonary embolism during follow up. After four months, all deep cerebral veins and cavernous sinuses, 94% of superior sagittal sinuses, 80% of straight sinuses, 73% of jugular veins, 58% of transverse sinuses, and 41% of sigmoid sinuses had recanalised. No further recanalisation was observed thereafter.. The results suggest that recanalisation only occurs within the first four months following cerebral venous thrombosis and not thereafter, irrespective of oral anticoagulation.

Topics: Adult; Aged; Anticoagulants; Cerebral Angiography; Female; Follow-Up Studies; Heparin; Humans; Intracranial Thrombosis; Magnetic Resonance Imaging; Male; Middle Aged; Outcome Assessment, Health Care; Phlebography; Retreatment; Time Factors; Venous Thrombosis; Warfarin

Low molecular weight heparins (LMWHs) are frequently used during acute treatment of deep vein thrombosis, but their utility for long-term treatment needs to be defined. In this multi-centre trial, 378 patients with acute deep vein thrombosis were randomised to intravenous unfractionated heparin (group A), once daily subcutaneous LMWH (bemiparin) for one week (group B) or once daily bemiparin in a therapeutic dose for one week followed by a maintenance dose for 12 weeks (group C). Fifty-two per cent of patients in group A, 72% of group B and 72% of group C showed venographic reduction in thrombus size assessed objectively on day 14; 20% greater improvement in group B and C indicates not only non-inferiority of bemiparin (p = 0.00003) but also superiority (p = 0.004) compared to UFH. Day 84 venographic or Doppler sonographic recanalisation of the affected veins was demonstrated in 75.3%, 79.8% and 81.5% in groups A, B and C respectively. Mortality, recurrent thromboembolic events and bleeding were similar in the three groups. Both bemiparin regimens were more effective than UFH in reducing thrombus size during the acute phase of treatment. The efficacy in terms of recurrence of venous thromboembolism and safety of Bemiparin is similar to UFH. Bemiparin is also an effective alternative to warfarin for long-term treatment.

Topics: Adult; Aged; Female; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Molecular Weight; Phlebography; Time Factors; Treatment Outcome; Venous Thrombosis; Warfarin

Venous thromboembolic events (VTE) are serious complications in children and for which the standard of care, unfractionated heparin followed by oral anticoagulation (UFH/OA), is problematic. The objective of REVIVE was to compare the efficacy and safety of a low molecular weight heparin (reviparin-sodium) to UFH/OA for the treatment of VTE in children.. This multicenter, open-label study, with blinded central outcome adjudication, randomized patients with objectively confirmed VTE to receive either reviparin-sodium or UFH/OA. Dose adjustments were made using nomograms. The efficacy outcome was based on recurrent VTE and death due to VTE during the 3-month treatment period. The safety outcomes were major bleeding, minor bleeding and death. Due to slow patient accrual, REVIVE was closed prematurely.. At 3 months, with reviparin-sodium, 2/36 patients (5.6%) had recurrent VTE or death compared to 4/40 patients (10.0%) receiving UFH/OA (odds ratio=0.53; 95% CI=(0.05, 4.00); Fisher's exact test: 2P=0.677). There were 7 major bleeds, 2/36 (5.6%) in the reviparin-sodium group and 5/40 (12.5%) in UFH/OA group (odds ratio=0.41; 95% confidence interval 0.04, 2.76); Fisher's exact test: P=0.435). There were 5 deaths during the study period, 1 (2.8%) in the reviparin-sodium group and 4 (10.0%) in the UFH/OA group. All five deaths were unrelated to VTE but one was due to an intracranial hemorrhage in the UFH/OA group.. Although limited by small sample size, REVIVE provides valuable information on the incidence of recurrent VTE, major bleeding and problematic issues associated with therapy of VTE in children.

Topics: Administration, Oral; Adolescent; Child; Child, Preschool; Drug Therapy, Combination; Heparin; Heparin, Low-Molecular-Weight; Humans; Infant; International Cooperation; Pulmonary Embolism; Thromboembolism; Thrombolytic Therapy; Treatment Outcome; Venous Thrombosis; Warfarin

The optimal means of achieving therapeutic oral anticoagulation in the outpatient setting has not been determined.. To compare a 10-mg dosing nomogram with a 5-mg nomogram that has been suggested to be sufficient for warfarin initiation.. Randomized, controlled clinical trial.. Outpatient venous thromboembolism services of four tertiary care hospitals.. 201 of 210 consecutive patients with objectively confirmed diagnoses of acute venous thromboembolism.. All patients were treated with subcutaneous low-molecular-weight heparin for a minimum of 5 days until a therapeutic international normalized ratio (INR) was achieved. Patients were randomly assigned to initially receive a 10-mg or 5-mg dose of warfarin.. The primary end point was time in days to therapeutic INR. Secondary end points were the proportion of patients who had achieved a therapeutic INR by day 5, the total number of INR assessments, the number of INR measurements greater than 5.0, incidence of recurrent venous thromboembolism and major bleeding, and survival.. 210 consecutive patients met the inclusion criteria. Of these, 9 were excluded and 201 were randomly assigned to study groups (104 to the 10-mg group and 97 to the 5-mg group). Demographic characteristics of both groups were similar. Patients in the 10-mg group achieved therapeutic INR 1.4 days earlier than patients in the 5-mg group (P < 0.001). Eighty-three percent of patients in the 10-mg group achieved a therapeutic INR by day 5 versus 46% in the 5-mg group (P < 0.001). Fewer INR assessments were performed in the 10-mg group than in the 5-mg group (8.1 vs. 9.1; P = 0.04). There were no significant differences between the two groups in recurrent events, major bleeding, survival, and number of INR measurements greater than 5.0.. The 10-mg warfarin initiation nomogram is superior to the 5-mg nomogram because it allows more rapid achievement of a therapeutic INR.

Topics: Acute Disease; Ambulatory Care; Anticoagulants; Double-Blind Method; Drug Administration Schedule; Female; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Male; Middle Aged; Pulmonary Embolism; Venous Thrombosis; Warfarin

Patients with cancer have a substantial risk of recurrent thrombosis despite the use of oral anticoagulant therapy. We compared the efficacy of a low-molecular-weight heparin with that of an oral anticoagulant agent in preventing recurrent thrombosis in patients with cancer.. Patients with cancer who had acute, symptomatic proximal deep-vein thrombosis, pulmonary embolism, or both were randomly assigned to receive low-molecular-weight heparin (dalteparin) at a dose of 200 IU per kilogram of body weight subcutaneously once daily for five to seven days and a coumarin derivative for six months (target international normalized ratio, 2.5) or dalteparin alone for six months (200 IU per kilogram once daily for one month, followed by a daily dose of approximately 150 IU per kilogram for five months).. During the six-month study period, 27 of 336 patients in the dalteparin group had recurrent venous thromboembolism, as compared with 53 of 336 patients in the oral-anticoagulant group (hazard ratio, 0.48; P=0.002). The probability of recurrent thromboembolism at six months was 17 percent in the oral-anticoagulant group and 9 percent in the dalteparin group. No significant difference between the dalteparin group and the oral-anticoagulant group was detected in the rate of major bleeding (6 percent and 4 percent, respectively) or any bleeding (14 percent and 19 percent, respectively). The mortality rate at six months was 39 percent in the dalteparin group and 41 percent in the oral-anticoagulant group.. In patients with cancer and acute venous thromboembolism, dalteparin was more effective than an oral anticoagulant in reducing the risk of recurrent thromboembolism without increasing the risk of bleeding.

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Dalteparin; Drug Therapy, Combination; Female; Hemorrhage; Humans; Injections, Subcutaneous; Male; Middle Aged; Neoplasms; Pulmonary Embolism; Secondary Prevention; Survival Analysis; Thromboembolism; Venous Thrombosis; Warfarin

This randomized, controlled, multicentre study evaluated the efficacy and tolerability of the oral direct thrombin inhibitor ximelagatran, compared with a low-molecular-weight heparin (dalteparin) followed by warfarin, in the treatment of deep vein thrombosis (DVT) of the lower extremity. Patients with acute DVT received oral ximelagatran (24, 36, 48 or 60 mg twice daily) or dalteparin and warfarin for 2 weeks. Evaluation of paired venograms from 295 of 350 patients showed regression of the thrombus in 69% of patients treated with ximelagatran and 69% of patients treated with dalteparin and warfarin. Progression was observed in 8% and 3% of patients, respectively. Changes in thrombus size according to the Marder score were similar in all groups. Treatment discontinuation due to bleeding occurred in two patients receiving ximelagatran (24- and 36-mg groups) and in two patients receiving dalteparin and warfarin. Reduction in pain, edema and circumference of the affected leg was similar in all groups. Oral ximelagatran appears to be a promising alternative to current anticoagulant therapy to limit the progression of acute DVT, and it seems to possess a wide therapeutic window.

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Azetidines; Benzylamines; Dalteparin; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Leg; Male; Middle Aged; Phlebography; Prodrugs; Radionuclide Imaging; Treatment Outcome; Venous Thrombosis; Warfarin

Warfarin is very effective in preventing recurrent venous thromboembolism but is also associated with a substantial risk of bleeding. After three months of conventional warfarin therapy, a lower dose of anticoagulant medication may result in less bleeding and still prevent recurrent venous thromboembolism.. We conducted a randomized, double-blind study, in which 738 patients who had completed three or more months of warfarin therapy for unprovoked venous thromboembolism were randomly assigned to continue warfarin therapy with a target international normalized ratio (INR) of 2.0 to 3.0 (conventional intensity) or a target INR of 1.5 to 1.9 (low intensity). Patients were followed for an average of 2.4 years.. Of 369 patients assigned to low-intensity therapy, 16 had recurrent venous thromboembolism (1.9 per 100 person-years), as compared with 6 of 369 assigned to conventional-intensity therapy (0.7 per 100 person-years; hazard ratio, 2.8; 95 percent confidence interval, 1.1 to 7.0). A major bleeding episode occurred in nine patients assigned to low-intensity therapy (1.1 events per 100 person-years) and eight patients assigned to conventional-intensity therapy (0.9 event per 100 person-years; hazard ratio, 1.2; 95 percent confidence interval, 0.4 to 3.0). There was no significant difference in the frequency of overall bleeding between the two groups (hazard ratio, 1.3; 95 percent confidence interval, 0.8 to 2.1).. Conventional-intensity warfarin therapy is more effective than low-intensity warfarin therapy for the long-term prevention of recurrent venous thromboembolism. The low-intensity warfarin regimen does not reduce the risk of clinically important bleeding.

Topics: Age Factors; Aged; Anticoagulants; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Pulmonary Embolism; Risk Factors; Secondary Prevention; Treatment Outcome; Venous Thrombosis; Warfarin

Many patients with the antiphospholipid antibody syndrome and recurrent thrombosis receive doses of warfarin adjusted to achieve an international normalized ratio (INR) of more than 3.0. However, there are no prospective data to support this approach to thromboprophylaxis.. We performed a randomized, double-blind trial in which patients with antiphospholipid antibodies and previous thrombosis were assigned to receive enough warfarin to achieve an INR of 2.0 to 3.0 (moderate intensity) or 3.1 to 4.0 (high intensity). Our objective was to show that high-intensity warfarin was more effective in preventing thrombosis than moderate-intensity warfarin.. A total of 114 patients were enrolled in the study and followed for a mean of 2.7 years. Recurrent thrombosis occurred in 6 of 56 patients (10.7 percent) assigned to receive high-intensity warfarin and in 2 of 58 patients (3.4 percent) assigned to receive moderate-intensity warfarin (hazard ratio for the high-intensity group, 3.1; 95 percent confidence interval, 0.6 to 15.0). Major bleeding occurred in three patients assigned to receive high-intensity warfarin and four patients assigned to receive moderate-intensity warfarin (hazard ratio, 1.0; 95 percent confidence interval, 0.2 to 4.8).. High-intensity warfarin was not superior to moderate-intensity warfarin for thromboprophylaxis in patients with antiphospholipid antibodies and previous thrombosis. The low rate of recurrent thrombosis among patients in whom the target INR was 2.0 to 3.0 suggests that moderate-intensity warfarin is appropriate for patients with the antiphospholipid antibody syndrome.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Double-Blind Method; Female; Follow-Up Studies; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Myocardial Infarction; Pulmonary Embolism; Secondary Prevention; Stroke; Venous Thrombosis; Warfarin

In a previous study of the prevention of venous thromboembolism after total knee replacement, the efficacy of ximelagatran, an oral direct thrombin inhibitor that does not require monitoring of coagulation or dose adjustment, was found to be similar to that of warfarin at a dose of 24 mg of ximelagatran twice daily. The purpose of the present study was to determine whether a higher dose of ximelagatran is superior to warfarin.. This randomized, double-blind trial compared a regimen of 7 to 12 days of oral ximelagatran, at a dose of 24 or 36 mg twice daily, starting the morning after surgery, with warfarin therapy started the evening of the day of surgery. The composite end point of venous thromboembolism and death from all causes and the incidence of bleeding were the primary outcome measures.. Among the 1851 patients in the efficacy analysis, oral ximelagatran at a dose of 36 mg twice daily was superior to warfarin with respect to the primary composite end point of venous thromboembolism and death from all causes (20.3 percent vs. 27.6 percent; P=0.003). There were no significant differences between these two groups with respect to major bleeding (incidence, 0.8 percent and 0.7 percent, respectively), perioperative indicators of bleeding, wound characteristics, or the composite secondary end point of proximal deep-vein thrombosis, pulmonary embolism, and death (2.7 percent vs. 4.1 percent; P=0.17).. The efficacy of oral ximelagatran, administered starting the morning after total knee replacement, was superior to that of warfarin for prevention of venous thromboembolism. Rates of hemorrhagic complications with the two drugs were similar.

Topics: Administration, Oral; Aged; Anticoagulants; Arthroplasty, Replacement, Knee; Azetidines; Benzylamines; Double-Blind Method; Drug Administration Schedule; Female; Hemorrhage; Humans; Male; Middle Aged; Prodrugs; Pulmonary Embolism; Thromboembolism; Treatment Outcome; Venous Thrombosis; Warfarin

The optimal duration of thromboprophylaxis after major orthopedic surgery is controversial. Although oral anticoagulants are still widely used for the prevention of venous thromboembolism after hip replacement, to our knowledge no study has assessed the benefit of prolonging anticoagulation beyond the hospital stay.. Consecutive patients who had received warfarin sodium prophylaxis after total hip arthroplasty were randomized to stop taking the drug at the time of hospital discharge or to continue taking it for 4 more weeks. The rate of symptomatic and asymptomatic venous thromboembolic events (as shown by compression ultrasonography of the proximal-vein system) occurring during the study period was compared between the 2 groups. The study was prematurely terminated after the inclusion of the first 360 patients because a statistically significant and clinically relevant superiority of extended over short-term thromboprophylaxis was observed.. Objectively confirmed venous thromboembolic complications were recorded in 10 patients: 9 (5.1%) in the group of 176 control patients, and 1 (0.5%) in the group of 184 patients who continued the warfarin treatment. The absolute difference in the incidence of events was 4.57% (95% confidence interval [CI], 1.15-7.99). The relative risk of venous thromboembolism developing in control patients compared with patients assigned to extended thromboprophylaxis was 9.4 (95% CI, 1.2-73.5). The number needed to treat was 22. Major bleeding developed in 1 patient who was randomized to the extended prophylaxis group (0.5%; 95% CI, 0.02-3.0) compared with none in the control group.. Extending prophylaxis with warfarin for a few more weeks beyond the hospital stay has the potential to considerably improve the outcome of patients who undergo hip arthroplasty.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Female; Follow-Up Studies; Hemorrhage; Humans; International Normalized Ratio; Italy; Male; Middle Aged; Postoperative Complications; Prospective Studies; Time Factors; Treatment Outcome; Venous Thrombosis; Warfarin

One mg daily warfarin was compared to variable dose warfarin (PT 1.3-1.5 times the normal PT), as prophylaxis against deep vein thrombosis (DVT) following unilateral hip replacement for degenerative joint disease (DJD). Ninety-eight patients entered onto study after having had negative color Doppler ultrasounds of the legs. Patients receiving 1 mg began therapy 7 days preoperatively and continued daily until discharge. Patients receiving the variable dose took 5 mg the night preoperatively, and thereafter daily based upon the daily PT. Seventy-eight patients completed the study protocol. No patient completing the protocol had DVT or pulmonary embolus (PE). Based upon intent to treat for all registered patients, one from each group had DVT after withdrawal from study. For patients receiving 1 mg warfarin daily, PTs extended none or slightly. Therefore, 1 mg warfarin can be used to prevent postoperative DVT following elective hip surgery.

Topics: Adult; Aged; Aged, 80 and over; Arthroplasty, Replacement, Hip; Blood Loss, Surgical; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Prothrombin Time; Treatment Outcome; Ultrasonography, Doppler, Duplex; Venous Thrombosis; Warfarin

Warfarin is used for prophylaxis of venous thromboembolism in patients undergoing total knee arthroplasty. However, it is associated with rates of deep venous thrombosis (DVT) of approximately 38% to 55% and requires routine coagulation monitoring and frequent dose adjustment. Ximelagatran, an oral direct thrombin inhibitor, has shown promising efficacy and tolerability in patients undergoing total hip or knee arthroplasty.. To compare the efficacy and safety of ximelagatran and warfarin for prophylaxis of venous thromboembolism after total knee arthroplasty.. Randomized, double-blind, parallel-group trial.. 74 North American hospitals.. 680 patients who had undergone total knee arthroplasty.. 7 to 12 days of treatment with oral ximelagatran, 24 mg twice daily, starting on the morning after surgery, or warfarin (target international normalized ratio, 2.5 [range, 1.8 to 3.0]), starting on the evening of the day of surgery.. Principal end points were asymptomatic DVT on mandatory venography; symptomatic DVT confirmed by ultrasonography or venography; symptomatic, objectively proven pulmonary embolism; and bleeding. All were assessed by blinded adjudication locally and at a central study laboratory.. On central adjudication, incidence of venous thromboembolism was 19.2% (53 of 276 patients) in the ximelagatran group and 25.7% (67 of 261 patients) in the warfarin group (difference, -6.5 percentage points [95% CI, -13.5 to 0.6 percentage points]; P = 0.070). On local assessment, incidence was 25.4% in the ximelagatran group and 33.5% in the warfarin group (P = 0.043). In the ximelagatran and warfarin groups, respectively, major bleeding occurred in 1.7% and 0.9% of patients and minor bleeding occurred in 7.8% and 6.4% of patients. No variables related to bleeding differed significantly between the two groups.. For prophylaxis of venous thromboembolism, fixed-dose ximelagatran started the morning after total knee arthroplasty is well tolerated and at least as effective as warfarin, but it does not require coagulation monitoring or dose adjustment.

Topics: Administration, Oral; Aged; Anticoagulants; Arthroplasty, Replacement, Knee; Azetidines; Benzylamines; Double-Blind Method; Female; Hemorrhage; Humans; Male; Phlebography; Thrombin; Venous Thrombosis; Warfarin

Venous thromboembolic diseases are treated initially with low molecular weight heparin followed by oral coumarins.. To investigate an orally available direct thrombin inhibitor for the acute treatment of venous thromboembolism as well as for prophylaxis of recurrent events.. The direct thrombin inhibitor ximelagatran was compared with subcutaneous LMW heparins followed by oral warfarin in a double-blind randomized prospective multicenter trial in patients with acute VTE. A pharmacokinetic study was performed in the VTE patients. For assessing the prevention of recurrent VTE, double-blind prospective randomized studies were conducted as follows: a) ximelagatran compared to warfarin for 6 months, and b) prolonged anticoagulation of ximelagatran vs. placebo for 18 months after termination of 6 months coumarin therapy.. Two dose-finding studies and the pharmacokinetic analysis of ximelagatran in acute VTE were completed. About 2,500 patients were randomized to investigate 2 x 36 mg ximelagatran versus 2 x 1 mg/kg body weight enoxaparin followed by warfarin. The study hypothesized that the efficacy was equal in both treatment regimens for recurrent VTE documented by objective methods. The second study, with 1,234 patients, aimed to demonstrate a reduced incidence of recurrent thromboembolic events documented by objective methods after 18 months of treatment with 2 x 24 mg ximelagatran daily compared to placebo.. These large-scale clinical trials will soon yield the results of the comparison between oral ximelagatran and subcutaneous LMW heparin for treatment of acute VTE, and of warfarin for prophylaxis of recurrent events for 6 months and for a prolonged prophylaxis for another 18 months.

Topics: Administration, Oral; Anticoagulants; Azetidines; Benzylamines; Double-Blind Method; Drug Administration Schedule; Heparin, Low-Molecular-Weight; Humans; Injections, Subcutaneous; Venous Thrombosis; Warfarin

Patients undergoing rehabilitation after thromboembolic stroke have a relatively high incidence of venous thromboembolism (VTE). Warfarin, with a target international normalized ratio (INR) of 2.0-3.0 is effective for the prevention of VTE. However, because stroke is a major risk factor for bleeding with warfarin, a less intense regimen (target INR < 2.0), might safely prevent VTE in stroke rehabilitation patients.. This study was a randomized, double-blind, placebo-controlled trial of 2 mg of warfarin in patients undergoing rehabilitation following completed stroke. The major efficacy endpoint was symptomatic, objectively proven VTE or asymptomatic VTE detected by monthly duplex ultrasonography (DU) of the proximal leg veins or mandatory bilateral contrast venography performed at the end of the study. The major safety endpoint was bleeding.. There were 475 patients screened for enrollment, 355 had one or more exclusion criterion, and 17 had previously undetected proximal DVT on admission. Of the 103 eligible and consenting patients, 56 received warfarin and 47 received placebo. Of the randomized patients, 88 had successful venography (47 warfarin and 41 placebo). In the warfarin group, three (8%) patients had DVT and one (2%) had proximal DVT whereas in the placebo group, seven (20%) had DVT and five (13%) had proximal DVT. The risk ratio for any DVT in warfarin-treated patients relative to placebo-treated patients was 0.39 (95% confidence interval (CI), 0.13-1.37). For proximal DVT, the risk ratio was 0.17 (95% CI, 0.01-1.4). No patients suffered major bleeding.. A fixed dose of 2 mg of warfarin per day in patients undergoing stroke rehabilitation is safe and associated with a relative risk reduction of about 80% in the incidence of proximal DVT and 60% in overall DVT.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Double-Blind Method; Female; Humans; International Normalized Ratio; Male; Middle Aged; Phlebography; Stroke Rehabilitation; Treatment Outcome; Venous Thrombosis; Warfarin

To compare conventional treatment (heparin and warfarin) of iliofemoral venous thrombosis with multimodality treatment (lysis and stenting).. Several studies have reported on conventional therapy for iliofemoral venous thrombosis with disappointing results. However, more recent studies have reported better results with multimodality treatment.. Fifty-one consecutive patients with extensive iliofemoral venous thrombosis were treated during a 10-year period. If there were no contraindications, patients were given the option to choose between conventional therapy (group 1) and multimodality therapy (group 2). The multimodality treatment strategy included catheter-directed lysis followed by percutaneous transluminal balloon angioplasty (PTA) and stenting for residual iliac stenoses. All patients underwent routine venous duplex imaging at 30 days, 3 months, 6 months, and every 6 months thereafter.. There were 33 patients in group 1 and 18 patients in group 2. Demographic and clinical characteristics were comparable for both groups. Initial lysis was achieved in 16 of 18 patients (89%) in group 2. Ten of 18 patients in group 2 had residual stenosis after lysis (8 primary and 2 secondary to malignancy), and they were treated with PTA/stenting with an initial success rate of 90%. Two patients in group 1 (6%) had a symptomatic pulmonary embolism (none in group 2). At 30 days, venous patency and symptom resolution were achieved in 1 of 33 patients (3%) in group 1 versus 15 of 18 (83%) in group 2. Kaplan-Meier analysis showed primary iliofemoral venous patency rates at 1, 3, and 5 years of 24%, 18%, and 18% and 83%, 69%, and 69% for groups 1 and 2, respectively. Long-term symptom resolution was achieved in 10 of 33 patients (30%) in group 1 versus 14 of 18 (78%) in group 2. Kaplan-Meier life table analysis showed similar survival rates at 1, 3, and 5 years of 100%, 93%, and 85% for group 1 and 100%, 93%, and 81% for group 2.. Lysis/stenting treatment was more effective than conventional treatment in patients with iliofemoral vein thrombosis.

Topics: Angioplasty, Balloon; Anticoagulants; Combined Modality Therapy; Femoral Vein; Fibrinolytic Agents; Follow-Up Studies; Heparin; Humans; Iliac Vein; Risk Factors; Stents; Survival Analysis; Time Factors; Vascular Patency; Venous Thrombosis; Warfarin

Patients treated with total knee arthroplasty are at high risk for the development of venous thromboembolism postoperatively. This study compared the efficacy and safety of two common thromboprophylactic agents, enoxaparin (a low-molecular-weight heparin) and warfarin.. Three hundred and forty-nine patients were included in a prospective, randomized, multicenter, open-label, parallel-group clinical trial. Treatment with enoxaparin (30 mg, administered subcutaneously twice daily) or warfarin (adjusted to an international normalized ratio of 2 to 3) was initiated during the immediate postoperative period, within eight hours after the surgery, and was continued for four to fourteen days. Venous thromboembolism was defined as deep-vein thrombosis documented by contrast venography, symptomatic deep-vein thrombosis documented by lower-extremity ultrasonography, or symptomatic pulmonary embolism confirmed by a positive lung scan or pulmonary angiography.. In the all-treated-patients group, eighty (45%) of the 176 warfarin-treated patients had venous thromboembolism: fifty-nine (34%) had distal deep-vein thrombosis; twenty (11%), proximal deep-vein thrombosis; and one (0.6%), pulmonary embolism. Venous thromboembolism developed in significantly fewer (p = 0.0001) enoxaparin-treated patients (forty-four of 173; 25%): forty-one (24%) had distal deep-vein thrombosis, three (2%) had proximal deep-vein thrombosis, and none had pulmonary embolism. The enoxaparin-treated patients also had a significantly lower prevalence of proximal deep-vein thrombosis (p = 0.002). The estimated odds for the development of venous thromboembolism were 2.52 times greater (95% confidence interval, 2.00 to 3.19) with warfarin than they were with enoxaparin. Major hemorrhage occurred in four warfarin-treated patients and nine enoxaparin-treated patients; with the numbers available, this difference was not significant (p = 0.17). Clinically important operative-site hemorrhage occurred in six (3%) of the warfarin-treated patients and twelve (7%) of the enoxaparin-treated patients (p = 0.15).. A fixed 30-mg subcutaneous dose of enoxaparin, administered twice daily, with the first dose administered within eight hours after the completion of surgery, was significantly more effective than adjusted-dose warfarin in reducing the occurrence of asymptomatic venous thromboembolism, including proximal deep-vein thrombosis, in patients undergoing total knee arthroplasty. With the numbers available, there was no significant difference between groups with regard to the occurrence of major hemorrhagic complications; however, the rate of overall hemorrhagic complications was higher in the enoxaparin group.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Knee; Enoxaparin; Female; Hemorrhage; Humans; Male; Middle Aged; Postoperative Complications; Prospective Studies; Pulmonary Embolism; Treatment Outcome; Venous Thrombosis; Warfarin

In patients with idiopathic deep venous thrombosis, continuing anticoagulant therapy beyond three months is associated with a reduced incidence of recurrent thrombosis during the period of therapy. Whether this benefit persists after anticoagulant therapy is discontinued is controversial.. Patients with a first episode of idiopathic proximal deep venous thrombosis who had completed three months of oral anticoagulant therapy (with warfarin, in 97 percent of the cases and acenocoumarol in 3 percent) were randomly assigned to the discontinuation of oral anticoagulants or to their continuation for nine additional months. The primary study outcome was recurrence of symptomatic, objectively confirmed venous thromboembolism during at least two years of follow-up.. The primary intention-to-treat analysis showed that of 134 patients assigned to continued oral anticoagulant therapy, 21 had a recurrence of venous thromboembolism (15.7 percent; average follow-up, 37.8 months), as compared with 21 of 133 patients assigned to the discontinuation of oral anticoagulant therapy (15.8 percent; average follow-up, 37.2 months), resulting in a relative risk of 0.99 (95 percent confidence interval, 0.57 to 1.73). During the initial nine months after randomization (after all patients received three months of therapy), 1 patient had a recurrence while receiving oral anticoagulant therapy (0.7 percent), as compared with 11 of the patients assigned to the discontinuation of oral anticoagulant therapy (8.3 percent; P=0.003). The incidence of recurrence after the discontinuation of treatment was 5.1 percent per patient-year in patients in whom oral anticoagulant therapy was discontinued after 3 months (95 percent confidence interval, 3.2 to 7.5 percent; average interval since discontinuation, 37.2 months) and 5.0 percent per patient-year in patients who received an additional 9 months of oral anticoagulant therapy (95 percent confidence interval, 3.1 to 7.8 percent; average interval since discontinuation, 29.4 months). None of the recurrences were fatal. Four patients had non-fatal major bleeding during the extended period of anticoagulant therapy (3.0 percent).. In patients with idiopathic deep venous thrombosis, the clinical benefit associated with extending the duration of anticoagulant therapy to one year is not maintained after the therapy is discontinued.

Topics: Acenocoumarol; Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Humans; International Normalized Ratio; Middle Aged; Recurrence; Time Factors; Treatment Outcome; Venous Thrombosis; Warfarin

The role of ultrasound screening for proximal deep-vein thrombosis (DVT) following major hip surgery is controversial. 202 consecutive patients, who had received warfarin prophylaxis after total hip arthroplasty underwent a bilateral ultrasound assessment of the proximal vein system (using the criterion of vein compressibility) before hospital discharge. In the 9 patients (4.5%; 95% CI, 2.1-8.3%) with positive test anticoagulant treatment was successfully continued for three months. In all the remaining 193 patients the warfarin treatment was withdrawn. A second ultrasound test was performed 15 days later, and showed a new (asymptomatic) abnormality compatible with proximal DVT in 2 patients (1.0%; 95% CI, 0.1-3.7%). All other 191 patients remained asymptomatic until the completion of a 3-month follow-up period (rate of symptomatic thromboembolism, 0/191, 0%; 95% CI, 0-1.9%). Because of the relatively high incidence of proximal DVT in patients undergoing major orthopaedic surgery under warfarin prophylaxis, screening for proximal DVT at hospital discharge in these patients is indicated. The negativity of this test has the potential of safely preventing the extension of anticoagulation beyond hospital stay. A larger controlled study in which the value of this strategy is tested against the prolongation of oral anticoagulation in patients with a negative ultrasound screening at discharge is indicated.

Topics: Aged; Aged, 80 and over; Arthroplasty, Replacement, Hip; Cohort Studies; Drug Monitoring; Female; Follow-Up Studies; Humans; Incidence; International Normalized Ratio; Male; Mass Screening; Middle Aged; Prospective Studies; Ultrasonography; Venous Thrombosis; Warfarin

Widespread use of adjusted low-dose warfarin has been limited by the inconvenience of outpatient laboratory monitoring and the perceived risk of bleeding complications. We sought to determine if the dose of warfarin could be lowered safely even further, eliminating the need for laboratory monitoring and lowering the complication rate. Two hundred forty-five Patients undergoing primary total joint arthroplasty (n = 245) were randomized prospectively to adjusted low-dose warfarin (international normalized ratio [INR], 1.4-1.8) or fixed minidose warfarin (2 mg daily, regardless of INR) before hospital discharge. Prophylaxis continued for 6 weeks, with twice-weekly laboratory monitoring. Patients were followed for bleeding, thromboembolic events, and minor reported complications of warfarin therapy. With the numbers available, the rates of thromboembolic and bleeding events were not significantly different using equivalence analysis. Of patients in the fixed group, 8% had INRs >3.1, necessitating a decrease in dosage to 1 mg. Although such a fixed-dose protocol may simplify outpatient prophylaxis, intermittent monitoring still would be required because a subset of patients achieve a moderate level of anticoagulation and would be at risk for bleeding complications.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement; Chi-Square Distribution; Female; Humans; International Normalized Ratio; Male; Middle Aged; Postoperative Complications; Prospective Studies; Prothrombin Time; Pulmonary Embolism; Treatment Outcome; Venous Thrombosis; Warfarin

The purpose of this study was to establish the safety and efficacy of sodium warfarin in the secondary prophylaxis of venous thrombosis in patients with cancer. This was an inception cohort study of patients enrolled in an anticoagulation clinic between July 1991 and October 1996. The rates of bleeding and recurrent thrombosis were evaluated in all the patients, and the results in patients with cancer (n = 104) were compared with those without cancer (n = 208). The rate of major hemorrhage was 0.4% and 0.3% per treatment month in the patients with cancer and those without cancer, respectively. The rates of recurrent thrombosis were 1.2% and 0.2% per treatment month in the patients with cancer compared with those without cancer, respectively. We conclude that warfarin is safe when used for the secondary prophylaxis of patients with cancer who have had a venous or arterial thrombosis, and the risk of major hemorrhage is not significantly different when compared with the risk in patients without cancer. The rate of recurrent thrombosis is approximately sixfold higher in patients with cancer being treated with warfarin for secondary prophylaxis of thrombosis compared with patients without cancer. Nonetheless, the rate of recurrent thrombosis is not overly excessive, and warfarin can be viewed as a relatively effective form of therapy for these patients.

Topics: Anticoagulants; Female; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Venous Thrombosis; Warfarin

The length of time after an episode of venous thromboembolism during which the risk of newly diagnosed cancer is increased is not known, and whether vitamin K antagonists have an antineoplastic effect is controversial.. In a prospective, randomized study of the duration of oral anticoagulation (six weeks or six months) after a first episode of venous thromboembolism, patients were questioned annually about any newly diagnosed cancer. After a mean follow-up of 8.1 years, we used the Swedish Cancer Registry to identify all diagnoses of cancer and causes of death in the study population. The observed numbers of cases of cancer were compared with expected numbers based on national incidence rates, and the standardized incidence ratios were calculated.. A first cancer was diagnosed in 111 of 854 patients (13.0 percent) during follow-up. The standardized incidence ratio for newly diagnosed cancer was 3.4 (95 percent confidence interval, 2.2 to 4.6) during the first year after the thromboembolic event and remained between 1.3 and 2.2 for the following five years. Cancer was diagnosed in 66 of 419 patients (15.8 percent) who were treated for six weeks with oral anticoagulants, as compared with 45 of 435 patients (10.3 percent) who were treated for six months (odds ratio, 1.6; 95 percent confidence interval, 1.1 to 2.4). The difference was mainly due to the occurrence of new urogenital cancers, of which there were 28 cases in the six-week group (6.7 percent) and 12 cases in the six-month group (2.8 percent) (odds ratio, 2.5; 95 percent confidence interval, 1.3 to 5.0). The difference in the incidence of cancer between the treatment groups became evident only after two years of follow-up, and it remained significant after adjustment for sex, age, and whether the thromboembolism was idiopathic or nonidiopathic. Older age at the time of the venous thrombosis and an idiopathic thromboembolism were also independent risk factors for a diagnosis of cancer. No difference in the incidence of cancer-related deaths was detected.. The risk of newly diagnosed cancer after a first episode of venous thromboembolism is elevated during at least the following two years. Subsequently, the risk seems to be lower among patients treated with oral anticoagulants for six months than among those treated for six weeks.

Topics: Administration, Oral; Age Factors; Anticoagulants; Drug Administration Schedule; Humans; Incidence; Neoplasms; Prospective Studies; Pulmonary Embolism; Retrospective Studies; Risk Factors; Thromboembolism; Time Factors; Urogenital Neoplasms; Venous Thrombosis; Vitamin K; Warfarin

Based on the current understanding that venous thrombosis starts perioperatively, administration of just-in-time low-molecular-weight heparin immediately before or in close proximity after hip arthroplasty may be more effective than usual clinical practice.. We performed a randomized, double-blind trial comparing subcutaneous dalteparin sodium given once daily immediately before or early after surgery with the use of postoperative warfarin sodium in 1472 patients undergoing elective hip arthroplasties. The primary end point was deep vein thrombosis detected using contrast venography performed after surgery (mean, 5. 7 days) in each group.. The frequencies of deep vein thrombosis for patients with interpretable venograms receiving preoperative and postoperative dalteparin for all deep vein thrombosis were 36 (10.7%) of 337 (P<.001) and 44 (13.1%) of 336 (P<.001), respectively, vs 81 (24.0%) of 338 for warfarin; for proximal deep vein thrombosis, 3 (0.8%) of 354 (P =.04) and 3 (0.8%) of 358 (P =.03), respectively, vs 11 (3.0%) of 363. Relative risk reductions for the dalteparin groups ranged from 45% to 72%. Symptomatic thrombi were less frequent in the preoperative dalteparin group (5/337 patients [1.5%]) vs the warfarin group (15/338 patients [4.4%]) (P =.02). Serious bleeding was similar among groups. Increased major bleeding at the surgical site was observed for patients receiving preoperative dalteparin vs warfarin (P =.01).. A modified dalteparin regimen in close proximity to surgery resulted in substantive risk reductions for all and proximal deep vein thrombosis, compared with warfarin therapy. Such findings have not been observed with low-molecular-weight heparin therapy commenced 12 hours preoperatively or 12 to 24 hours postoperatively vs oral anticoagulants. Increased major but not serious bleeding occurred in patients receiving preoperative dalteparin. Dalteparin therapy initiated postoperatively provided superior efficacy vs warfarin without significantly increased overt bleeding.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Dalteparin; Double-Blind Method; Humans; Injections, Subcutaneous; Middle Aged; Phlebography; Postoperative Care; Preoperative Care; Prognosis; Prothrombin Time; Venous Thrombosis; Warfarin

No randomized trials have directly evaluated the need for extended out-of-hospital thromboprophylaxis for patients who have hip arthroplasty in the United States or Canada. The uncertainty as to the need for extended prophylaxis in North American patients is complicated by early hospital discharge, resulting in a short thromboprophylaxis interval.. To resolve this uncertainty, we performed a randomized double-blind trial in 569 patients who underwent hip arthroplasty comparing the use of dalteparin sodium started immediately before surgery or early after surgery and extended out-of-hospital to an overall interval of 35 days with the use of warfarin sodium in-hospital and placebo out-of-hospital.. For patients with interpretable venograms in the preoperative, postoperative, and combined dalteparin groups, new proximal vein thrombosis out-of-hospital was observed in 1.3%, 0. 7% (P =.04), and 1.0% (P =.02) of patients, respectively, compared with 4.8% in the in-hospital warfarin/out-of-hospital placebo group. The respective overall cumulative frequencies of all deep vein thrombosis were 30 (17.2%) of 174 patients (P<.001), 38 (22.2%) of 171 (P =.003), and 68 (19.7%) of 345 (P<.001) in the dalteparin groups compared with 69 (36.7%) of 188 for the in-hospital warfarin/out-of-hospital placebo group. For proximal deep vein thrombosis, the respective frequencies were 5 (3.1%) of 162 (P =.02), 3 (2.0%) of 151 (P =.007), and 8 (2.6%) of 313 (P =.002) compared with 14 (9.2%) of 153. No major bleeding occurred during the extended prophylaxis interval.. Extended dalteparin prophylaxis resulted in significantly lower frequencies of deep vein thrombosis compared with in-hospital warfarin therapy. Despite in-hospital thromboprophylaxis, patients having hip arthroplasty in the United States and Canada remain at moderate risk out-of-hospital. The number needed to treat provides a public health focus; only 24 to 28 patients require extended prophylaxis to prevent 1 new out-of-hospital proximal vein thrombosis. Recent studies demonstrate that asymptomatic deep vein thrombi cause the postphlebitic syndrome; thus, extended out-of-hospital prophylaxis will lessen the burden to both the patient and society.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Canada; Dalteparin; Double-Blind Method; Humans; Incidence; Injections, Subcutaneous; Inpatients; Middle Aged; Outpatients; Phlebography; Postoperative Care; Preoperative Care; United States; Venous Thrombosis; Warfarin

Warfarin is effective in the treatment and prevention of many venous thromboembolic disorders, but it often leads to bleeding.. To develop a multicomponent program of management of warfarin therapy and to determine its effect on the frequency of warfarin-related major bleeding in older patients.. Randomized, controlled trial.. University hospital in Cleveland, Ohio.. 325 patients 65 years of age or older who started warfarin therapy during hospitalization.. Patients were stratified according to baseline risk for major bleeding and were randomly assigned to receive the intervention (n = 163) or usual care (n = 162) by their primary physicians for 6 months. The intervention consisted of patient education about warfarin, training to increase patient participation, self-monitoring of prothrombin time, and guideline-based management of warfarin dosing.. Major bleeding, death, recurrent venous thromboembolism, and therapeutic control of anticoagulant therapy at 6 months.. In an intention-to-treat analysis, major bleeding was more common at 6 months in the usual care group than in the intervention group (cumulative incidence, 12% vs. 5.6%; P = 0.0498, log-rank test). The most frequent site of major bleeding in both groups was the gastrointestinal tract. Death and recurrent venous thromboembolism occurred with similar frequency in both groups at 6 months. Throughout 6 months, the proportion of total treatment time during which the international normalized ratio was within the therapeutic range was higher in the intervention group than in the usual care group (56% vs. 32%; P < 0.001). After 6 months, major bleeding occurred with similar frequencies in the intervention and usual care groups.. A multicomponent comprehensive program of warfarin management reduced the frequency of major bleeding in older patients. Although the generalizability and cost-effectiveness of this program remain to be demonstrated, these findings support the premise that efforts to reduce the likelihood of major bleeding will lead to safe and effective use of warfarin therapy in older patients.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Double-Blind Method; Drug Monitoring; Female; Hemorrhage; Humans; Male; Patient Care Planning; Patient Education as Topic; Prothrombin Time; Recurrence; Self Care; Venous Thrombosis; Warfarin

It is well-known that peri-operative and post-operative venous thrombosis are common. Trials in Europe have shown that extended out-of-hospital prophylaxis with a low-molecular-weight heparin reduces the rate of deep vein thrombosis in patients undergoing elective hip surgery. North American investigators of limited-outcome descriptive studies, however, have suggested that out-of-hospital prophylaxis is not necessary. To resolve this uncertainty, NAFT (North American Fragmin Trial) was conducted, the results of which are summarized in this paper. The findings of NAFT support the favourable findings of the European studies on extended prophylaxis. Furthermore, European data have shown extended out-of-hospital prophylaxis to be cost-effective. On the basis of the aggregate data, it is felt that the A2 recommendation made by the Fifth American College of Chest Physicians consensus conference for extended prophylaxis should be changed to an A1 recommendation.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Cost-Benefit Analysis; Dalteparin; Decision Making; Double-Blind Method; Drug Administration Schedule; Drug Costs; Elective Surgical Procedures; Follow-Up Studies; Hematoma; Humans; North America; Postoperative Complications; Postoperative Period; Practice Guidelines as Topic; Safety; Treatment Outcome; Venous Thrombosis; Warfarin

Patients who have a first episode of venous thromboembolism in the absence of known risk factors for thrombosis (idiopathic thrombosis) are often treated with anticoagulant therapy for three months. Such patients may benefit from longer treatment, however, because they appear to have an increased risk of recurrence after anticoagulant therapy is stopped.. In this double-blind study, we randomly assigned patients who had completed 3 months of anticoagulant therapy for a first episode of idiopathic venous thromboembolism to continue receiving warfarin, with the dose adjusted to achieve an international normalized ratio of 2.0 to 3.0, or to receive placebo for a further 24 months. Our goal was to determine the effects of extended anticoagulant therapy on rates of recurrent symptomatic venous thromboembolism and bleeding.. A prespecified interim analysis of efficacy led to the early termination of the trial after 162 patients had been enrolled and followed for an average of 10 months. Of 83 patients assigned to continue to receive placebo, 17 had a recurrent episode of venous thromboembolism (27.4 percent per patient-year), as compared with 1 of 79 patients assigned to receive warfarin (1.3 percent per patient-year, P<0.001). Warfarin resulted in a 95 percent reduction in the risk of recurrent venous thromboembolism (95 percent confidence interval, 63 to 99 percent). Three patients assigned to the warfarin group had nonfatal major bleeding (two had gastrointestinal bleeding and one genitourinary bleeding), as compared with none of those assigned to the placebo group (3.8 vs. 0 percent per patient-year, P=0.09).. Patients with a first episode of idiopathic venous thromboembolism should be treated with anticoagulant agents for longer than three months.

Topics: Anticoagulants; Double-Blind Method; Drug Administration Schedule; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Multivariate Analysis; Probability; Pulmonary Embolism; Risk Factors; Secondary Prevention; Thromboembolism; Venous Thrombosis; Warfarin

The purpose of this study was to assess the rate of deep vein thrombosis (DVT) resolution and DVT outcomes as functions of the level of oral anticoagulation therapy achieved with warfarin.. In 33 consecutive patients, a series of 35 limbs with acute symptomatic DVT was followed throughout 1 year of anticoagulation therapy. All the patients underwent 5 days of intravenous unfractionated sodium heparin therapy that was adjusted in dose to prolong the activated thromboplastin time to 2.0 to 2.5 times the control. In addition, warfarin was administered for a period of 6 months, with a target international normalized ratio (INR) between 2.0 and 3.0. All the patients underwent venous duplex scanning and physical examination at the time of diagnosis and at 1 week, 1 month, 3 months, 6 months, and 1 year.. At the end of the 1-year study period, the rate of complete DVT resolution was 68%. The median INR values in patients with complete DVT resolution were significantly higher than those of patients with incomplete DVT resolution after 1, 3, and 6 months of treatment with warfarin. In addition, the proportion of patients with INR values below therapeutic range was significantly higher in patients with incomplete DVT resolution than in patients with complete DVT resolution after 1, 3, and 6 months of treatment with warfarin. The presence of occlusive thrombi was associated with incomplete DVT resolution. Of the patients with occlusive thrombi, 62% had chronic venous insufficiency symptoms develop, whereas only 11% of the patients with nonocclusive thrombi (P =.003) had these symptoms develop.. Despite 6 months of oral anticoagulant therapy, almost one third of thrombi did not resolve completely. The INR values were significantly higher in those patients with complete DVT resolution. These results suggest that the maintenance of an INR level between 2.0 and 3.0 throughout oral anticoagulation therapy will minimize the rate of incomplete DVT resolution.

Topics: Administration, Oral; Aged; Anticoagulants; Female; Follow-Up Studies; Humans; Male; Middle Aged; Partial Thromboplastin Time; Prospective Studies; Prothrombin Time; Time Factors; Ultrasonography, Doppler, Pulsed; Venous Thrombosis; Warfarin

The purpose of this study was to assess the rate of postoperative deep vein thrombosis (DVT) as a function of oral anticoagulation therapy after total hip replacement surgery.. A total of 125 patients completed the study. All the patients received sequential gradient pneumatic compression over elastic stockings until hospital discharge. In addition, all the patients underwent postoperative heparin therapy followed by oral warfarin therapy, adjusted in dose to maintain a goal international normalized ratio (INR) level of 2.0 to 3.0. Warfarin therapy and compression stockings were continued for 1 month after surgery. Bilateral duplex scanning was performed 1 and 4 weeks after surgery to assess the rate of DVT.. Nineteen of the 125 patients had DVT develop (15.2%). Of those thromboses, six (31.6%) and 13 (68%) were detected 1 week and 1 month after surgery, respectively. The rate of proximal DVT was 2.4% (3 of 125) 1 week after surgery and rose to 8.2% (10 of 122) 1 month after surgery. Most DVT cases (64%; 12 of 19) were asymptomatic. The patients in whom DVT developed had significantly lower INR values during the second to fourth postoperative weeks than did those patients without thrombosis, and no differences in INR values were found during the first postoperative week.. The risk of the development of DVT extends beyond hospital discharge in patients who undergo total hip replacement, despite a regimen of prolonged oral anticoagulation therapy. This is particularly true in patients whose INR values did not reach therapeutic range during the first postoperative month. Therefore, thrombosis prophylaxis regimens on the basis of the administration of warfarin should try to maintain INR values within therapeutic range during the entire first postoperative month to minimize the incidence of DVT.

Topics: Administration, Oral; Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Bandages; Case-Control Studies; Female; Humans; Male; Postoperative Care; Postoperative Complications; Postoperative Period; Time Factors; Ultrasonography, Doppler, Duplex; Venous Thrombosis; Warfarin

We conducted a prospective cohort study to evaluate clinical and economic end points achieved by a pharmacist-managed anticoagulation service compared with usual care (50 patients/group). The primary therapeutic end point was the time between starting heparin therapy and surpassing the activated partial thromboplastin time therapeutic threshold. The primary economic end point was the direct variable cost of hospitalization from admission to discharge. No significant differences between groups were noted for the primary therapeutic end point. Total hospital costs were significantly lower for patients receiving pharmacist-managed care than for those receiving usual care ($1594 and $2014, respectively, 1997 dollars, p=0.04). Earlier start of warfarin (p=0.05) and shorter hospital stay (5 and 7 days, p=0.05) were associated with the pharmacist-managed group.

Topics: Anticoagulants; Cohort Studies; Female; Heparin; Hospital Costs; Humans; Length of Stay; Male; Middle Aged; Partial Thromboplastin Time; Pharmacy Service, Hospital; Pulmonary Embolism; Time Factors; Venous Thrombosis; Warfarin

The long-term risk for recurrent deep venous thrombosis (DVT) and the incidence of post-thrombotic syndrome (PTS) after long-term anticoagulation (LTA) therapy have been widely debated. In this study, we compare the results of short-term anticoagulation therapy versus conventional LTA therapy in patients with DVT of the lower extremity.. Baseline assessments of DVT symptoms and risk factors were recorded in 105 patients. Diagnosis was made using duplex ultrasound/venography. Patients were sequentially assigned to 1 of the following treatment protocols: (A) conventional LTA therapy, which included initial intravenous standard heparin followed by warfarin on days 3 to 5 and was continued for 3 months for patients without pulmonary embolism (PE); or (B) short-term therapy, which included the same heparin therapy followed by warfarin on days 2 to 3 and was continued for 6 weeks only. Clinical and duplex ultrasound follow-up was done at 6 weeks, 3 and 6 months, and every 6 months thereafter.. Risk factors, location of DVT, and mean age of the 2 groups were comparable. Mean follow-up was 59 months. There were 4 immediate major complications in patients of group A (4 of 54 [7%]; 2 PEs and 2 significant bleeds) and 3 in patients of group B (3 of 51 [6%]; 1 PE and 2 bleeds). On long-term follow-up, 18 of 43 (42%) patients in group A and 20 of 44 (46%) patients in group B had PTS. Similarly, 10 of 43 (23%) patients in group A and 9 of 44 (20%) patients in group B had 1 or more recurrent thromboembolic events (not statistically significant). A significant difference was demonstrated only in patients with cancer; LTA was favored in reducing recurrent DVT and PTS. Two other patients in group A had late significant complications secondary to warfarin (hemorrhage in 1 and coumadin necrosis in the other), with no complications in group B. The mean number of days of hospitalization were fewer for patients in group B (5 versus 8 days), which is mainly due to earlier initiation of warfarin therapy for group B.. In this study of our local population, we observed that short-term anticoagulation therapy was as effective as LTA therapy and less costly for use in most patients. It may also carry less risk of long-term warfarin complications, such as bleeding or skin necrosis.

Topics: Anticoagulants; Drug Therapy, Combination; Follow-Up Studies; Heparin; Humans; Leg; Middle Aged; Prospective Studies; Recurrence; Risk Factors; Time Factors; Treatment Outcome; Venous Thrombosis; Warfarin

Orgaran (danaparoid sodium injection) is a novel antithrombotic agent. Early studies suggest that this compound may be beneficial in preventing deep vein thrombosis in predisposed patients. This multicenter, randomized, assessor blinded, clinical trial compared subcutaneous danaparoid with warfarin for the prevention of deep vein thrombosis in patients undergoing hip replacement surgery. Bilateral venography was used to detect thrombi. Patients also underwent follow-up examinations 1, 2, and 3 months after discontinuation of the study to determine the after effects of treatment. Nearly 27% of patients who received warfarin and 14.6% of patients who received danaparoid developed deep vein thrombosis, a risk reduction of 46%. The absolute difference in the incidence of deep vein thrombosis was 12.3% in favor of danaparoid. The incidence of venographically documented proximal deep vein thrombosis was 1.5% for danaparoid and 4.1% for warfarin. These results demonstrate that danaparoid is more effective than warfarin in preventing deep vein thrombosis following hip replacement surgery. The preoperative administration of danaparoid does not increase surgical blood loss compared with warfarin.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Blood Loss, Surgical; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Female; Heparitin Sulfate; Humans; Male; Middle Aged; Postoperative Complications; Single-Blind Method; Treatment Outcome; Venous Thrombosis; Warfarin

Ardeparin sodium has recently received approval by the Food and Drug Administration for prophylaxis against venous thromboembolism in patients undergoing elective total knee replacement. However, this low-molecular-weight heparin has not been previously evaluated in a randomized controlled trial for treatment of established acute deep venous thrombosis.. The study included patients with ultrasound-documented acute symptomatic deep venous thrombosis of the legs. They had to be deemed appropriate for discharge home to receive subcutaneous low-molecular-weight heparin. Patients were randomized to receive ardeparin with a 2-day hospitalization or unfractionated heparin sodium with a 5-day hospitalization. Both groups received warfarin sodium. Follow-up ultrasound examinations were undertaken at 6 weeks.. Of the 80 patients enrolled, 75 had follow-up ultrasonography. Evaluation of baseline vs 6-week venous scans demonstrated that, overall, 31 of the 39 ardeparin-treated patients improved, compared with 21 of the 36 patients assigned to receive unfractionated heparin (P=.05). The 95% confidence interval for the difference in improvement was 0.6% to 42% in favor of ardeparin. Median charges for ardeparin and unfractionated heparin were $2815 and $6500, respectively (P<.001). There were no differences in bleeding or patient satisfaction between the 2 groups.. The results of this small preliminary trial suggest that ardeparin can be administered effectively and safely to selected patients with acute deep venous thrombosis and that, with proper nursing and home services, it can help decrease the duration of hospitalization.

Topics: Anticoagulants; Confidence Intervals; Drug Approval; Female; Follow-Up Studies; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hospitalization; Humans; Infusions, Intravenous; Injections, Subcutaneous; Leg; Length of Stay; Male; Middle Aged; Patient Satisfaction; Ultrasonography; United States; United States Food and Drug Administration; Venous Thrombosis; Warfarin

Topics: Humans; Venous Thrombosis; Warfarin

Evidence suggests that an apixaban-based strategy to treat acute venous thromboembolism (VTE) in patients with End-Stage Kidney Disease (ESKD) may be safer than a warfarin-based strategy. Apixaban has an additional advantage of not requiring bridging with heparin which often necessitates long hospitalizations for patients with ESKD. We sought to determine if an apixaban-based strategy is associated with less healthcare utilization than a warfarin-based strategy.. We employed a new-user, active-comparator retrospective cohort study using inverse probability of treatment weights (IPTW) to adjust for confounding demographic and clinical variables. Patients with ESKD newly initiated on either apixaban or warfarin for an acute VTE between 2014 and 2018 in the United States Renal Data System were included. Outcomes were presence of index hospitalization, length of index hospitalization, total hospital days, total hospital days excluding index hospitalization, total emergency department (ED) visits that did not result in hospitalization, and total skilled nursing facility days.. At six months, patients who received apixaban were less likely to have an index hospitalization, had a shorter index hospitalization (median of 4.0 vs 8.0 days, p < 0.001), and had fewer total hospital days. The IPTW and index year-adjusted incidence rate ratios of total hospital days at one, three, and six months were 0.83 (95 % confidence intervals (CI) 0.79-0.86), 0.84 (95 % CI 0.81-0.88), and 0.88 (95 % CI 0.83-0.92) for apixaban compared to warfarin.. Among patients with ESKD and VTE, resource utilization for an apixaban-based strategy appears to be lower than for a warfarin-based strategy.

Topics: Anticoagulants; Humans; Kidney Failure, Chronic; Patient Acceptance of Health Care; Pyridones; Retrospective Studies; United States; Venous Thromboembolism; Venous Thrombosis; Warfarin

Coronavirus disease 2019 was spread worldwide, as a pandemic, from December 2019. Venous thromboembolism events can inflict patients with coronavirus disease 2019 during the hospitalization or convalescent period. Therefore, monitoring of these patients, in terms of venous thromboembolism events signs and symptoms, and timely management of antithrombotic agents are of great importance.. A 45-year-old Iranian man, who is the first author of this case report, was infected by severe acute respiratory syndrome coronavirus 2 and displayed the typical signs and symptoms of coronavirus disease 2019. Although reverse transcription polymerase chain reaction for coronavirus disease 2019, and specific immunoglobulin M and immunoglobulin G against severe acute respiratory syndrome coronavirus 2, were negative at first, chest computed tomography scan showed the characteristic pattern of lung involvement of a coronavirus disease 2019 infection including bilateral and multilobar ground-glass opacities. At that time, there were no signs or symptoms of deep-vein thrombosis or pulmonary thromboembolism, so these were not investigated. About 30 hours after hospital discharge, the patient presented back to the hospital with acute-onset chest pain. We instantly tested his blood for D-dimer, and sent him to take a Doppler sonography of his lower legs and a chest computed tomography angiography in search of pulmonary thromboembolism and deep-vein thrombosis. Although we could confirm pulmonary thromboembolism with computed tomography angiography in our patient, there were no signs or symptoms of venous thromboembolism in his lower legs, and color Doppler sonography of lower limbs was normal. So, the patient was treated with rivaroxaban as an antithrombotic agent. After some days, he was discharged in good condition. About 1 month later, he was referred to our hospital because of left lower limb edema. Although he was under antithrombotic therapy, color Doppler sonography of lower limbs revealed acute deep-vein thrombosis of the left leg. Hence, we decided to shift antithrombotic therapy from rivaroxaban to warfarin, as it is more potent than rivaroxaban in recurrent venous thromboembolism and when taking new oral anticoagulants. Unlike rivaroxaban, which needs no blood test to monitor its efficacy but has a warning for signs and symptoms of bleeding, warfarin therapy must be monitored carefully by regular blood tests for prothrombin time and international normalized ratio to maintain them in the therapeutic range. The patient was informed about the bleeding cautions, and required regular check of prothrombin time and international normalized ratio to maintain them in the proper and advised range of treatment (international normalized ratio therapeutic range 2-3).. In the case of unexpected recurrent venous thromboembolism in coronavirus disease 2019, especially when patients are taking rivaroxaban or other new oral anticoagulants, such drugs should be substituted by warfarin, with routine follow-up, to maintain the value of prothrombin time and international normalized ratio within the therapeutic range.

Topics: Anticoagulants; COVID-19; Decision Making; Fibrinolytic Agents; Hemorrhage; Humans; Iran; Male; Middle Aged; Pulmonary Embolism; Rivaroxaban; SARS-CoV-2; Venous Thromboembolism; Venous Thrombosis; Warfarin

To evaluate the efficacy and safety of direct oral anticoagulants (DOACs) compared to warfarin in patients with inferior vena cava (IVC) thrombus.. This was a single-system, retrospective cohort study of hospitalized adult patients with IVC thrombus treated with a DOAC or warfarin therapy. The primary efficacy endpoint was the thrombus resolution on imaging, and the primary safety endpoint was major bleeding, both assessed within 6 months of hospital discharge. Secondary endpoints included hospitalization for a bleeding-related event, pulmonary embolism, or death within 6 months of hospital discharge.. A total of 33 patients were included in the study. Twenty-three (70%) patients received a DOAC, and 10 (30%) received warfarin. Of the 10 patients with repeat imaging available, complete resolution was noted in two (33%) DOAC patients and no warfarin patients (p = .5). Major bleeding occurred in two (8.7%) DOAC patients and one (10%) warfarin patient (p = .9). No significant differences in secondary endpoints were observed between groups.. There were no differences in efficacy and safety between patients receiving DOACs or warfarin for the treatment of IVC thrombus, although results are limited by the small patient population and number of patients with repeat imaging available.

Topics: Administration, Oral; Adult; Anticoagulants; Hemorrhage; Humans; Retrospective Studies; Stroke; Vena Cava, Inferior; Venous Thrombosis; Warfarin

The efficacy of direct oral anticoagulants (DOACs) compared with warfarin for the treatment of venous thromboembolism (VTE), and the recurrence of VTE after discontinuation of anticoagulation therapy in research are limited.Methods and Results: This retrospective study enrolled 893 patients with acute VTE between 2011 and 2019. The cohort was divided into the transient risk, unprovoked, continued cancer treatment, and cancer remission groups. The following were compared between DOACs and warfarin: composite outcome of all-cause death, VTE recurrence, bleeding and composite outcome of VTE-related death, recurrence and bleeding. In the continued cancer treatment group, more bleeding was seen in warfarin-treated patients than in patients treated with DOACs (53.2% vs. 31.2%, [P=0.048]). In addition, composite outcome of VTE-related death and recurrence after discontinuation of anticoagulation therapy (n=369) was evaluated. The continued cancer treatment group (multivariate analysis: HR: 3.62, 95% CI: 1.84-7.12, P<0.005) and bleeding-related discontinuation of therapy (HR: 2.60, 95% CI: 1.32-5.13, P=0.006) were independent predictors of the event after discontinuation of anticoagulation therapy. VTE recurrence after discontinuation of anticoagulation therapy in the cancer remission group was 1.6% and a statistically similar occurrence was found in the transient risk group (12.4%) (P=0.754).. DOACs may decrease bleeding incidence in patients continuing to receive cancer treatment. In patients with bleeding-related discontinuation of anticoagulation therapy, VTE recurrence may increase. Discontinuation of anticoagulant therapy might be a treatment option in patients who have completed their cancer treatment.

Topics: Administration, Oral; Anticoagulants; Hemorrhage; Humans; Recurrence; Retrospective Studies; Venous Thromboembolism; Venous Thrombosis; Warfarin

Rivaroxaban, as a novel oral anticoagulant agent, emerged in thrombosis management. This study aimed to compare the efficacy and safety of once-daily rivaroxaban versus dose-adjusted warfarin for cerebral venous thrombosis treatment in a real-world clinical setting. This is a prospective cohort study based on the real-world clinical data analysis of the patients with imaging-confirmed CVT enrolled from August 2016 through January 2020 and their outcomes were followed up. Patients were grouped according to their treatment strategies: rivaroxaban (15-20 mg daily) or warfarin (dosage-adjusted according to international normalized ratio), which were matched 1:2 on the propensity score. The primary efficacy outcome was recanalization assessed by magnetic resonance venography. Thrombus burden, CVT recurrence and modified Rankin Scale (mRS) were also compared. The safety outcome was major bleeding. Baseline characteristics were well balanced between the 33 patients in rivaroxaban group and 49 in warfarin group after propensity score matching. During 6-month (median) follow-up, 29 patients (87.9%) in rivaroxaban group and 38 patients (77.6%) in warfarin group obtained recanalization (OR, 1.44; 95% CI 0.63-3.30). The thrombus reduction at the 6-month follow-up did not reach statistical difference (p = 0.118). No CVT recurrence was observed in both groups. All patients in rivaroxaban group obtained favorable functional outcomes (mRS = 0-2), whereas in warfarin group, 1 patient remained physically disable (mRS = 3) at the follow-up. No major bleeding events occurred in two groups. Rivaroxaban might have the same or stronger efficacy in facilitating CVT recanalization and preventing CVT recurrence with a lower incidence of bleeding than that of warfarin in Chinese population.

Topics: Anticoagulants; Hemorrhage; Humans; Intracranial Thrombosis; Prospective Studies; Retrospective Studies; Rivaroxaban; Treatment Outcome; Venous Thrombosis; Warfarin

Great interest exists in standardizing the anticoagulant choice for patients requiring treatment of distal deep vein thrombosis (DDVT). In the present multicenter, retrospective cohort study, we evaluated the outcomes of patients with DDVT who had been treated with warfarin vs direct oral anticoagulants (DOACs; ie, rivaroxaban, apixaban, edoxaban, dabigatran).. Queries were built for the TriNetX database (TriNetX LLC, Cambridge, Mass), a federated network of healthcare organizations across the United States that provides de-identified patient data through aggregated counts and statistical summaries. International Classification of Diseases, 10th revision, diagnostic codes were used to identify eligible patients. Data from January 1, 2013 to January 1, 2020 were reviewed. Statistical analyses, including propensity matching, were performed using TriNetX's internal software. The inclusion criterion was treatment with either warfarin or a DOAC started within the first 24 hours of diagnosis of an isolated thrombosis of the following veins: anterior tibial, posterior tibial, peroneal, or calf muscular veins. The exclusion criteria were a history of an adverse reaction to anticoagulant agents, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection, thrombophilia, mechanical heart valve, chronic proximal DVT (PDVT) and/or DDVT, and 6-month history of the following: acute PDVT, pulmonary embolism (PE), or anticoagulant usage. The outcomes measured included the incidence of mortality, PE, PDVT, stroke, myocardial infarction, and major bleeding within 6 months after initiating anticoagulation therapy.. In a cohort of 6509 patients, 1570 were treated with warfarin and 4939 were treated with a DOAC drug. After propensity matching for age, sex, ethnicity, and comorbidities, the DOAC cohort had a significantly lower incidence of PE (1.795% vs 3.590%; P = .0020) and major bleeding (7.949% vs 10.513%; P = .0134). Differences in the incidence of mortality, PDVT, myocardial infarction, and stroke were not statistically significant.. Before the present study, no strong evidence was available to suggest an optimal treatment modality for DDVT requiring anticoagulation therapy. The data from the present study suggest that patients receiving DOACs for the treatment of DDVT will have significantly lower rates of progression to PE and a lower incidence of major bleeding compared with patients receiving warfarin. This suggests that DOACs are superior to warfarin for treatment of DDVT.

Topics: Administration, Oral; Anticoagulants; COVID-19; Hemorrhage; Humans; Myocardial Infarction; Pulmonary Embolism; Retrospective Studies; SARS-CoV-2; Stroke; United States; Venous Thrombosis; Warfarin

Ovarian vein thrombosis (OVT) may cause maternal mortality by inducing pulmonary thromboembolism (PTE). However, the prevalence, etiology, risk factors, prognosis, and optimal treatments for asymptomatic OVT during and after pregnancies are unclear, which therefore requires a high clinical index of suspicion for certain diagnoses due to its vague presentation. We herein present a case of asymptomatic postpartum OVT that extended toward the inferior vena cava (IVC), resulting in a potential risk of PTE.. A 30-year-old postpartum woman presented with slight dyspnea after an uneventful vaginal delivery at 40 weeks of gestation. We checked her laboratory data to exclude lethal thrombosis; D-dimer levels were 85.6 μg/mL. We performed computed tomography (CT) to search the presence of PTE and deep vein thrombosis (DVT); although no signs of PTE and DVT in her legs were detected, CT and trans-abdominal ultrasonography (TAUS) revealed a right OVT. Heparin was administered, and D-dimer levels decreased; warfarin at a dose of 2 mg/day was subsequently administered to control anti-coagulopathy. However, D-dimer was re-elevated despite adequate anticoagulation treatment, and extension of the right OVT to the IVC was detected by CT and TAUS. With warfarin administration, CT and TAUS showed the disappearance of right OVT. The patient was discharged from the hospital 17 days after delivery.. Even asymptomatic postpartum OVT may lead to PTE. Universal screening guidelines and optimal treatment strategies for asymptomatic OVT in pregnant and postpartum women should be established through future studies.

Topics: Adult; Female; Humans; Ovary; Postpartum Period; Pregnancy; Pulmonary Embolism; Thrombosis; Venous Thrombosis; Warfarin

Portal vein system thrombosis (PVST) is a common postoperative complication brought by laparoscopic splenectomy and pericardial disconnection (LSD) among patients who suffered from portal hypertension and hypersplenism. This research lies mainly in probing into the risk factors of PVST and evaluating the effects of warfarin on PVST prevention.. We took 131 individuals who have carried out LSD from January 2015 to January 2021. Patients were divided into warfarin group (n = 68) and aspirin group (n = 63). Meanwhile, thrombosis factors were analyzed in PVST arm (n = 48) and non-PVST arm (n = 83).. We analyzed the early postoperative anticoagulation effect, 20 patients (29.4%) in the warfarin group developed PVST, and 28 patients (44.4%) in the aspirin group. The chance to PVST during the first year after operation was lower in the warfarin group than in the aspirin group (F = 13.43, P = 0.006). Risk factors for PVST were analyzed, and diabetes, the diameter of the portal vein and splenic vein, and the velocity of portal blood flow were statistically significant between the PVST arm and non-PVST arm (P <  < 0.05). Multiple logistic regression analyses have shown that diabetes, portal vein diameter, splenic vein diameter, and the velocity of portal blood flow were the risk factors of PVST.. The portal vein diameter, splenic vein diameter, portal vein flow velocity, and diabetes are risk factors for the PVST after LSD. The prophylactic use of warfarin anticoagulation markedly decreases the probability of occurrence of the PVST in patients with portal hypertension after LSD compared to aspirin.

Topics: Anticoagulants; Aspirin; Humans; Hypertension, Portal; Laparoscopy; Liver Cirrhosis; Portal Vein; Risk Factors; Splenectomy; Thrombosis; Venous Thrombosis; Warfarin

Topics: Catheterization, Central Venous; Central Venous Catheters; Humans; Male; Pain; Venous Thrombosis; Warfarin

Patients with end-stage kidney disease (ESKD) are at significantly increased risk for both thrombosis and bleeding relative to those with normal renal function. The optimal therapy of venous thromboembolism (VTE) in patients with ESKD is unknown.. To compare the safety and effectiveness of apixaban relative to warfarin in patients with ESKD and acute VTE.. New-user, active-comparator retrospective United States population-based cohort with inverse probability of treatment weighting, using the United States Renal Data System data from 2014 to 2018. We included adults with ESKD on hemodialysis or peritoneal dialysis who were newly initiated on apixaban or warfarin for an acute VTE.. The coprimary outcomes were major bleeding, recurrent VTE, and all-cause mortality within 6 months of anticoagulant initiation. Secondary outcomes were intracranial hemorrhage and gastrointestinal bleeding. The primary analyses were based on intent-to-treat defined by the first drug received and accounted for competing risks of death. Sensitivity analyses included varied follow-up time, as-treated analyses, and dose-specific apixaban subgroups.. The apixaban and warfarin cohorts included 2302 and 9263 patients, respectively. Apixaban was associated with a lower risk of major bleeding (hazard ratio [HR] 0.81, 95% confidence interval [CI]: 0.70-0.94), intracranial bleeding (HR 0.69, 95% CI 0.48-0.98), and gastrointestinal bleeding (HR 0.82, 95% CI 0.69-0.96). Recurrent VTE and all-cause mortality were not significantly different between the groups.. Apixaban was associated with a lower risk of bleeding relative to warfarin when used to treat acute VTE in patients with ESKD on dialysis.

Topics: Adult; Anticoagulants; Cohort Studies; Gastrointestinal Hemorrhage; Humans; Kidney Failure, Chronic; Pyrazoles; Pyridones; Retrospective Studies; United States; Venous Thromboembolism; Venous Thrombosis; Warfarin

Performing percutaneous renal biopsy procedures in lupus nephritis (LN) and nephrotic syndrome presents a unique challenge to the nephrologist because of the risk of bleeding from the procedure and the hypercoagulable state in hypoalbuminemia. The management of a patient with venous thrombosis with perinephric hematoma post renal biopsy can be difficult if occurred.. We are presenting a case of perinephric hematoma following percutaneous renal biopsy in a 23-year-old man with lupus nephritis, nephrotic syndrome, and lower limbs deep vein thrombosis (DVT). The patient developed persistent frank haematuria, flank pain and acute urinary retention post-procedure. We have withheld his oral warfarin three days before the procedure, and no anticoagulation was given subsequently. Initial CT Angiography (CTA) renal showing stable hematoma and no visible evidence of vascular injury. Three weeks later, the patient still has persistent frank haematuria and a repeated CTA renal revealed new bilateral renal vein thrombosis. Considering the high risk of worsening symptomatic venous thrombosis, we gave subcutaneous enoxaparin sodium and restart oral warfarin despite ongoing haematuria. The frank haematuria resolved within two days of anticoagulation with no radiological evidence of worsening of the perinephric hematoma. The follow-up ultrasonography a month later showed resolution of the hematoma and renal vein thrombosis with no adverse effect.. Our experience, in this case, highlighted the importance of case selection for percutaneous renal biopsy among high-risk patients. Additionally, a prolonged frank haematuria in post-renal biopsy with nephrotic syndrome warranted a reassessment, as a clinical presentation of post-procedure perinephric hematoma and renal vein thrombosis can overlap. We also demonstrated that restarting anticoagulation earlier than four weeks in a patient with renal vein thrombosis and post-renal biopsy perinephric hematoma can be safe in the selective case.

Topics: Adult; Biopsy; Enoxaparin; Gastrointestinal Hemorrhage; Hematoma; Hematuria; Humans; Kidney Diseases; Lupus Nephritis; Male; Nephrotic Syndrome; Renal Veins; Ureteral Diseases; Venous Thrombosis; Warfarin; Young Adult

Deep venous thrombosis (DVT) poses a major challenge to public health worldwide. Endothelial cell injury evokes inflammatory and oxidative responses that contribute to thrombus formation. Tea polyphenol (TP) in the form of epigallocatechin-3-gallate (EGCG) has anti-inflammatory and oxidative effect that may ameliorate DVT. However, the precise mechanism remains incompletely understood. The current study was designed to investigate the anti-DVT mechanism of EGCG in combination with warfarin (an oral anticoagulant). Rabbits were randomly divided into five groups. A DVT model of rats was established through ligation of the inferior vena cava (IVC) and left common iliac vein, and the animals were orally administered with EGCG, warfarin, or vehicle for seven days. In vitro studies included pretreatment of human umbilical vein endothelial cells (HUVECs) with different concentrations of EGCG for 2 h before exposure to hydrogen peroxide. Thrombus weight and length were examined. Histopathological changes were observed by hematoxylin-eosin staining. Blood samples were collected for detecting coagulation function, including thrombin and prothrombin times, activated partial thromboplastin time, and fibrinogen levels. Protein expression in thrombosed IVCs and HUVECs was evaluated by Western blot, immunohistochemical analysis, and/or immunofluorescence staining. RT-qPCR was used to determine the levels of AGTR-1 and VEGF mRNA in IVCs and HUVECs. The viability of HUVECs was examined by CCK-8 assay. Flow cytometry was performed to detect cell apoptosis and ROS generation was assessed by 2',7'-dichlorofluorescein diacetate reagent. In vitro and invivo studies showed that EGCG combined with warfarin significantly reduced thrombus weight and length, and apoptosis in HUVECs. Our findings indicated that the combination of EGCG and warfarin protects HUVECs from oxidative stress and prevents apoptosis. However, HIF-1α silencing weakened these effects, which indicated that HIF-1α may participate in DVT. Furthermore, HIF-1α silencing significantly up-regulated cell apoptosis and ROS generation, and enhanced VEGF expression and the activation of the PI3K/AKT and ERK1/2 signaling pathways. In conclusion, our results indicate that EGCG combined with warfarin modifies HIF-1α and VEGF to prevent DVT in rabbits through anti-inflammation via the PI3K/AKT and ERK1/2 signaling pathways.

Topics: Animals; Anticoagulants; Catechin; Eosine Yellowish-(YS); Fibrinogen; Hematoxylin; Human Umbilical Vein Endothelial Cells; Humans; Hydrogen Peroxide; Hypoxia-Inducible Factor 1, alpha Subunit; MAP Kinase Signaling System; Phosphatidylinositol 3-Kinases; Polyphenols; Proto-Oncogene Proteins c-akt; Rabbits; Rats; Reactive Oxygen Species; RNA, Messenger; Signal Transduction; Tea; Thrombin; Vascular Endothelial Growth Factor A; Venous Thrombosis; Warfarin

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, acquired clonal haematological disease characterized by complement-mediated haemolysis, bone marrow failure and venous thrombosis. Anticomplement therapy eculizumab improves survival and reduces complications. Severe acute respiratory distress syndrome corona virus 2 (SARS-CoV-2) disease 2019 (COVID-19) is associated with high incidence of both venous and arterial thrombosis in hospitalized patients with pneumonia. Deep venous thrombosis (DVT) as the presenting symptom of COVID-19 is a rare event. We describe a well-controlled PNH patient on eculizumab for more than 5 years who presented with DVT, while on warfarin, as the first sign of COVID-19. To our knowledge, this is the first described case of DVT in a PNH patient with COVID-19.

Topics: Adult; Antibodies, Monoclonal, Humanized; Anticoagulants; Complement Inactivating Agents; COVID-19; Hemoglobinuria, Paroxysmal; Humans; Male; SARS-CoV-2; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Humans; Neoplasms; Thrombosis; Venous Thrombosis; Warfarin

Warfarin belongs to a medication class called anticoagulants or blood thinners. It is used for the treatment to prevent blood clots from forming or growing larger. Patients with venous thrombosis, pulmonary embolism, or who have suffered a heart attack, have an irregular heartbeat, or prosthetic heart valves are prescribed with warfarin. It is challenging to find optimal doses due to inter-patient and intra-patient variabilities and narrow therapeutic index. This work presents an individualized warfarin dosing method by utilizing the individual patient model generated using limited clinical data of the patients with chronic conditions under warfarin anticoagulation treatment. Then, the individual precise warfarin dosing is formalized as an optimal control problem, which is solved using the DORBF control approach. The efficiency of the proposed approach is compared with results obtained from practiced clinical protocol.

Topics: Anticoagulants; Humans; Pulmonary Embolism; Thrombosis; Venous Thrombosis; Warfarin

Portal vein thrombosis (PVT) is a poorly described complication of inflammatory bowel disease (IBD). We sought to better characterize presentations, compare treatments, and assess outcomes in IBD-related PVT.. We conducted a retrospective investigation of IBD-related PVT at our institution. Multivariable Cox proportional hazards modeling was used to estimate adjusted hazard ratios across treatments.. Sixty-three patients with IBD-related PVT (26 with Crohn disease, 37 with ulcerative colitis) were followed for a median 21 months (interquartile ratio [IQR] = 9-52). Major risk factors included intra-abdominal surgery (60%), IBD flare (33%), and intra-abdominal infection (13%). Primary hematologic thrombophilias were rare and did not impact management. Presentations were generally nonspecific, and diagnosis was incidental. Ninety-two percent of patients (58/63) received anticoagulation (AC), including 23 who received direct oral anticoagulants (DOACs), 22 who received warfarin, and 13 who received enoxaparin. All anticoagulated patients started AC within 3 days of diagnosis. Complete radiographic resolution (CRR) of PVT occurred in 71% of patients. We found that DOACs were associated with higher CRR rates (22/23; 96%) relative to warfarin (12/22; 55%): the hazard ratio of DOACs to warfarin was 4.04 (1.83-8.93; P = 0.0006)). Patients receiving DOACs required shorter courses of AC (median 3.9 months; IQR = 2.7-6.1) than those receiving warfarin (median 8.5 months; IQR = 3.9-NA; P = 0.0190). Incidence of gut ischemia (n = 3), symptomatic portal hypertension (n = 3), major bleeding (n = 4), and death (n = 2) were rare, and no patients receiving DOACs experienced these adverse outcomes.. We show that early and aggressive use of AC can lead to excellent outcomes in IBD-associated PVT and that DOACs are associated with particularly favorable outcomes in this setting.

Topics: Anticoagulants; Humans; Inflammatory Bowel Diseases; Portal Vein; Retrospective Studies; Venous Thrombosis; Warfarin

Endovenous revascularization is the standard in the management of acute thrombotic, chronic post-thrombotic iliocaval or iliofemoral obstruction, and nonthrombotic iliac vein lesions. The purpose of this study is to describe our single-center experience of postprocedure anticoagulation and antiplatelet regimens used after endovenous revascularization for a variety of venous occlusive conditions.. We conducted a retrospective analysis of 100 consecutive patients who underwent endovenous stenting for iliocaval or iliofemoral obstruction from January 1, 2014, to April 30, 2018. Patients treated with direct oral anticoagulants, warfarin, or low-molecular-weight heparin (LMWH) with or without antiplatelet therapy were identified. Demographic, procedural, patency, and follow-up data were collected. Stent patency was evaluated using duplex Doppler ultrasound examination or contrast venography.. Seventy-one of 100 patients were treated with direct oral anticoagulant therapy (DOAC). Sixteen (23%) were lost to follow-up, leaving 55 (77%) available for analysis. The mean follow-up was 14 months (range, 1-43 months) with 32 patients (58%) followed for 12 months or longer. Primary, primary-assisted, and secondary-assisted patency rates were 87%, 97%, and 98%, respectively, at 12 months. In the non-DOAC group (patients treated with warfarin or LMWH), these rates were 87%, 93%, and 95%, respectively, at 12 months. Antiplatelet therapy, including clopidogrel, aspirin, or both, was used in 53 of 55 patients in the DOAC cohort and 18 of 19 patients in the non-DOAC group.. Our-single center retrospective analysis demonstrates acceptable primary patency rates when using DOAC therapy compared with those treated with warfarin or LMWH.

Topics: Administration, Oral; Anticoagulants; Chronic Disease; Endovascular Procedures; Factor Xa Inhibitors; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Postthrombotic Syndrome; Retrospective Studies; Stents; Tertiary Care Centers; Time Factors; Treatment Outcome; Vascular Patency; Venous Thrombosis; Warfarin

The purpose of this study was to evaluate the efficacy and safety of direct oral anticoagulants vs. warfarin for portal vein thrombosis treatment.. This was a single-center, retrospective study. Adult patients initiated on a direct oral anticoagulant or warfarin for treatment of a new portal vein thrombosis were included. The primary failure outcome was the absolute difference in recurrent thromboembolic events 90 days following initiation of a direct oral anticoagulant vs. warfarin. The primary safety outcome was the absolute difference in bleeding events 90 days following initiation of a direct oral anticoagulant vs. warfarin. Descriptive statistics, Fisher's exact, and Student's t-tests were utilized as appropriate.. Thirty-three patients were included. Thirteen (39.4%) patients received direct oral anticoagulants, and 20 (60.6%) received warfarin. None of the patients receiving direct oral anticoagulants experienced a primary failure event compared to four receiving warfarin (P < 0.001). None of the patients receiving direct oral anticoagulants experienced a primary safety event vs. one receiving warfarin (P < 0.001).. Direct oral anticoagulants appear to be effective and safe in the treatment of portal vein thrombosis and in preventing recurrent thromboembolic events. Future studies with larger sample sizes are warranted to confirm direct oral anticoagulants' efficacy in portal vein thrombosis.

Topics: Administration, Oral; Adult; Anticoagulants; Humans; Portal Vein; Retrospective Studies; Venous Thrombosis; Warfarin

Splanchnic vein thrombosis (SVT) is an uncommon but potentially life-threatening disease usually related to different underlying clinical conditions. The risk of SVT recurrences is high over time in patients with an underlying permanent prothrombotic condition. Vitamin K antagonists (VKA) represent the mainstay of treatment for SVT. Data about the efficacy and safety of direct oral anticoagulants (DOACs) are reported in the literature for the treatment of acute SVT, but less is known about their application for the secondary prophylaxis of venous thromboembolism (VTE). The aim of this study was to assess the efficacy and safety of long-term DOACs therapy in patients at high-risk of thrombosis, compared to VKA.. This is a retrospective single-centre study including 70 patients with SVT on long-term anticoagulant treatment with VKA followed-up at our Units between January 2017 and December 2019. All the patients were at high thrombotic risk defined as the presence of a permanent prothrombotic condition requiring long-term anticoagulation. During follow-up, 28 patients were shifted to DOACs and their clinical outcomes were compared to those of the patients who continued VKA therapy. All the arterial and venous thrombotic events of the splanchnic and extra-splanchnic districts as well as the haemorrhagic adverse events occurring during follow-up were recorded.. Of the seventy patients enrolled in the study, 36 patients (51.4%) had a single-segment involvement thrombosis (28.5% of portal vein, 7.1% of superior mesenteric vein, 4.3% of splenic vein, 11.5% of hepatic veins) and 34 patients (48.6%) had multi-segment involvement at the time of diagnosis. 42 patients (60%) continued VKA therapy and 28 (40%) were switched to DOACs. Median follow-up was 6 years (range 2-8) during VKA and 1.9 years (range 1-5.2) during DOACs. The incidence of thrombotic events was similar between patients on VKA and those on DOACs. Patients on VKA developed deep vein thrombosis (DVT), and of the patients on DOACs 1 developed NSTEMI and 1 DVT. No major haemorrhagic events occurred. Minor bleedings occurred in 26% of patients on VKA and in none of the DOACs patients (P: 0.09).. Our results highlight that DOACs could represent an effective and safe alternative to the VKA for secondary prophylaxis in SVT patients at high risk of thrombosis.

Topics: Acenocoumarol; Adult; Anticoagulants; Budd-Chiari Syndrome; Duration of Therapy; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Mesenteric Ischemia; Middle Aged; Portal Vein; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Secondary Prevention; Thiazoles; Venous Thrombosis; Warfarin

IgG-specific and polyspecific PF4-dependent enzyme-immunoassays (EIAs) have exceptionally high sensitivity (≥99%) for diagnosis of heparin-induced thrombocytopenia (HIT), a drug reaction caused by platelet-activating antibodies detectable by serotonin-release assay (SRA). The IgG-specific EIAs are recommended for screening, as their high sensitivity is accompanied by relatively high specificity vis-à-vis polyspecific EIAs. We investigated the frequency of SRA-positive/EIA-negative (SRA+/EIA-) HIT, prompted by referral to our reference HIT laboratory of serial blood samples from a patient ("index case") with false-negative IgG-specific EIAs. Despite initial clinical suspicion for HIT, repeat negative IgG-specific EIAs prompted heparin resumption, which triggered recurrent thrombocytopenia and near-fatal cardiac arrest, indicating likely post-heparin HIT-associated anaphylactoid reaction. Further investigations revealed a strong-positive SRA, whether performed with heparin alone, PF4 alone, or PF4/heparin, with inhibition by Fc receptor-blocking monoclonal antibody (indicating IgG-mediated platelet activation); however, five different IgG-specific immunoassays yielded primarily negative (or weak-positive) results. To investigate the frequency of SRA+/EIA- HIT, we reviewed the laboratory and clinical features of patients with this serological profile during a 6-year period in which our reference laboratory investigated for HIT using both SRA and IgG-specific EIA. Although ~0.2% of 8546 patients had an SRA+/EIA- profile, further review of 15 such cases indicated clerical/laboratory misclassification or false-positive SRA in all, with no SRA+/EIA- HIT case identified. We conclude that while SRA+/EIA- HIT is possible-as shown by our index case-this clinical picture is exceptionally uncommon. Moreover, the requirement for a positive EIA is a useful quality control maneuver that reduces risk of reporting a false-positive SRA result.

Topics: Adult; Anaphylaxis; Anticoagulants; Autoantibodies; Autoantigens; Blood Platelets; Drug Therapy, Combination; False Negative Reactions; Female; Heart Arrest; Heparin; Humans; Immunoenzyme Techniques; Immunoglobulin G; Immunoglobulin M; Medical Errors; Obesity; Platelet Activation; Platelet Factor 4; Pulmonary Embolism; Recurrence; Sensitivity and Specificity; Serotonin; Thrombocytopenia; Venous Thrombosis; Warfarin

To compare the results of conservative and endovascular treatment of deep vein thrombosis followed by acute severe venous insufficiency.. Two statistically valid groups of patients with deep vein thrombosis and acute severe venous insufficiency were compared. Warfarin was administered in the first group, endovascular methods - in the second group (. In the first group, each third patient had hemorrhagic complications that required cessation of anticoagulant therapy in 1.3% of patients. In the second group, hemorrhagic events occurred in 10% of patients and were managed by lowering Apixaban dosage. Complete restoration of lumen patency was detected in 23.3% in the first group and 93.3% in the second group. Partial restoration developed in 63.3% and 6.7%, occlusion in 13.3% and 0%, respectively. Only 23.3% of patients in the first group had no clinical evidence of venous congestion. Mild congestion was found in 20%, severe - in 56.7% of cases. In the second group, 6.7% of patients had minimal venous congestion.. Сравнить результаты традиционного консервативного и эндоваскулярного лечения больных тромбозом глубоких вен с развитием тяжелой степени острой венозной недостаточности.. Проведено сравнение результатов лечения двух статистически однородных групп пациентов с тромбозом глубоких вен нижних конечностей и тяжелой степенью острой венозной недостаточности. В 1-й группе (. В 1-й группе на фоне лечения варфарином у каждого третьего больного развились те или иные проявления геморрагического синдрома, что потребовало отменить антикоагулянтную терапию у 13,3% больных, во 2-й группе — у 10%, проявления корригировали снижением дозы апиксабана. Полное восстановление просвета вен произошло в 1-й группе у 23,3%, во 2-й группе у 93,3%, частичное — соответственно у 63,3 и 6,7%, окклюзия развилась у 13,3 и 0%. В 1-й группе клинические нарушения венозного оттока отсутствовали у 23,3% больных, легкая степень выраженности зарегистрирована у 20%, тяжелая — у 56,7%. Во 2-й группе минимальные нарушения венозного оттока отмечены лишь у 6,7% больных.

Topics: Acute Disease; Anticoagulants; Blood Vessel Prosthesis Implantation; Conservative Treatment; Endovascular Procedures; Humans; Pyrazoles; Pyridones; Stents; Thrombectomy; Thrombolytic Therapy; Treatment Outcome; Vascular Patency; Venous Insufficiency; Venous Thrombosis; Warfarin

New Oral Anticoagulants (NOACs) such as Rivaroxaban are introduced as alternatives to conventional vitamin-K antagonists in the long-term treatment of thrombotic events due to their lower bleeding risk. There is a lack of evidence on the effectiveness and safety of Rivaroxaban in Cerebral venous thrombosis (CVT). This study aims to assess the effectiveness and bleeding risk of Rivaroxaban in comparison with Warfarin for the treatment of CVT.. 36 patients with diagnosis of CVT were included. Clinical and background information was assessed on admission and patients were followed for at least 12 months. Measured outcomes were modified Rankin Scale (mRS), evidence of recanalization on contrast-enhanced Brain MR venography (MRV) and major or minor bleeding. Patients were divided into two groups according to the type of oral anticoagulant (Rivaroxaban vs Warfarin). Groups were compared in terms of final outcomes and side effects.. Overall, 13 (36.11%) patients received Warfarin and 23 (63.89%) received Rivaroxaban. Optimal mRS score (0-1) was attained in 9 of 10 (90%) of patients treated with Rivaroxaban and 19 of 22 (86.36%) of patients received Warfarin. MRV showed complete or partial recanalization in 12 of 14 (85.71%) patients treated with Rivaroxaban and all patients in the Warfarin group. There was no significant difference between the two groups in terms of major and minor hemorrhage.. Rivaroxaban holds promise for the treatment of CVT.

Topics: Adult; Anticoagulants; Factor Xa Inhibitors; Female; Humans; Intracranial Thrombosis; Male; Middle Aged; Rivaroxaban; Treatment Outcome; Venous Thrombosis; Warfarin

Ovarian vein thrombosis (OVT) is a condition most commonly associated with malignancy, hypercoagulable disorders, pelvic surgery, trauma, inflammatory bowel disease and the postpartum period. Idiopathic bilateral OVT is extremely rare. We report the case of a 30-year-old African-American woman who presented with bilateral lower pelvic pain and nausea. She had no recent pelvic infections nor a personal or family history of malignancy or thrombophilia. Workup results for a hypercoagulable state was negative. A CT scan of the abdomen and pelvis revealed bilateral OVT. Treatment included novel oral anticoagulants or warfarin, with comparison studies showing a similar risk-benefit ratio. Repeat imaging is recommended after 40-60 days to determine the necessity for further anticoagulation. Emphasis is placed on starting anticoagulation early in order to reduce the risk of extension of the thrombus into the inferior vena cava, conversion to pulmonary embolism or increase in the risk of infection.

Topics: Adult; Anticoagulants; Female; Humans; Ovary; Thrombosis; Vena Cava, Inferior; Venous Thrombosis; Warfarin

Over the years, the internet has enabled considerable progress in the management of chronic diseases, especially hypertension and diabetes. It also provides novel opportunities in online anticoagulation management. Nevertheless, there is insufficient evidence regarding the effectiveness of online anticoagulation management.. This study explored the effectiveness and safety of warfarin management via the Alfalfa app, so as to provide evidence in support of anticoagulant management through online services.. In this retrospective, observational cohort study, 824 patients were included. In the offline group, patients went to the hospital clinic for warfarin management. In the Alfalfa app group, patients reported the dose of warfarin, current international normalized ratio (INR) value, and other related information through the Alfalfa app. Physicians or pharmacists used the app to adjust the dose of warfarin and determined the time for the next blood INR testing. Patients completed INR testing by point-of-care at home or hospital. The primary outcome of the study was the percentage of time in therapeutic range (TTR). Secondary outcomes included minor and major bleeding events, thrombotic events, warfarin-related emergency department visits, hospital admissions, and high INR values.. The TTR and percentage of INR values in the range were significantly higher in the Alfalfa app group than in the offline group (79.35% vs 52.38%, P<.001; 3314/4282, 77.39% vs 2005/4202, 47.72%, P<.001, respectively). Patients managed via the Alfalfa app had lower rates of subtherapeutic (172/4282, 4.02% vs 388/4202, 9.23%; P<.001), supratherapeutic (487/4282, 11.37% vs 882/4202, 20.99%; P<.001), and extreme subtherapeutic INR values (290/4282, 6.77% vs 910/4202, 21.66%; P<.001). Additionally, the Alfalfa app group had lower incidences of major bleeding (2/425, 0.5% vs 12/399, 3.0%; P=.005), warfarin-related emergency department visits (13/425, 3.1% vs 37/399, 9.3%; P<.001), and hospital admissions (1/425, 0.2% vs 12/399, 3.0%; P=.001) compared with the offline group. However, the Alfalfa app group had a higher incidence of minor bleeding than the offline group (45/425, 10.6% vs 20/399, 5.0%; P=.003). There were similar incidences in extreme supratherapeutic INR values (19/4282, 0.44% vs 17/4202, 0.40%; P=.78) and thromboembolic events (1/425, 0.2% vs 1/399, 0.3%; P=.53) between the two groups.. Warfarin management is superior via the Alfalfa app than via offline services in terms of major bleeding events, warfarin-related emergency department visits, and hospital admissions.

Topics: Anticoagulants; Cohort Studies; Humans; Medicago sativa; Mobile Applications; Retrospective Studies; Venous Thrombosis; Warfarin

Data on clinical outcomes for nonvitamin K antagonist oral anticoagulant (NOACs) and warfarin in patients with atrial fibrillation and cancer are limited, and patients with active cancer were excluded from randomized trials. We investigated the effectiveness and safety for NOACs versus warfarin among patients with atrial fibrillation with cancer.. In this nationwide retrospective cohort study from Taiwan National Health Insurance Research Database, we identified a total of 6274 and 1681 consecutive patients with atrial fibrillation with cancer taking NOACs and warfarin from June 1, 2012, to December 31, 2017, respectively. Propensity score stabilized weighting was used to balance covariates across study groups.. There were 1031, 1758, 411, and 3074 patients treated with apixaban, dabigatran, edoxaban, and rivaroxaban, respectively. After propensity score stabilized weighting, NOAC was associated with a lower risk of major adverse cardiovascular events (hazard ratio, 0.63 [95% CI, 0.50–0.80]; P=0.0001), major adverse limb events (hazard ratio, 0.41 [95% CI, 0.24–0.70]; P=0.0010), venous thrombosis (hazard ratio, 0.37 [95% CI, 0.23–0.61]; P<0.0001), and major bleeding (hazard ratio, 0.73 [95% CI, 0.56–0.94]; P=0.0171) compared with warfarin. The outcomes were consistent with either direct thrombin inhibitor (dabigatran) or factor Xa inhibitor (apixaban, edoxaban, and rivaroxaban) use, among patients with stroke history, and among patients with different type of cancer and local, regional, or metastatic stage of cancer (P interaction >0.05). When compared with warfarin, NOAC was associated with lower risk of major adverse cardiovascular event, and venous thrombosis in patients aged <75 but not in those aged ≥75 years (P interaction <0.05).. Thromboprophylaxis with NOACs rather than warfarin should be considered for the majority of the atrial fibrillation population with cancer.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Cohort Studies; Female; Hemorrhage; Humans; Male; Middle Aged; Neoplasms; Propensity Score; Retrospective Studies; Stroke; Taiwan; Treatment Outcome; Venous Thrombosis; Vitamin K; Warfarin

In ambulant patients with lower limb DVT managed with Warfarin, there is a need for initial treatment and short time "bridging" with a rapidly acting anticoagulant until there is a stable therapeutic INR. In this study, results from bridging with subcutaneous low molecular weight heparin (LMWH) or oral Rivaroxaban were compared.. One hundred and twenty-four patients received LMWH and 98 patients received Rivaroxaban, both in addition to Warfarin. Patients were assessed at 1 and 4 weeks after treatment initiation for thrombus progression, bleeding, clinic attendance and INR.. The treatment groups were well matched. There were no significant differences between the treatment groups for any of the end-points at either 1 week or 4 weeks.. In ambulant patients with DVT treated with Warfarin both Rivaroxaban and LMWH are suitable for use in the early phase of Warfarin treatment until therapeutic INR is achieved. Rivaroxaban is a suitable alternative to LMWH for patients who prefer not to have injections.

Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Rivaroxaban; Venous Thrombosis; Warfarin

The in vitro conversion of (1S,3S)-1-dimethoxylethyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid, (1S,3S)-DCCA, in rat plasma is monitored by HPLC-FT-ICR-MS. We show that the in vitro conversion of (1S,3S)-DCCA in rat plasma for 1 h leads to forming (6S/12aS)-bisdimethoxyethylheptachpyridone, reflecting intermolecular condensation of (1S,3S)-DCCA, and the in vitro conversion of (6S/12aS)-bisdimethoxyethylheptachpyridone in rat plasma for 1 h leads to forming (6S/12aS)-heptachpyridone, reflecting hydrolysis of (6S/12aS)-bisdimethoxyethylheptachpyridone. At a dose of 1.0 μmol/kg (6S/12aS)-heptachpyridone orally inhibits venous thrombosis and arterial thrombosis in vivo. Bleeding time, clotting time and international normalized ratio show that at this dose (6S/12aS)-heptachpyridone has no bleeding risk, does not lengthen clotting time and does not change the exogenous coagulation pathway. We also show that the reactions promoted by rat plasma are easy to practice by chemical synthesis. Thus our findings build a bridge across the in vivo conversion and the application.

Topics: Animals; Blood; Carbazoles; Diketopiperazines; Fibrinolytic Agents; Hydrolysis; Male; Rats, Sprague-Dawley; Vena Cava, Inferior; Venous Thrombosis

Topics: Anticoagulants; Humans; Postthrombotic Syndrome; Rivaroxaban; Venous Thrombosis; Warfarin

Thrombosis resolution is an important component of treatment for deep vein thrombosis (DVT) and multiple anticoagulants are now available. It is unknown whether rivaroxaban contributes to a higher degree of thrombus resolution compared to conventional anticoagulation with warfarin. Our objective was to compare thrombus resolution for rivaroxaban versus warfarin treated patients with acute lower extremity DVT. Consecutive patients treated for proximal or distal lower extremity DVT with rivaroxaban were identified from the Mayo Thrombophilia Clinic Anticoagulants Registry (November 2015-June 2016) and compared to patients treated with warfarin. Ultrasonography/Doppler images were analyzed by two independent radiologists blinded to anticoagulant and using a standardized assessment algorithm. A total of 111 patients with DVT were studied. Sixty-three rivaroxaban treated patients were compared to 48 warfarin treated patients over a median follow up of 92 and 97 days, respectively. Percentage of patients with total or partial resolution of thrombosis was similar in rivaroxaban and warfarin treated groups (95.2% vs. 91.7%, p = 0.46, respectively); also the proportion of patients with total thrombus resolution was not significantly different (38.1% vs. 29.2%, p = 0.42, respectively). There was no significant difference in the proportion of patients with no thrombus resolution between rivaroxaban and warfarin treated groups either (4.8% vs. 2.1%, p = 0.63). Thrombus propagation with warfarin therapy was observed in 6.3% of patients treated with warfarin and in none of the patients from the rivaroxaban group (p = 0.08). Resolution of acute lower extremity DVT in patients treated with rivaroxaban is similar to those treated with warfarin.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Factor Xa Inhibitors; Female; Humans; Lower Extremity; Male; Middle Aged; Registries; Rivaroxaban; Ultrasonography, Doppler; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Humans; Postthrombotic Syndrome; Rivaroxaban; Venous Thrombosis; Warfarin

We describe the case of a 72-year-old gentleman who was referred to our institution for management of cardiogenic shock from a massive pulmonary embolism. Right heart catheterization revealed a low cardiac index and markedly elevated pulmonary pressures, suggested long-standing venous thromboembolic (VTE) disease that evolved into chronic thromboembolic pulmonary hypertension (CTEPH). The patient was cannulated to veno-arterial extra-corporeal membrane oxygenation and eventually treated with pulmonary embolectomy and thromboendarterectomy. Subsequently discovered inferior vena cava clot and left iliac deep vein thrombosis were treated with suction and mechanical thrombectomy. Intravascular ultrasound of the left lower extremity venous system identified iliac vein compression syndrome (IVCS) as the culprit of the patient's VTE and CTEPH. A left iliac stent was placed and the patient was discharged on Warfarin for anticoagulation. The case illustrates the rapidly expanding armamentarium for VTE treatment and proposes IVCS as a new, potentially underrecognized risk factor for CTEPH.

Topics: Aged; Anticoagulants; Embolectomy; Endarterectomy; Endovascular Procedures; Extracorporeal Membrane Oxygenation; Hemodynamics; Humans; Hypertension, Pulmonary; Male; May-Thurner Syndrome; Pulmonary Embolism; Risk Factors; Stents; Thrombectomy; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis; Warfarin

Post-thrombotic syndrome (PTS) is a complication of deep vein thrombosis (DVT). Residual vein thrombus (RVT) on Doppler Ultrasound can be associated with PTS. Limited data are available on the effect of direct oral anticoagulants (DOACs) on the long-term outcome of PTS. This study aimed to compare the prevalence of PTS and RVT, in patients with previous DVT treated with rivaroxaban or enoxaparin/warfarin. A total of 129 patients with previous proximal lower limb DVT and treated with rivaroxaban (n = 71) or enoxaparin/warfarin (n = 58) for at least 3 months were included. The Villalta scale for PTS was performed after treatment. The median duration of the DVT symptoms before anticoagulation was 7 days for both groups. The rate of PTS was 50.7% in the patients treated with rivaroxaban and 69% in the enoxaparin/warfarin group. Enoxaparin/warfarin showed an increased prevalence of PTS (P = .018). An analysis in 3 different models showed that the relative risk of PTS decreased by 76% with rivaroxaban use when compared with enoxaparin/warfarin treatment. In addition, 93 of the 129 patients were evaluated regarding the presence of RVT, of which, 11 (24.4%) and 31 (64.6%) presented with RVT for rivaroxaban and enoxaparin/warfarin, respectively (P < .0001). The RVT analysis excluded the possibility of RVT as a mediator of the association between type of treatment and PTS when comparing rivaroxaban with enoxaparin/warfarin (odds ratio (OR) = 0.14; 95% confidence interval (CI): 0.1-1.0, P = .051) with rivaroxaban compared with enoxaparin/warfarin. Rivaroxaban treatment was associated with a lower risk of PTS when compared to enoxaparin/warfarin; RVT however, was not a mediator in the association between PTS and type of treatment.

Topics: Adult; Anticoagulants; Brazil; Cross-Sectional Studies; Enoxaparin; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Postthrombotic Syndrome; Prevalence; Retrospective Studies; Risk Factors; Rivaroxaban; Time Factors; Treatment Outcome; Venous Thrombosis; Warfarin

Topics: Afibrinogenemia; Anticoagulants; Blood Coagulation Tests; Codon, Nonsense; Fibrinogen; Genetic Predisposition to Disease; Genetic Testing; Humans; Male; Middle Aged; Recurrence; Thrombelastography; Venous Thrombosis; Warfarin

Differences in the performance of suggested warfarin dosing algorithms among different ethnicities and genotypes have been reported; this necessitates the development of an algorithm with enhanced performance for specific population groups. Previous warfarin dosing algorithms underestimated warfarin doses in. A total of 109 patients carrying. This is the first study to develop and validate a warfarin dosing algorithm based on data from

Topics: Adult; Aged; Aged, 80 and over; Algorithms; Anticoagulants; Asian People; Atrial Fibrillation; Cytochrome P-450 CYP2C9; Dose-Response Relationship, Drug; Female; Genotype; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Regression Analysis; Republic of Korea; Venous Thrombosis; Vitamin K Epoxide Reductases; Warfarin

In Asia, little information is available about contemporary real-world treatment patterns for venous thromboembolism (VTE).Methods and Results:Consecutive patients (n=11,414) from the Taiwan National Health Insurance Research Database with initial VTE and taking oral anticoagulants between May 1, 2014 and June 30, 2016 were included. The temporal trends of using oral anticoagulants and pharmacomechanical therapy during the study period were evaluated. The efficacy and safety of nonvitamin K antagonist oral anticoagulants (NOACs) vs. warfarin were compared. Propensity score analysis (NOACs n=3,647 vs. warfarin n=3,647) was used to balance covariates between groups, and Cox proportional hazards models with adjustment were used to estimate the risks of clinical outcomes. The use of NOACs increased from 0.3% to 60.2% for VTE treatment during the study period. Pharmacomechanical therapy was used in 9.60%, 8.22%, and 5.63% from 2014 through 2016. NOACs were associated with a 16% risk reduction (adjusted hazard ratio [aHR] 0.84, 95% confidence interval [CI] 0.77-0.93) in all-cause mortality and a 21% risk reduction (aHR 0.79, 95% CI 0.65-0.96) in recurrent VTE vs. warfarin. Overall, NOACs were associated with a lower risk of major bleeding compared with warfarin (aHR 0.804, 95% CI 0.648-0.998).. In real-world practice, NOACs have become the major anticoagulant used for Asians with VTE. Although NOACs had a lower risk of recurrent VTE and major bleeding compared with warfarin in Taiwan, we still need a large-scale randomized controlled trial to confirm the findings.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Databases, Factual; Drug Utilization; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Mechanical Thrombolysis; Middle Aged; Practice Patterns, Physicians'; Pulmonary Embolism; Risk Assessment; Risk Factors; Taiwan; Thromboembolism; Thrombolytic Therapy; Time Factors; Treatment Outcome; Venous Thrombosis; Warfarin

Low molecular weight heparins (LMWHs) and direct oral anticoagulants (DOACs) are among the recommended treatment options for cancer-associated thrombosis (CAT) in the 2019 National Comprehensive Care Network guidelines. Little is known about the current utilization of DOACs in CAT patients, particularly on the inpatient to outpatient therapy transition. This study assessed real-world treatment patterns of CAT in hospital/ED in adult cancer patients (≥ 18 years) diagnosed with CAT during a hospital visit in IQVIA's Hospital Charge Data Master database between July 1, 2015 and April 30, 2018, and followed their outpatient medical and pharmacy claims to evaluate the initial inpatient/ED and outpatient anticoagulants received within 3 months post-discharge. Results showed that LMWH and unfractionated heparin (UFH) were the most common initial inpatient/ED CAT treatments (35.2% and 27.4%, respectively), followed by DOACs (9.6%); 20.8% of patients received no anticoagulants. Most DOAC patients remained on DOACs from inpatient/ED to outpatient settings (71.4%), while 24.1%, 43.5%, and 0.1% of patients treated with LMWH, warfarin, or UFH respectively, remained on the same therapy after discharge. In addition, DOACs were the most common initial post-discharge outpatient therapy. Outpatient treatment persistence and adherence appeared higher in patients using DOACs or warfarin versus LMWH or UFH. This study shows that DOACs are used as an inpatient/ED treatment option for CAT, and are associated with less post-discharge treatment switching and higher persistence and adherence. Further research generating real-world evidence on the role of DOACs to help inform the complex CAT clinical treatment decisions is warranted.

Topics: Aged; Aged, 80 and over; Ambulatory Care; Anticoagulants; Databases, Factual; Drug Substitution; Drug Utilization; Factor Xa Inhibitors; Female; Heparin; Humans; Inpatients; Male; Medication Adherence; Middle Aged; Neoplasms; Patient Discharge; Practice Patterns, Physicians'; Retrospective Studies; Time Factors; Treatment Outcome; United States; Venous Thrombosis; Warfarin

Oral anticoagulation options for patients with venous thromboembolism (VTE) include vitamin K antagonists like warfarin. Good warfarin control is linked to outcomes of therapy, and the SAMe-TT

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation; Female; Humans; Male; Middle Aged; Queensland; Retrospective Studies; Venous Thromboembolism; Venous Thrombosis; Warfarin

The incidence of venous thromboembolism (VTE) following arthroplasty and hip fracture surgery remains an important metric for quality and financial reasons. An audit at our institution between 2006-2010 showed a higher VTE rate than international data did at the time. This study aims to determine rates of DVT and PE in patients undergoing hip and knee arthroplasty and hip fracture surgery at Waitemata District Health Board (Waitemata DHB) between 1 January 2013 and 31 December 2016.. This study is a retrospective review of all VTE within three months of elective hip or knee replacement or hip fracture surgery. Data were identified for the period between 2013 and 2016 from Waitemata DHB patient databases, including a dedicated VTE database.. The current rates of deep vein thrombosis (DVT) and pulmonary embolism (PE) at our institution following hip or knee arthroplasty or hip fracture surgery are 1.5% and 0.6% respectively, a lower rate than 2.3% and 0.9% respectively in 2006-2010. DVTs were significantly more prevalent after hip fracture surgery than after elective hip or knee arthroplasty, and 71% of DVTs were confined to the distal veins. Of the patients undergoing surgery, 93% received post-operative chemoprophylaxis, mainly aspirin or low molecular-weight heparin (LMWH).. There has been a significant reduction in VTE rates following elective hip and knee joint replacement and hip fracture surgery between the time periods. This occurred over a period when Waitemata DHB introduced a multi-modal, interdisciplinary team approach to VTE prophylaxis utilising enhanced recovery after surgery (ERAS) pathways. These measures may therefore have contributed to the reduction in VTEs.

Topics: Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Female; Heparin, Low-Molecular-Weight; Hip Fractures; Humans; Incidence; Male; Medical Audit; New Zealand; Orthopedic Procedures; Platelet Aggregation Inhibitors; Postoperative Complications; Pulmonary Embolism; Venous Thromboembolism; Venous Thrombosis; Warfarin

Randomized controlled trials leading to the approval of apixaban and rivaroxaban for venous thromboembolism (VTE) did not include patients with upper extremity deep vein thrombosis (UE-DVT). We sought to evaluate the safety and effectiveness of rivaroxaban and apixaban for the treatment of acute UE-DVT. Consecutive patients with VTE enrolled into the Mayo Clinic VTE Registry, between March 1, 2013 and December 31, 2019, were followed prospectively. Clinical, demographic and imaging data were collected at the time of study recruitment. Patients with a diagnosis of acute UE-DVT who received rivaroxaban, apixaban, LMWH or warfarin were included. Recurrent VTE, major bleeding, clinical-relevant non-major bleeding (CRNMB), and death were assessed at 3-month intervals. During the study period, 210 patients with acute UE-DVT were included; 63 were treated with apixaban, 39 with rivaroxaban, and 108 with LWMH and/or warfarin. Overall 51% had catheter-associated UE-DVT, 60% had a diagnosis of malignancy, and 14% had concurrent pulmonary embolism. Malignancy was more common in patients treated with LMWH/warfarin (67% vs 52%, P = .03). At 3 months of follow up, one (0.9%) recurrent VTE occurred in a patient treated with LMWH/warfarin and one (1.0%) patient treated with apixaban or rivaroxaban (P = .97). Major bleeding occurred in three patients treated with LMWH/warfarin, and in none of those treated with apixaban or rivaroxaban (P = .09). Clinical-relevant non-major bleeding occurred in one patient (0.9%) treated with LWMH/warfarin and two patients (2.0%) treated with apixaban or rivaroxaban (P = .53). Treatment of UE-DVT with apixaban or rivaroxaban appears to be as safe and effective as LMWH/warfarin.

Topics: Aged; Female; Follow-Up Studies; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Registries; Rivaroxaban; Upper Extremity; Venous Thrombosis; Warfarin

Topics: Administration, Oral; Anticoagulants; Antithrombins; Atrial Fibrillation; Cardiac Surgical Procedures; Dabigatran; Drug Substitution; Female; Humans; Middle Aged; Pulmonary Veins; Pulmonary Veno-Occlusive Disease; Treatment Outcome; Vascular System Injuries; Venous Thrombosis; Warfarin

We aimed to validate the Men Continue and HERDOO2 (HERDOO2), D-dimer, age, sex, hormonal therapy (DASH), and updated Vienna recurrent venous thromboembolism prediction models in a population composed entirely of first unprovoked pulmonary embolism, and to analyze the impact of the addition of the pulmonary vascular obstruction index (PVOI) on score accuracy.. Analyses were based on the double-blind, randomized PADIS-PE trial, which included 371 unprovoked pulmonary embolism patients initially treated for 6 months, successively randomized to receive an additional 18 months of warfarin or placebo, and subsequently followed-up for 2 years.. The HERDOO2, DASH, and updated Vienna scores displayed C-statistics of 0.61 (95% CI 0.54-0.68), 0.60 (95% CI 0.53-0.66), and 0.58 (95% CI 0.51-0.66), respectively. Only the HERDOO2 score identified low recurrence risk patients (<3%/year) after anticoagulation was stopped. When added to either of the prediction models, PVOI measured at pulmonary embolism diagnosis, after 6 months of anticoagulation, or both, improved scores' C-statistics between +0.06 and +0.11 points and consistently led to identifying at least 50% of patients who experienced recurrence but in whom the scores would have indicated against extended anticoagulation.. In patients with a first unprovoked pulmonary embolism, the HERDOO2 score is able to identify patients with a low recurrence risk after treatment discontinuation. Addition of PVOI improves accuracy of all scores.. URL: http://www.controlled-trials.com. Unique identifier: NCT00740883.

Topics: Adult; Age Factors; Aged; Anticoagulants; Duration of Therapy; Female; Fibrin Fibrinogen Degradation Products; Humans; Male; Middle Aged; Proportional Hazards Models; Pulmonary Embolism; Randomized Controlled Trials as Topic; Recurrence; Risk Assessment; Sex Factors; Venous Thromboembolism; Venous Thrombosis; Ventilation-Perfusion Scan; Warfarin

Dengue fever is a hemorrhagic fever caused by flaviviruses. Hemorrhagic manifestations are well known to be associated with dengue fever, though the thrombotic events are only seldom reported. Underlying pathophysiology of thrombotic events is multifactorial and the management is challenging due to associated thrombocytopenia and bleeding tendency. We report a case of dengue shock syndrome with severe thrombocytopenia complicated by ilio-femoral deep vein thrombosis.. A 16 year old boy presented with dengue fever. He had dengue shock syndrome after entering the critical phase on the fifth day of the illness. With the recovery from the critical phase he developed deep vein thrombosis involving right external iliac, common femoral and superficial femoral veins. There were no provocative factors other than dengue fever itself. His platelet count was 12,000/μl at the time of diagnosis with deep vein thrombosis. Anticoagulation was started with intravenous unfractionated heparin 500 IU/hour while closely being observed for bleeding complications. 1000 IU/hour dose was commenced with the recovery of the platelet count above 50,000/μl. Thrombophilia screening was negative and he was discharged on warfarin. Venous duplex done after 6 weeks showed normal lower limb venous flow and warfarin was omitted after three months.. With dengue fever, complications like deep vein thrombosis can be easily missed given its rarity and that the major concern is on hemorrhagic complications. Management is challenging due to associated thrombocytopenia and hemorrhagic complications.

Topics: Administration, Intravenous; Adolescent; Anticoagulants; Antigens, Viral; Dengue Virus; Femoral Vein; Heparin; Humans; Lower Extremity; Male; Severe Dengue; Thrombocytopenia; Treatment Outcome; Venous Thrombosis; Warfarin

Topics: Adult; Anticoagulants; Basal Ganglia Hemorrhage; Betacoronavirus; Brain; Cerebral Angiography; Cerebral Hemorrhage; Comorbidity; Computed Tomography Angiography; Coronavirus Infections; COVID-19; Diabetes Mellitus, Type 2; Endothelium, Vascular; Female; Frontal Lobe; Heparin, Low-Molecular-Weight; Humans; Hypertension; Magnetic Resonance Imaging; Male; Middle Aged; Myocardial Ischemia; Pandemics; Pneumonia, Viral; Pulmonary Embolism; Retrospective Studies; Risk Factors; SARS-CoV-2; Severity of Illness Index; Tomography, X-Ray Computed; Venous Thrombosis; Warfarin

We describe an extremely rare case of idiopathic spontaneous extensive venous thrombosis in a young man involving the inferior vena cava, the iliac veins and both renal veins associated with right haemorrhagic renal infarction with non-functioning right kidney.

Topics: Administration, Intravenous; Adult; Computed Tomography Angiography; Drug Substitution; Fibrinolytic Agents; Flank Pain; Heparin; Humans; Iliac Vein; Infarction; Kidney; Kidney Function Tests; Male; Renal Veins; Treatment Outcome; Vena Cava, Inferior; Venous Thrombosis; Warfarin

Limited economic evaluation data for rivaroxaban compared with standard of care (SoC) exists in China. The objective of this analysis was to evaluate the cost-effectiveness of rivaroxaban compared with current SoC (enoxaparin overlapped with warfarin) for the treatment of acute deep vein thrombosis (DVT) in China.. A Markov model was adapted from a payer's perspective to evaluate the costs and quality-adjusted life years (QALYs) of patients with DVT treated with rivaroxaban or enoxaparin/warfarin. Clinical data from the EINSTEIN-DVT trial were obtained to estimate the transition probabilities. Data on Chinese health resource use, unit costs and utility parameters were collected from previously published literature and used to estimate the total costs and QALYs. The time horizon was set at 5 years and a 3-month cycle length was used in the model. A 5% discount rate was applied to the projected costs. One-way sensitivity analyses and probabilistic sensitivity analyses were undertaken to assess the impact of uncertainty on results.. Rivaroxaban therapy resulted in an increase of 0.008 QALYs and was associated with lower total costs compared with enoxaparin/warfarin (US$4744.4 vs US$5572.4, respectively), demonstrating it to be a cost-saving treatment strategy. The results were mainly sensitive to length of hospitalisation due to DVT on enoxaparin/warfarin, cost per day of hospitalisation and the difference in length of stay of rivaroxaban-treated and enoxaparin/warfarin-treated patients.. Rivaroxaban therapy resulted in a cost saving compared with enoxaparin/warfarin for the anticoagulation treatment of patients with hospitalised acute DVT in China.. NCT00440193; Post-results.

Topics: Anticoagulants; China; Cost-Benefit Analysis; Enoxaparin; Humans; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis; Warfarin

This analysis examined the frequency of dural arteriovenous fistulae (dAVF) after cerebral venous thrombosis (CVT) in patients included in a randomized controlled trial comparing dabigatran etexilate with dose-adjusted warfarin (RE-SPECT CVT [A Clinical Trial Comparing Efficacy and Safety of Dabigatran Etexilate With Warfarin in Patients With Cerebral Venous and Dural Sinus Thrombosis]), who had systematic follow-up magnetic resonance (MR) imaging.. RE-SPECT CVT was a Phase 3, prospective, randomized, parallel-group, open-label, multicenter, exploratory trial with blinded end point adjudication. We allocated patients with acute CVT to dabigatran 150 mg twice daily or dose-adjusted warfarin, for 24 weeks and obtained a standardized MR protocol including time-of-flight MR angiography, 3-dimensional phase-contrast venography, and 3-dimensional contrast-enhanced MR venography at the end of the treatment period. A blinded adjudication committee assessed the presence of dAVF in a predefined substudy of the trial.. We analyzed development of dAVF in 112 of 120 randomized patients; 57 allocated to dabigatran and 55 to warfarin. For 3 (2.7%) of these 112 patients, quality of follow-up imaging was insufficient to evaluate dAVF. A dAVF (Borden I) was found in 1 patient (0.9%) allocated to warfarin; however, this dAVF was already present at baseline. The patient did not present with hemorrhage at baseline or during the trial and was asymptomatic at follow-up.. Despite systematic imaging, we found no new dAVF 6 months after CVT. Routine follow-up cerebral MR angiography aiming to detect new dAVF 6 months after CVT has a very low yield. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02913326.

Topics: Adult; Anticoagulants; Antithrombins; Arteriovenous Fistula; Central Nervous System Vascular Malformations; Cerebral Angiography; Cerebral Veins; Cranial Sinuses; Dabigatran; Female; Humans; Imaging, Three-Dimensional; Intracranial Thrombosis; Magnetic Resonance Angiography; Male; Meningeal Arteries; Middle Aged; Randomized Controlled Trials as Topic; Secondary Prevention; Sinus Thrombosis, Intracranial; Venous Thrombosis; Warfarin

A case of a possible interaction between cannabidiol and warfarin is presented along with a brief overview of cytochrome enzymes involved in these drugs' metabolism.. A 46-year-old male taking warfarin for treatment of a deep venous thrombosis was initiated on a Food and Drug Administration (FDA)-approved cannabidiol product (Epidiolex, Greenwich Biosciences) for intractable epilepsy. The patient's International Normalized Ratio (INR) was monitored closely during cannabidiol initiation and dose titration. The patient required a nearly 20% warfarin dose reduction to maintain an INR within the goal range after starting therapy with cannabidiol. There is 1 other case report describing a clinically significant interaction between cannabidiol (specifically Epidiolex) and warfarin in a patient receiving warfarin who was enrolled in a study involving the initiation and titration of cannabidiol; that patient developed a supratherapeutic INR of 6.86 and required a 30% reduction in the weekly warfarin dose to reachieve the goal INR.. A previously published report suggesting an interaction between cannabidiol and warfarin is supported by this case report. INR should be monitored frequently in patients taking warfarin who begin to take FDA-approved cannabidiol. Additional studies should be performed to clarify the interaction potential of cannabidiol and warfarin.

Topics: Anticoagulants; Cannabidiol; Dose-Response Relationship, Drug; Drug Interactions; Drug Resistant Epilepsy; Humans; International Normalized Ratio; Male; Middle Aged; Venous Thrombosis; Warfarin

Debate over the ideal agent for venous thromboembolism (VTE) prophylaxis after total hip arthroplasty (THA) has led to changes in prescribing trends of commonly used agents. We investigate variation in utilisation and the differences in VTE incidence and bleeding risk in primary THA after administration of aspirin, warfarin, enoxaparin, or factor Xa inhibitors.. 8829 patients were age/sex matched from a large database of primary THAs performed between 2007 and 2016. Utilisation was calculated using compound annual growth rate. Incidence of postoperative deep venous thrombosis (DVT), pulmonary embolism (PE), bleeding-related complications, postoperative anaemia, and transfusion were identified at 2 weeks, 30 days, 6 weeks, and 90 days.. Aspirin use increased by 33%, enoxaparin by 7%, and factor Xa inhibitors by 31%. Warfarin use decreased by 1%. Factor Xa inhibitors (1.7%) and aspirin (1.7%) had the lowest incidence of DVT followed by enoxaparin (2.6%), and warfarin (3.7%) at 90 days. Factor Xa inhibitors (12%) and aspirin (12%) had the lowest incidence of blood transfusion followed by warfarin (15%) and enoxaparin (17%) at 90 days. There was no difference in incidence of blood transfusion or bleeding-related complications nor any detectable difference in symptomatic PE incidence.. The utilisation of aspirin and factor Xa inhibitors increased over time. Aspirin and factor Xa inhibitors provided improved DVT prophylaxis with lower rates of postoperative anaemia compared to enoxaparin and warfarin.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Aspirin; Enoxaparin; Factor Xa Inhibitors; Female; Humans; Incidence; Male; Middle Aged; Pulmonary Embolism; Venous Thromboembolism; Venous Thrombosis; Warfarin

A 73-year-old man presented for evaluation of weakness and black tarry stools that occurred 1 day prior to admission. His medical history is significant for diabetes mellitus, stage 3 chronic kidney disease and deep vein thrombosis on warfarin. He was admitted to the hospital and was found to have acute kidney injury and gastrointestinal bleeding due to a supratherapeutic International Normalized Ratio. His hospital course was complicated by persistent decline in his renal function. He was given intravenous fluid resuscitation, fresh frozen plasma and packed red blood cells for his acute blood loss anaemia. Urinalysis was consistent with acute tubular necrosis. Given the persistent rise in creatinine, a kidney biopsy was obtained, and was significant for mild inflammatory changes, without evidence of vasculitis or allergic interstitial nephritis. Histopathological examination with tissue fixation revealed cholesterol embolisation. Given that he had no recent endovascular procedure or instrumentation, this atheroembolic event was attributed to his warfarin use.

Topics: Aged; Anticoagulants; Diagnosis, Differential; Embolism, Cholesterol; Gastrointestinal Hemorrhage; Humans; Male; Muscle Weakness; Nephritis, Interstitial; Venous Thrombosis; Warfarin

Topics: Adult; Anticoagulants; Edema; Female; Humans; Low Back Pain; May-Thurner Syndrome; Venous Thrombosis; Warfarin

to compare two anticoagulant therapy (ACT) regimens in the treatment of venous thrombosis (VT) in patients after catheter interventions - electrophysiological studies (EFIs) and ablations: enoxaparin followed by warfarin, and rivaroxaban monotherapy.. The study included patients from 18 years and older with heart rhythm disorders and planned catheter ablation. When parietal venous thrombosis (VT) were detected at the femoral vein puncture site, all patients were randomly assigned to two treatment groups. In group I enoxaparin 1 mg/kg was prescribed every 12 hours with switching to warfarin after 7 days with maintenance of the target INR values (2.0-3.0). In group II rivaroxaban therapy was started at a dose of 15 mg twise/day for 21 days with a further transition to a dose of 20 mg/day. The total period of observation and treatment of patients was at least 3 months.. 408 patients were observed, 42 (10.3%) patients with parietal VT were divided into two treatment groups. In group I (n=16) complete lysis of VT was noted by the 7th day of treatment in 7 (58.3%) patients, however this scheme was associated with a greater risk of complications (р=0.003) at the puncture site in the form of arteriovenous fistulae (n=1; 8.3%) and intermuscular hematomas (n=4; 25%). In group II (n=26), no complications were noted, the lysis time of VT was on average 21 days (n=18; 69.2%). Complete lysis of VT was noted in both groups at the time of the control observation point (3rd month).. The efficiency of the two VT treatment regimens was comparable. Enoxaparin therapy is associated with a high risk of local complications, namely intermuscular hematomas (n=4; 25%) and arteriovenous fistulas (n=1; 8.3%). Rivaroxaban monotherapy is safer (p=0.003); in Group II none of the patients had any complications.. Цель исследования: сравнить две схемы антикоагулянтной терапии (АКТ) в лечении венозных тромбозов (ВТ) у пациентов после внутрисердечных катетерных вмешательств - электрофизиологических исследований (ЭФИ) и абляций: эноксапарина с последующим назначением варфарина и монотерапии ривароксабаном. Материалы и методы. В исследование включали пациентов от 18 лет с нарушениями ритма сердца и планируемыми катетерными вмешательствами. При выявлении пристеночного ВТ в месте пункции бедренной вены пациентов рандомизировали на две группы лечения: в группе I проводилась АКТ эноксапарином 1 мг/кг каждые 12 ч с переходом на варфарин через 7 дней с поддержанием целевых значений международного нормализованного отношения (2,0-3,0), в группе II - АКТ ривароксабаном 15 мг 2 раза/сут в течение 21 дня с дальнейшим переходом на дозу 20 мг/сут. Срок наблюдения и лечения пациентов составил 3 мес. Результаты. Наблюдали 408 пациентов, из них 42 (10,3%) пациента с пристеночным ВТ распределили на две группы лечения. В группе I (n=16) у 7 (58,3 %) больных отмечен полный лизис ВТ к 7-му дню лечения, однако эта схема сопряжена с большим риском осложнений (р=0,003) со стороны места пункции в виде артериовенозных соустий (n=1; 6,25%), межмышечных гематом (n=4; 25%). В группе II (n=26) осложнений не отмечалось, время лизиса ВТ в среднем составило 21 день (n=18; 69,2%). В обеих группах на момент проведения контрольной точки наблюдения (3-й месяц) отмечен полный лизис ВТ. Заключение. Эффективность двух схем лечения ВТ оказалась сопоставимой. Терапия эноксапарином сопряжена с большим риском развития местных осложнений: межмышечных гематом (n=4; 25%), артериовенозных соустий (n=1; 8,3%). Монотерапия ривароксабаном была более безопасна (р=0,003), в группе II осложнений не отмечено.

Topics: Anticoagulants; Cardiac Catheters; Enoxaparin; Humans; Rivaroxaban; Treatment Outcome; Venous Thrombosis; Warfarin

Topics: Aged, 80 and over; Arthroplasty; Echocardiography; Female; Foramen Ovale, Patent; Heart Ventricles; Hip; Humans; Multimodal Imaging; Pulmonary Embolism; Thrombosis; Venous Thrombosis; Warfarin

To study the incidence, clinical risk factors and outcome of thrombotic events in pediatric age group of 1 mo-12 y.. This prospective observational study was conducted in a tertiary care institute from September 2015 through October 2017. Forty nine children with thrombosis from 1 mo-12 y were enrolled.. Out of 49 cases, 30 (61.2%) were due to venous thromboembolism (VTE) and 19 (38.8%) were of arterial thromboembolism (ATE). The cumulative average annual incidence for VTEs was found to be 38.2 (n = 30) and for ATEs it was found to be 24.2 (n = 19) per 10,000 hospital admissions over 2 y of study period. With total of 19 (38.7%), catheters were the leading cause of thrombosis followed by infection numbering to 10 cases (20.4%). Total 42.8% cases (n = 21) achieved complete resolution. Partial resolution was noted in 53.2% of cases (n = 26) and no resolution in 4% cases (n = 2). Total seven (14.3%) deaths were recorded during the study period.. The present study showed that thrombosis is an emerging problem in tertiary care setting adding to both mortality and morbidity in children. Central venous catheters followed by infection were the leading cause of thrombosis in this study.

Topics: Activated Protein C Resistance; Anticoagulants; Antithrombin III; Child; Child, Preschool; Female; Heparin; Heparin, Low-Molecular-Weight; Humans; Incidence; Infant; Male; Prospective Studies; Risk Factors; Thrombosis; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis; Warfarin

Topics: Aged; Anticoagulants; Blood Coagulation; Female; Heparin; Humans; Treatment Outcome; Vena Cava, Inferior; Venous Thrombosis; Warfarin

Thromboembolic events after total joint arthroplasty are potentially devastating complications. This study evaluated the efficacy of 4 different anticoagulants in preventing deep venous thrombosis and pulmonary embolism after total joint arthroplasty. The demographics and anticoagulant use (warfarin, enoxaparin, and aspirin with and without outpatient mechanical pumps) for patients who underwent primary unilateral total joint arthroplasties performed by a single surgeon from January 2013 to October 2014 were retrospectively reviewed. All patients underwent lower extremity ultrasound at the 3-week postoperative visit. A total of 613 primary unilateral total joint arthroplasties met the study inclusion criteria. There were 288 primary total knee arthroplasties and 325 primary total hip arthroplasties. The patients were 62.2% female, having a mean age of 67.6±10.6 years and a mean body mass index of 30.2±5.9 kg/m

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Chemoprevention; Drug Therapy, Combination; Enoxaparin; Female; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Postoperative Complications; Retrospective Studies; Venous Thrombosis; Warfarin

Renown Health (Reno, Nevada), a large, locally owned, not-for-profit integrated health care network, has developed an institution-wide policy to shift the treatment of deep vein thrombosis (DVT) from a short-acting anticoagulant and vitamin K antagonist to the direct oral anticoagulant rivaroxaban combined with pharmacy-directed follow-up at an outpatient anticoagulation clinic. We examined data on hospitalizations and costs pre-/post-policy change.. Data were obtained from the electronic health records of adults with newly diagnosed DVT treated at Renown Health. A quasi-experimental design was used to evaluate patients who received a DVT diagnosis before versus after the policy change. Primary outcomes were number of all-cause inpatient nights at 30 and 60 days post-DVT index date. Secondary outcomes were costs of all-cause overnight stays at 30 and 60 days post-DVT index. Outcomes were evaluated in propensity-weighted logistic regression and generalized linear models.. There were 343 patients pre-policy change and 266 post-policy change. In the first 30 days postindex, the mean (95% CI) numbers of propensity-weighted all-cause inpatient nights were 1.27 (0.83-1.95) prechange and 0.66 (0.42-1.02) postchange (P = 0.038). Mean propensity-weighted estimated all-cause hospital costs in patients diagnosed as outpatients were $7848 ($4990-$12,344) prechange and $2466 ($1553-$3915) postchange (P <0.001). Mean costs of all-cause overnight stays in inpatient-diagnosed DVT patients were $8907 prechange and $7449 postchange (P = 0.600). In the first 60 days postindex, the mean number of all-cause inpatient nights (P = 0.219) and mean costs of all-cause overnight stays (P = 0.275) were not significantly different before and after the policy change.. Changing institutional policy to increase the utilization of a direct oral anticoagulant and pharmacist-led outpatient anticoagulation clinics may reduce length of hospital stay and decrease health care expenditures in the treatment of DVT.

Topics: Adult; Aged; Anticoagulants; Female; Health Care Costs; Hospitalization; Humans; Inpatients; Male; Middle Aged; Organizational Policy; Outpatients; Rivaroxaban; Venous Thrombosis; Warfarin

Many strategies for venous thromboembolism (VTE) prophylaxis following hip and knee arthroplasty exist, with extensive controversy regarding the optimum strategy to minimize risk of VTE and bleeding complications. Data from the American Board of Orthopedic Surgery Part II (oral) Examination case list database was analyzed to determine efficacy, complication rates, and prescribing patterns for different prophylactic strategies.. The American Board of Orthopedic Surgery case database was queried utilizing Current Procedural Terminology codes 27447 and 27130 for primary total knee and hip arthroplasty, respectively. Geographic region, patient age, gender, deep vein thrombosis prophylaxis strategy, and complications were obtained. Less aggressive prophylaxis patterns were considered if only aspirin and/or sequential compression devises were utilized. More aggressive VTE prophylaxis patterns were considered if any of low-molecular-weight heparin (enoxaparin), warfarin, rivaroxaban, fondaparinux, or other strategies was used.. In total, 22,072 cases of primary joint arthroplasty were analyzed from 2014 to 2016. The national rate of less aggressive VTE prophylaxis strategies was 45.4%, while more aggressive strategies were used in 54.6% of patients. Significant regional differences in prophylactic strategy patterns exist between the 6 regions. The predominant less aggressive prophylaxis pattern was aspirin with sequential compression devises at 84.8% with 14.8% receiving aspirin alone. Use of less aggressive prophylaxis strategy was significantly associated with patients having no complications (95.5% vs 93.0%). Use of more aggressive prophylaxis patterns was associated with higher likelihood of mild thrombotic (0.9% vs 0.2%), mild bleeding (1.3% vs 0.4%), moderate thrombotic (1.2% vs 0.4%), moderate bleeding (2.7% vs 2.1%), severe thrombotic (0.1% vs 0.0%), severe bleeding events (1.2% vs 0.9%), infections (1.9% vs 1.3%), and death within 90 days (0.7% vs 0.3%). Similar results were found in subgroup analysis of total hip and knee arthroplasty patients.. It was not possible to ascertain the individual rationale for use of more aggressive VTE prophylaxis strategies; however, more aggressive strategies were associated with higher rates of bleeding and thrombotic complications. Less aggressive strategies were not associated with a higher rate of thrombosis.. Therapeutic Level III.. All views expressed in the study are the sole views of the authors and do not represent the views of the American Board of Orthopedic Surgery.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Databases, Factual; Enoxaparin; Female; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Orthopedic Procedures; Orthopedics; Practice Patterns, Physicians'; Risk Factors; Rivaroxaban; United States; Venous Thromboembolism; Venous Thrombosis; Warfarin

Topics: Behcet Syndrome; Humans; Thrombosis; Vasculitis; Venous Thrombosis; Warfarin

To evaluate the accuracy and predictive performance of Bayesian dosing for warfarin in Chinese patients.. Six multiple linear regression algorithms (Wei, Lou, Miao, Huang, Gage and IWPC) and a Bayesian method implemented in Warfarin Dose Calculator were compared with each other.. Six multiple linear regression warfarin dosing algorithms had similar predictive ability, except Miao and Lou. The mean prediction error of Bayesian priori and posteriori method were 0.01 mg/day (95% CI: -0.18 to 0.19) and 0.17 mg/day (95% CI: -0.05 to 0.29), respectively, and Bayesian posteriori method demonstrated better performance in all dose ranges.. The Bayesian method showed a good potential for warfarin maintenance dose prediction in Chinese patients requiring less than 6 mg/day.

Topics: Adult; Aged; Aged, 80 and over; Algorithms; Anticoagulants; Atrial Fibrillation; Bayes Theorem; Cytochrome P-450 CYP2C9; Dose-Response Relationship, Drug; Ethnicity; Female; Genotype; Humans; International Normalized Ratio; Linear Models; Male; Middle Aged; Pharmacogenetics; Pulmonary Embolism; Venous Thrombosis; Warfarin

Ischemic stroke is a complex multifactorial disorder. Anticoagulation is a growing research area, with the main goal of preventing systemic embolization and stroke. We report the case of a 41-year-old woman with antiphospholipid syndrome who was unsuccessfully treated with Dabigatran, a new oral anticoagulant, as she developed a major stroke involving the right carotid artery, due to deep venous thrombosis with pulmonary embolism. We therefore suggest a closer monitoring of the safety and efficacy of dabigatran. Moreover, in the presence of multifactorial causes of pro-coagulation, we believe that warfarin should remain the mainstay of oral anticoagulation.

Topics: Abortion, Spontaneous; Acenocoumarol; Adult; Antiphospholipid Syndrome; Antithrombins; Carotid Arteries; Computed Tomography Angiography; Dabigatran; Female; Follow-Up Studies; Humans; Product Surveillance, Postmarketing; Pulmonary Embolism; Stroke; Treatment Outcome; Venous Thrombosis; Warfarin

Topics: Achilles Tendon; Aged; Anticoagulants; Factor V; Humans; Inappropriate Prescribing; Incidental Findings; Male; Mutation; Thrombophilia; Unnecessary Procedures; Venous Thrombosis; Warfarin

This study evaluated the trends in anticoagulation use after total hip arthroplasty (THA), and the effectiveness and safety of rivaroxaban compared to warfarin.. This retrospective database analysis used healthcare claims from the Truven Health MarketScan database (2010-2015). Patients undergoing elective THA were followed for use of anticoagulants after surgery. Logistic regression models were used to compare differences in deep vein thrombosis (DVT), pulmonary embolism (PE), and adverse events, within 90 days after THA, among warfarin and rivaroxaban users. Inverse probability treatment weighting was used to account for selection bias.. There were 12,876 users of warfarin and 10,892 users of rivaroxaban in commercially insured (CI) patients, and 7416 warfarin users and 4739 rivaroxaban users in Medicare supplement (MS) patients. Warfarin use decreased over time in both insurance cohorts, whereas rivaroxaban use increased from 2011 to 2015. Warfarin users were significantly more likely to experience both DVT (CI: odds ratio [OR] 2.63, 95% confidence interval 1.97-3.50; MS: OR 1.78, 95% confidence interval 1.38-2.29) and PE (CI: OR 2.60, 95% confidence interval 2.04-3.31; MS: OR 2.09, 95% confidence interval 1.66-2.65). There was no significant difference in rates of bleeding between the 2 agents, but warfarin users had higher odds of periprosthetic joint infection in both cohorts (CI: OR 1.57, 95% confidence interval 1.16-2.13; MS: OR 1.79, 95% confidence interval 1.14-2.81).. There has been an increase in prophylaxis with rivaroxaban, and a decrease in warfarin use after elective THA over 4 years. Warfarin users were more likely to experience DVT and PE than rivaroxaban, and bleeding risks were similar.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Databases, Factual; Female; Health Services; Hemorrhage; Humans; Male; Medicare; Middle Aged; Odds Ratio; Pulmonary Embolism; Retrospective Studies; Rivaroxaban; United States; Venous Thrombosis; Warfarin

To compare the rates of deep venous thrombosis (DVT), rates of pulmonary embolus (PE), and complication profiles of warfarin and low-molecular-weight heparin (LMWH) in patients undergoing operative fixation of hip fractures.. Retrospective cohort study.. Insurance-based database of more than 22 million patient records.. Adult hip fracture patients who were treated operatively and received chemoprophylaxis from 2007 to 2016. A total of 7594 patients met inclusion criteria and were available for final analysis.. Pharmacological anticoagulation with warfarin or LMWH to prevent postoperative venous thromboembolism after hip fracture surgery.. Development of DVT or PE within 30 and 90 days of surgery.. Patients prescribed warfarin had higher rates of DVT and PE compared with those prescribed LMWH. Patients on warfarin were more likely to develop a postoperative hematoma and to be readmitted within 30 and 90 days compared with those on LMWH. Patients in both groups had similar rates of total complications.. Patients prescribed warfarin after hip fractures had higher rates of DVT and PE compared with those prescribed LMWH, although both agents had similar complication profiles.. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Topics: Aged; Aged, 80 and over; Anticoagulants; Chemoprevention; Female; Follow-Up Studies; Fracture Fixation, Internal; Heparin, Low-Molecular-Weight; Hip Fractures; Humans; Incidence; Male; Middle Aged; Postoperative Complications; Retrospective Studies; United States; Venous Thrombosis; Warfarin

To evaluate the cost of healthcare with respect to the quality of anticoagulation in patients with deep vein thrombosis (DVT) treated with warfarin in daily practice via the database analysis of a tertiary care center in the period 2010 to 2013.. Of 258 307 records in total, 42 582 unique patients with DVT and 32 012 patients with international normalized ratio (INR) measurements were included. Overall, 6720 unique patients with DVT diagnosis and one or more INR measurements were identified, and the records of 4377 out of 6720 unique patients were validated and included in the analysis data set. The cost analysis was based on direct medical costs from the payer's perspective. Cost items were related to healthcare resource utilization (inpatient and outpatient services) during the study period, which provided a basis for calculation of per-patient, outpatient, inpatient, and total direct medical costs.. Mean outpatient, inpatient, and total hospital admission costs were $578, $2195, and $2785, respectively, for patients with time in the therapeutic range of 70% or more, whereas the same costs were $571, $2163, and $3192, respectively, for patients with time in the therapeutic range of less than 70%.. Our findings for a retrospective cohort of patients with DVT undergoing warfarin therapy reveal that patients spent 70% or more, as opposed to less than 70%, of follow-up time within the therapeutic INR range and that outpatient care, as opposed to inpatient care, was associated with lower healthcare costs. Given the significant contribution that hospital stay makes to the cost burden of DVT, our findings also highlight the association between poor warfarin anticoagulant control and increased hospitalization costs.

Topics: Adolescent; Adult; Anticoagulants; Cost-Benefit Analysis; Databases, Factual; Female; Health Care Costs; Hospitalization; Humans; Male; Middle Aged; Retrospective Studies; Tertiary Care Centers; Turkey; Venous Thrombosis; Warfarin; Young Adult

Congenital abnormalities and pregnancy losses due to the teratogenic effects of warfarin are prevalent among the South African population. These are potentially preventable if the challenges and barriers faced by at-risk women are understood and addressed effectively.. To determine the practice, knowledge and attitudes regarding the teratogenic risks experienced by women administered warfarin.. A descriptive study was performed. Quantitative data were collected through a researcher-administered questionnaire. The target population comprised 101 women of reproductive age who received warfarin treatment and attended a single tertiary-level anticoagulation clinic.. Patient-related challenges identified in this study are: language barriers, poor understanding of basic terminology and mathematics, poor contraceptive and family planning practices, lack of knowledge regarding the risks of warfarin in pregnancy and passive attitudes towards information attainment.. Interventions are necessary to address the challenges in such settings. These include increased awareness of the teratogenic potential of specific chronic medications among healthcare providers, patients and the public. Standardised management protocols for women of reproductive age initiated on teratogenic medications should be implemented, including contraceptive and family planning discussions at follow-up visits. Improvement of the counselling skills of healthcare providers and the availability of translators or healthcare providers fluent in local languages could assist in risk reduction.

Topics: Abnormalities, Drug-Induced; Adolescent; Adult; Anticoagulants; Attitude to Health; Communication Barriers; Contraception Behavior; Embolism; Family Planning Services; Female; Health Knowledge, Attitudes, Practice; Heart Valve Prosthesis Implantation; Humans; Middle Aged; Patient Education as Topic; Pregnancy; Venous Thrombosis; Warfarin; Young Adult

Hypercoagulability can lead to thromboembolic events that are a life-threatening complication of nephrotic syndrome (NS). Conventional anticoagulants are first-line treatment in the presence of demonstrated thrombosis in NS. Direct-acting oral anticoagulants (DOACs) have provided useful alternatives for the prevention and treatment of thromboembolic events.. A 59-year-old male developed lower limbs deep vein thrombosis (DVT) during the early course of NS but presented poor response to oral therapeutic doses of rivaroxaban. The decision was made to switch from rivaroxaban to heparin and subsequently bridged to warfarin. The patient presented significant clinical symptom improvement.. NS with Lower limbs DVT.. Rivaroxaban was discontinued and switch to heparin and subsequently bridged to warfarin.. Venography result of both lower limb vein showed the venous wall was smooth without obvious stenosis or obstruction. Edema of the patient's lower limbs gradually improved and disappeared.. The existing published data on the application of DOACs in NS are limited. DOACs have an immediate anticoagulant effect and have demonstrated safety and efficacy and required no routine monitoring, however, application of these agents in NS likely requires further investigation before widespread adoption.

Topics: Anticoagulants; Humans; Male; Middle Aged; Nephrotic Syndrome; Rivaroxaban; Thrombophilia; Venous Thrombosis; Warfarin

We aimed to investigate the association between obesity and deep venous thrombosis (DVT) in a country with a high prevalence of obesity. This is a retrospective cohort study of patients who presented with DVT between 2008 and 2012. Data were analyzed and compared based on body mass index (BMI), and patients were classified into normal (<25), overweight (≥25 to <30), obese I (30 to <35), obese II (35 to <40), and obese III (≥40). Among 662 patients with DVT, 28% were overweight and 49% were obese. The mean age was 50.3 (16.5) years, and 51% were females. Diabetes mellitus and prior venous thromboembolism were significantly higher among obese patients. History of malignancy was more common in nonobese patients. Protein S and antithrombin III deficiency and hyperhomocysteinemia were more prevalent among morbid obese patients. Also, obese patients had higher incidence of thrombosis in the distal veins ( P = .03). Warfarin use and long-term therapy were more frequent in obese than nonobese. Postthrombotic syndrome was comparable in obese and nonobese groups. Recurrent DVT was higher in obese I ( P < .01), whereas mortality rates were greater in nonobese groups ( P = .001). Malignancy, diabetes mellitus, and common femoral vein involvement were predictors of mortality, whereas BMI ≥30 was the predictor of survival. Cox regression models showed that after adjusting for age, sex, pulmonary embolism, and duration of warfarin treatment, BMI ≥40 had better survival (hazard ratio: 0.177, 95% confidence interval: 0.045-0.691, P = .013). There is a significant association between obesity and DVT. Obese patients have characteristic risk factors and better survival. This obesity paradox needs further studies to assess its clinical and pharmacotherapeutic implications.

Topics: Adult; Aged; Antithrombin III; Diabetes Complications; Disease-Free Survival; Female; Follow-Up Studies; Humans; Male; Middle Aged; Obesity; Postthrombotic Syndrome; Prospective Studies; Protein S; Survival Rate; Venous Thrombosis; Warfarin

Since 2010, four oral anticoagulants have been approved for marketing in addition to warfarin for treatment of thromboembolic disease. Limited head-to-head data exist comparing these treatments, leaving patients and clinicians with little guidance for selecting a strategy that balances recurrence reduction with bleeding risk. In the dabigatran, apixaban, rivaroxban, edoxaban and warfarin comparative effectiveness research study, we compare all five currently available oral anticoagulant agents for the extended treatment of deep venous thrombosis and pulmonary embolism, as well as no extended treatment, and evaluate whether results differ in specific sub-populations. As our population includes Medicare novel anticoagulant users and large numbers of commercially insured and Medicaid patients, our results will likely be transportable to the majority of US patients experiencing a DVT or pulmonary embolism.. NCT03271450.

Topics: Anticoagulants; Antithrombins; Comparative Effectiveness Research; Dabigatran; Factor Xa Inhibitors; Humans; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Research Design; Rivaroxaban; Thiazoles; Venous Thrombosis; Warfarin

We assessed the efficacy and safety of direct oral anticoagulants (DOACs) for the treatment of deep venous thrombosis (DVT) in the chronic phase through comparison with conventional warfarin therapy.A total of 807 consecutive patients who were diagnosed with having DVT in the chronic phase were included (484 patients to warfarin therapy and 323 patients to DOAC therapy). The condition of leg veins was assessed 3 to 6 months after starting the therapies by ultrasound examination. Major bleeding and mortality during the therapies were followed-up.There was no significant difference between the two groups in the thrombosis improvement rate (DOAC group: 91.2% versus warfarin group: 88.9%). There was no significant difference between the two groups in major bleeding (DOAC group: 1.8% versus warfarin group: 1.8%). In patients with active cancer, the DOAC group had a borderline higher thrombosis improvement rate than the warfarin group (92.1% versus 80.0%, P = 0.05). The proportion of major bleeding in the patients with active cancer was slightly higher in the warfarin group than in the DOAC group (4.3% versus 2.8%; P = 0.71). Active cancer was not an independent risk factor for major bleeding and recurrence in the DOAC group (OR 2.68, 95% CI 0.51-14.1; P = 0.24 and OR 0.65, 95% CI 0.20-2.07; P = 0.47).In treatment using oral anticoagulants for DVT in the chronic phase, DOACs exhibited equal efficacy and safety as warfarin did. Particularly DOACs appear to be an attractive therapeutic option for cancer-associated DVT in chronic phase, with relatively low anticipated rates of recurrence and major bleeding.

Topics: Administration, Oral; Aged; Anticoagulants; Antithrombins; Chronic Disease; Dabigatran; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Female; Humans; Male; Pyrazoles; Pyridines; Pyridones; Recurrence; Thiazoles; Treatment Outcome; Ultrasonography; Venous Thrombosis; Warfarin

The aims of this study were to compare the efficacy of two agents, aspirin and warfarin, for the prevention of venous thromboembolism (VTE) after simultaneous bilateral total knee arthroplasty (SBTKA), and to elucidate the risk of VTE conferred by this procedure compared with unilateral TKA (UTKA).. A retrospective, multi-institutional study was conducted on 18 951 patients, 3685 who underwent SBTKA and 15 266 who underwent UTKA, using aspirin or warfarin as VTE prophylaxis. Each patient was assigned an individualised baseline VTE risk score based on a system using the Nationwide Inpatient Sample. Symptomatic VTE, including pulmonary embolism (PE) and deep vein thrombosis (DVT), were identified in the first 90 days post-operatively. Statistical analyses were performed with logistic regression accounting for baseline VTE risk.. The adjusted incidence of PE following SBTKA was 1.0% (95% confidence interval (CI) 0.86 to 1.2) with aspirin and 2.2% (95% CI 2.0 to 2.4) with warfarin. Similarly, the adjusted incidence of VTE following SBTKA was 1.6% (95% CI 1.1 to 2.3) with aspirin and 2.5% (95% CI 1.9 to 3.3) with warfarin. The risk of PE and VTE were reduced by 66% (odds ratio (OR) 0.44, 95% CI 0.25 to 0.78) and 38% (OR 0.62, 95% CI 0.38 to 1.0), respectively, using aspirin. In addition, the risk of PE was 204% higher for patients undergoing SBTKA relative to those undergoing UTKA. For each ten-point increase in baseline VTE risk, the risk of PE increased by 25.5% for patients undergoing SBTKA compared with 10.5% for those undergoing UTKA. Patients with a history of myocardial infarction or peripheral vascular disease had the greatest increase in risk from undergoing SBTKA instead of UTKA.. Aspirin is more effective than warfarin for the prevention of VTE following SBTKA, and serves as the more appropriate agent for VTE prophylaxis for patients in all risk categories. Furthermore, patients undergoing SBTKA are at a substantially increased risk of VTE, even more so for those with significant underlying risk factors. Patients should be informed about the risks associated with undergoing SBTKA. Cite this article:

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Knee; Aspirin; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Incidence; Logistic Models; Male; Middle Aged; Platelet Aggregation Inhibitors; Postoperative Complications; Pulmonary Embolism; Retrospective Studies; Risk Factors; Venous Thromboembolism; Venous Thrombosis; Warfarin

The incidence of venous thromboembolism (VTE) is lower in Asian populations than in Western populations. The objective of the present study was to evaluate the annual age- and sex-adjusted incidence (ASR) of VTE from 2009 to 2013 in South Korea. In addition, annual change in the pattern of VTE treatment during the study period was estimated because a new direct oral anticoagulant (DOAC) had become available and was covered by health insurance in Korea beginning in January 2013. VTE cases from 2009 to 2013 were retrospectively identified based on both diagnostic and medication codes of anticoagulants used for initial treatment using the Korean Health Insurance Review and Assessment Service (HIRA) databases. The incidence of VTE increased yearly. It was significantly higher in the older population than in the younger population, and it was higher in females than in males. In 2009, ASRs of VTE, deep vein thrombosis, and pulmonary embolism were 21.3, 8.1, and 13.2 cases per 100,000 individuals, respectively in 2009. These increased to 29.2, 12.7, and 16.6 cases per 100,000, respectively, in 2013. Prescription rates of warfarin and low-molecular-weight heparin decreased with the introduction of a new anticoagulant in 2013. The proportion of subjects who underwent mechanical procedures decreased annually. The ASR of VTE in Korea continuously increased from 2009 to 2013, reflecting an increased awareness and detection of VTE as well as improved survival of patients with cancer and other morbidities. Following its introduction, DOAC rapidly replaced other anticoagulants for the treatment of VTE.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Child; Child, Preschool; Female; Heparin, Low-Molecular-Weight; Humans; Incidence; Infant; Infant, Newborn; Male; Middle Aged; Pulmonary Embolism; Republic of Korea; Retrospective Studies; Rivaroxaban; Sex Factors; Venous Thromboembolism; Venous Thrombosis; Warfarin; Young Adult

Topics: Anticoagulants; Antithrombins; Clinical Trials as Topic; Dabigatran; Hemorrhage; Pulmonary Embolism; Pyrazoles; Pyridones; Risk Factors; Rivaroxaban; Survival Analysis; Venous Thrombosis; Warfarin

Anomalies of the inferior vena cava (AIVC) are rare but well-recognized anatomic abnormalities that can lead to clinically significant deep vein thrombosis (DVT) in a subset of otherwise healthy patients. This report illustrates an uncommon congenital anomaly that military clinicians should consider when evaluating unprovoked DVT in young patients.. Single case report and literature review.. We describe a case of a 24-yr-old United States Marine who presented with abdominal pain for 2 wk. After conservative therapy failed, a contrast-enhanced abdominal computed tomography (CT) scan was performed. The CT scan revealed an absent inferior vena cava with evidence of right venous thrombophlebitis. We include four contrast-enhanced helical CT scans that illustrate this phenomenon.. Due to the lack of available studies and data, we do not know the relative risk of DVT in patients with AIVC. However, the literature review suggests that there is a pro-thrombogenic effect of this congenital anomaly. Clinicians should include AIVC in their differential when treating young, otherwise healthy patients with unprovoked DVT. This population is much more likely to have an AIVC than the general population. In addition to thrombophilia markers, a contrast-enhanced CT scan should be considered as part of the initial workup.

Topics: Anticoagulants; Computed Tomography Angiography; Contrast Media; Humans; Iliac Artery; Male; Military Personnel; Radiology, Interventional; Thrombolytic Therapy; United States; Vena Cava, Inferior; Venous Thrombosis; Warfarin; Young Adult

Deep vein thrombosis (DVT) is a common disease that is diagnosed in approximately 1 in 1000 adults annually. Extensive DVT can lead to life- or limb-threatening diagnoses such as phlegmasia cerulea dolens (PCD), phlegmasia alba dolens, and venous gangrene. PCD, also known as massive iliofemoral venous thrombosis, is rare, and a severe complication of DVT.. We report a case of a 94-year-old bedridden woman with past medical history of dementia, hypertension, pulmonary embolism, DVT, and atrial fibrillation. The patient was admitted to the hospital for bright red blood per rectum and an elevated international normalized ratio (INR) of 5.7. On admission, her dose of warfarin was suspended and she was given 4 units of fresh frozen plasma as well as 10 mg of i.v. vitamin K. She was discharged home with an INR normalized to 1.3 and cessation of her rectal bleeding. At discharge, she was not restarted on warfarin, nor was any bridging therapy used. The patient returned to the Emergency Department a week later for worsening pain and bluish discoloration of her bilateral lower extremities. An ultrasound (US) examination showed that she had developed bilateral PCD, after INR reversal. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians commonly care for patients who present with acute DVT or treat patients on anticoagulant therapy who require cessation of medications or administration of prothrombotic agents to reverse bleeding. Cases of extensive clot burden leading to PCD have been reported in the literature, however, reports of bilateral PCD secondary to cessation of warfarin have been scarce. PCD should be considered carefully as one of the complications in warfarin reversal, as it requires immediate attention and surgical intervention to prevent limb loss.

Topics: Aged, 80 and over; Anticoagulants; Female; Hemorrhage; Humans; Lower Extremity; Rectum; Ultrasonography; Venous Thrombosis; Vitamin K; Warfarin

We present a case of cerebral venous sinus thrombosis (CVST) as a rare complication of herpes simplex virus (HSV) encephalitis. A young man with no pertinent medical history was diagnosed with HSV encephalitis. After initial treatment, he showed improvement in symptomatology until day 6 when he acutely developed new neurological deficits. An urgent MRI brain showed changes in left temporal lobe consistent with HSV encephalitis and lack of flow void in superior sagittal sinus. Subsequent magnetic resonance venography confirmed the diagnosis of superior sagittal sinus thrombosis along with thrombosis of bilateral frontoparietal cortical draining veins. Anticoagulation was immediately initiated and oral anticoagulation was continued for 1 year. He made complete recovery subsequently. Our case serves as a reminder for the treating clinicians to consider CVST in patients with HSV encephalitis who develop an unexpected new neurological deficits during early phase of appropriate treatment.

Topics: Acyclovir; Adult; Anticoagulants; Antiviral Agents; Cerebral Veins; Diagnosis, Differential; Encephalitis, Herpes Simplex; Heparin; Humans; Hydrocephalus; Magnetic Resonance Imaging; Male; Simplexvirus; Superior Sagittal Sinus; Temporal Lobe; Venous Thrombosis; Warfarin

Topics: Adult; Cesarean Section; Delivery, Obstetric; Diagnosis, Differential; Female; Follow-Up Studies; Hematoma; Humans; Ovary; Pregnancy; Pregnancy, Multiple; Puerperal Disorders; Pulmonary Embolism; Rectus Abdominis; Risk Factors; Sepsis; Tinzaparin; Tomography, X-Ray Computed; Venous Thrombosis; Warfarin

Topics: Clinical Trials, Phase III as Topic; Enoxaparin; Germany; Guideline Adherence; Humans; Pulmonary Embolism; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Risk Assessment; Secondary Prevention; Survival Analysis; Venous Thrombosis; Warfarin

We report a 24year old female who presented with sudden and severe headaches after recent carbon monoxide poisoning. Imaging revealed an acute cerebral venous thrombosis. Prior studies have suggested that carbon monoxide is a risk factor for an acute hypercoagulable state (i.e. DVT). However, little data is available regarding the correlation between carbon monoxide poisoning and cerebral venous thrombosis. This case demonstrates that such a correlation should be considered in acute intracerebral thrombotic events.

Topics: Anticoagulants; Aspirin; Carbon Monoxide Poisoning; Female; Headache Disorders; Humans; Intracranial Thrombosis; Neuroimaging; Treatment Outcome; Venous Thrombosis; Warfarin; Young Adult

Topics: Administration, Oral; Adult; Anticoagulants; Female; Humans; Vena Cava, Inferior; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Brachiocephalic Veins; Cardiomyopathies; Defibrillators, Implantable; Edema; Face; Heparin; Humans; Jugular Veins; Male; Middle Aged; Treatment Outcome; Ultrasonography, Doppler, Color; Venous Thrombosis; Warfarin

Rivaroxaban, a factor Xa inhibitor used as a direct oral anticoagulant, is beneficial over warfarin in terms of food-drug interactions and the need for therapeutic monitoring in patients with acute venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism. Because there is little data regarding VTE treatment in Japan, a real-world survey of Japanese patients being treated with rivaroxaban for VTE is needed.. The Japanese Registry of Rivaroxaban Effectiveness & Safety for the Prevention of Recurrence in Patients with Deep Vein Thrombosis and Pulmonary Embolism has been established to investigate the clinical outcomes of rivaroxaban for the initial treatment and prevention of symptomatic recurrent VTE in Japanese patients with acute symptomatic/asymptomatic VTE. 150 institutions in Japan will enrol patients in the study; the target enrolment is 1000. All patients will be followed up two times a year for at least 18 months and up to 3 years after their enrolment. The primary outcome is symptomatic recurrent VTE occurring during the study period. The principal safety outcome is clinically relevant bleeding (ie, major bleeding or clinically relevant non-major bleeding) occurring during treatment. A clinical events committee will adjudicate all outcomes.. The study protocol has been approved by the Nihon University Itabashi Hospital, Clinical Research Ethics Committee and all local institutional ethics committees of the participating hospitals. Findings of the study will be presented in scientific sessions and will be published in peer-reviewed journals.. NCT03091621,UMIN000025072; Pre-results.

Topics: Anticoagulants; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Japan; Male; Prospective Studies; Pulmonary Embolism; Recurrence; Registries; Research Design; Risk Factors; Rivaroxaban; Venous Thrombosis; Warfarin

Background and Purpose- Deep vein thrombosis (DVTs) is a common disease with high morbidity if it progresses to pulmonary embolus (PE). Anticoagulation is the treatment of choice; warfarin has long been the standard of care. Early experience with direct oral anticoagulants (DOACs) suggests that these agents may be may be a safer and equally effective alternative in the treatment of DVT/PE. Nontraumatic intracranial hemorrhage (ICH) is one of the most devastating potential complications of anticoagulation therapy. We sought to compare the rates of ICH in patients treated with DOACs versus those treated with warfarin for DVT/PE. Methods- The MarketScan Commercial Claims and Medicare Supplemental databases were used. Adult DVT/PE patients without known atrial fibrillation and with prescriptions for either a DOAC or warfarin were followed for the occurrence of inpatient admission for ICH. Coarsened exact matching was used to balance the treatment cohorts. Cox proportional-hazards regressions and Kaplan-Meier survival curves were used to estimate the association between DOACs and the risk of ICH compared with warfarin. Results- The combined cohort of 218 620 patients had a median follow-up of 3.0 months, mean age of 55.4 years, and was 52.1% women. The DOAC cohort had 26 980 patients and 8 ICH events (1.0 cases per 1000 person-years), and the warfarin cohort had 191 640 patients and 324 ICH events (3.3 cases per 1000 person-years; P<0.0001). The DOAC cohort had a lower hazard ratio for ICH compared with warfarin in both the unmatched (hazard ratio=0.26; P=0.0002) and matched (hazard ratio=0.20; P=0.0001) Cox proportional-hazards regressions. Conclusions- DOACs show superior safety to warfarin in terms of risk of ICH in patients with DVT/PE.

Topics: Administration, Oral; Adult; Aged; Anticoagulants; Atrial Fibrillation; Cohort Studies; Female; Follow-Up Studies; Humans; Intracranial Hemorrhages; Male; Middle Aged; Pulmonary Embolism; Retrospective Studies; Venous Thrombosis; Warfarin

Topics: Adolescent; Angioplasty; Anticoagulants; Balloon Valvuloplasty; Diagnosis, Differential; Edema; Enoxaparin; Female; Hemiplegia; Humans; Leg; May-Thurner Syndrome; Stents; Thrombectomy; Tissue Plasminogen Activator; Ultrasonography; Ultrasonography, Doppler; Venous Thrombosis; Warfarin

Patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) are at high risk of deep vein thrombosis (DVT) postoperatively, necessitating the use of prophylaxis medications. This investigation used a large claims database to evaluate trends in postoperative DVT prophylaxis and rates of DVT within 6 months after THA or TKA.. Truven Health MarketScan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits databases were reviewed from 2004 to 2013 for patients who underwent THA or TKA. Data were collected on patient age, sex, Charlson Comorbidity Index, and hypercoagulability diagnoses. Postoperative medication claims were reviewed for prescribed aspirin, warfarin, enoxaparin, fondaparinux, rivaroxaban, and dabigatran.. A total of 369,483 patients were included in the analysis, of which 239,949 patients had prescription medication claims. Warfarin was the most commonly prescribed anticoagulant. Patients with a hypercoagulable diagnosis had markedly more DVTs within 6 months after THA or TKA. More patients with a hypercoagulable diagnosis were treated with warfarin or lovenox than other types of anticoagulants. A multivariate regression analysis was performed, showing that patients prescribed aspirin, fondaparinux, and rivaroxaban were markedly less likely than those prescribed warfarin or enoxaparin to have a DVT within 6 months after THA or TKA.. After THA and TKA, warfarin is the most commonly prescribed prophylaxis. Patients with hypercoagulability diagnoses are at a higher risk of postoperative DVT. The likelihood of DVT within 6 months of THA and TKA was markedly higher in patients treated with warfarin and lovenox and markedly lower in those treated with aspirin, fondaparinux, and rivaroxaban.. Level III.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Clinical Decision-Making; Dabigatran; Databases, Factual; Enoxaparin; Female; Fondaparinux; Humans; Male; Middle Aged; Postoperative Complications; Retrospective Studies; Rivaroxaban; Venous Thrombosis; Warfarin

Management of otogenic cerebral venous thrombosis (OCVT) is controversial. Despite the modern antibiotic era OCVT still represents a potential life-threatening condition. This study aims to report the clinical presentation and management in a series of children with OCTV. The coexisting intracranial complications (ICC), the extent of the surgical treatment and the role of hypocoagulation were the analysed outcomes.. Retrospective chart review of patients aged less than 16 years and consecutively treated for OCVT at a tertiary university hospital between January 2007 and March 2015.. Sixteen children with ages ranging between 25 months and 16 years (9 girls/7 boys) with OCVT were identified. Acute otitis media was the causative factor in the majority of cases (n = 13). The remaining cases resulted from chronic otitis media with cholesteatoma (COMC). Eleven patients were under antibiotic therapy prior to admission. Other ICC were simultaneously present: intracranial abscess (n = 6); otitic hydrocephalus (n = 3); and meningitis (n = 1). Thrombus extension correlated with the presence of additional ICC (p = 0.035). Treatment in all cases comprised of broad-spectrum antibiotics, mastoidectomy, and long-range hypocoagulation with warfarin. Transtympanic ventilation tubes were inserted in all cases but one with COMC. Perioperative sigmoid sinus exposure was performed in seven patients, with drainage of perisinus empyema in three cases. Five children underwent simultaneous craniotomy for intracranial abscess drainage. Follow-up imaging performed in 12 cases revealed partial or complete recanalization in three and seven cases, respectively. After a mean hypocoagulation duration of nine months, no hemorrhagic or major neurologic complications were observed.. The clinical course of OCVT can be masked by previous antibiotic therapy. As such, a high suspicion index is needed for diagnosis. Simultaneous ICC appears to be more frequently found if an extensive thrombosis was present. The high recanalization rate in this series with low morbidity and no mortality can be obtained with a timely combination of antibiotics, mastoidectomy with transtympanic tube insertion and hypocoagulation. However, the decision to start hypocoagulation and its duration should be undertaken on an individual basis owing the possible adverse effects. Prospective and case-control studies are still needed to better clarify the role of the hypocoagulation treatment in OCVT.

Topics: Adolescent; Anti-Bacterial Agents; Anticoagulants; Brain Abscess; Child; Child, Preschool; Cholesteatoma, Middle Ear; Drainage; Female; Humans; Hydrocephalus; Infant; Intracranial Thrombosis; Male; Mastoidectomy; Meningitis; Otitis Media; Retrospective Studies; Venous Thrombosis; Warfarin

To assess the time in therapeutic range in patients on warfarin anti-coagulation therapy.. The retrospective chart review was conducted at Aga Khan University Hospital, Karachi, and comprised data of patients having undergone anti-coagulation with warfarin from January 2013 to April 2015. To determine the mean time in therapeutic range, Rosendaal method was used. Association of time in therapeutic range with the composite outcome, bleeding and thromboembolic events was also assessed. Percentage of patients with time in therapeutic range <60% was calculated.. There were 92 patients whose median time in therapeutic range was 34.9% (interquartile range: 20.0- 55.7). Overall, 71(77.2%) patients had time in therapeutic range below 60% which had statistically significant correlation with the composite outcome (p<0.05). Number of comorbids was significant in predicting time in therapeutic range and patients with time in therapeutic range< 60% (p<0.05).. Subjects had poor anti-coagulation quality. It might be prudent to move towards novel oral anticoagulant drugsas the first choice for therapeutic anti-coagulation.

Topics: Adult; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Needs Assessment; Outcome Assessment, Health Care; Pakistan; Thromboembolism; Venous Thrombosis; Warfarin

Topics: Adrenomedullin; Adult; Aged; Ankle Brachial Index; Anticoagulants; Asymptomatic Diseases; Atrial Fibrillation; Atrial Natriuretic Factor; C-Reactive Protein; Cardiovascular Diseases; Carotid Intima-Media Thickness; Female; Fibrinogen; Germany; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Phenprocoumon; Protein Precursors; Pulmonary Embolism; Risk Factors; Stroke; Stroke Volume; Vascular Stiffness; Venous Thrombosis; Warfarin

Dengue fever is a mosquito-borne viral disease with a very high incidence in Southeast Asia. Most patients with dengue fever recover following a self-limiting febrile illness, while a small proportion may progress to develop severe disease with complications such as acute liver failure, acute kidney injury, and multiorgan failure. Secondary bacterial infections and thrombotic events are very rare.. A 38-year-old previously healthy Sri Lankan woman from Colombo, Sri Lanka, presented with dengue shock syndrome leading to acute liver failure and kidney injury. She was managed with intravenously administered fluid resuscitation with close monitoring of her hemodynamic status, and hemodialysis. Her renal and liver functions and platelet count improved gradually, but the fever persisted and there was a neutrophil leukocytosis. A clinical examination and investigations to identify a focus of secondary infection revealed staphylococcal infective endocarditis. She was started on intravenously administered vancomycin, but as the response was poor the antibiotic was changed to intravenously administered linezolid, to which the response was good. She also developed right proximal femoral deep vein thrombosis, and was commenced on subcutaneous enoxaparin and warfarin. Enoxaparin was stopped after her international normalized ratio reached the desirable range, and warfarin was continued for 3 months.. Dengue virus is known to cause endothelial dysfunction that allows bacteria to invade tissues, defective functioning and reduction in the number of cells of the immune system, and alteration of cytokines leading to immune dysregulation, predisposing patients to develop secondary bacterial infections. Evidently, patients with dengue fever who have prolonged fever (more than 5 days) and acute kidney injury are at high risk for concurrent bacteremia. Dengue virus interferes with the components of the anti-clotting pathway, such as thrombomodulin-thrombin-protein C complex. It also activates endothelial cells and increases the expression of procoagulant factors. These factors may predispose patients with dengue viral infections to develop thrombotic complications. Therefore it is important to be aware of the possibility of serious secondary bacterial infections occurring following dengue viral infections, especially in patients with prolonged fever and acute kidney injury, and to keep in mind that thrombotic events may occur as complications of dengue viral infections.

Topics: Acute Kidney Injury; Adult; Anticoagulants; Coinfection; Dengue; Endocarditis, Bacterial; Enoxaparin; Female; Fluid Therapy; Humans; Linezolid; Liver Failure, Acute; Renal Dialysis; Treatment Outcome; Venous Thrombosis; Warfarin

Background Standard treatment for deep venous thromboembolism involves parenteral anticoagulation overlapping with a vitamin K antagonist, an approach that is effective but associated with limitations including the need for frequent coagulation monitoring. The direct oral anticoagulant rivaroxaban is similarly effective to standard therapy as a single-drug treatment for venous thromboembolism and does not require routine coagulation monitoring. The aim of this analysis was to project the long-term costs and outcomes for rivaroxaban compared to standard of care (tinzaparin/warfarin). Methods A total of 184 patients who were under anticoagulant therapy with warfarin or rivaroxaban for extended deep venous thromboembolism were retrospectively evaluated; 59 received rivaroxaban and 125 received warfarin therapy. Assessments were made on age, gender, place of residence, the duration of anticoagulation, mean international normalized ratio value, the effective rate of international normalized ratio (time in the therapeutic range), bleeding-related complication rate, duration of hospitalization due to complications, the number of annual outpatient department admission, cost for drug, cost for hospitalization, cost for outpatient department admission and international normalized ratio measurements. Results The annual outpatient cost is higher in warfarin group (147.09 ± 78 vs. 62.32 ± 19.79 USD p < 0.001). But annual drug cost is higher in rivaroxaban group (362.6 vs. 71.55 ± 31.01 USD p < 0.001). Overall cost of rivaroxaban group is higher than warfarin group (476.25 ± 36.78 vs. 364.82 ± 174.44 USD). Warfarin is not cost-effective when non-drug costs (342.5 ± 174.44 vs. 113.65 ± 36.77) and hospital costs (173.85 ± 122.73 vs. 64.9 ± 23.55 USD) were analyzed. Conclusion This analysis suggests that rivaroxaban has lower costs than warfarin in terms of outpatient department admission and hospital costs due to complications; however, warfarin was more economic when all cost parameters were considered. Time in the therapeutic range was found as 56% for warfarin that should be taken into account while analyzing costs and benefits.

Topics: Adult; Aged; Ambulatory Care; Anticoagulants; Blood Coagulation; Cost Savings; Cost-Benefit Analysis; Drug Costs; Drug Monitoring; Factor Xa Inhibitors; Female; Health Care Costs; Hemorrhage; Hospital Costs; Humans; International Normalized Ratio; Male; Middle Aged; Models, Economic; Retrospective Studies; Risk Factors; Rivaroxaban; Thromboembolism; Time Factors; Treatment Outcome; Venous Thrombosis; Warfarin

Portal vein thrombosis (PVT) is a common complication in cirrhosis. The aim of this study was to determine risk factors for PVT, assess the efficacy of anticoagulant therapy, and evaluate the effects of PVT on patients with cirrhosis undergoing elective transjugular intrahepatic portosystemic shunt (TIPSS). A total of 101 patients with cirrhosis undergoing elective TIPSS were prospectively studied. After TIPSS, all patients received preventive therapy for PVT and were followed up at 3, 6, 12, and 24 months. Clinical outcomes were compared between patients who developed PVT after TIPSS and those who did not. Multivariate analysis showed that white blood cell count (relative risk [RR]: 0.377; 95% confidence interval [CI]: 0.132-0.579; P = .001), Child-Turcotte-Pugh score (RR: 1.547; 95% CI: 1.029-2.365; P = .032), and ascites (RR: 1.264; 95% CI: 1.019-1.742; P = .040) were independent predictors for PVT. Warfarin treatment within 12 months achieved significantly higher rates of complete recanalization than aspirin or clopidogrel in patients with PVT (54.5% vs 31.3%; P = .013), although adverse events were similar between the 2 groups ( P > .05). Patients without PVT had significantly lower 2-year cumulative rates of variceal rebleeding (15.9% vs 36.6%; P = .023), shunt dysfunction (27.0% vs 46.8%; P = .039), hepatic encephalopathy (24.1% vs 42.6%; P = .045), and hepatocellular carcinoma (11.4% vs 31.2%; P = .024) and markedly higher 2-year cumulative survival rates (89.8% vs 72.9%; P = .041) than those with PVT. The PVT is associated with poorer clinical outcomes in TIPSS-treated patients, and warfarin is both safe and more effective in recanalizing PVT than aspirin or clopidogrel.

Topics: Adult; Aged; Aged, 80 and over; Aspirin; Clopidogrel; Elective Surgical Procedures; Female; Fibrosis; Humans; Male; Middle Aged; Portal Vein; Portasystemic Shunt, Transjugular Intrahepatic; Risk Factors; Ticlopidine; Treatment Outcome; Venous Thrombosis; Warfarin

Deep vein thrombosis (DVT) and pulmonary embolism are collectively known as venous thromboembolism (VTE), which is a common vascular disease and a major cause of morbidity and mortality worldwide. We compare effectiveness and safety of rivaroxaban versus warfarin in a prospective cohort of routine care patients with incident unprovoked VTE.. In this propensity-matched cohort study, we linked nationwide Danish health registries to identify all patients with a first hospital diagnosis of unprovoked VTE who were new users of rivaroxaban or warfarin. Excluded patients included those who had not been residents in Denmark for at least 1 year before VTE diagnosis, patients with outpatient VTE diagnosis only, patients with other indications for oral anticoagulation treatment, patients with previous experience of oral anticoagulation, patients who did not have a prescription for rivaroxaban or warfarin within 7 days of VTE, and patients who redeemed prescriptions for both rivaroxaban and warfarin, or other oral anticoagulants. Primary effectiveness outcome was recurrent VTE and primary safety outcome was major bleeding. We used propensity matching and Cox regression to compare rates of the outcomes with rivaroxaban versus standard treatment.. From Dec 9, 2011, to Feb 28, 2016, we identified 29 963 patients with incident VTE. After exclusion, we identified 1734 propensity-matched patients given rivaroxaban (1751 before propensity matching) and 2945 propensity-matched patients given warfarin. The rate of recurrent VTE at 6 months' follow-up was 9·9 incidents per 100 person-years with rivaroxaban versus 13·1 incidents per 100 person-years with warfarin, yielding a hazard ratio (HR) of 0·74 (95% CI 0·56-0·96). The rate of major bleeding was 2·4 per 100 person-years at 6 months in rivaroxaban users versus 2·0 in warfarin users (HR 1·19, 95% CI 0·66-2·13).. In this clinical practice setting, rivaroxaban in patients with unprovoked VTE was associated with reduced risk of recurrent VTE compared with standard treatment, without compromising safety.. Obel Family Foundation.

Topics: Administration, Oral; Aged; Anticoagulants; Denmark; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Propensity Score; Prospective Studies; Pulmonary Embolism; Recurrence; Rivaroxaban; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis; Warfarin

To report a case of successful use of unfractionated heparin (UFH) infusion to treat cerebral venous sinus thrombosis (CVST).. A 54-year-old female with a history of ovarian cancer addressed through palliative care, presents to the Emergency Department complaining of nausea, vomiting and headache for the last 72h. The patient was on a home regimen of enoxaparin 1.5mg/kg subcutaneously daily for recent pulmonary embolism and deep vein thrombosis that developed while on warfarin therapy previously. CT scan showed superior sagittal sinus thrombosis. UFH infusion was initiated and continued for 48h until the headache dissipated.. Stable CVST may be treated with UFH infusion; however, there is limited literature that describes UFH dosing for CVST management.. UFH may be considered as one of the pharmacological agents to manage CVST. The dosing for UFH bolus and infusion is similar to treatment dose for pulmonary embolism/deep vein thrombosis management with goal anti-Xa between 0.3 and 0.7units/mL.

Topics: Anticoagulants; Comorbidity; Drug Administration Schedule; Enoxaparin; Female; Heparin; Humans; Infusions, Intravenous; Middle Aged; Pulmonary Embolism; Sinus Thrombosis, Intracranial; Treatment Outcome; Venous Thrombosis; Warfarin

We describe the case of a patient with Budd-Chiari syndrome who presented with an unusual membranous obstruction of the inferior vena cava complicated by massive portal vein thrombosis (PVT). The patient underwent percutaneous transluminal balloon angioplasty through the right groin and was prescribed oral warfarin for 6 months. Treatment resulted in the complete disappearance of the PVT. This therapeutic strategy should be considered in the management of other cases of this rare, complex disease.

Topics: Administration, Oral; Angioplasty, Balloon; Anticoagulants; Budd-Chiari Syndrome; Computed Tomography Angiography; Humans; Male; Middle Aged; Multidetector Computed Tomography; Phlebography; Portal Vein; Treatment Outcome; Vena Cava, Inferior; Venous Thrombosis; Warfarin

There is considerable debate regarding the ideal agent for venous thromboembolism (VTE) prophylaxis after TKA. Numerous studies and meta-analyses have yet to provide a clear answer and often omit one or more of the commonly used agents such as aspirin, warfarin, enoxaparin, and factor Xa inhibitors.. Using a large database analysis, we asked: (1) What are the differences in VTE incidence in primary TKA after administration of aspirin, warfarin, enoxaparin, or factor Xa inhibitors? (2) What are the differences in bleeding risk among these four agents? (3) How has use of these agents changed with time?. We queried a combined Humana and Medicare database between 2007 and Quarter 1 of 2016, and identified all primary TKAs performed using ICD-9 and Current Procedural Terminology codes. All patients who had any form of antiplatelet or anticoagulation prescribed within 1 year before TKA were excluded from our study cohort. We then identified patients who had either aspirin, warfarin, enoxaparin, or factor Xa inhibitors prescribed within 2 weeks of primary TKA. Each cohort was matched by age and sex. Elixhauser comorbidities and Charlson Comorbidity Index for each group were calculated. We identified 1016 patients with aspirin, and age- and sex-matched 6096 patients with enoxaparin, 6096 patients with warfarin, and 5080 patients with factor Xa inhibitors. Using ICD-9 codes, with the understanding that patients at greater risk may have had more-attentive surveillance, the incidence of postoperative deep venous thrombosis (DVT), pulmonary embolism (PE), bleeding-related complications (bleeding requiring surgical intervention, hemorrhage, hematoma, hemarthrosis), postoperative anemia, and transfusion were identified at 2 weeks, 30 days, 6 weeks, and 90 days postoperatively. A four-way chi-squared test was used to determine statistical significance. Utilization was calculated using compound annual growth rate.. There was a difference in the incidence of DVT at 90 days (p < 0.01). Factor Xa inhibitors (2.9%) had the lowest incidence of DVT followed by aspirin (3.0%) and enoxaparin (3.5%), and warfarin (4.8%). There was a difference in the incidence of PE at 90 days (p < 0.01). Factor Xa inhibitors (0.9%) had the lowest incidence of PE followed by enoxaparin (1.1%), aspirin (1.2%), and warfarin (1.6%). There was a difference in the incidence of postoperative anemia at 90 days (p < 0.01). Aspirin (19%) had the lowest incidence of postoperative anemia followed by warfarin (22%), enoxaparin (23%), and factor Xa inhibitors (23%). There was a difference in the incidence of a blood transfusion at 90 days (p < 0.01). Aspirin (7%) had the lowest incidence of a blood transfusion followed by factor Xa inhibitors (9%), warfarin (12%), and enoxaparin (13%). There were no differences in bleeding-related complications (p = 0.81) between the groups. Aspirin use increased at a compound annual growth rate of 30%, enoxaparin at 3%, and factor Xa inhibitors at 43%, while warfarin use decreased at a compound annual growth rate of -3%.. Factor Xa inhibitors had the highest growth in utilization during our study period, followed by aspirin, when compared with enoxaparin and warfarin. When selected for the right patient, factor Xa inhibitors provided improved VTE prophylaxis compared with enoxaparin and warfarin, with a lower rate of blood transfusion. Aspirin provided comparable VTE prophylaxis compared with factor Xa inhibitors with improved VTE prophylaxis compared with enoxaparin and warfarin with the lowest risk of bleeding.. Level III, therapeutic study.

Topics: Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Knee; Aspirin; Cohort Studies; Databases, Factual; Enoxaparin; Factor Xa Inhibitors; Female; Humans; Incidence; Male; Middle Aged; Postoperative Complications; Postoperative Hemorrhage; Pulmonary Embolism; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis; Warfarin

Rates of venous thromboembolism in contemporary studies of primary total knee arthroplasty (TKA) have been reported to be as high as 3.5%. Although drug prophylaxis is effective, the best option among these regimens is not well established. The purpose of this study was to evaluate the comparative effectiveness and safety of aspirin, low-molecular-weight heparin, synthetic pentasaccharide factor Xa inhibitors, and vitamin K antagonist.. Data were from a US total joint replacement registry, with 30,499 patients receiving unilateral TKA from May 16, 2006, to December 31, 2013. Patients received either aspirin (324-325 mg daily), enoxaparin (40-60 mg daily), fondaparinux (2.5 mg daily), or warfarin (all doses) and were followed up 90 days postoperatively on several outcomes: deep vein thrombosis, pulmonary embolism, major bleeding, wound complications, infection, and death.. There was no evidence that fondaparinux, enoxaparin, or warfarin were superior to aspirin in the prevention of pulmonary embolism, deep vein thrombosis, or venous thromboembolism or that aspirin was safer than these alternatives. However, enoxaparin was found to be as safe as aspirin with respect to bleeding, and fondaparinux was as safe as aspirin for risk of wound complications.. Among TKA patients, we did not find evidence for decreased effectiveness or increased safety with use of aspirin, but enoxaparin had comparable safety to aspirin for bleeding and fondaparinux had comparable safety to aspirin for wound complications.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Knee; Aspirin; Cohort Studies; Enoxaparin; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Polysaccharides; Pulmonary Embolism; Venous Thromboembolism; Venous Thrombosis; Warfarin

The efficacy and safety or rivaroxaban versus enoxaparin/vitamin K antagonist for treatment and prevention recurrence of venous thromboembolism (VTE) was demonstrated in the randomised EINSTEIN trials. We assessed the effectiveness and safety of rivaroxaban versus warfarin in VTE patients managed in routine practice. Using US MarketScan claims from 1/2012-6/2015, we included adults with a primary diagnosis of deep vein thrombosis (DVT) or pulmonary embolism (PE) during a hospitalisation/emergency department visit, newly-initiated on rivaroxaban or warfarin within 30-days after the VTE and with ≥180-days of continuous medical/prescription benefits prior to the VTE (baseline). Patients with a claim for anticoagulation at baseline were excluded. Recurrent VTE, major bleeding, intracranial haemorrhage (ICH) and gastrointestinal bleeding (GIB) were assessed. Differences in baseline characteristics between cohorts were adjusted for using inverse probability of treatment weights based on propensity-scores. Patients had a maximum of 12-months period of follow-up post-VTE or until endpoint occurrence, switch/discontinuation of index anticoagulation, insurance disenrollment or end-of-follow-up. Cox regression was performed and reported as hazard ratios (HRs) with 95 % confidence intervals (CIs). In total, 13,609 rivaroxaban and 32,244 warfarin users experiencing VTE were included. Rivaroxaban was associated with an 19 % (95 %CI=10-27 %) reduction in recurrent VTE and a 21 % (95 %CI=4-35 %) reduction in major bleeding hazard versus warfarin. Rivaroxaban was also associated with significantly decreased hazards of ICH (HR=0.40) and GIB (HR=0.72). Rivaroxaban appears to reduce patients' hazard of both recurrent VTE and major bleeding in routine practice. These results appear consistent with EINSTEIN and post-marketing registry studies.

Topics: Anticoagulants; Databases, Factual; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Proportional Hazards Models; Pulmonary Embolism; Recurrence; Retrospective Studies; Risk Factors; Rivaroxaban; Time Factors; Treatment Outcome; United States; Venous Thromboembolism; Venous Thrombosis; Warfarin

A 39-year-old man with nephrotic syndrome was admitted due to right dorsal pain. Contrast-enhanced CT led to a diagnosis of renal vein thrombosis and segmental pulmonary thromboembolism. Treatment with heparin and warfarin was started. After 1 month, pulmonary thromboembolism recurred. Warfarin was switched to edoxaban, and steroid therapy was initiated, which led to the remission of nephrotic syndrome and the disappearance of renal vein thrombosis. The efficacy of edoxaban was demonstrated; however, this drug has not been routinely selected for patients with renal disease. Our results suggest that edoxaban is also effective for treating venous thrombosis patients with nephrotic syndrome.

Topics: Adult; Factor Xa Inhibitors; Heparin; Humans; Male; Nephrotic Syndrome; Pulmonary Embolism; Pyridines; Renal Veins; Thiazoles; Treatment Outcome; Venous Thrombosis; Warfarin

Stroke can occur in patients on warfarin despite anticoagulation. Patients with a low international normalized ratio (INR) should theoretically be at greater risk for ischemia than those who are therapeutic. Therefore, INR may be able to indicate whether new neurological deficits are more likely strokes or stroke mimics in patients on warfarin. This study evaluates the association and predictive value of INR in determining the likelihood of ischemia.. Patients were identified using the acute stroke registry at a Primary Stroke Center from January 2013 through December 2014. All adult patients undergoing evaluation for acute stroke with prior documented use of warfarin and an INR level at presentation were included. Data were collected regarding patient demographics, medical comorbidities, stroke severity, reason for anticoagulation, and laboratory studies including INR. Student t tests and χ2 analysis were used to evaluate factors associated with increased likelihood of ischemia (stroke or transient ischemic attack) versus mimic. Significant results were entered into a multivariable regression analysis. Sensitivity and specificity analyses were conducted to determine the predictive value of INR for ischemic risk.. 116 patients were included; 46 were diagnosed with ischemia, 70 were diagnosed as mimics. 75% of patients were on warfarin for atrial fibrillation versus 25% for venous thrombosis. A statistically significant difference in mean INR for patients with ischemia (n = 46) versus mimics (n = 70) was observed (1.7 vs. 2.8; p < 0.001). In multivariable analysis, both sub-therapeutic INR (p < 0.001) and atrial fibrillation (p = 0.014) were predictors of ischemia. In patients with an INR ≥2, the predictive value of having a non-ischemic etiology was 79%. No patient with an INR of ≥3.6 was found to have ischemia.. Sub-therapeutic INR and atrial fibrillation are strongly associated with ischemia in patients on warfarin presenting with acute neurologic symptoms. Ischemia is far less likely in patients with an INR of ≥2 and rare in those with an INR ≥3.6. This study shows that the INR value of a patient on warfarin can help stratify patients' risk for acute ischemic stroke and guide further neurologic imaging and workup.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Female; Humans; International Normalized Ratio; Male; Retrospective Studies; Stroke; Venous Thrombosis; Warfarin

Antiphospholipid syndrome (APS) is an autoimmune disorder characterised by thrombosis and/or pregnancy morbidity in the presence of antiphospholipid antibodies (aPLs) based on the Sydney criteria. We aimed to explore the clinico-laboratory features and treatment strategies of APS patients retrospectively.. The medical records of APS patients registered under Hospital Universiti Sains Malaysia (Kelantan state) between 2000 and 2015 were reviewed.. A total of 17 APS subjects (age 40.7 ± 12.8 years) including 11 primary (64.7%) and six secondary APS (35.3%) patients were identified. The follow-up period was 9.5 ± 6.7 years with male:female ratio of 1.0:4.7. Pregnancy morbidity was the most common clinical manifestation (11/14; 78.6%) followed by recurrent venous thrombosis (10/17; 58.8%). For other clinical features, menorrhagia was the most frequently observed manifestation (4/14; 28.6%) followed by aPLs-associated thrombocytopenia (4/17; 23.5%) and ovarian cyst (3/14; 21.4%). LA and aCL were positive in 94.1% (16/17) and 81.8% (9/11) of the patients, respectively. APTT value (76.7 ± 17.0 sec) was significantly high (p < 0.05). Low intensity warfarin alone was successful to maintain target INR (2.0 - 3.0) and prevent recurrence of thrombosis.. The tendency of pregnancy morbidity in this cohort of Malaysian Kelantanese APS patients was high compared to other previously reported APS cohorts. Low intensity warfarin was successful in preventing recurrence of thrombosis, however, APS women receiving long-term anticoagulants should be monitored for possible occurrence of menorrhagia and ovarian cysts.

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Female; Humans; Malaysia; Male; Middle Aged; Pregnancy; Pregnancy Complications; Retrospective Studies; Venous Thrombosis; Warfarin

This study explored the association between the CYP2C9*3/CYP2D6*10/CYP3A5*3 genetic polymorphisms with lower extremity deep venous thrombosis (LEDVT) and the warfarin maintenance dose.. Five hundred thirty-six patients who were pathologically diagnosed with LEDVT after surgery were included in the LEDVT group. At the same time, 540 patients without LEDVT who underwent surgery were recruited as the control group. Patients were given warfarin at an initial dose of 2.5-3.0 mg. Blood samples were collected to detect the initial and stable international normalized ratio (INR) values. The warfarin maintenance dose was obtained if the INR remained within a range of 2.0-3.0 for 3 consecutive days. The genotype distribution and haplotype analysis of the CYP2C9*3/CYP2D6*10/CYP3A5*3 alleles were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) testing and SHEsis software, respectively. Logistic regression analysis was used to analyze the risk and protective factors for LEDVT.. The A/G genotypes, G/G genotypes, and G allele of CYP3A5*3 in the LEDVT group were observed with increased frequency compared with the control group. The LEDVT group displayed a higher ACG haplotype frequency, and lower ACA and ATA haplotype frequencies than the control group. Age, diabetes, low-density lipoprotein, CYP3A5*3 and the ACG haplotype were independent risk factors for LEDVT. High-density lipoprotein and the ACA haplotype were independent protective factors for LEDVT. The genotype distributions of the CYP2C9*3, CYP2D6*10, and CYP3A5*3 genetic polymorphisms were associated with the warfarin maintenance dose.. The CYP3A5*3 genetic polymorphism may be an important risk factor for LEDVT. Moreover, CYP2C9*3, CYP2D6*10, and CYP3A5*3 are associated with the warfarin maintenance dose.

Topics: Aged; Alleles; Anticoagulants; Case-Control Studies; Cytochrome P-450 CYP2C9; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP3A; Dose-Response Relationship, Drug; Female; Gene Frequency; Genetic Association Studies; Haplotypes; Humans; International Normalized Ratio; Lower Extremity; Male; Middle Aged; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Venous Thrombosis; Warfarin

Intravenous immunoglobulin (IVIG) is a widely used agent as the first choice of treatment of immune thrombocytopenic purpura (ITP). IVIG has several side effects, but it is a relatively safe treatment. Life-threatening thrombosis has been reported in adults and rarely in children. We report a case of a 14-year-old boy with dural venous sinus thrombosis and pulmonary embolism after treatment with IVIG for ITP. The patient was treated with low-molecular-weight heparin followed by warfarin and the symptoms were recovered. If a patient with ITP shows mental change or respiratory difficulty, we should consider thrombosis as well as hemorrhage.

Topics: Adolescent; Anticoagulants; Biopsy; Bone Marrow; Hematologic Tests; Heparin, Low-Molecular-Weight; Humans; Immunoglobulins, Intravenous; Magnetic Resonance Angiography; Male; Pulmonary Embolism; Purpura, Thrombocytopenic, Idiopathic; Sinus Thrombosis, Intracranial; Tomography, X-Ray Computed; Treatment Outcome; Venous Thrombosis; Warfarin

Portal vein thrombosis (PVT) is a serious complication in liver cirrhosis with portal hypertension. We examined the treatment, recurrence and prognosis of PVT in cirrhotic patients.. The study subjects were all 90 cirrhotic patients with PVT treated with danaparoid sodium (DS) at our department between July 2007 and September 2016. The mean age was 68 years and mean Child-Pugh score was 7. All patients received 2500 U/day of DS for 2 weeks, and repeated in those who developed PVT recurrence after the initial therapy.. Complete response was noted in 49% (n = 44), partial response (shrinkage ≥70%) in 33% (n = 30), and no change (shrinkage <70%) in 18% (n = 16) of the patients after the initial course of treatment. DS treatment neither caused adverse events, particularly bleeding or thrombocytopenia, nor induced significant changes in serum albumin, total bilirubin, prothrombin time, and residual liver function. Re-treatment was required in 44 patients who showed PVT recurrence and 61% of these responded to the treatment. The cumulative recurrence rates at 1 and 2 posttreatment years were 26 and 30%, respectively. The recurrence rates were significantly lower in patients with acute type, compared to the chronic type (p = 0.0141). The cumulative survival rates at 1 and 3 years after treatment (including maintenance therapy with warfarin) were 83 and 60%, respectively, and were significantly higher in patients with acute type than chronic type (p = 0.0053).. We can expect prognostic improvement of liver cirrhosis by warfarin following two-week DS therapy for the treatment of PVT in patients with liver cirrhosis safety and effectiveness. An early diagnosis of PVT along with the evaluation of the volume of PVT on CT and an early intervention would contribute to the higher efficacy of the treatment.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Chondroitin Sulfates; Contrast Media; Dermatan Sulfate; Female; Heparitin Sulfate; Humans; Hypertension, Portal; Liver Cirrhosis; Male; Middle Aged; Portal Vein; Recurrence; Survival Rate; Tomography, X-Ray Computed; Treatment Outcome; Venous Thrombosis; Warfarin

The purpose of this study was to evaluate the effectiveness of Factor Xa inhibitors (XaI) for thromboprophylaxis following hip fracture surgery in a large cohort of patients, and compare XaI against warfarin and enoxaparin.. Patients undergoing hip fracture surgery from 2007 to 2015 were identified in a large claims database. Patients prescribed warfarin, XaI, or enoxaparin within 2 weeks of surgery were identified and grouped into cohorts. Medical comorbidities and complication incidences, including deep venous thrombosis (DVT), pulmonary embolism (PE), and bleeding complications were calculated. Chi-square analysis was performed and adjusted residuals calculated to determine significant differences.. DVT rates were significantly different between groups at thirty days only (5.03% warfarin, 2.91% XaI, 3.48% enoxaparin, p=0.047). PE rates were significantly different at all time points; enoxaparin had the lowest rates. There were no differences in the rates of other complications.. XaI are an option for thromboprophylaxis in hip fracture patients, although their possible decreased effectiveness against PE compared to enoxaparin should be considered.. This study compares the effectiveness of Factor Xa inhibitors to warfarin and enoxaparin for hip fracture patients, using a large national database. In this study, Factor Xa inhibitors had similar effectiveness for DVT prophylaxis compared to these agents.

Topics: Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Databases, Factual; Enoxaparin; Factor Xa Inhibitors; Female; Hip Fractures; Humans; Incidence; Male; Middle Aged; Postoperative Complications; Pulmonary Embolism; Secondary Prevention; Treatment Outcome; Venous Thrombosis; Warfarin

Acute mesenteric ischemia poses a diagnostic challenge due to nonspecific clinical clues and lack of awareness owing to its rarity. Ischemia due to mesenteric venous thrombosis has a good prognosis compared to arterial cause and can be managed conservatively with early diagnosis. The portomesenteric venous system is an unusual site of thrombosis in patients with protein S deficiency, and its thrombosis is an uncommon cause of acute mesenteric ischemia.. We present a case of a 27-year-old Mongolian man who presented with acute abdominal pain increasing in severity, and refractory to repeated attempts at treatment with a misdiagnosis of acute peptic ulcer disease. Contrast-enhanced computed tomography of his abdomen detected complete occlusion of the superior mesenteric vein, an extension of acute thrombus into the portal vein, and ischemic mid-jejunal loops. Early diagnosis and immediate anticoagulation with continuous intravenous infusion of unfractionated heparin prevented subsequent consequences. On further workup, our patient was diagnosed with isolated protein S deficiency. We started lifelong thromboprophylaxis with warfarin to prevent recurrence and our patient was asymptomatic on the latest follow-up 5 months after discharge.. Despite accurate detection of acute mesenteric ischemia by contrast-enhanced computed tomography, high index of suspicion is indispensable for its early diagnosis. Early diagnosis and immediate anticoagulation will prevent subsequent complications and need for surgical intervention. Young patients without known risk factors presenting with venous thrombosis in atypical sites should be investigated for prothrombotic diseases.

Topics: Abdominal Pain; Adult; Anticoagulants; Humans; Male; Mesenteric Ischemia; Mesenteric Veins; Portal Vein; Protein S Deficiency; Thrombolytic Therapy; Tomography, X-Ray Computed; Treatment Outcome; Venous Thrombosis; Warfarin

Portal vein thrombosis (PVT) is common in patients with cirrhosis undergoing transjugular intrahepatic portosystemic shunt (TIPS). This study had 3-fold aims: to assess risk factors for PVT; to determine the efficacy of anticoagulant therapy; to investigate the impact of PVT on clinical outcomes in TIPS-treated cirrhosis.Between June 2012 and February 2016, 126 TIPS-treated patients with cirrhosis were enrolled and studied prospectively. Enrolled patients were screened for PVT before TIPS and at 3, 6, 12, and 24 months post-TIPS. All patients received warfarin (1.5-3.0 mg/day) or aspirin (100 mg/day) or clopidogrel (75 mg/day) post-TIPS. Results of patients with and without PVT (baseline and de novo) were compared.White blood cell (WBC) counts (odds ratio (OR): 0.430, 95% confidence interval (CI): 0.251-0.739, P = .002) and Child-Turcotte-Pugh (CTP) score (OR: 2.377, 95% CI: 1.045-5.409, P = .039) were significant baseline predictors for PVT in TIPS-treated patients with cirrhosis. Warfarin resulted in markedly greater rates of complete recanalization than aspirin or clopidogrel (P < .05) in patients with PVT. Patients with PVT had markedly higher 2-year cumulative rates of variceal rebleeding, shunt dysfunction, hepatic encephalopathy, and hepatocellular carcinoma, and prominently lower overall survival than those without PVT (P < .05).In TIPS-treated patients with cirrhosis, lower WBC count and higher CTP score were independent baseline predictors for PVT; patients with PVT had worse clinical outcomes than those without; warfarin may be more effective in recanalizing PVT than aspirin or clopidogrel.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Clopidogrel; Female; Humans; Leukocyte Count; Liver Cirrhosis; Male; Middle Aged; Portal Vein; Portasystemic Shunt, Transjugular Intrahepatic; Prospective Studies; Risk Factors; Severity of Illness Index; Ticlopidine; Venous Thrombosis; Warfarin

Although venous thromboembolism (VTE) including deep venous thrombosis (DVT) and pulmonary embolism is a major health problem in the world, it is an infrequent disease among young people. It is always mandatory to look at the underlying conditions for VTE, and in young patients, inherited prothrombotic factors should also be evaluated, especially in case of unprovoked VTE. Anomalies of inferior vena cava (IVC) are very rare in the general population. In this case report we describe rare occurrence of extensive DVT in a young male patient with rare anomaly of IVC - duplication of IVC - as a predisposition factor for DVT. Physicians need to be reminded of the IVC anomalies that should be considered in young patients with idiopathic DVT of lower extremity, which may require extended anticoagulant treatment.

Topics: Adult; Anticoagulants; Drug Therapy, Combination; Heparin, Low-Molecular-Weight; Humans; Male; Multidetector Computed Tomography; Vascular Malformations; Vena Cava, Inferior; Venous Thrombosis; Warfarin

A previously healthy 44-year-old male presented with fever, abdominal pain, liver dysfunction and lymphadenopathy. He was diagnosed as having acute cytomegalovirus (CMV) infection with elevated CMV-IgG and IgM, and observed with supportive therapy. He was admitted to our hospital with prolonged fever lasting for a month. Enhanced CT revealed multiple thromboses in the right pulmonary artery and superior mesenteric vein. Follow-up CT after one week revealed new-onset thromboses in the left pulmonary artery and common iliac vein. Screening tests for thrombophilia were negative. His symptoms were improved with anticoagulant therapy with intravenous heparin, followed by oral warfarin. He was discharged on admission day 28 with good condition. Follow-up CT after 6 months revealed complete resolution of the thromboses. Anticoagulant therapy was stopped after 9 months, and he has been well without recurrence. Though vascular thrombosis is a rare complication, we must be alert to the signs and symptoms of thrombosis in patients with acute CMV infection.

Topics: Adult; Anticoagulants; Cytomegalovirus Infections; Humans; Male; Treatment Outcome; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Chemical and Drug Induced Liver Injury; Factor Xa Inhibitors; Hemorrhage; Humans; International Normalized Ratio; Pulmonary Embolism; Pyridines; Stroke; Thiazoles; Venous Thrombosis; Warfarin

The purpose of this study was to evaluate the risks of bleeding, deep venous thrombosis (DVT), endovenous heat induced thrombosis (EHIT) and failure of ablation on patients who undergo ablation while on oral anticoagulation.. We compared 378 (3.4%) out of 11252 patients (group A) who had undergone 724 endovenous ablation of the saphenous veins from January 1, 2011 to September 30, 2014 while on oral anticoagulation to a randomly selected 375 patients (group B) who underwent 641endovenous ablation in the same time period but were not on anticoagulation. The demographic data, history of DVT, the Clinical, Etiologic, Anatomic, Pathologic (CEAP) classification and the VCSS (Venous Clinical Severity Score) scores were analyzed. The indications for anticoagulation, the anticoagulants used were recorded. The primary endpoints were bleeding, development of DVT or EHIT, and failure of ablation.. Patients in group A were older, had more men, more history of DVT and PE, had higher CEAP and VCSS scores compared to group B. The type of anticoagulation used was warfarin in 77.2% direct oral inhibitors (DOIs) in 22.8%. The rate of failure of ablation at 3 days was 39 (5.6%) for Group A and 3 (0.5%) for Group B (P<0.0001) and at one month it was 46 (10.1%) vs. 27 (6.7%) (P=0.086). The number of EHIT cases in group A at 3 days was 2 (0.3%), compared to 6 (0.9%) in group B (P=0.016) and at 1 month it was 0 compared to 4 (1.0%) (P=0.0483). The DVT, SVT, hematoma and wound infection rates were similar in the two groups.. Ablation of the saphenous veins in patients who are on oral anticoagulation is safe and does not increase the risk of bleeding or hematoma, but it may slightly lower the incidence of EHIT and increase the incidence of failure of ablation.

Topics: Ablation Techniques; Adult; Aged; Aged, 80 and over; Anticoagulants; Female; Hemorrhage; Humans; Male; Middle Aged; Postoperative Complications; Retrospective Studies; Risk Factors; Saphenous Vein; Treatment Outcome; Ultrasonography, Doppler, Duplex; United States; Varicose Veins; Venous Insufficiency; Venous Thrombosis; Warfarin; Young Adult

The HAS-BLED model is widely utilized to assess patients' bleed risk prior to anticoagulant therapy including warfarin. Some of the variables assessed in the model are also known to influence warfarin control, commonly measured by time in therapeutic range (TTR). The aim of the study was to determine whether the HAS-BLED risk tool is a good predictor of bleed risk and warfarin control in deep vein thrombosis (DVT) patients. Retrospective data were collected for DVT warfarin care patients at Sullivan Nicolaides Pathology. Data included age, medical history and concurrent drug therapy to calculate HAS-BLED scores. INR results were used to calculate TTR with the Rosendaal method and mean TTR used for analysis and comparison. The eligible 533 patients had a mean TTR of 78.3%. Categorization according to HAS-BLED score resulted in 150 patients classified as low-risk, 331 as moderate-risk and 52 as high-risk with a haemorrhagic incidence per patient of 0.08, 0.53 and 0.54, respectively. Patients in the low-, moderate- and high-risk HAS-BLED categories had a mean TTR of 81%, 79% and 65%, respectively, with significant differences (p < 0.001) found in TTR between the low- and high-risk and moderate- and high-risk categories. In an Australian DVT population, the HAS-BLED score accurately predicts decreasing warfarin control with increasing risk category, and patients with scores ≥3 achieve poor control as indicated by a TTR <70%. In addition to predicting bleed risk, the HAS-BLED tool may also predict the potential benefit of warfarin treatment and hence influence choice of anticoagulant therapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Australia; Female; Hemorrhage; Humans; Incidence; International Normalized Ratio; Male; Middle Aged; Models, Biological; Retrospective Studies; Risk Assessment; Venous Thrombosis; Warfarin; Young Adult

Topics: Aged; Angiography; Anticoagulants; Aspirin; Chest Pain; Diagnosis, Differential; Dyspnea; Electrocardiography; Female; Heparin; Humans; Lower Extremity; Pulmonary Embolism; Tomography, X-Ray Computed; Ultrasonography; Venous Thrombosis; Warfarin

Topics: Aged; Antineoplastic Agents; Female; Humans; Lymph Node Excision; Neoadjuvant Therapy; Ovarian Neoplasms; Rupture, Spontaneous; Salpingo-oophorectomy; Shock, Hemorrhagic; Splenic Rupture; Venous Thrombosis; Warfarin

HIV-infected patients are at an increased risk of developing venous thromboembolism (VTE), and minimal data are available to describe the need for extended treatment.. To evaluate the frequency of and determine predictive risk factors for extended anticoagulation of VTE in HIV-infected patients in rural, western Kenya.. A retrospective chart review was conducted at the Anticoagulation Monitoring Service affiliated with Moi Teaching and Referral Hospital and the Academic Model Providing Access to Healthcare. Data were collected on patients who were HIV-infected and receiving anticoagulation for lower-limb deep vein thrombosis. The need for extended anticoagulation, defined as receiving ≥7 months of warfarin therapy, was established based on patient symptoms or Doppler ultrasound-confirmed diagnosis. Evaluation of the secondary outcomes utilized a univariate analysis to identify risk factors associated with extended anticoagulation.. A total of 71 patients were included in the analysis; 27 patients (38%) required extended anticoagulation. The univariate analysis showed a statistically significant association between the need for extended anticoagulation and achieving a therapeutic international normalized ratio within 21 days in both the unadjusted and adjusted analysis. Patients with a history of opportunistic infections required an extended duration of anticoagulation in the adjusted analysis: odds ratio = 3.42; 95% CI = 1.04-11.32; P = 0.04.. This study shows that there may be a need for increased duration of anticoagulation in HIV-infected patients, with a need to address the issue of long-term management. Guideline recommendations are needed to address the complexity of treatment issues in this population.

Topics: Adult; Anticoagulants; Female; Health Care Rationing; HIV Infections; Humans; International Normalized Ratio; Kenya; Male; Medical Records; Middle Aged; Retrospective Studies; Risk Factors; Rural Population; Time Factors; Ultrasonography, Doppler; Venous Thromboembolism; Venous Thrombosis; Warfarin

People infected with HIV are prone to venous thrombosis. Treatment of thrombosis is primarily with warfarin. No studies have addressed the effects of HIV infection on warfarin dose. The aims of this study were to determine whether the therapeutic dose of warfarin and induction time to therapeutic dose in HIV-infected patients differ from that in HIV-uninfected patients.. A prospective and retrospective descriptive study of induction time to therapeutic warfarin dose, as well as of ambulant therapeutic warfarin dose, was performed. HIV-infected and HIV-uninfected patients being treated after deep venous thrombosis with or without pulmonary embolism were compared. Sex and use of antiretroviral drugs (ARVs) were also compared in the groups.. 234 patients were entered into the study. Induction time to therapeutic warfarin dose did not differ between the 2 groups. The mean therapeutic dose of warfarin was higher in the HIV-infected than the HIV-uninfected group: 6.06 vs 5.72 mg/day, but this was not statistically significant (p=0.29). There was no difference in therapeutic warfarin dose between ARV-naïve groups-HIV-uninfected and HIV-infected patients not on ARVs.. There appears to be little effect of HIV infection on warfarin dosing. Warfarin therapy should be administered conventionally in HIV-infected patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; CD4 Lymphocyte Count; Female; HIV Infections; Humans; International Normalized Ratio; Male; Middle Aged; Prospective Studies; Pulmonary Embolism; Retrospective Studies; South Africa; Venous Thrombosis; Warfarin; Young Adult

The direct oral anticoagulants, e.g., dabigatran etexilate (DE), are effective and well tolerated treatments for venous thromboembolism (VTE). Net clinical benefit (NCB) is a useful concept in weighing potential benefits against potential harm of comparator drugs. The NCB of DE vs. warfarin in VTE treatment was compared. Post-hoc analyses were performed on pooled data from the 6-month RE-COVER® and RE-COVER™ II trials, and data from the RE-MEDY™ trial (up to 36 months), to compare the NCB of DE (150 mg twice daily) and warfarin [target international normalized ratio (INR) 2.0-3.0]. Patients (≥18 years old) had symptomatic proximal deep vein thrombosis and/or pulmonary embolism. NCB was the composite of cardiovascular endpoints (non-fatal events of recurrent VTE, myocardial infarction, stroke or systemic embolism), all-cause death, and bleeding outcomes, all weighted equally. A broad definition of NCB included major bleeding events (MBE) and clinically relevant non-major bleeding events as bleeding outcomes, while a narrow definition included just MBE. The pooled dataset totalled 5107 patients from RE-COVER/RE-COVER II and 2856 patients from RE-MEDY. When NCB was narrowly defined, NCB was similar between DE and warfarin. When broadly defined, NCB was superior with DE vs. warfarin [RE-COVER/RE-COVER II, hazard ratio (HR) 0.80; 95% confidence interval (CI), 0.68-0.95 and RE-MEDY, HR 0.73; 95% CI 0.59-0.91]. These findings were unaffected by warfarin time in therapeutic range. The NCB of DE was similar or superior to warfarin, depending on the NCB definition used, regardless of the quality of INR control.

Topics: Adult; Aged; Clinical Trials as Topic; Dabigatran; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Pulmonary Embolism; Stroke; Venous Thromboembolism; Venous Thrombosis; Warfarin

Early reports suggested that the risk of gastrointestinal bleeding (GIB) was higher for patients on non-vitamin K antagonist oral anticoagulants (NOACs) than for those on warfarin. We compared the incidence of GIB in our patients on NOACs with those on warfarin.. We used our VA pharmacy database to identify patients taking NOACs (dabigatran, rivaroxaban, and apixaban) or warfarin between January 2011 and June 2015, and used the VistA system to identify those who were hospitalized for GIB. We included only patients with clinically significant GIB, defined as documented GI blood loss with a hemoglobin drop ≥2 g/dl, hemodynamic instability, and/or need for endoscopic evaluation, angiography, or surgery.. We identified 803 patients on NOACs and 6,263 on warfarin. One hundred and fifty-eight patients on warfarin had GIB (2.5%), compared with only five patients (0.6%) on NOACs (odds ratio=4.13; 95% confidence interval: 1.69-10.09). Blood transfusion for GIB was significantly more common in patients on warfarin than on NOACs (64.6% vs. 20%, P=0.04). Within 90 days of GIB hospitalization, 12 patients (7.6%) in the warfarin group died, whereas there were no deaths in the NOAC group.. In our patients, the incidence of GIB for those on warfarin was more than four times that for those on NOACs. Blood transfusions for GIB were more common in warfarin patients, and no NOAC patients died of GIB. In contrast to early reports, our findings suggest that the risk of GIB and subsequent complications is considerably lower for patients on NOACs than for patients on warfarin.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Blood Transfusion; Dabigatran; Female; Gastrointestinal Hemorrhage; Hemoglobins; Humans; Incidence; Male; Pulmonary Embolism; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Venous Thrombosis; Warfarin

Pulmonary embolism and deep venous thrombosis are the two most important manifestations of venous thromboembolism (VTE), which is the third most common life-threatening cardiovascular disease in the United States. Anticoagulation is the mainstay of VTE treatment. Most patients with deep venous thrombosis or low-risk pulmonary embolism can be treated in the outpatient setting with low-molecular-weight heparin and a vitamin K antagonist (warfarin) or direct-acting oral anticoagulants. Inpatient treatment of VTE begins with parenteral agents, preferably low-molecular-weight heparin. Unfractionated heparin is used if a patient is hemodynamically unstable or has severe renal insufficiency, high bleeding risk, hemodynamic instability, or morbid obesity. Direct-acting oral anticoagulants are an alternative; however, concerns include cost and use of reversing agents (currently available only for dabigatran, although others are in development). If warfarin, dabigatran, or edoxaban is used, low-molecular-weight or unfractionated heparin must be administered concomitantly for at least five days and, in the case of warfarin, until the international normalized ratio becomes therapeutic for 24 hours. Hemodynamically unstable patients with a low bleeding risk may benefit from thrombolytic therapy. An inferior vena cava filter is not indicated for patients treated with anticoagulation. Current guidelines recommend anticoagulation for a minimum of three months. Special situations, such as active cancer and pregnancy, require long-term use of low-molecular-weight or unfractionated heparin. Anticoagulation beyond three months should be individualized based on a risk/benefit analysis. Symptomatic distal deep venous thrombosis should be treated with anticoagulation, but asymptomatic patients may be monitored with serial imaging for two weeks and treated only if there is extension.

Topics: Anticoagulants; Education, Medical, Continuing; Heparin; Humans; Pulmonary Embolism; United States; Venous Thrombosis; Warfarin

Results of treatment of 71 patients, suffering an acute idiopathic deep veins thrombo'\ sis (DVT) of lower extremities,were analyzed. In 32 (45.1%) patients rivaroxaban was\ applied, in 39 (54.9%) — varfarin. The term of anticoagulant therapy was determined in\ accordance to the D—dimers level. Recurrence of the DVT, of massive hemorrhage or\ pulmonary thromboembolism in the follow—up groups were absent. In 29 (74.4%)\ patientsa constant dose of varfarin was lined up during minimal recommended period.\ For reduction of the DVT occurrence risk a rivaroxaban may serve as an alternative to\ varfarin.

Topics: Adult; Aged; Anticoagulants; Biomarkers; Drug Administration Schedule; Female; Femoral Vein; Fibrin Fibrinogen Degradation Products; Humans; Leg; Male; Middle Aged; Prospective Studies; Pulmonary Embolism; Rivaroxaban; Venous Thrombosis; Warfarin

Warfarin is the most commonly prescribed anticoagulant drug; however, a narrow therapeutic range and a high risk of bleeding or stroke complicate its clinical use. Warfarin resistance was defined as prolonged warfarin requirements of more than 15 mg/day to achieve therapeutic anticoagulation or failure to achieve therapeutic anticoagulation with more than 20 mg/day. The resistance is associated with polymorphisms of the vitamin K epoxide reductase-oxidase complex (VKORC1) and cytochrome P450-2C9 (CYP2C9) genes, which affect warfarin pharmacodynamics and pharmacokinetics, respectively. Identification of the VKORC1 -1639 (A/G) and CYP2C9 (*1/*2/*3) allelic variants was performed using the PGX-Thrombo Strip in 41 patients with warfarin resistance compared with 30 patients with normal warfarin response out of 352 diagnosed cases of deep vein thrombosis. In warfarin-resistant patients, the VKORC1-1639 genotype frequencies were GG 0.756, GA 0.244 and AA 0.0, whereas in warfarin responder patients, they were: GG 0.333, GA 0.400 and AA 0.276 with P ≤ 0.001. The CYP2C9 genotype frequencies showed nonsignificant difference in both group of patients (P = 0.31). Our results suggest that the VKORC1-1639 GG and the wild type CYP2C9*1*1genotypes are associated with the high-dose requirement for warfarin therapy, and that VKORC1-1639 GG is responsible for warfarin resistance and failure in Egyptian patients.

Topics: Adult; Alleles; Anticoagulants; Arabs; Cytochrome P-450 CYP2C9; Drug Administration Schedule; Egypt; Female; Gene Expression; Gene Frequency; Genotype; Humans; Male; Metabolism, Inborn Errors; Middle Aged; Polymorphism, Genetic; Prospective Studies; Venous Thrombosis; Vitamin K Epoxide Reductases; Warfarin

To describe a case of subtherapeutic international normalized ratio (INR) associated with concomitant use of warfarin and banana flakes in a patient with diarrhea.. A man in his 30s was hospitalized for an elective procedure, but his stay was complicated by cerebral venous thrombosis requiring intravenous infusion of unfractionated heparin, ventilator-associated pneumonia, bacteremia requiring broad-spectrum antimicrobials and percutaneous endoscopic gastrostomy tube placement, and diarrhea. Eventually, the heparin was transitioned to warfarin. After several days of therapeutic INR, the INR became subtherapeutic and remained so for 3 days. The decreased INR correlated temporally with initiation of consistent administration of dried banana flakes to treat diarrhea and the subsequent decrease in the rate and extent of diarrhea. Diarrhea decreases the amount and activity of vitamin K-producing intestinal flora and dietary vitamin K absorption, resulting in increased INR. Resolution of diarrhea secondary to banana flakes administration in this patient may have contributed to the decreased INR by causing a relative increase in vitamin K-producing flora and vitamin K absorption. A probability score of 5 was obtained upon applying the Drug Interaction Probability Scale modified to address interactions between warfarin and dietary supplements, indicating a probable interaction between warfarin and banana flakes.. Concomitant use of warfarin and banana flakes supplements may result in a reduced rate and extent of diarrhea and may be associated with subtherapeutic INR and decreased warfarin efficacy. Practitioners must be aware of this potential interaction and closely monitor INR and adjust warfarin doses accordingly.

Topics: Adult; Anticoagulants; Cerebrovascular Disorders; Diarrhea; Dietary Supplements; Drug Interactions; Humans; International Normalized Ratio; Male; Musa; Venous Thrombosis; Vitamin K; Warfarin

Topics: Adult; Anticoagulants; Exercise; Female; Headache; Humans; Migraine without Aura; Pulmonary Embolism; Venous Thrombosis; Warfarin

For many years, the standard of care for patients diagnosed with deep vein thrombosis (DVT) has been low-molecular-weight heparin (LMWH) bridging to an oral Vitamin-K antagonist (VKA). The availability of new non-VKA oral anticoagulants (NOAC) agents as monotherapy may reduce the likelihood of hospitalization for DVT patients.. To compare hospital visit costs of DVT patients treated with rivaroxaban and LMWH/warfarin.. A retrospective claim analysis was conducted using the MarketScan Hospital Drug Database for care provided between January 2011 and December 2013. Adult patients using rivaroxaban or LMWH/warfarin with a primary diagnosis of DVT during the first day of a hospital visit were identified (i.e., index hospital visit). Based on propensity-score methods, historical LMWH/warfarin patients (i.e., patients who received LMWH/warfarin before the approval of rivaroxaban) were matched 4:1 to rivaroxaban patients. The hospital-visit cost difference between these groups was evaluated for the index hospital visit, as well as for total hospital-visit costs (i.e., including index and subsequent hospital visit costs).. All rivaroxaban users (n = 134) in the database were well-matched with four LMWH/warfarin users (n = 536). The mean hospital-visit costs were $5257 for the rivaroxaban cohort and $6764 in the matched-cohort of patients using LMWH/warfarin. The $1508 cost difference was statistically significant between cohorts (95% CI = [-$2296; -$580]; p-value = 0.002). Total hospital-visit costs were lower for rivaroxaban compared to LMWH/warfarin users within 1, 2, 3, and 6 months after index visit (significantly lower within 1 and 3 months, p-values <0.05) LIMITATIONS: Limitations were inherent to administrative-claims data, completeness of baseline characteristics, adjustments restricted to observational factors, and lastly the sample size of the rivaroxaban cohort.. The availability of rivaroxaban significantly reduced the costs of hospital visits in patients with DVT treated with rivaroxaban compared to LMWH/warfarin.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Female; Heparin, Low-Molecular-Weight; Hospitalization; Humans; Insurance Claim Review; Male; Middle Aged; Residence Characteristics; Retrospective Studies; Rivaroxaban; Sex Factors; Socioeconomic Factors; Venous Thrombosis; Warfarin

Prothrombin complex concentrates (PCCs) are commonly used to rapidly reverse warfarin-associated coagulopathy; however, venous thromboembolism (VTE) is an established adverse event.. To determine risk factors for VTE AFTER administration of a three-factor prothrombin complex concentrate (3F-PCC) for warfarin-associated intracranial hemorrhage (ICH).. Retrospective chart review of all patients with a warfarin-associated ICH who received a 3F-PCC at a single tertiary care hospital between 2008 and 2013. Outcomes were VTE events (defined as deep vein thrombosis [DVT], pulmonary embolism [PE], limb ischemia, transient ischemic attack, cerebrovascular accident, non-ST-segment elevation myocardial infarction, ST-segment elevation myocardial infarction, and unexplained sudden death) occurring within 30 days of 3F-PCC administration. Risk factors in subjects with and without VTE complications were compared via Fisher's exact test, Student's t-test, Mann-Whitney U test, and univariate logistic regression as appropriate.. Two hundred nine subjects received 3F-PCC for warfarin-associated ICH. There were 22 VTE events in 19 subjects (9.1%). Baseline characteristics of subjects with and without VTE were similar. There was a significant increase in VTE events in 29 subjects who were taking warfarin for a previous PE or DVT (36.8% vs. 11.6%, p = 0.007; logistic regression odds ratio 4.455, p = 0.005).. Patients with a prior history of PE or DVT who were given 3F-PCC for warfarin-associated ICH were 4.5 times more likely to sustain a VTE within 30 days. A careful analysis of risks and benefits of rapidly reversing anticoagulation must be made prior to the administration of 3F-PCC in this patient population.

Topics: Aged; Anticoagulants; Blood Coagulation Factors; Emergency Service, Hospital; Female; Humans; Intracranial Hemorrhages; Logistic Models; Male; Pulmonary Embolism; Retrospective Studies; Risk Factors; Venous Thromboembolism; Venous Thrombosis; Warfarin

Three- and four-factor prothrombin complex concentrates (PCC) are gaining popularity for acute reversal of vitamin K antagonist-associated bleeding. Although acute thrombosis after PCC administration has been described, it seems to be rare.. An 83-year-old woman on warfarin for history of deep venous thrombosis (DVT) presented to the Emergency Department with life-threatening gastrointestinal bleeding, requiring urgent PCC administration. After stabilization, she subsequently developed a new limb-threatening upper-extremity DVT. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: As PCC therapy gains popularity for reversal of anticoagulant-induced bleeding in urgent bleeding scenarios, the emergency physician must be aware of the complications of PCC administration, including new limb-threatening DVT.

Topics: Aged, 80 and over; Anticoagulants; Blood Coagulation Factors; Female; Fibrinolytic Agents; Gastrointestinal Hemorrhage; Heparin; Humans; Upper Extremity; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Blood Coagulation Factors; Child; Enoxaparin; Female; Headache; Hemorrhage; Heparin Antagonists; Humans; Protamines; Treatment Outcome; Venous Thrombosis; Vitamin K; Warfarin

Anticoagulation treatment is effective in preventing both death and recurrence in patients with venous thromboembolism (VTE), but at the same time confers a substantial risk of bleeding complications. The aim of this study was to examine the rate of and predictors for bleeding complications in VTE patients on warfarin with high treatment quality. In total 13,859 patients on warfarin for VTE between January 1st 2006 and December 31th 2011 were retrieved from the national quality register Auricula. The cohort was matched with the Swedish National Patient Register for complications and background characteristics, the Cause of Death Register for date and cause of death and the Swedish Prescribed Drug Register for retrieved medication. The rate of major bleeding was 2.36 per 100 treatment years, increasing with age from 1.25 to 4.33 for those under 60 or over 80 years of age, respectively. Factors found to independently increase the risk of bleeding complications were increasing age HR 1.02, cardiac failure HR 1.39, Chronic pulmonary disease HR 1.41, alcohol abuse HR 3.33, anaemia HR 1.75, hypertension HR 1.29 and a history of major bleeding HR 1.69. Warfarin as treatment for VTE is safe with a low rate of bleeding complications at least for the younger patient. In an era of NOAK, warfarin has a comparable safety profile among VTE patients and is still a valid treatment option.

Topics: Aged; Aged, 80 and over; Female; Hemorrhage; Humans; Male; Middle Aged; Registries; Sweden; Venous Thromboembolism; Venous Thrombosis; Warfarin

A 69-year-old man was admitted to hospital with abdominal pain. In the four years prior to his presentation, he had undergone repeated transarterial chemoembolizations and injections for hepatocellular carcinoma. He underwent his 8th transcatheter arterial therapy one month prior to admission. Abdominal X-rays and contrast-enhanced computed tomography showed large amounts of small intestinal gas and venous thrombosis from the portal vein to the superior mesenteric vein, respectively. The thrombosis was reduced after anticoagulation therapy (heparin, antithrombin III, danaparoid sodium and warfarin). This is the first case report of paralytic ileus due to superior mesenteric venous thrombosis after transcatheter arterial therapy for hepatocellular carcinoma with an arterioportal shunt.

Topics: Abdominal Pain; Aged; Anticoagulants; Carcinoma, Hepatocellular; Embolization, Therapeutic; Humans; Intestinal Pseudo-Obstruction; Liver Neoplasms; Male; Mesenteric Ischemia; Mesenteric Veins; Portal Vein; Radiography; Thrombophlebitis; Treatment Outcome; Venous Thrombosis; Warfarin

This study's purpose was to present our institution's experience with the use of a risk stratification protocol for venous thromboembolism (VTE) prophylaxis in joint arthroplasty in which "routine" risk patients receive a mobile compression device in conjunction with aspirin and "high"-risk patients receive warfarin for thromboprophylaxis.. This was a prospective study of patients undergoing primary or revision knee or hip arthroplasty. Exclusion criteria were patients with a current deep vein thrombosis, history of pulmonary embolism, chronic warfarin therapy, planned multiple surgeries, and prolonged postoperative immobilization. Patients were stratified as either routine or high risk. Routine risk patients received mobile compression devices for 10 days and aspirin twice daily for 6 weeks, whereas high-risk patients received warfarin for 4 weeks and compression stockings for 6 weeks.. A total of 3143 total joint arthroplasties were enrolled (2222, 70.7% "routine"; 921, 29.3% "high risk"). The rate of symptomatic VTE within 6 weeks postoperatively was 0.7% (95% CI 0.3%-1.0%) in the standard vs 0.5% (95% CI 0.01%-1.0%) in the high-risk cohort (P = .67), and within 6 months postoperatively was 0.6% (95% CI 0.3%-1.0%) in the standard vs 1.1% (95% CI 0.4%-1.8%) in the high-risk cohort (P = .23). The rate of major bleeding events was significantly lower in the routine (0.4%; 95% CI 0.1%-0.6%) vs high-risk (2.0%; 95% CI 1.0%-3.0%; P < .001) cohort.. This study demonstrates that use of a risk stratification protocol allowed the avoidance of more aggressive anticoagulation in 70% of patients while achieving a low overall incidence of symptomatic VTE.

Topics: Adult; Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Postoperative Period; Prospective Studies; Pulmonary Embolism; Risk Assessment; Stockings, Compression; Venous Thromboembolism; Venous Thrombosis; Warfarin

Topics: Aged, 80 and over; Anticoagulants; Blood Coagulation Factors; Coronary Thrombosis; Female; Femoral Vein; Gastrointestinal Hemorrhage; Hemostatics; Humans; Male; Middle Aged; Stroke; Thrombosis; Venous Thrombosis; Warfarin

Maintaining acceptable international normalized ratio (INR) control among deep vein thrombosis (DVT) patients taking warfarin is challenging. We evaluated prescribers' behavior to out-of-range INRs in DVT patients following initial INR stabilization. Following INR stabilization, a below-range INR was associated with fewer subsequent measurements and warfarin-dosing adjustments, and a longer time to re-achieve a therapeutic INR compared to an above-range INR.

Topics: Adult; Aged; Anticoagulants; Female; Humans; International Normalized Ratio; Male; Middle Aged; Practice Patterns, Physicians'; Venous Thrombosis; Warfarin; Young Adult

Topics: Angiography; Angioplasty, Balloon; Anticoagulants; Female; Humans; Iliac Vein; May-Thurner Syndrome; Mechanical Thrombolysis; Postpartum Period; Tomography, X-Ray Computed; Ultrasonic Therapy; Vena Cava Filters; Venous Thrombosis; Warfarin; Young Adult

To assess the effectiveness of anticoagulant therapy (ACT) for the treatment of patients with deep venous thrombosis (DVT) of the lower extremities.. The study considered ultrasonic characteristics of lysis of the proximal part of thrombus: localization and nature of venous thrombosis, the length and diameter of the proximal floating part of the thrombus, and duration of the venous thrombosis. Depending on the ACT options patients were divided into 3 groups: Group 1 (18 patients) received rivaroxaban, group 2 (19 patients) received enoxaparin sodium with subsequent transition to warfarin, and 3 group (19 patietns) received enoxaparin sodium, followed by administration of rivaroxaban.. Treatment with rivaroxaban was preferable over standard ACT with enoxaparin/warfarin with regards to the lysis of thrombus when duration of thrombosis did not exceed 10 days. In 10.5% of patients who received warfarin flotation of thrombi remained for 14 days; the length of the floating part of the thrombi did not exceed 3 cm. Such circumstances and inability to reach a therapeutic INR value required cava filter placement. Treatment with enoxaparin sodium followed by the administration of rivaroxaban was found to be the most efficient ACT regimen as there was no negative dynamics of ultrasound characteristics of lysis of thrombi at any duration of the disease.. Цель исследования - провести оценку эффективности антикоагулянтной терапии (АКТ) при лечении больных тромбозом глубоких вен (ТГВ) нижних конечностей. Материал и методы. Учитывались ультразвуковые характеристики лизиса проксимальной части тромба: локализация и характер венозного тромбоза, длина и диаметр флотирующей верхушки тромба, а также давность венозного тромбоза. В соответствии с намеченной тактикой АКТ пациенты разделены на 3 группы: 1-я группа (18 человек) получала ривароксабан, 2-я группа (19 человек) - эноксапарин натрия с последующим переходом на варфарин и 3-я группа (19 человек) получала эноксапарин натрия с последующим назначением ривароксабана. Результаты. Установлено, что ривароксабан предпочтительнее стандартной АКТ эноксапарином/варфарином в лизисе тромбов при давности венозного тромбоза менее 10 сут. На фоне варфаринотерапии в 10,5% случаев сохранялась флотация до 3 см более 14 дней, что при отсутствии достижения терапевтического значения МНО потребовало имплантации кава-фильтра. Схемой АКТ, при которой отсутствовала отрицательная ультразвуковая динамика лизиса тромба на любом сроке заболевания, оказалось применение эноксапарина натрия с последующим назначением ривароксабана.

Topics: Aged; Anticoagulants; Drug Monitoring; Enoxaparin; Female; Humans; International Normalized Ratio; Lower Extremity; Male; Middle Aged; Rivaroxaban; Thrombosis; Treatment Outcome; Ultrasonography; Venous Thrombosis; Warfarin

The purpose of this study was to analyze the difference in duration of anticoagulation and dose of warfarin required to reach a therapeutic international normalized ratio [(INR) of 2 to 3] in patients with hypercoagulable conditions as compared to controls. To our knowledge, this study is the first in the literature to delineate such a difference.. A retrospective chart review was performed in a tertiary care hospital. The total study population was 622. Cases (n=125) were patients with a diagnosis of a hypercoagulable syndrome who developed venous thromboembolism. Controls (n=497) were patients with a diagnosis of venous thromboembolism in the absence of a hypercoagulable syndrome and were matched for age, sex, and race.. The total dose of warfarin required to reach therapeutic INR in cases was higher (50.7±17.6 mg) as compared to controls (41.2±17.7 mg). The total number of days required to reach therapeutic INR in cases was 8.9±3.5 days as compared to controls (6.8±2.9 days). Both of these differences were statistically significant (p<0.001).. Patients with hypercoagulable conditions require approximately 10 mg of additional total warfarin dose and also require, on average, 2 extra days to reach therapeutic INR as compared to controls.. Amaç: Bu çalışmanın amacı kontrollerle karşılaştırıldığında hiperkoagülabilite durumları olan hastalarda terapötik uluslararası düzeltme oranında (INR) 2 ile 3 aralığına ulaşmak için gerekli warfarin doz ve antikoagülan süresindeki farklılığı analiz etmektir. Bildiğimiz kadarıyla; bu farklılığı tarifleyen literatürdeki ilk çalışmadır. Gereç ve Yöntemler: Retrospektif dosya taraması 3. basamak hastanede yapıldı. Toplam çalışmaya alınan hasta sayısı 622 idi. Venöz tromboembolizmi olan bu hastalardan 125’inin hiperkoagülabilite sendromu olup yaş, cins ve etnik kökeni aynı 497 kontrol hastasında hiperkoagülabilite sendromu yoktu. Bulgular: Hastalarda terapötik INR’ye ulaşmak için gerekli total warfarin dozu (50,7±17,6 mg) kontrollerin dozu (41,2±17,7 mg) ile karşılaştırıldığında yüksekti. Terapötik INR’ye ulaşmak için gerekli total gün sayısı hastalarda 8,9±3,5 gün olup kontrollerde 6,8±2,9 gün idi. Her iki karşılaştırmada da istatistiksel farklılık anlamlı bulundu (p<0,001). Sonuç: Hiperkoagülabilite durumları olan hastalarda terapötik INR’ye ulaşmak için kontrollere göre yaklaşık 10 mg ek total warfarin dozu ve ortalama 2 ek gün gereklidir.

Topics: Adult; Aged; Anticoagulants; Blood Coagulation; Case-Control Studies; Female; Humans; International Normalized Ratio; Male; Middle Aged; Odds Ratio; Retrospective Studies; Thrombophilia; Time Factors; Venous Thrombosis; Warfarin

The optimal prophylaxis for prevention of venous thromboembolic events (VTEs) after revision total joint arthroplasty (TJA) remains unknown. The objective of this study was to evaluate whether aspirin, known to be effective for prevention of VTEs after primary arthroplasty, is also effective after revision TJA.. We studied 2997 consecutive patients who underwent revision TJA between 2005 and 2013 and were treated with intermittent pneumatic compression devices and either aspirin (534 patients) or warfarin (2463 patients) for VTE prophylaxis. Pertinent data including the incidence of symptomatic VTEs, bleeding events, infection, and mortality were retrieved from our prospectively collected database.. The incidence of symptomatic VTEs was significantly higher in the warfarin group at 1.75% (43 of 2463) compared with 0.56% (3 of 534) in the aspirin group (odds ratio: 3.2; 95% CI: 1.03-16.3; P = .03). There was a higher rate of bleeding events with administration of warfarin (1.5%) compared with aspirin (0.4%; P = .02; odds ratio: 4.1; 95% CI: 1.2-34.0). The rate of surgical site infection was similar between the aspirin group and the warfarin group (1.61% and 1.70%, respectively).. Administration of aspirin as prophylaxis against VTEs after revision arthroplasty may be a viable option as it appears to be more effective than warfarin in prevention of symptomatic VTEs and is associated with a lower rate of complications.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Female; Hemorrhage; Humans; Incidence; Intermittent Pneumatic Compression Devices; Male; Middle Aged; Odds Ratio; Philadelphia; Platelet Aggregation Inhibitors; Postoperative Complications; Pulmonary Embolism; Reoperation; Retrospective Studies; Surgical Wound Infection; Venous Thromboembolism; Venous Thrombosis; Warfarin

This study aimed to compare medication adherence and treatment persistence of patients on warfarin versus rivaroxaban in Singapore. A secondary objective was to identify significant covariates influencing adherence.. A retrospective cohort study was conducted where data from September 2009 to October 2014 was retrieved from the hospital electronic databases. Prescription records of rivaroxaban patients with 3 months or more of continuous prescription were extracted and compared against those of patients on warfarin. Primary outcome of adherence was determined based on the medication possession ratio (MPR), while treatment persistence was determined by outpatient clinic appointment gaps.. A total of 94 rivaroxaban and 137 warfarin users were analysed by complete case analysis. The MPR of warfarin patients was lower than rivaroxaban patients by 10% (95% CI, 6.4% to 13.6%; P <0.0001). Also, there were more warfarin patients who had gaps in treatment persistence compared to those prescribed rivaroxaban (8.0% vs 1.1%; P = 0.03). Significant factors affecting medication adherence were age and duration of anticoagulant use. For every 10-year increase in age, MPR increased by 1.7% (95% CI, 0.7% to 2.8%). Similarly, for every year increase in duration of use, MPR increased by 1.8% (95% CI, 0.6% to 3.0%). Race, gender, concomitant medication and type of residence were not found to be significant covariates in the multivariable analysis.. Patients on rivaroxaban are likely to be more adherent to their prescribed oral anticoagulant with increasing age and duration of treatment influencing adherence.

Topics: Adult; Age Factors; Anticoagulants; Databases, Factual; Factor Xa Inhibitors; Female; Humans; Male; Medication Adherence; Middle Aged; Pulmonary Embolism; Retrospective Studies; Rivaroxaban; Singapore; Venous Thrombosis; Warfarin

Portal vein system thrombosis (PVST) is an alarming and potentially life-threatening complication of laparoscopic splenectomy and azygoportal disconnection (LSD). The objective of this study was to investigate negative and positive predictors of PVST after LSD in patients receiving anticoagulant regimens with aspirin or warfarin.. Seventy-five consecutive patients who underwent LSD from 2013 to 2014 were retrospectively reviewed. Patients received anticoagulant regimen with warfarin (n = 35) or aspirin (n = 40) according to individual preference. International normalized ratio (INR) and the incidence of PSVT were compared in patients received anticoagulant regimen with warfarin or aspirin on postoperative days (POD) 7, 30, and 90, and factors associated with PVST at these time points were determined by univariate and logistic multivariable regression analyses.. Portal vein diameter was an independent negative predictor of PVST on PODs 7, 30, and 90. Anticoagulation with warfarin was an independent positive predictor of PVST on PODs 30 and 90, and INR was an independent positive predictor of PVST on POD 90. Dynamic changes in the incidence of PVST on the day of admission and on PODs 7, 30, and 90 differed significantly between the warfarin and aspirin groups (P = 0.002). No patient experienced perioperative bleeding.. Portal vein diameter was an independent negative predictor, while anticoagulation therapy with warfarin and INR were independent positive predictors, of PVST after LSD. Early anticoagulation with warfarin is safe and effective for the prevention of PVST after LSD.

Topics: Adult; Anticoagulants; Azygos Vein; Esophageal and Gastric Varices; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Hypersplenism; Hypertension, Portal; Laparoscopy; Liver Cirrhosis; Male; Middle Aged; Portal Vein; Retrospective Studies; Splenectomy; Venous Thrombosis; Warfarin

D-dimer levels are closely related to the clinical status of deep vein thrombosis (DVT). This study aimed to investigate the factors which were associated with the normalization of D-dimer level by vitamin K antagonist (VKA) therapy, the maintenance of normal D-dimer levels for 6 months during VKA therapy, and the recurrent elevations of D-dimer above normal level after VKA withdrawal, in DVT of the legs.. The 469 consecutive patients with first-episode leg swelling were examined. All blood tests were measured from the initially sampled blood before the administration of medications.. Of the 469 patients, 288 (61.4%) showed positive D-dimer test. Radiologic examinations, including Doppler ultrasound and computed tomography venography, of the 288 patients revealed positive DVT of the legs in 135 (46.9%) patients and of these, 122 with total follow-up durations of >6 months were enrolled in this study. Linear regression analysis of 100 patients who experienced D-dimer normalization revealed initial D-dimer levels were positively correlated with D-dimer normalization time during VKA therapy (P = 0.010). Logistic regression analysis showed initial D-dimer level was negatively associated with the normalization of D-dimer levels by VKA therapy (P = 0.045), and being a woman (P = 0.005) and having lower protein C (P = 0.002) level had negative impacts on the maintenance of normal D-dimer levels for 6 months during VKA therapy. Finally, after VKA withdrawal, the recurrent elevations of D-dimer above normal level were more likely to occur in women than in men (P = 0.004).. From these observations, it is suggested that higher initial D-dimer level, lower protein C level, and female gender may be the adverse risk factors for the treatment of DVT of the legs using VKA.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Biomarkers; Chi-Square Distribution; Computed Tomography Angiography; Drug Administration Schedule; Female; Fibrin Fibrinogen Degradation Products; Humans; Linear Models; Logistic Models; Lower Extremity; Male; Middle Aged; Perfusion Imaging; Phlebography; Predictive Value of Tests; Protein C; Retrospective Studies; Risk Factors; Sex Factors; Time Factors; Tomography, Emission-Computed, Single-Photon; Treatment Outcome; Ultrasonography, Doppler; Up-Regulation; Venous Thromboembolism; Venous Thrombosis; Vitamin K; Warfarin; Young Adult

Behçet's disease is an inflammatory systemic disorder, characterized by a relapsing and remitting course, it manifests with oral and genital ulcerations, skin lesions, uveitis, vasculitis, central nervous system and gastrointestinal involvement. The main histopathological finding is widespread vasculitis of the arteries and veins. Therapy is variable and depends largely on the severity of the disease and organ involvement. There is common practice to treat with anticoagulation in patients suffering from vessel thrombosis, but there are no control trials to support this tendency. Anticoagulation treatment can cause major bleeding events in patients suffering from aneurysms. In this case report we describe a treatment dilemma in a patient suffering from deep vein thrombosis and pulmonary aneurysms.

Topics: Adolescent; Aneurysm; Anticoagulants; Behcet Syndrome; Biological Therapy; Cyclophosphamide; Fibrinolytic Agents; Glucocorticoids; Hemorrhage; Humans; Immunosuppressive Agents; Male; Medication Therapy Management; Pulmonary Artery; Radiography; Secondary Prevention; Severity of Illness Index; Treatment Outcome; Ultrasonography; Urokinase-Type Plasminogen Activator; Venous Thrombosis; Warfarin

Venous gangrene complicating deep vein thrombosis in the context of anticoagulation use in patients with gynecologic malignancy is rarely reported. We report an unusual presentation of venous gangrene of the lower limbs associated with warfarin therapy in a 53-year-old woman from the Cook Islands with an occult ovarian cancer.. A 53-year-old woman of Cook Islands origin presented with exertional dyspnea, rapid atrial fibrillation, bilateral lower limb edema, and painful digital ischemia of her hallux. She was on warfarin therapy for atrial fibrillation and had a stable therapeutic international normalized ratio. Bilateral proximal lower limb deep vein thrombosis and digital gangrene subsequently developed in the setting of a supratherapeutic international normalized ratio and platelet count depletion. Her warfarin was reversed and heparin therapy was commenced with resulting correction of her thrombocytopenia.. We would like to attract the attention of the reader to the potential hazard of the use of warfarin in patients with malignancy. In our case, we also demonstrated a predictive value of supratherapeutic international normalized ratio and platelet count depletion that could herald massive thrombosis and gangrene in a patient who was previously stable on warfarin therapy. Early recognition and prompt reversal of warfarin in these circumstances is essential to correct the unbalanced prothrombotic process that leads to extensive thrombosis and gangrene. The outlook of such cases remains dismal and results in extensive morbidity and mortality.

Topics: Anticoagulants; Atrial Fibrillation; Female; Gangrene; Heparin; Humans; International Normalized Ratio; Ischemia; Middle Aged; Obesity, Morbid; Ovarian Neoplasms; Thrombocytopenia; Toes; Ultrasonography, Doppler; Venous Thrombosis; Warfarin

The CIVIQ questionnaire was used to evaluate quality of life of patients presenting with deep vein thrombosis of lower limbs in different variants of anticoagulant therapy. The study included a total of 170 patients who were depending on the variant of anticoagulant therapy subdivided into 3 groups: Group One (comprising 48 patients) taking rivaroxaban as monotherapy; Group Two (consisting of 73 subjects) receiving low molecular weight heparin (enoxaparin sodium) followed by adjusting the warfarin dose, and Group Three (including 49 patients) receiving low molecular weight heparin (enoxaparin sodium) followed by rivaroxaban. The total value of the level of quality of life in all groups showed a tendency towards restoration. However, patients taking warfarin during the follow-up period were found to have negative dynamics by the 6th month of treatment. It was revealed that quality of life on all parameters was higher in patients taking rivaroxaban and lower in those taking warfarin. The parameters of the physical component of health turned out to depend upon the degree of recanalization of the thrombus. After 6 months of anticoagulant therapy patients taking rivaroxaban (Groups One and Three) were found to have good recanalization in 87.5 and 87.7% of cases, respectively, while in Group Two being observed in 54.8% of patients only. Taking an anticoagulant at a fixed dose not requiring laboratory control (rivaroxaban) increases patient compliance, thus leading to improvement of both mental and social wellbeing.. С помощью опросника CIVIQ исследовано качество жизни больных с тромбозом глубоких вен нижних конечностей при различных вариантах антикоагулянтной терапии. В исследование включено 170 больных, которые в зависимости от варианта антикоагулянтной терапии были разделены на 3 группы: 1 группа (48 человек) – больные принимали ривароксабан в качестве монотерапии; 2 группа (73 человека) – пациенты получали низкомолекулярный гепарин (эноксапарин натрия) с последующим подбором дозы варфарина; 3 группа (49 человек) – пациенты получали низкомолекулярный гепарин с последующим приёмом ривароксабана. Суммарное значение уровня качества жизни во всех группах имело тенденцию к восстановлению. Однако, у пациентов, принимавших варфарин в амбулаторном периоде, наблюдалась отрицательная динамика к 6 месяцу лечения. Выявлено, что качество жизни по всем параметрам выше у больных, принимающих ривароксабан, чем у получавших лечение варфарином. Показатели физического компонента здоровья зависят от степени реканализации вен. Через 6 месяцев антикоагулянтной терапии у больных, принимавших ривароксабан (1 и 3 группы), хорошая реканализация отмечена в 87,5 и 87,7% случаев соответственно, а во 2 группе – только у 54,8% пациентов. Приём антикоагулянта в фиксированной дозе, не требующей лабораторного контроля (ривароксабан), повышает приверженность пациентов к лечению, что приводит к улучшению качества жизни.

Topics: Adult; Aged; Anticoagulants; Drug Administration Schedule; Enoxaparin; Female; Humans; Lower Extremity; Male; Middle Aged; Quality of Life; Rivaroxaban; Surveys and Questionnaires; Treatment Outcome; Ultrasonography, Doppler, Duplex; Vascular Patency; Venous Thrombosis; Warfarin

Acute pancreatitis is an acute inflammatory process of the pancreas that can trigger a systemic inflammatory response. Pulmonary embolism refers to obstruction of the pulmonary artery or one of its branches by material (usually a thrombus) that originated elsewhere in the body. Extensive lower limb deep vein thrombosis with pulmonary embolism is a rare complication of acute pancreatitis that has been described in a few case reports. Deep vein thrombosis and hypercoagulable states in pancreatitis are thought to be due to release of pancreatic proteolytic enzymes from a cyst that is connected to the pancreatic duct and penetrates into a vessel. Proteolytic damage or inflammation of the vessels may also play a significant part. Acute pancreatitis also causes a systemic inflammatory response that has effects on an endothelium-dependent relaxing response for acetylcholine.. A 38-year-old Sri Lankan man presented with acute pancreatitis and later he developed progressive abdominal distention with bilateral ankle edema. A contrast-enhanced computed tomographic scan showed two pancreatic pseudocysts and deep vein thrombosis in both lower limbs, as well as a pulmonary embolism involving the right lower lobe pulmonary artery and the left segmental pulmonary arteries. One of the pseudocysts in the head of the pancreas was compressing the inferior vena cava without direct communication. The patient's thrombophilia screen result was negative. He was started on subcutaneous enoxaparin 1 mg/kg twice daily and warfarin to achieve a target international normalized ratio of 2-3.. Deep vein thrombosis with pulmonary embolism is a rare but life-threatening complication of acute pancreatitis. Once diagnosed, early treatment with intravenous heparin or thrombolysis is effective. Patients with severe acute pancreatitis may be at risk of deep vein thrombosis due to immobilization and other mechanisms, but anticoagulation as prophylaxis is often not used. However, it may be considered on a case-by-case basis in patients with pancreatitis who are acutely ill and immobilized, need intensive care unit admission, and have multiple risk factors for deep vein thromboembolism. Further studies must be undertaken to determine guidelines for deep vein thromboembolism prophylaxis in these patients.

Topics: Adult; Anticoagulants; Enoxaparin; Humans; Male; Pancreatitis; Pulmonary Embolism; Tomography, X-Ray Computed; Treatment Outcome; Ultrasonography, Doppler; Vena Cava Filters; Venous Thrombosis; Warfarin

A 66-year-old man with acute ischemic stroke in the setting of lung adenocarcinoma developed acute-onset deep vein thrombosis (DVT) of the lower limbs after changing to warfarin from a heparin combination. The diagnosis of warfarin-resistant DVT was established based on the laboratory data and clinical evaluation. Heparin administration resulted in good control of thrombin regulation. Cancer patients are at high risk of venous thromboembolism, and the combination of these 2 conditions is known as Trousseau's syndrome.. Our report suggests that heparin administration may provide good control of thromboembolic events, although there is no established medical treatment to extend the survival of patients with Trousseau's syndrome.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Aged; Anticoagulants; Diffusion Magnetic Resonance Imaging; Humans; Lung Neoplasms; Male; Stroke; Tomography Scanners, X-Ray Computed; Venous Thrombosis; Warfarin

Topics: Adult; Anticoagulants; Contraceptives, Oral, Hormonal; Enoxaparin; Ethinyl Estradiol; Female; Fibrinolytic Agents; Humans; Smoking; Thrombectomy; Thrombolytic Therapy; Urokinase-Type Plasminogen Activator; Vascular Malformations; Vena Cava, Inferior; Venous Thrombosis; Warfarin

A 41-year-old female with hereditary deficiency of antithrombin III (ATIII) was diagnosed with atrial septal defect( ASD) and scheduled for the closure of ASD. She had been taking warfarin since she suffered from deep vein thrombosis 10 years ago. Preoperative management of anticoagulation included discontinuation of warfarin, and supplementation of antithrombin with heparin infusion. On the day of operation, antithrombin activity was maintained above 80% by administering antithrombin, and closure of ASD was carried out under standard cardiopulmonary bypass support using heparin. Heparin infusion was continued with antithrombin supplementation until prothrombin time-international normalized ratio(PT-INR) recovered to around 2.5 with warfarin. Her intra-and postoperative courses did not show any thromboembolic events, and she was discharged 20 days after the surgery.

Topics: Adult; Anticoagulants; Antithrombin III; Antithrombin III Deficiency; Cardiac Surgical Procedures; Female; Heart Septal Defects, Atrial; Heparin; Humans; International Normalized Ratio; Postoperative Complications; Preoperative Care; Thrombin Time; Treatment Outcome; Venous Thrombosis; Warfarin

This case report describes a young man who presented with 9-day history of sudden-onset epigastric and right-sided lower abdominal pain. He was tachycardiac with temperature of 102°F. Tenderness was present in the peri-umbilical area and right iliac fossa. Investigations revealed a raised total leucocyte count (predominantly neutrophilic). Triphasic CTscan abdomen found thrombosis of right portal vein and its hepatic tributaries alongwith superior mesenteric vein (SMV) and its tributaries. Co-existent fluid in right hemipelvis abutting the cecum and appendiceal tip was suggestive of acute appendicitis. He was resuscitated with fluids and analgesics and started on intravenous metronidazole and ceftriaxone. Anticoagulation with subcutaneous heparin was commenced and eventually switched over to warfarin. Appendicectomy was not performed as the patient responded to conservative treatment. Appendicitis is associated with multiple complications but secondary venous thrombosis has rarely been reported with it.

Topics: Acute Disease; Adult; Anti-Infective Agents; Anticoagulants; Appendicitis; Humans; Male; Mesenteric Veins; Metronidazole; Portal Vein; Tomography, X-Ray Computed; Treatment Outcome; Venous Thrombosis; Warfarin

Topics: Female; Humans; Middle Aged; Necrosis; Venous Thrombosis; Warfarin

A 13-year-old adolescent girl with blunt abdominal injury was transferred to our hospital. Enhanced computed tomography (CT) showed not only retroperitoneal hematoma around the inferior vena cava and left common iliac vein but also thrombus extending from the left common iliac vein to the femoral vein.. Enhanced CT performed on the second day revealed no increase in retroperitoneal hematoma and a new small thrombus in the popliteal vein. Anticoagulant therapy was therefore started with administration of unfractionated heparin. Administration of warfarin was started on the 12th day and heparin administration was stopped on the 14th day. The patient was discharged on the 19th day with continuation of warfarin administration. Enhanced CT performed 10 months after injury showed no thrombus, and the administration of warfarin was then stopped.. She was successfully treated with the appropriate start time and control of anticoagulation therapy based on careful evaluation of her general condition.

Topics: Abdominal Injuries; Adolescent; Female; Heparin; Humans; Tomography, X-Ray Computed; Treatment Outcome; Venous Thrombosis; Warfarin; Wounds, Nonpenetrating

Compared with low-molecular-weight heparin (LMWH) and warfarin, the oral anticoagulant rivaroxaban has advantages, such as simplified care, that may lead to less health care resource utilization.. A retrospective, matched-cohort analysis was conducted using claims dated between January 2011 and December 2013 from the Truven Health Analytics MarketScan databases. Adult patients who had a primary diagnosis of deep vein thrombosis (DVT) during an outpatient or emergency room (ER) visit after November 2, 2012, and who were treated with rivaroxaban or LMWH/warfarin on the same day, were identified. Patients were observed over 1, 2, 3, and 4 weeks after the DVT diagnosis. The mean numbers of hospitalizations for all causes and for venous thromboembolism (VTE) (which included those for DVT or pulmonary embolism), as well as other health care resource utilization (ER, outpatient, and other visits), and the associated health care costs and pharmacy costs, were evaluated and compared between cohorts using the Lin method.. All of the 512 rivaroxaban-treated patients were well matched with the LMWH/warfarin-treated patients. The mean numbers of all-cause hospitalizations were significantly lower in the rivaroxaban users compared with those in the LMWH/warfarin users over 1 week (0.012 vs 0.032; P = 0.044) and 2 weeks (0.022 vs 0.048; P = 0.040). The corresponding mean numbers of VTE-related hospitalizations were significantly lower with rivaroxaban over 1 week (0.008 vs 0.028; P = 0.020), 2 weeks (0.016 vs 0.042; P = 0.020), and 4 weeks (0.034 vs 0.068; P = 0.036). The mean numbers of all-cause and VTE-related outpatient visits were also significantly lower in rivaroxaban users compared with those in LMWH/warfarin users over 1, 2, 3, and 4 weeks (all, P < 0.001). In terms of all-cause and VTE-related ER and other visits, no statistically significant differences were found between cohorts over the first 4 weeks. The associated mean all-cause total health care costs were significantly lower in the rivaroxaban users compared with those in the LMWH/warfarin users over 1 week (US $2332 vs $3428; P < 0.001) and 2 weeks ($3108 vs $4524; P < 0.001); moreover, significantly lower mean costs related to all-cause hospitalizations (weeks 1 and 2) and pharmacy (weeks 1-4) were observed in patients treated with rivaroxaban, while no differences were found in costs related to ER visits (weeks 1-4), outpatient visits (weeks 1-4), or other visits (with the exception of week 1).. Patients with DVT treated with rivaroxaban after an outpatient/ER visit had significantly lower mean numbers of hospitalizations and outpatient visits, as well as lower mean total, hospitalization, and pharmacy costs during the first 2 weeks of treatment compared with those in matched LMWH/warfarin users.

Topics: Adult; Aged; Anticoagulants; Databases, Factual; Female; Health Care Costs; Heparin, Low-Molecular-Weight; Hospitalization; Humans; Male; Middle Aged; Outpatients; Pulmonary Embolism; Retrospective Studies; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis; Warfarin

The balance between the efficacy and safety of anticoagulant therapy in patients aged ≥100years receiving anticoagulant therapy for venous thromboembolism (VTE) is uncertain.. We used data from the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to assess the rate of VTE recurrences, bleeding events, and mortality appearing during the course of anticoagulant therapy in VTE patients aged ≥100years.. Of 61,173 patients enrolled in RIETE as of January 2016, 47 (0.08%) were aged ≥100years. Of these, 10 (21%) were men, 21 (45%) presented with pulmonary embolism (PE), and 26 with deep vein thrombosis alone. Overall, 35 patients (74%) had severe renal insufficiency, 14 (30%) chronic heart failure, 30 (64%) anemia, 16 (34%) were taking antiplatelets, and 6 (13%) corticosteroids or non-steroidal anti-inflammatory drugs. Most patients (95%) were treated initially with low-molecular-weight heparin (LMWH) (mean daily dose, 168±42IU/kg). Then, 14 (30%) switched to vitamin K antagonists and 29 (62%) kept receiving long-term LMWH therapy (mean, 148±51IU/kg/day). During the course of anticoagulant therapy (mean duration, 139days), mortality was high (15/47; 32%). Two patients died of PE (initial PE one, recurrent PE one) and 5 (11%) had minor bleeding, but no major bleeding was reported.. Among patients with acute VTE aged ≥100years, the risk of VTE recurrences during the course of anticoagulation outweighed the risk of bleeding. Our data suggest the use of standard anticoagulant therapy in this patient population, even if they have severe renal insufficiency.

Topics: Aged, 80 and over; Anemia; Anticoagulants; Comorbidity; Female; Heart Failure; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Pulmonary Embolism; Recurrence; Registries; Renal Insufficiency; Spain; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis; Warfarin

Topics: Adult; Aneurysm, False; Aneurysm, Ruptured; Drug Overdose; Dyspnea; Echocardiography, Doppler, Color; Humans; Leg Ulcer; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Male; Treatment Outcome; Venous Thrombosis; Ventricular Dysfunction, Left; Warfarin

A case of supratherapeutic International Normalized Ratio (INR) values and hematomas subsequent to concomitant administration of warfarin and intravesical gemcitabine is reported.. A 90-year-old man with bladder cancer refractory to bacillius Calmette-Guérin was diagnosed with deep vein thrombosis (DVT) and started on warfarin one month before starting treatment with intravesical gemcitabine 2 g (one dose per week for six weeks). Before intravesical gemcitabine was started, the patient reached consecutive therapeutic INR values. During the first five cycles of intravesical gemcitabine, the patient began to experience critically elevated INRs, which resulted in hospitalization and led to the discovery of hematomas. At hospital discharge, the decision was made to discontinue warfarin permanently given the patient's history of critically elevated INRs. Instead, enoxaparin was initiated due to the patient's history of DVT and active malignancy. Enoxaparin was started at a therapeutic, renally adjusted dosage of 60 mg subcutaneously once daily after the patient's hematomas resolved and hemoglobin level stabilized. The patient was cleared for discharge to his home after 17 days of hospitalization. He was scheduled to follow up with both urology and hematology departments regarding any further treatment for bladder cancer. A week after discharge, the patient's family decided that he would not receive the last (sixth) cycle of intravesical gemcitabine. To our knowledge, this is the first reported case of an interaction between intravesical gemcitabine and warfarin.. A 90-year-old man on a stable dose of warfarin experienced an increase in INR values after receiving intravesical gemcitabine for the treatment of bladder cancer.

Topics: Administration, Intravesical; Aged, 80 and over; Anticoagulants; Antimetabolites, Antineoplastic; BCG Vaccine; Carcinoma, Transitional Cell; Deoxycytidine; Drug Interactions; Enoxaparin; Gemcitabine; Humans; International Normalized Ratio; Male; Urinary Bladder Neoplasms; Venous Thrombosis; Warfarin

A 34-year-old man presented with an acute onset of upbeat nystagmus, slurred speech, and limb and truncal ataxias. The patient had a history of limb ataxia and gait disturbance previously treated as brainstem encephalitis with corticosteroids 3 years previously. Brain magnetic resonance imaging showed pontine developmental venous anomaly (DVA) and hemorrhagic infarction within the drainage territory of the DVA. Three months later, the patient exhibited recurrent limb ataxia, double vision, and numbness of the left side of the body. The brain magnetic resonance imaging revealed recurrent hemorrhagic venous infarction within the same territory of the pontine DVA. Laboratory tests disclosed a hypercoagulable state owing to a decrease of protein S activity despite the normal antigen level. Genetic testing indicated that the patient was a homozygous carrier of protein S Tokushima. The patient's severe disability remained unchanged in spite of treatment with anticoagulation therapy using warfarin. We propose that further research on hereditary coagulopathy be carried out in patients with recurrent episodes of DVA-related infarction.

Topics: Adult; Anticoagulants; Blood Coagulation; Blood Coagulation Tests; Brain Infarction; Central Nervous System Vascular Malformations; Cerebral Angiography; Cerebral Veins; DNA Mutational Analysis; Homozygote; Humans; Intracranial Hemorrhages; Intracranial Thrombosis; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Male; Mutation; Pons; Protein S; Protein S Deficiency; Recurrence; Treatment Outcome; Venous Thrombosis; Warfarin

Evidence from clinical trials shows rivaroxaban to be effective for the treatment of deep vein thrombosis. Switching to rivaroxaban following failure of indirect anticoagulants in deep vein thrombosis has not been demonstrated in a real-life setting.. A 43-year-old white woman was switched from warfarin to rivaroxaban for the treatment of thrombosis of her right common femoral vein after saphenectomy. The reason for the switch was due to the instability of anti-coagulation therapy with vitamin K antagonists over a period of 3 months during which she did not reach the "therapeutic range" of prothrombin time-international normalized ratio. The ineffectiveness of the conventional oral anticoagulant was confirmed by persistence of moderate-high values of fibrin D dimers (780 ng/ml) and by residual vein thrombosis at an ultrasound examination. Objectively, her right leg appeared to be still edematous and warm and pain was elicited by deep palpation. Rivaroxaban was administered after warfarin discontinuation (prothrombin time-international normalized ratio = 1.43) at a dosage of 15 mg every 12 hours for 3 weeks, followed by 20 mg once daily for 3 months. After this period, her objective symptoms significantly improved, with reduction of edema of her lower limb and pain relief. Her fibrin D dimer values returned to normal (210 ng/ml). An ultrasound showed recanalization of the obstructed venous segment.. In this case report, a switch to rivaroxaban from warfarin was shown to be effective and safe for the treatment of postoperative deep vein thrombosis, whereas standard oral anticoagulation therapy, which required dose adjustments over a period of 3 months, was not able to stabilize the therapeutic range of prothrombin time-international normalized ratio nor improve our patient's outcome.

Topics: Adult; Anticoagulants; Drug Administration Schedule; Female; Humans; Lower Extremity; Postoperative Complications; Rivaroxaban; Treatment Outcome; Venous Thrombosis; Warfarin

Venous thromboembolism, including deep vein thrombosis and pulmonary embolism, results in a substantial healthcare system burden. This retrospective observational study compared hospital length of stay (LOS) and hospitalization costs for patients with venous thromboembolism treated with rivaroxaban versus those treated with warfarin.. Hospitalizations for adult patients with a primary diagnosis of deep vein thrombosis or pulmonary embolism who were initiated on rivaroxaban or warfarin were selected from MarketScan's Hospital Drug Database between November 1, 2012, and December 31, 2013. Patients treated with warfarin were matched 1:1 to patients treated with rivaroxaban using exact and propensity score matching. Hospital LOS, time from first dose to discharge, and hospitalization costs were reported descriptively and with generalized linear models (GLMs). The final study cohorts each included 1223 patients (751 with pulmonary embolism and 472 with deep vein thrombosis). Cohorts were well matched for demographic and clinical characteristics. Mean (±SD) LOS was 3.7±3.1 days for patients taking rivaroxaban and 5.2±3.7 days for patients taking warfarin, confirmed by GLM-adjusted results (rivaroxaban 3.7 days, warfarin 5.3 days, P<0.001). Patients with provoked venous thromboembolism admissions showed longer LOSs (rivaroxaban 5.1±4.5 days, warfarin 6.5±5.6 days, P<0.001) than those with unprovoked venous thromboembolism (rivaroxaban 3.3±2.4 days, warfarin 4.8±2.8 days, P<0.001). Days from first dose to discharge were 2.4±1.7 for patients treated with rivaroxaban and 3.9±3.7 for patients treated with warfarin when initiated with parenteral anticoagulants (P<0.001), and 2.7±1.7 and 3.7±2.1, respectively, when initiated without parenteral anticoagulants (P<0.001). Patients initiated on rivaroxaban incurred significantly lower mean total hospitalization costs ($8688±$9927 versus $9823±$9319, P=0.004), confirmed by modeling (rivaroxaban $8387 [95% confidence interval, $8035-$8739]; warfarin $10 275 [95% confidence interval, $9842-$10 708]).. Rivaroxaban was associated with significantly shorter hospital LOS and lower hospitalization costs compared with warfarin.

Topics: Adolescent; Adult; Aged; Anticoagulants; Case-Control Studies; Female; Hospital Costs; Hospitalization; Humans; Length of Stay; Male; Middle Aged; Pulmonary Embolism; Retrospective Studies; Rivaroxaban; United States; Venous Thrombosis; Warfarin; Young Adult

Antiphospholipid syndrome (APS), autoantibodies directed against phospholipid-binding proteins are associated with cause vascular thrombosis. Patients with APS requiring renal transplantation are at risk of early graft loss due to arterial or venous thrombosis, or thrombotic microangiopathy (TMA). Here, we report 3 cases of successful renal transplantation in patients with APS.. A 53-year-old man with end-stage renal disease (ESRD) had experienced bilateral deep venous thrombosis (DVT) in the lower extremities 16 years ago and was administered warfarin. However, he frequently experienced recurrent DVT despite of anticoagulation therapy. Before the surgery, APS was confirmed based on positive results lupus anticoagulant in serological tests. A 40-year-old man with polycystic kidney disease and a history recurrent DVT tested positive for lupus anticoagulant and anticardiolipin antibodies. Lastly, a 42-year-old woman with ESRD was diagnosed with APS 7 years ago. She also developed DVT and tested positive for lupus anticoagulant and anti-B2-glycoprotein 1.. Warfarin was stopped 5 days before living donor renal transplantation and intravenous heparin therapy was started. During surgery, bolus heparin injections (3000 U) were administered to prevent arterial or venous thrombosis. Heparin was substituted with warfarin on postoperative day 4. The third patient (42/F) developed clinical rejection indicated by increased serum creatinine levels and donor-specific antibodies (DSA) and received steroid pulse therapy, plasmapheresis, and rituximab. This treatment restored graft function to within the normal range. The latest graft function in all patients was maintained at normal levels in the outpatient clinic.. Living donor renal transplantation may be successful in patients with APS following perioperative anticoagulation therapy. However, because of the high risk of TMA or vascular thrombosis in the early postoperative period, close monitoring for hypercoagulability and continuous anticoagulation is essential for maintaining graft function.

Topics: Adult; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Autoantibodies; Drug Substitution; Female; Graft Rejection; Heparin; Humans; Kidney Failure, Chronic; Kidney Transplantation; Living Donors; Male; Middle Aged; Plasmapheresis; Recurrence; Treatment Outcome; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Diagnosis, Differential; Female; Hepatic Veins; Humans; Liver Circulation; Liver Cirrhosis; Magnetic Resonance Imaging; Middle Aged; Phlebography; Portal Vein; Predictive Value of Tests; Ultrasonography, Doppler, Color; Vascular Malformations; Venous Thrombosis; Warfarin

Allograft renal vein thrombosis is a rare complication of kidney transplantation. Most cases occur in the first 2 weeks after transplantation, but there are cases described many years after the transplant surgery. Allograft loss is the usual outcome.. We present a case of a renal transplant recipient with allograft renal vein thrombosis associated with deep venous thrombosis of a lower limb, 9 years after transplantation. He was successfully treated with anticoagulation alone, with recovery of allograft function.. The patient was given unfractioned heparin and elastic compression stockings. Five days later, the patient recovered diuresis and hemodialysis treatment was discontinued. Doppler ultrasound was done and revealed partial re-permeabilization of allograft renal vein, with maximal velocity of 15 cm/s. After 30 months of follow-up, the patient was maintained on oral anticoagulation with warfarin, and no thromboembolic or hemorrhagic events were documented. The patient's serum creatinine was stable, between 1.6 and 1.8 mg/dL.. Our patient demonstrated that anticoagulation alone and dialytic support might be able to promote total recovery of allograft function after renal vein thrombosis.

Topics: Allografts; Anticoagulants; Heparin; Humans; Kidney Transplantation; Male; Middle Aged; Postoperative Complications; Renal Dialysis; Renal Veins; Stockings, Compression; Transplantation, Homologous; Venous Thrombosis; Warfarin

In Ireland, Warfarin is the primary anticoagulant prescribed in the secondary prevention of provoked DVT. We completed a comprehensive cost analysis of a trial group of 24 patients treated with Rivaroxaban (between November 2013 and December 2014), versus a control group treated with Warfarin (between January 2008 and November 2013). The groups were matched for gender (3/7 M/F ratio), DVT type (5 proximal, 19 distal DVTs), provoking factor (20 traumatic, 4 atraumatc), and age. We calculated the cost for each group based on drug administration and clinic costs (labour, sample analysis, and additional costs). Warfarin patients attended clinic 14.58 times; Rivaroxaban patients attended 2.92 times. Overall, the cost per patient on Rivaroxaban is €273.30 versus €260.68 with warfarin. This excludes patient costs which would further increase cost of Warfarin therapy.

Topics: Anticoagulants; Costs and Cost Analysis; Drug Costs; Factor Xa Inhibitors; Female; Humans; Ireland; Male; Rivaroxaban; Secondary Prevention; Venous Thrombosis; Warfarin

The purpose of this study was to determine the percentage of time that patients are therapeutic when prescribed warfarin for chemical thromboprophylaxis following a hip or knee arthroplasty procedure. One hundred eighty-four patients receiving warfarin for 4weeks postoperatively, dosed using a Web-application accounting for patient demographics, INR levels, and concomitant medication use, were included. Patients with a target INR range between 1.7 and 2.7 were therapeutic for only 54.4% of the time (32.5% subtherapeutic, 13.0% supratherapeutic) while patients with a target INR range between 2.0 and 3.0 were therapeutic for only 45.9% of the time (39.2% subtherapeutic, 14.8% supratherapeutic). Patients receiving warfarin for chemical thromboprophylaxis are within their targeted INR range for only a limited period of time during their postoperative course.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Drug Monitoring; Female; Humans; International Normalized Ratio; Male; Middle Aged; Retrospective Studies; Venous Thrombosis; Warfarin

Guidelines for warfarin treatment of venous thromboembolism (VTE) recommend targeting an international normalized ratio (INR) level of 2-3. This study examines the association between INR levels and VTE recurrence among warfarin-treated patients.. A retrospective cohort study in the MedMining electronic health record database included adults treated with warfarin for VTE in 2004-2011. INR levels during warfarin use were categorized as below therapeutic range (<2), in range (2-3), or above range (>3), with time in each category estimated using the Rosendaal method. Recurrent VTE was noted from 30 days after the initial VTE to end of follow-up, which ranged up to 8 years. The incidence of recurrent VTE was calculated, and association with time-varying INR levels estimated using Cox models.. Of 1753 qualifying patients, 867 had deep vein thrombosis, and 886 had pulmonary embolism. Mean age was 58 years, and 50.7% were female. Across all follow-up time, VTE recurrences were observed in 134 (7.6%) patients, at a rate of 3.2 (95% confidence interval [CI]: 0.7-9.1) events per 100 person-years. The risk of VTE recurrence was greater during time spent with INR <2 than with INR in the therapeutic range (hazard ratio [HR]: 3.37; 95% CI: 2.16-5.27). Low platelet counts also predicted greater risk of VTE recurrence (HR: 2.13; 95% CI: 1.24-3.67).. Exposure to warfarin and other anticoagulants was estimated based on prescription data and may be inaccurate. The study data include care within a single health system; thus, care received outside of the health system may be missing, and results may not be generalizable to the broader US population.. Approximately 8% of patients experienced a recurrent VTE during follow-up. Subtherapeutic INR levels were associated with a more than three-fold increased risk of VTE recurrence.

Topics: Anticoagulants; Cohort Studies; Databases, Factual; Drug Monitoring; Female; Humans; Incidence; International Normalized Ratio; Male; Middle Aged; Proportional Hazards Models; Pulmonary Embolism; Retrospective Studies; Risk Assessment; Secondary Prevention; Venous Thromboembolism; Venous Thrombosis; Warfarin

Anticoagulants carry a significant risk of gastrointestinal bleeding (GIB). Data regarding the safety of anticoagulation continuation/cessation after GIB are limited. We sought to determine the safety and risk of continuation of anticoagulation after GIB.. We conducted a prospective observational cohort study on consecutive patients admitted to the hospital who had GIB while on systemic anticoagulation. Patients were classified into two groups at hospital discharge after GIB: those who resumed anticoagulation and those who had anticoagulation discontinued. Patients in both groups were contacted by phone 90 days after discharge to determine the following outcomes: (i) thromboembolic events, (ii) hospital readmissions related to GIB, and (iii) mortality. Univariate and multivariate Cox proportional hazards were used to determine factors associated with thrombotic events, rebleeding, and death.. We identified 197 patients who developed GIB while on systemic anticoagulation (n=145, 74% on warfarin). Following index GIB, anticoagulation was discontinued in 76 patients (39%) at discharge. In-hospital transfusion requirements, need for intensive care unit care, and etiology of GIB were similar between the two groups. During the follow-up period, 7 (4%) patients suffered a thrombotic event and 27 (14%) patients were readmitted for GIB. Anticoagulation continuation was independently associated on multivariate regression with a lower risk of major thrombotic episodes within 90 days (hazard ratio (HR)=0.121, 95% confidence interval (CI)=0.006-0.812, P=0.03). Patients with any malignancy at time of GIB had an increased risk of thromboembolism in follow-up (HR=6.1, 95% CI=1.18-28.3, P=0.03). Anticoagulation continuation at discharge was not significantly associated with an increased risk of recurrent GIB at 90 days (HR=2.17, 95% CI=0.861-6.67, P=0.10) or death within 90 days (HR=0.632, 95% CI=0.216-1.89, P=0.40).. Restarting anticoagulation at discharge after GIB was associated with fewer thromboembolic events without a significantly increased risk of recurrent GIB at 90 days. The benefits of continuing anticoagulation at discharge may outweigh the risks of recurrent GIB.

Topics: Aged; Aged, 80 and over; Anticoagulants; Benzimidazoles; beta-Alanine; Cohort Studies; Dabigatran; Enoxaparin; Female; Gastrointestinal Hemorrhage; Heparin; Humans; Ischemic Attack, Transient; Longitudinal Studies; Male; Middle Aged; Morpholines; Patient Readmission; Prospective Studies; Pulmonary Embolism; Pyrazoles; Pyridones; Recurrence; Rivaroxaban; Stroke; Thiophenes; Thromboembolism; Venous Thrombosis; Warfarin; Withholding Treatment

Hereditary protein C deficiency (PCD) is an autosomal inherited disorder associated with high risk for venous thromboembolism (VTE). This study aimed to explore the functional consequences of two missense mutations, p.Asp297His and p.Val420Ile, responsible for type I/II PCD and recurrent deep vein thrombosis (DVT) in a Chinese family. The plasma protein C activities (PC:A) of the proband and his sister were reduced to 4% and 5% of normal activity. However, protein C antigen (PC:Ag) concentrations were not equally decreased, with levels of 90.5% and 88.7%, respectively. Two missense mutations p.Asp297His and p.Val420Leu were identified in the protein C gene (PROC). The PC:A and PC:Ag levels in heterozygous state for p.Asp297His were 66% and 64.8%, whereas in heterozygous state for p.Val420Leu, these levels were 67% and 145%, respectively. Wild type (WT) and two mutant PROC cDNA expression plasmids were constructed and transfected into HEK 293T cells. Western blot analysis revealed that both p.Asp297His and p.Val420Leu showed a normal intracellular protein level. The extracellular protein level and specific activity of p.Asp297His were equally reduced to 37.7 ± 4.3% and 22.1 ± 2.5%, respectively. Mutant p.Val420Leu showed a relatively higher PC:Ag level and undetectable PC:A. Immunofluorescence staining revealed that WT and p.Val420Leu proteins were largely co-localized with both the protein disulfide isomerase (PDI) and cis-Golgi Marker (GM130), while the PC p.Asp297His mutant protein was mainly co-localized with PDI and much less co-localized with GM130. The thrombosis symptom in this family was associated with the two missense mutations in the PROC gene.

Topics: Asian People; Female; Fluorescent Antibody Technique; Gene-Environment Interaction; HEK293 Cells; Heterozygote; Humans; Male; Mutation, Missense; Pedigree; Protein C; Protein C Deficiency; Risk Factors; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Coronary Artery Disease; Dyspnea; Echocardiography, Transesophageal; Embolism; Foramen Ovale, Patent; Humans; Intracranial Embolism; Magnetic Resonance Angiography; Male; Middle Aged; Multimodal Imaging; Pulmonary Embolism; Renal Artery Obstruction; Ultrasonography, Doppler; Venous Thrombosis; Warfarin

Ovarian vein thrombosis is a rare diagnosis typically seen in the early peripartum period but also in other thrombophilic states such as postsurgery, pelvic inflammatory disease, malignancy, or sepsis. We describe a case of idiopathic ovarian vein thrombosis in a healthy woman far outside the peripartum window.. The patient is a 29-year-old woman, gravida 3 para 2102, with no significant surgical or medical history referred for 8 months of severe left lower quadrant pain. An ultrasonogram revealed a nonocclusive left ovarian vein thrombosis. Hypercoagulable workup and all other laboratory tests were normal. The thrombus resolved within 2 months of starting oral anticoagulation therapy.. This case demonstrates the importance of including idiopathic ovarian vein thrombosis in the differential diagnosis of nonperipartum females with pelvic pain.

Topics: Adult; Anticoagulants; Female; Humans; Ovary; Veins; Venous Thrombosis; Warfarin

Post-thrombotic syndrome (PTS) is a common complication of deep venous thrombosis (DVT) of the iliofemoral venous system leading to significant morbidity and high health care costs. It has been recently shown that percutaneous endovenous intervention (PEVI) can effectively reduce the incidence of PTS. The role of new oral anticoagulants (NOACs) in combination with PEVI in the reduction of PTS has not been previously studied. This report sought to evaluate the role of PEVI plus NOACs in the reduction of PTS in acute symptomatic femoropopliteal and iliac DVT. We studied 127 patients with acute lower extremity DVT who had undergone PEVI plus administration of NOACs. All had received a minimum of 3 months of anticoagulation with a NOAC following PEVI. The mean follow-up was 22±5 months. The patients were evaluated for development of PTS, bleeding, recurrent venous thromboembolism (VTE), duration of hospitalization and mortality. There was no in-hospital bleeding. The mean duration of hospitalization was 46±9 hours. DVT occurred in two patients who had been later switched to warfarin. There were four non-VTE-related deaths. PTS developed in five patients (3%), two of whom were those who had been switched to warfarin. Their mean Villalta score was 6.2±0.9. We conclude that the combination of PEVI plus NOAC and low dose aspirin is associated with a very low rate of PTS with the severity being only mild. This approach leads to very low rates of bleeding and recurrent VTE and promotes early discharge.

Topics: Administration, Oral; Anticoagulants; Female; Hemorrhage; Humans; Incidence; Lower Extremity; Male; Postthrombotic Syndrome; Risk Factors; Time Factors; Venous Thrombosis; Warfarin

Venous stasis is generally accepted to be a predisposing factor for venous thrombosis. However, benign causes of inferior vena cava (IVC) obstruction with associated thrombus formation have not been well described. We herein present a case of IVC compression caused by a distended ileal neobladder measuring 2,000 mL in capacity that led to IVC thrombosis. Following transurethral drainage for six weeks and anticoagulation therapy with warfarin for six months, the thrombus completely disappeared. The patient was considered to have a hypercoagulable state resulting from an acute urinary tract infection, a condition that may be associated with an increased risk of thrombosis.

Topics: Humans; Male; Middle Aged; Tomography, X-Ray Computed; Urologic Surgical Procedures; Vena Cava, Inferior; Venous Thrombosis; Warfarin

Pulmonary tuberculosis remains an important public health problem globally and one of the most prevalent infectious diseases in Sri Lanka. It can cause a wide variety of complications but hematological manifestations are rare. According to our literature survey, this is the first reported case of the disease associated with deep vein thrombosis in Sri Lanka.. A 37 year old Sri Lankan Sinhalese female presented with fever of one month's duration with productive cough and two weeks painless left lower limb swelling. Chest X-ray showed bilateral inflammatory shadows with a cavitatory lesion on the right apical region. A computed tomographic pulmonary angiography scan excluded pulmonary embolism. She had rising mycoplasma antibody titre (four fold). Acute deep vein thrombosis of the left lower limb was confirmed by venous duplex. Pulmonary tuberculosis was confirmed with positive culture for Mycobacterium tuberculosis. She was treated with clarythromycin, enoxaparin, warfarin and anti tuberculus drugs. It was difficult to maintain her International Normalizing Ratio in the therapeutic range due to drug interactions and poor compliance. At five months of presentation she died of massive pulmonary embolism.. Our case emphasizes that patients with severe pulmonary tuberculosis are at risk of developing thromboembolism and superadded infections. It should be noted that even though starting anti tuberculosis drugs improved haemostatic disturbances, achieving the target International Normalizing Ratio was difficult due to drug interactions. Therefore these patients should be closely followed up to prevent complications and death from pulmonary embolism.

Topics: Adult; Antitubercular Agents; Clarithromycin; Drug Antagonism; Enoxaparin; Fatal Outcome; Female; Humans; Leg; Mycobacterium tuberculosis; Pulmonary Embolism; Treatment Failure; Tuberculosis, Pulmonary; Venous Thrombosis; Warfarin

A 27-year-old man developed extensive hepatic portal venous gas (HPVG) shortly after staging colonoscopy for active, ulcerating, terminal ileal Crohn's disease. Non-operative management was instigated with broad-spectrum antibiotics and thromboprophylaxis. Radiology at 72 h demonstrated resolution of HPVG but revealed fresh non-occlusive left portal vein thrombus. Anticoagulation with warfarin was continued for 1 year, during which the thrombus initially progressed and then organised with recanalisation of the portal vein. There were no long-term clinical consequences. HPVG has previously been documented as a rare complication of inflammatory bowel disease and endoscopic intervention. We hypothesise that the barotrauma sustained during endoscopy, in association with active ulceration and mucosal friability, predisposes to the influx of gas and bacteria into the portal system. We describe successful non-operative management of HPVG in this setting and draw attention to an additional complication of portal venous thrombosis, highlighting the importance of thromboprophylaxis and serial radiological examination.

Topics: Adult; Anti-Bacterial Agents; Anticoagulants; Colonoscopy; Crohn Disease; Embolism, Air; Humans; Ileitis; Liver; Male; Portal Vein; Prognosis; Tomography, X-Ray Computed; Treatment Outcome; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Blood Coagulation; Brachiocephalic Veins; Child; Chylothorax; Computed Tomography Angiography; Heparin; Humans; Male; Nephrotic Syndrome; Treatment Outcome; Venous Thrombosis; Warfarin

Venous limb gangrene (VLG) can occur in cancer patients, but the clinical picture and pathogenesis remain uncertain. We identified 10 patients with metastatic cancer (7 pathologically proven) who developed severe venous limb ischemia (phlegmasia/VLG) after initiating treatment of deep-vein thrombosis (DVT); in 8 patients, cancer was not known or suspected at presentation. The patients exhibited a novel, clinically distinct syndrome: warfarin-associated supratherapeutic international normalized ratio (INR; median, 6.5) at onset of limb ischemia, rising platelet count during heparin anticoagulation, and platelet fall after stopping heparin. Despite supratherapeutic INRs, patient plasma contained markedly elevated thrombin-antithrombin (TAT) complex levels (indicating uncontrolled thrombin generation) and protein C (PC) depletion; this profile resembles the greatly elevated TAT/PC activity ratios reported in patients with warfarin-associated VLG complicating heparin-induced thrombocytopenia. Analyses of vitamin K-dependent factors in 6 cancer patients with available serial plasma samples showed that variations in the INR corresponded most closely with changes in factor VII, with a highly collinear relationship between VII and PC. We conclude that venous limb ischemia/gangrene is explained in some cancer patients by profoundly disturbed procoagulant-anticoagulant balance, whereby warfarin fails to block cancer-associated hypercoagulability while nonetheless contributing to severe PC depletion, manifest as a characteristic supratherapeutic INR caused by parallel severe factor VII depletion.

Topics: Aged; Anticoagulants; Antithrombin III; Blood Coagulation Factors; Blood Platelets; Female; Follow-Up Studies; Gangrene; Heparin; Humans; International Normalized Ratio; Ischemia; Leg; Male; Middle Aged; Neoplasms; Peptide Hydrolases; Prognosis; Protein C Deficiency; Syndrome; Venous Thrombosis; Vitamin K; Warfarin

Anticoagulant responses to warfarin vary among patients, based on genetic factors, diet, concomitant medications, and disease state. We evaluated the effectiveness and safety of a 10mg warfarin initiation nomogram in an Asian population. Retrospective cross-sectional audit studies were conducted from March 2009 to March 2010. The use of a 10mg-loading dose to initiate warfarin treatment resulted in 33(84.6%) patients attaining a therapeutic INR within four days (mean time, 2.6 days). There was no significant correlation between age, gender, race, and serum albumin for the time to reach a therapeutic INR. A significant correlation was noted for patient's baseline INR and time to reach a therapeutic INR (P<0.05). No significant differences were observed in time to reach a therapeutic INR in patients treated with specific class of concomitant drugs or patients with specific disease states. The overall incidence of over-anticoagulation was 35.9%; however, no bleeding episodes were encountered. In conclusion, the use of a 10mg warfarin nomogram was effective in rapidly achieving a therapeutic INR. However, the nomogram's safety is debatable owing to the high over-anticoagulation rate warfarin-administered patients. Caution is recommended in the initiation of warfarin treatment using the 10mg nomogram.

Topics: Adult; Aged; Anticoagulants; Asian People; Atrial Fibrillation; Coronary Thrombosis; Cross-Sectional Studies; Humans; Malaysia; Male; Middle Aged; Nomograms; Pulmonary Embolism; Retrospective Studies; Stroke; Venous Thrombosis; Warfarin

Target-specific anticoagulants such as rivaroxaban facilitate immediate discharge of low-risk venous thromboembolism (VTE; including deep vein thrombosis [DVT] and pulmonary embolism [PE]) allowing treatment at home instead of hospitalization.. The objective was to compare costs accrued over 6 months by patients diagnosed with low-risk VTE and treated at home with rivaroxaban versus usual care with heparin-warfarin.. This case-control study calculated costs using the established charge-to-cost ratio from UB-04 billing claims of patients diagnosed at two metropolitan hospitals. Patients were defined as low risk by the Hestia criteria. All patients were anticoagulated for 6 months. Control patients were treated with usual care using low-molecular-weight heparin (LMWH) and then warfarin. Case patients were treated with an initial dose of rivaroxaban in the ED followed by same-day discharge home with rivaroxaban. Medians were compared by Mann-Whitney U-test.. Fifty cases and 47 controls were identified. Groups were well matched according to mean age, Charlson comorbidity score, and proportions by sex and location of thrombus. For all VTEs, median hospital charges for 6 months after diagnosis were $11,128 (interquartile range [IQR] = $8,110 to $23,390) for controls, compared with $4,787 (IQR = $3,042 to $7,596) for cases (Mann-Whitney U-test p < 0.001). Subgroup analyses of the first week of therapy, PE, DVT, and inpatient pharmacy costs retained significance, with costs for rivaroxaban-treated PE patients 57% lower than control PE patients (p < 0.001) and 56% lower for DVT patients (p = 0.003).. Cost of medical care was lower for low-risk VTE patients discharged immediately from the ED with rivaroxaban therapy compared with patients treated with LMWH-warfarin.

Topics: Adult; Aged; Anticoagulants; Case-Control Studies; Emergency Service, Hospital; Female; Heparin, Low-Molecular-Weight; Hospitalization; Humans; Male; Middle Aged; Pulmonary Embolism; Rivaroxaban; Statistics, Nonparametric; Venous Thrombosis; Warfarin

MicroRNAs are small single stranded molecules that play a crucial role in regulation of physiological and pathological processes. Recent studies showed that VKORC1 gene contains an highly evolutionary conserved binding site for mir-133. Moreover, in human hepatocytes mir-133 is constitutively co-expressed with VKORC1. Since VKORC1 protein is the target of warfarin treatment, the aim of this study was to verify if genetic variations in MIR133A1, MIR133A2 and MIR133B could contribute to warfarin dose variability. By direct sequencing, we identified 4 SNPs in MIR133A2 gene and 1 SNP in MIR133B gene. Three SNPs in MIR133A2 were in complete linkage disequilibrium and correlated with warfarin dose: indeed, for each SNP, patients carrying the GA or AA genotype required a MWWD significantly higher than the wildtype genotype (P=0.019). We also inferred the haplotypes in MIR133A2 gene. The GC haplotype required a MWWD significantly lower than AT haplotype (P=0.012). The multiple linear regression analysis confirmed that rs45547937 (as tag SNP) in MIR133A2 could be involved in warfarin dosing variability, (P=0.016). These results seem to suggest that also polymorphisms in miRNA precursors may potentially affects drug response variability.

Topics: Adult; Age Distribution; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Genetic Predisposition to Disease; Humans; Italy; Linkage Disequilibrium; Male; MicroRNAs; Middle Aged; Mutation; Pharmacogenetics; Polymorphism, Single Nucleotide; Prevalence; Risk Factors; Sex Distribution; Treatment Outcome; Venous Thrombosis; Vitamin K Epoxide Reductases; Warfarin

In many patients with deep vein thrombosis and pulmonary embolism (venous thromboembolism, VTE), biomarkers or genetic risk factors have not been identified. To discover novel plasma metabolites associated with VTE risk, we employed liquid chromatography-mass spectrometry-based untargeted metabolomics, which do not target any specific metabolites. Using the Scripps Venous Thrombosis Registry population for a case-control study, we discovered that 10:1 and 16:1 acylcarnitines were low in plasmas of the VTE patient group compared with matched controls, respectively. Data from targeted metabolomics studies showed that several long-chain acylcarnitines (10:1, 12:0, 12:2, 18:1, and 18:2) were lower in the VTE group. Clotting assays were used to evaluate a causal relationship for low acylcarnitines in patients with VTE. Various acylcarnitines inhibited factor Xa-initiated clotting. Inhibition of factor Xa by acylcarnitines was greater for longer acyl chains. Mechanistic studies showed that 16:0 acylcarnitine had anticoagulant activity in the absence of factor Va or phospholipids. Surface plasmon resonance investigations revealed that 16:0 acylcarnitine was bound to factor Xa and that binding did not require the γ-carboxy glutamic acid domain. In summary, our study identified low plasma levels of acylcarnitines in patients with VTE and showed that acylcarnitines have anticoagulant activity related to an ability to bind and inhibit factor Xa.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Carnitine; Case-Control Studies; Factor Xa; Factor Xa Inhibitors; Female; Humans; Male; Metabolomics; Middle Aged; Protein Binding; Protein Structure, Tertiary; Risk Factors; Venous Thrombosis; Warfarin

To explore physician practice patterns with regard to antithrombotic therapy, including antiplatelets and anticoagulants, in long-term care residents and compare resulting embolic complications.. Conducted between August 2012 and March 2013, this study was a retrospective chart review of 400 residents of a long-term care facility. Electronic charts from October 2005 through January 2013 were selected using systematic random sampling.. Approximately one-third of residents (29.6%) received anticoagulants, 27.3% received antiplatelets, 15.8% received both, and 27.3% did not receive any antithrombotic therapy. The most commonly prescribed antithrombotic drugs were aspirin (37.5%) and warfarin (22.1%). The type of antithrombotic therapy was significantly associated with medical history, including deep vein thrombosis (P = 0.03), the presence of atrial fibrillation (P = 0.001) and other nonsurgical medical conditions (P = 0.0001). Weight (P = 0.009) and body mass index (P = 0.007) also were significantly associated with type of antithrombotic therapy, indicating that heavier residents and those with a higher body mass index were more likely to receive both anticoagulants and antiplatelets. There was no difference in the number of embolic complications among groups.. Physicians are more disposed to initiate and maintain residents on aspirin while being more cautious when prescribing anticoagulants such as warfarin, dabigatran, heparin, and enoxaparin. In some residents, anticoagulants were not used at all, even when residents had particular risk factors, demonstrating that at times physicians may err on the side of overcautiousness. Antithrombotic therapy should be individualized for each resident based on bleeding risk, comorbidities, and benefits of a particular therapy for our most vulnerable populations.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Body Mass Index; Drug Therapy, Combination; Hemorrhage; Humans; Long-Term Care; Male; New York; Platelet Aggregation Inhibitors; Practice Patterns, Physicians'; Residential Facilities; Retrospective Studies; Risk Assessment; Venous Thrombosis; Warfarin

In this issue of Blood, Warkentin et al describe a novel clinical syndrome of warfarin-associated severe venous limb ischemia occurring in a series of 10 patients with malignancy after initiating treatment of deep venous thrombosis. Patients in this series also demonstrated a decline in platelet counts after stopping heparin, warfarin-associated supratherapeutic international normalized ratios (INRs), and evidence of persistent thrombin generation despite anticoagulation.

Topics: Anticoagulants; Female; Gangrene; Humans; Ischemia; Leg; Male; Neoplasms; Venous Thrombosis; Warfarin

Polymorphisms in cytochrome P450 2C9 and vitamin K epoxide reductase complex, subunit 1 genes (CYP2C9 and VKORC1, respectively) were previously shown to affect the warfarin dose required in anticoagulant therapy of deep vein thrombosis (DVT). However, little is known about the role of these genetic variants in the Thai population.. To identify the effect of CYP2C9 and VKORC1 genetic variants on warfarin dosage in the Thai population with DVT.. Genotyping of CYP2C9 (*2 and *3) and VKORC1 promoter (-1 639G>A) variants were carried out in 97 Thai DVT patients receiving constant warfarin therapy and with a stable international normalized ratio using real-time PCR assays.. VKORC1 AA, GA, and GG genotype frequencies were found to be 49.5%, 46.4%, and 4.1%, respectively, while those of CYP2C9 genotypes were 88.7% for *1/*1 and 11.3%for *1/*3. The CYP2C9*2 variant was not present in the patients studied. The mean daily warfarin dose required to maintain a therapeutic INR differed significantly according to VKORC1 genotype, with 3.6 mg/day required for AA, 4.7 mg/day for GA, and 7.4 mg/day for GG (p-value < 0.001). The CYP2C9 genotype did not significantly affect the warfarin dosage requirement (p-value = 0.29).. These findings underline the impact of VKORC1 genotypes on the wide variation in warfarin maintenance dosing in Thai patients with DVT.

Topics: Adult; Aged; Anticoagulants; Asian People; Cytochrome P-450 CYP2C9; Female; Genetic Variation; Genotype; Humans; International Normalized Ratio; Male; Middle Aged; Polymorphism, Single Nucleotide; Real-Time Polymerase Chain Reaction; Venous Thrombosis; Vitamin K Epoxide Reductases; Warfarin

The relative efficacy and safety of dabigatran etexilate and warfarin have been evaluated in two head-to-head, phase III, treatment of acute venous thromboembolism (VTE) trials, and one extended prophylaxis trial, in patients with high risk of recurrent VTE. Dabigatran etexilate demonstrated similar efficacy to warfarin, and was associated with a reduced risk of major or clinically relevant bleeds. Based on results of these trials, and real-life disease prognosis following discontinuation of anticoagulation treatment, we evaluated the cost-utility of dabigatran etexilate compared with warfarin in six months anticoagulation, and in extended, up to 24 months anticoagulation, in patients with acute VTE, acute deep-vein thrombosis (DVT) or acute, symptomatic, pulmonary embolism (PE). Costs were analysed from the perspective of the National Health Services (NHS) and Public Social Services (PSS) in England and Wales. Outcomes were quantified in quality-adjusted life years (QALY). The estimated incremental, lifetime cost/QALY gain following acute, symptomatic VTE (DVT or PE) was £1,252/QALY when dabigatran etexilate or warfarin were administered for up to six months treatment. In treatment of acute, symptomatic PE and in DVT respective ratios were £1,767/QALY and £1,075/QALY. In extended, up to 24 months anticoagulation, dabigatran etexilate projected costs/QALY of £8,242/QALY, when compared with warfarin. Results obtained herein were robust across a number of sensitivity analyses and suggest dabigatran etexilate to be a cost-effective alternative to current standard of care when evaluated in six months treatment and in extended anticoagulation following acute VTE (DVT and/or PE).

Topics: Acute Disease; Anticoagulants; Cost-Benefit Analysis; Dabigatran; Drug Administration Schedule; Drug Costs; Hemorrhage; Humans; Kaplan-Meier Estimate; Models, Economic; Pulmonary Embolism; Quality-Adjusted Life Years; State Medicine; Time Factors; Treatment Outcome; United Kingdom; Venous Thromboembolism; Venous Thrombosis; Warfarin

The patient presented with syncope, without chest pain and dyspnea. There was no peripheral edema or nervous system signs. The electrocardiogram (ECG) showed QT-interval prolongation with T-wave inversion in anterior and inferior leads. T-wave inversion in the right-sided precordial leads should prompt consideration of right ventricular overload. The patient underwent computed tomography of the chest that demonstrated pulmonary embolism. Ultrasonography of the veins of the lower limbs revealed an isolated calf vein thrombosis.

Topics: Aged; Anticoagulants; Electrocardiography; Female; Humans; Leg; Long QT Syndrome; Pulmonary Embolism; Syncope; Tomography, X-Ray Computed; Ultrasonography; Venous Thrombosis; Warfarin

Not more effective than warfarin. The lower incidence of bleeding observed among patients selected for these trials must be weighed against the lack of either an antidote or a routine clotting test.

Topics: Blood Coagulation Tests; Factor Xa Inhibitors; Hemorrhage; Humans; Pulmonary Embolism; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Risk; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Aspirin; Drug Therapy, Combination; Early Ambulation; Heparin, Low-Molecular-Weight; Humans; Pulmonary Embolism; Stockings, Compression; Thrombocytopenia; Venous Thrombosis; Vitamin K; Warfarin

Peritoneal tuberculosis is an important problem in regions of the world where tuberculosis is still prevalent (Chest 1991; 99:1134). Atypical presentations such as portal vein thrombosis can delay diagnosis or result in misdiagnosis (Gut 1990; 31:1130, Acta ClinBelg 2012; 67(2):137-9, J Cytol Histol 2014; 5:278, Digestive Diseases and Sciences 1991; 36(1):112-115). A high index of suspicion is required for the diagnosis of peritoneal tuberculosis, as the analysis of peritoneal fluid for tuberculous bacillus is often ineffective, and may increase mortality due to delayed diagnosis. (Clin Effect Dis 2002;35: 409-13) In light of new evidence, peritoneal biopsy through laparoscopy or laparotomy has emerged as the gold standard for diagnosis (Clin Effect Dis 2002; 35: 409-13).. We report a case of a 35 year old Sri Lankan female employed in a Middle - Eastern country who presented with progressive abdominal distention and constitutional symptoms for four months duration. She had been investigated abroad and diagnosed with ascites with chronic portal vein thrombosis following which warfarin therapy had been commenced suspecting an underlying thrombophilia. Despite treatment her symptoms had worsened. Therefore she had decided to return to Sri Lanka for further evaluation. After ruling out inherited thrombophilic states and the antiphospholipid syndrome, further investigations revealed a transudative ascites and high inflammatory markers. The tuberculosis work up on peritoneal fluid was negative. Therefore, we proceeded with laparoscopy which showed multiple nodular deposits on abdominal wall, bowel and omentum and peritoneal biopsy revealed granulomatous inflammation with caseous type necrosis compatible with mycobacterium tuberculosis infection. This was confirmed by tuberculosis genome identification on the biopsy sample confirming a diagnosis of peritoneal tuberculosis with secondary portal vein thrombosis and cavernous formation due to local inflammation. The patient was started on anti-tuberculosis treatment and warfarin was discontinued, following which she made a remarkable recovery.. Peritoneal tuberculosis can present with unusual manifestations such as portal vein thrombosis and transudative ascites causing a diagnostic dilemma. Ascitic fluid analysis is generally not diagnostic. Under such circumstances peritoneal biopsy should be performed as it has a good diagnostic yield and accuracy.

Topics: Adult; Anticoagulants; Antitubercular Agents; Ascites; Ascitic Fluid; Diagnosis, Differential; Female; Humans; Laparoscopy; Mycobacterium tuberculosis; Peritonitis, Tuberculous; Portal Vein; Sri Lanka; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Antiparkinson Agents; Biotransformation; Dizziness; Drug Interactions; Drug Substitution; Drug Therapy, Combination; Factor Xa Inhibitors; Humans; Indans; Male; Middle Aged; Parkinson Disease; Rivaroxaban; Trihexyphenidyl; Venous Thrombosis; Warfarin

Not more effective than warfarin in three "non-inferiority" trials. Less bleeding but more acute coronary events with dabigatran, and still no antidote.

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; beta-Alanine; Blood Coagulation; Blood Coagulation Tests; Dabigatran; Drug Monitoring; Hemorrhage; Humans; Pulmonary Embolism; Risk Assessment; Risk Factors; Treatment Outcome; Venous Thrombosis; Warfarin

The mean time in target range for each centre, cTTR, has previously been shown to correlate to the rate of complications in poorly managed warfarin treatment. However less is known about the correlation when warfarin treatment is well managed.. The aim of this study was to examine the correlation between cTTR and the rate of complications in a real life setting with cTTR above 70%, with focus on patients with warfarin due to atrial fibrillation or secondary prevention of a VTE.. In total 66,605 patients with 89,293 treatment periods, corresponding to 179,624 treatment years, with warfarin treatment due to VTE or AF between January 1st 2006 and December 31th 2011, was retrieved from the national quality register AuriculA. The cohort was matched with the National Patient Register in Sweden for complications and background characteristics.. We found 172 centres and 68,797 treatment periods for AF and 166 centres and 20,496 treatment periods for VTE. Over 90% of the patients had a target range between INR 2-3. We found no correlation between increasing cTTR and reduction in the rate of complications for the AF patients. However, for VTE patients we saw a correlation between increasing cTTR and a reduced complication rate.. Our results show that at very high cTTR levels, above 70%, further improvements in cTTR do not correlate to less treatment complications at least for patients with AF.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cardiology; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Registries; Retrospective Studies; Sweden; Treatment Outcome; Venous Thrombosis; Warfarin

Superior ophthalmic vein thrombosis is a rare entity, but is associated with significant morbidities. We describe a case in which superior ophthalmic vein thrombosis occurred shortly after severe facial trauma.. A 77-year-old Japanese man was transferred to our tertiary hospital after a motor vehicle accident. Le Fort III facial bone fractures and a minor cerebral contusion were detected. Follow-up computed tomography scans detected dilatation of his left superior ophthalmic vein on day 3 and thrombosis on day 12; however, no causative carotid cavernous fistula was observed. As he did not present with any symptoms other than slight conjunctival congestion, a conservative management strategy was adopted along with anticoagulant therapy against deep venous thrombosis. The superior ophthalmic vein thrombosis resolved spontaneously and the conjunctival congestion also improved.. Superior ophthalmic vein thrombosis should be taken into consideration and managed properly after severe facial injuries, and further investigation of its cause is necessary to prevent morbidities.

Topics: Aged; Anticoagulants; Facial Injuries; Humans; Male; Orbit; Tomography, X-Ray Computed; Venous Thrombosis; Warfarin

The study was aimed at revealing the role of thrombophilic states in the pathogenesis of deep vein thrombosis and determining efficacy of pathogenetic prevention of venous thromboembolic complications. The study included a total of 84 patients presenting with lower limb deep vein thrombosis. The patients were subdivided into two groups. The patients of the Study Group (n=44) were examined for thrombophilic states, revealing of which was followed by prescribing specific lifelong therapy aimed at correction of the alterations revealed. The Control Group patients (n=40) received a carefully selected therapeutic dose of warfarin (until the value of the International Normalized Ratio was within the therapeutic range from 2 to 3) and were given recommendations on taking this agent for 6 months followed by discontinuation. The Study Group patients demonstrated less relapses of deep vein thromboses as compared with the Control Group patients. The symptoms of chronic venous insufficiency in the Study Group were also less pronounced. These results are in accord with the findings of ultrasonographic duplex scanning in the remote period after endured thrombosis. A conclusion was drawn on the necessity of carrying out further studies aimed at altering the recommended therapeutic regimen for patients in the remote period after sustained deep vein thrombosis.

Topics: Adult; Anticoagulants; Female; Follow-Up Studies; Humans; Lower Extremity; Male; Retrospective Studies; Thromboembolism; Ultrasonography, Doppler, Duplex; Venous Thrombosis; Warfarin

A young mother presented to a major trauma centre following a road traffic collision. Her admission CT traumagram demonstrated liver and renal lacerations, spinal and pelvic fractures with no abnormalities of the ovarian veins. Her inpatient course was uncomplicated other than a sustained, isolated raised C reactive protein. CT of the abdomen 1 week after injury demonstrated stable solid organ injuries and the additional, unexpected finding of a right ovarian vein thrombosis (OVT). A pragmatic approach was taken towards the management of the OVT given the haemorrhagic risk from her traumatic injuries. A multidisciplinary, consultant-led plan was made to slowly increase enoxaparin to a therapeutic dose under close surveillance and to then switch to warfarin following an outpatient consultation with a consultant haematologist. A MR venogram was performed after 3 months of anticoagulation, and this demonstrated complete resolution of the OVT and normal appearances of the ovary.

Topics: Accidents, Traffic; Anticoagulants; Enoxaparin; Female; Humans; Multiple Trauma; Ovary; Patient Care Team; Veins; Venous Thrombosis; Warfarin; Young Adult

Acute lower extremity deep vein thrombosis (DVT) occurs due to obstruction of large veins by thrombus and its clinical findings are pain and swelling. If not treated, it can cause morbidity and mortality. Oral warfarin or low molecular weight heparin are applied in traditional treatment. However, recently, endovascular procedures have gained increasing popularity in deep vein thrombosis. In this study we aimed to compare our early results of pharmacomechanical thrombectomy (PMT) versus oral anticoagulation for acute deep vein thrombosis.. We comprised 50 patients presented with acute DVT between January 2013 and June 2014, who received either adjusted subcutaneous low molecular weight heparin (LMWH) or PMT followed by intravenous unfractionated heparin (UFH) for 5 days. Warfarin was administered to PMT patients for 3 months and at least 6 months for the control group.. Median follow-up was 14 months (6-18 months). Recanalization within 6 months was found in 84.0%, femoral venous insufficiency was found in 36.0%, and postthrombotic syndrome (PTS) was found in 28.0% of the patients who received PMT treatment. The mean duration of symptoms was 11.0 days (range, 3-20 days). The mean duration of the procedure was 78.1 minutes (range, 55-100 min).. In contrast to medical therapy in the treatment of deep vein thrombosis, usage of catheter-directed thrombolysis experienced early recanalization with higher thrombus resolution. PMT with adjunctive thrombolytic therapy is an effective treatment modality in patients with significant DVT. Also, early thrombus removal in patients with acute DVT prevents development of postthrombotic morbidity. We believe that the efficacy and usage will increase with the experience of surgeons in the future.

Topics: Adult; Aged; Anticoagulants; Heparin; Heparin, Low-Molecular-Weight; Humans; Mechanical Thrombolysis; Middle Aged; Retrospective Studies; Venous Thrombosis; Warfarin

One of the rare causes of venous thromboembolism in pregnancy is antithrombin III deficiency. Antithrombin III deficiency is estimated to carry a 30% risk of venous thrombotic complication during each pregnancy and postpartum.. We present thea case of a A 21-year-old pregnant woman (Para 1+) with a history of large atrial septal defect repair at our hospital (Imam Ali Hospital, 2 May 2014). The patient, with unknown history of antithrombin III deficiency, was admitted at our emergency center with dyspnea and chest pain for the rule out of tamponade. She presented with a right atrial thrombosis in the second trimester of pregnancy despite the use of therapeutic doses of heparin and warfarin in the postoperative period as thromboembolic prophylaxis. The risk of warfarin emberyopaty led to termination of pregnancy, and successful redo-cardiac surgery outcome was achieved with the combined use of therapeutic anticoagulation and regular plasma-derived antithrombin concentrate infusions to normalize her antithrombin levels.. She recovered from the operation uneventfully, and wad discharged in the 12(th) postoperative day. In the 6(th) month of follow-up, antithrombin III increased to 70% in more stable level and transethoracic echocardiography showed no recurrence of right atrial thrombus formation. This case leads to further debate regarding whether full anticoagulation should be a worthy preventive measure for venous thromboembolic prophylaxis after an open heart surgery complicated by pregnancy in a women with inherited antithrombin III deficiency. This point may become more relevant as further experience is gained with the use of recombinant human antithrombin in known cases during open cardiac surgery.

Topics: Adult; Anticoagulants; Antithrombin III; Antithrombin III Deficiency; Antithrombins; Cardiac Surgical Procedures; Female; Heart Atria; Heart Septal Defects, Atrial; Humans; Postoperative Complications; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Second; Venous Thrombosis; Warfarin; Young Adult

Recent evidence has shown that high level of factor VIII is associated with increased risk of thromboembolism. High factor VIII levels are associated with a seven-fold increase in the risk of venous thrombosis. Renal vein thrombosis is usually associated with nephrotic syndrome, procoagulant state or oral contraceptive pills. We report a case of a lady who presented with bilateral renal vein thrombosis due to high factor VIII levels and oral contraceptive pills (OCP) use.

Topics: Adult; Anticoagulants; Contraceptives, Oral; Factor VIII; Female; Heparin; Humans; Renal Insufficiency; Renal Veins; Treatment Outcome; Ultrasonography, Doppler, Color; Venous Thrombosis; Warfarin

We report a rare case of a pulmonary vein stump thrombus detected by a contrast-enhanced computed tomography for transient syncope 2 days after upper division segmentectomy of the left lung for metastatic pulmonary tumor. The thrombus disappeared without embolic events after anticoagulation with intravenous heparin followed by oral warfarin. Considering this case and previous reports, thoracic surgeons should be aware of pulmonary vein stump thrombus, a latent source of systemic embolization, after pulmonary resection, especially lobectomy or segmentectomy of the left upper lobe. This possible serious complication can occur at any time from the early postoperative period.

Topics: Aged; Anticoagulants; Female; Heparin; Humans; Lung Neoplasms; Pneumonectomy; Postoperative Complications; Pulmonary Veins; Tomography, X-Ray Computed; Venous Thrombosis; Warfarin

The most effective agent for prophylaxis against venous thromboembolic disease after total joint arthroplasty (TJA) remains unknown. The paucity of literature comparing different methods of pulmonary embolism (PE) prophylaxis and fear of litigation make it difficult for surgeons to abandon the use of aggressive chemical prophylaxis.. We compared the (1) overall frequency of symptomatic PE, (2) risk of symptomatic PE after propensity matching that adjusted for potentially confounding variables, and (3) other complications and length of stay before and after propensity matching in patients undergoing TJA at our institution who received either aspirin or warfarin prophylaxis.. A total of 28,923 patients underwent TJA between January 2000 and June 2012 at our institution, had either aspirin (325 mg twice daily; 2800 patients) or warfarin prophylaxis (26,123 patients), and were registered in our institutional electronic database. The incidence of symptomatic PE, symptomatic deep vein thrombosis (DVT), hematoma formation, infection, wound complications, and mortality up to 90 days postoperatively was collected from the database. We performed multivariate analysis and 3:1 and 5:1 propensity score matching for comorbid and demographic variables.. The overall symptomatic PE rate was lower (p < 0.001) in patients receiving aspirin (0.14%) than in the patients receiving warfarin (1.07%). This difference did not change after matching. The aspirin group also had significantly fewer symptomatic DVTs and wound-related problems and shorter hospital stays, which did not change after matching.. After publication of the American Academy of Orthopaedic Surgeons' guidelines, some surgeons have utilized aspirin as thromboprophylaxis after TJA. Based on our findings from a large institutional database, aspirin offers suitable prophylaxis against symptomatic PE in selected patients.

Topics: Adult; Aged; Anticoagulants; Arthroplasty, Replacement; Aspirin; Female; Fibrinolytic Agents; Humans; Incidence; Length of Stay; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Philadelphia; Propensity Score; Pulmonary Embolism; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; Venous Thrombosis; Warfarin; Wound Healing

Spontaneous superior ophthalmic vein thrombosis (SOVT) is a rare entity. We describe three patients with spontaneous ophthalmic vein thrombosis, each with various risk factors.. A retrospective review of three patients with a diagnosis of superior ophthalmic vein thrombosis. Clinical characteristics, radiographic features, management techniques and outcomes are described.. All patients presented with unilateral painful proptosis. Two patients had intact light perception, whereas one patient presented with absent light perception. All patients had identifiable risk factors for thrombosis, which included sickle cell trait, hereditary hemorrhagic telangectasia and colon cancer with recurrent deep vein thrombosis. Anticoagulation was initiated in two patients. Resolution of proptosis was seen in all patients, with no recovery of vision in one patient.. Risk factors for spontaneous superior ophthalmic vein thrombosis are multifactorial. MRI and MRV confirm the diagnosis of SOVT. Despite urgent intervention devastating visual loss may occur.

Topics: Administration, Oral; Adult; Aged; Anticoagulants; Antihypertensive Agents; Colonic Neoplasms; Exophthalmos; Eye; Eye Pain; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Retrospective Studies; Risk Factors; Sickle Cell Trait; Telangiectasia, Hereditary Hemorrhagic; Tomography, X-Ray Computed; Veins; Venous Thrombosis; Visual Acuity; Warfarin

The concurrent use of cigarettes while on warfarin therapy is a common occurrence. Smoking cessation among patients on chronic warfarin therapy is suspected to reduce drug clearance that may require dose adjustments. This type of interaction is particularly important when dealing with narrow therapeutic medications, as is the case with warfarin. Our case describes a series of supratherapeutic international normalized ratios (INRs) due to smoking cessation while on concomitant warfarin therapy. Patient Case: A 51-year-old male presented to the anticoagulation clinic for management of his warfarin therapy for an acute deep vein thrombosis. After 2 months of stable, therapeutic INR levels, the patient abruptly decreased his smoking from 1 pack/day to one-half pack/day and then subsequently stopped smoking completely. The patient's smoking cessation resulted in a major modification of his required weekly warfarin dose to maintain a therapeutic INR (a 39% dose reduction).. This case exemplifies how certain lifestyle factors, such as smoking, can alter the pharmacokinetics of patients on chronic warfarin therapy. This is the first case to demonstrate a greater than 30% reduction in the weekly warfarin dose following smoking cessation.

Topics: Anticoagulants; Dose-Response Relationship, Drug; Drug Interactions; Humans; International Normalized Ratio; Male; Middle Aged; Smoking; Smoking Cessation; Venous Thrombosis; Warfarin

Refluxing perforators contribute to venous ulceration. We sought to describe patient characteristics and procedural factors that (1) impact rates of incompetent perforator vein (IPV) thrombosis with ultrasound-guided sclerotherapy (UGS) and (2) impact the healing of venous ulcers (CEAP 6) without axial reflux.. A retrospective review of UGS of IPV injections from January 2010 to November 2012 identified 73 treated venous ulcers in 62 patients. Patients had no other superficial or axial reflux and were treated with standard wound care and compression. Ultrasound imaging was used to screen for refluxing perforators near ulcer(s). These were injected with sodium tetradecyl sulfate or polidocanol foam and assessed for thrombosis at 2 weeks. Demographic data, comorbidities, treatment details, and outcomes were analyzed. Univariate and multivariable modeling was performed to determine covariates predicting IPV thrombosis and ulcer healing.. There were 62 patients (55% male; average age, 57.1 years) with active ulcers for an average of 28 months with compression therapy before perforator treatment, and 36% had a history of deep venous thrombosis and 30% had deep venous reflux. At a mean follow-up of 30.2 months, ulcers healed in 32 patients (52%) and did not heal in 30 patients (48%). Ulcers were treated with 189 injections, with an average thrombosis rate of 54%. Of 73 ulcers, 43 ulcers (59%) healed, and 30 (41%) did not heal. The IPV thrombosis rate was 69% in patients whose ulcers healed vs 38% in patients whose ulcers did not heal (P < .001). Multivariate models demonstrated male gender (P = .03) and warfarin use (P = .01) negatively predicted thrombosis of IPVs. A multivariate model for ulcer healing found complete IPV thrombosis was a positive predictor (P = .02), whereas a large initial ulcer area was a negative predictor (P = .08). Increased age was associated with fewer ulcer recurrences (P = .05). Predictors of increased ulcer recurrences were hypertension (P = .04) and increased follow-up time (P = .02). Calf vein thrombosis occurred after 3% (six of 189) of injections.. Thrombosis of IPVs with UGS increases venous ulcer healing in a difficult patient population. Complete closure of all IPVs in an ulcerated limb was the only predictor of ulcer healing. Men and patients taking warfarin have decreased rates of IPV thrombosis with UGS.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Comorbidity; Female; Humans; Injections, Intravenous; Linear Models; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Polidocanol; Polyethylene Glycols; Recurrence; Retrospective Studies; Risk Factors; Sclerosing Solutions; Sclerotherapy; Sex Factors; Sodium Tetradecyl Sulfate; Time Factors; Treatment Outcome; Ultrasonography, Interventional; Varicose Ulcer; Venous Thrombosis; Warfarin; Wound Healing; Young Adult

Topics: Adult; Anticoagulants; Combined Modality Therapy; Disseminated Intravascular Coagulation; Female; Heparin; Humans; Hypereosinophilic Syndrome; Platelet Transfusion; Portal Vein; Pulmonary Embolism; Radiography; Thrombophlebitis; Ultrasonography; Vena Cava Filters; Vena Cava, Inferior; Venous Thrombosis; Warfarin

We retrospectively analyzed the data of 24 children (whereof 11 neonates), with non-central venous line-related and nonmalignancy-related venous thromboembolism (VTE) at uncommon sites, referred to our Unit from January 1999 to January 2012. Thirty patients who also suffered deep vein thrombosis, but in upper/low extremities, were not included in the analysis. The location of rare site VTE was: portal (n=7), mesenteric (n=2) and left facial vein (n=1), spleen (n=3), lung (n=3), whereas 10 neonates developed renal venous thrombosis. The majority of patients (91.7%) had at least 1 risk factor for thrombosis. Identified thrombophilic factors were: antiphospholipid antibodies (n=2), FV Leiden heterozygosity (n=6), MTHFR C677T homozygosity (n=4), protein S deficiency (n=2), whereas all neonates had age-related low levels of protein C and protein S. All but 6 patients received low-molecular-weight heparin, followed by warfarin in 55% of cases, for 3 to 6 months. Prolonged anticoagulation was applied in selected cases. During a median follow-up period of 6 years, the clinical outcome was: full recovery in 15 patients, evolution to both chronic portal hypertension and esophageal varices in 2 children, and progression to renal failure in 7 of 10 neonates. Neonates are greatly vulnerable to complications after VTE at uncommon sites, particularly renal. Future multicentre long-term studies on neonatal and pediatric VTE at unusual sites are considered worthwhile.

Topics: Anticoagulants; Child; Esophageal and Gastric Varices; Factor V; Female; Follow-Up Studies; Heparin, Low-Molecular-Weight; Humans; Hypertension, Portal; Infant; Infant, Newborn; Male; Mesenteric Veins; Methylenetetrahydrofolate Reductase (NADPH2); Portal Vein; Protein S Deficiency; Pulmonary Veins; Renal Veins; Retrospective Studies; Spleen; Veins; Venous Thromboembolism; Venous Thrombosis; Warfarin

Topics: Fatal Outcome; Female; Heart Failure, Systolic; Humans; Male; Middle Aged; Myocardial Infarction; Pancreatic Neoplasms; Physician-Patient Relations; Urinary Tract Infections; Venous Thrombosis; Warfarin

The emergency department (ED) serves as the primary gateway for acute care and the source of health care of last resort. Emergency physicians are commonly expected to rapidly assess and treat patients with a variety of life-threatening conditions. However, patients do refuse recommended therapy, even when the consequences are significant morbidity and even mortality. This raises the ethical dilemma of how emergency physicians and ED staff can rapidly determine whether patient refusal of treatment recommendations is based on intact decision-making capacity and how to respond in an appropriate manner when the declining of necessary care by the patient is lacking a basis in informed judgment. This article presents a case that illustrates the ethical tensions raised by the refusal of life-sustaining care in the ED and how such situations can be approached in an ethically appropriate manner.

Topics: Adult; Anticoagulants; Cerebral Veins; Chest Pain; Chronic Pain; Emergency Service, Hospital; Fatal Outcome; Female; Flank Pain; Headache Disorders; Humans; Narcotics; Pulmonary Artery; Treatment Refusal; Venous Thrombosis; Vision Disorders; Warfarin

Rivaroxaban is the first oral factor Xa inhibitor approved in the US to reduce the risk of stroke and blood clots among people with non-valvular atrial fibrillation, treat deep vein thrombosis (DVT), treat pulmonary embolism (PE), reduce the risk of recurrence of DVT and PE, and prevent DVT and PE after knee or hip replacement surgery. The objective of this study was to evaluate the costs from a hospital perspective of treating patients with rivaroxaban vs other anticoagulant agents across these five populations.. An economic model was developed using treatment regimens from the ROCKET-AF, EINSTEIN-DVT and PE, and RECORD1-3 randomized clinical trials. The distribution of hospital admissions used in the model across the different populations was derived from the 2010 Healthcare Cost and Utilization Project database. The model compared total costs of anticoagulant treatment, monitoring, inpatient stay, and administration for patients receiving rivaroxaban vs other anticoagulant agents. The length of inpatient stay (LOS) was determined from the literature.. Across all populations, rivaroxaban was associated with an overall mean cost savings of $1520 per patient. The largest cost savings associated with rivaroxaban was observed in patients with DVT or PE ($6205 and $2742 per patient, respectively). The main driver of the cost savings resulted from the reduction in LOS associated with rivaroxaban, contributing to ∼90% of the total savings. Furthermore, the overall mean anticoagulant treatment cost was lower for rivaroxaban vs the reference groups.. The distribution of patients across indications used in the model may not be generalizable to all hospitals, where practice patterns may vary, and average LOS cost may not reflect the actual reimbursements that hospitals received.. From a hospital perspective, the use of rivaroxaban may be associated with cost savings when compared to other anticoagulant treatments due to lower drug cost and shorter LOS associated with rivaroxaban.

Topics: Administration, Oral; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Atrial Fibrillation; Computer Simulation; Cost Savings; Cost-Benefit Analysis; Factor Xa Inhibitors; Humans; Inpatients; Length of Stay; Models, Economic; Morpholines; Pulmonary Embolism; Randomized Controlled Trials as Topic; Retrospective Studies; Rivaroxaban; Thiophenes; United States; Venous Thrombosis; Warfarin

The purpose of present study was to evaluate the effects of maximal acute physical exercise on prothrombin time/international normalized ratio (PT/INR) in patients with primary antiphospholipid syndrome (PAPS) under oral anticoagulation with warfarin and the safety of acute exercise in regard to thrombosis and bleeding risk. Eighteen physically inactive women with PAPS (Sydney criteria) with exclusive venous events and without thrombocytopenia were included. All patients were under stable warfarin therapy (PT/INR target: 2.0-3.0). Eighteen age-matched healthy sedentary women without thrombosis/bleeding disorders were selected as controls. All subjects performed a maximal exercise test, and capillary blood samples were obtained pre-, post- and at 1-h post-exercise (recovery time) for PT/INR analysis using a portable CoaguCheck. PAPS patients and controls had similar mean age (31.50 ± 8.06 vs. 29.61 ± 7.05 years, p = 0.46) and body mass index (24.16 ± 3.67 vs. 24.66 ± 2.71 kg/m(2), p = 0.65). PAPS had a mild but significant increase in PT/INR value at 1-h post-exercise (recovery) compared with pre- (2.33 ± 0.34 vs. 2.26 ± 0.29, p = 0.001) and post-exercise (2.33 ± 0.34 vs. 2.26 ± 0.32, p = 0.001) that was observed in 61.11 % of these patients. None of the subjects had thrombotic or bleeding complications related to the acute exercise. Acute exercise in patients with PAPS with exclusive venous thrombosis was safe with a minor increase in PT/INR. This is an important step to introduce regular exercise training as a therapeutic tool in the management of these patients.

Topics: Administration, Oral; Adult; Anticoagulants; Antiphospholipid Syndrome; Blood Coagulation; Case-Control Studies; Exercise; Female; Hemorrhage; Humans; International Normalized Ratio; Longitudinal Studies; Patient Safety; Prothrombin Time; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Venous Thrombosis; Warfarin; Young Adult

Pulmonary thromboembolism (PTE) is a common clinical condition related to significant mortality. Furthermore, patients with PTE presenting with right heart thrombus show higher mortality due to rapid hemodynamic deterioration. But the optimal treatment of massive PTE is controversial although various methods have been developed and improved. Here, we presented a case of 56-yr-old woman with massive PTE showing hemodynamic collapse, who was successfully treated with extracorporeal membrane oxygenation (ECMO) adjunct to thrombolytic therapy even without thrombectomy. ECMO was useful for resuscitation and stabilization of the cardiopulmonary function. In conclusion, thrombolytic therapy complemented by ECMO may be an effective treatment option for acute massive PTE with hemodynamic instability.

Topics: Extracorporeal Membrane Oxygenation; Female; Heart; Heparin; Humans; Middle Aged; Myocardium; Pulmonary Artery; Pulmonary Embolism; Thrombolytic Therapy; Tissue Plasminogen Activator; Venous Thrombosis; Warfarin

In recent years there have been increasing evidence associating liver disease with hypercoagulability, rather than bleeding. The aim of the study was to evaluate the haemostatic potential in patients with liver disease.. We measured thrombin generation in the presence and absence of thrombomodulin in patients with portal vein thrombosis (PVT, n=47), Budd-Chiari syndrome (BCS, n=15) and cirrhosis (n=24) and compared the results to those obtained from healthy controls (n=21). Fifteen patients with PVT and 10 patients with BCS were treated with warfarin and were compared to an equal number of patients with atrial fibrillation matched for prothrombin time-international normalized ratio. We assessed resistance to thrombomodulin by using ratios [marker measured in the presence/absence of thrombomodulin].. There were no differences in thrombin generation between patients on warfarin treatment and their controls. Cirrhotic patients generated more thrombin in the presence of thrombomodulin and exhibited thrombomodulin resistance compared to controls [p=0.006 for endogenous thrombin potential (ETP) and p<0.001 for peak thrombin and both ratios ETP and peak] and patients with non-cirrhotic PVT (p=0.001, p=0.006, p<0.001, p<0.001 for ETP, peak, ratio ETP, ratio peak, respectively). The patients with cirrhotic PVT exhibited higher ETP (p=0.044) and peak (p=0.02) in the presence of thrombomodulin than controls, as well as thrombomodulin resistance (ETP and peak ratios: p=0.001).. Hypercoagulability and thrombomodulin resistance in patients with cirrhosis were independent of the presence of splanchnic vein thrombosis. The hypercoagulability in patients with cirrhotic PVT could have implications for considering longer or more intensive treatment with anticoagulants in this group.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Tests; Budd-Chiari Syndrome; Female; Hemostasis; Humans; Liver; Liver Cirrhosis; Male; Middle Aged; Splanchnic Circulation; Thrombin; Thrombomodulin; Venous Thrombosis; Warfarin; Young Adult

The increased risk of hemorrhage associated with anticoagulant therapy following traumatic brain injury creates a serious dilemma for medical management of older patients: Should anticoagulant therapy be resumed after traumatic brain injury, and if so, when?. To estimate the risk of thrombotic and hemorrhagic events associated with warfarin therapy resumption following traumatic brain injury.. Retrospective analysis of administrative claims data for Medicare beneficiaries aged at least 65 years hospitalized for traumatic brain injury during 2006 through 2009 who received warfarin in the month prior to injury (n = 10,782).. Warfarin use in each 30-day period following discharge after hospitalization for traumatic brain injury.. The primary outcomes were hemorrhagic and thrombotic events following discharge after hospitalization for traumatic brain injury. Hemorrhagic events were defined on inpatient claims using International Classification of Diseases, Ninth Revision, Clinical Modification codes and included hemorrhagic stroke, upper gastrointestinal bleeding, adrenal hemorrhage, and other hemorrhage. Thrombotic events included ischemic stroke, pulmonary embolism, deep venous thrombosis, and myocardial infarction. A composite of hemorrhagic or ischemic stroke was a secondary outcome.. Medicare beneficiaries with traumatic brain injury were predominantly female (64%) and white (92%), with a mean (SD) age of 81.3 (7.3) years, and 82% had atrial fibrillation. Over the 12 months following hospital discharge, 55% received warfarin during 1 or more 30-day periods. We examined the lagged effect of warfarin use on outcomes in the following period. Warfarin use in the prior period was associated with decreased risk of thrombotic events (relative risk [RR], 0.77 [95% CI, 0.67-0.88]) and increased risk of hemorrhagic events (RR, 1.51 [95% CI, 1.29-1.78]). Warfarin use in the prior period was associated with decreased risk of hemorrhagic or ischemic stroke (RR, 0.83 [95% CI, 0.72-0.96]).. Results from this study suggest that despite increased risk of hemorrhage, there is a net benefit for most patients receiving anticoagulation therapy, in terms of a reduction in risk of stroke, from warfarin therapy resumption following discharge after hospitalization for traumatic brain injury.

Topics: Adrenal Gland Diseases; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Injuries; Brain Ischemia; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Myocardial Infarction; Pulmonary Embolism; Retrospective Studies; Risk Assessment; Stroke; Thrombosis; Venous Thrombosis; Warfarin

We report two patients (70- and 49-year-old Japanese men) with acute exacerbation of chronic idiopathic thrombocytopenic purpura (ITP) and deep venous thrombosis of the lower extremities. Both were successfully managed with thrombopoietin receptor agonist (TPO-RA) administration. Both had ITP refractory to steroid treatment. Their immature platelet fraction (absolute-IPF) counts were increased and paralleled the platelet recoveries after TPO-RA (eltrombopag and romiplostim, respectively) without progression of thrombosis. Although ITP has recently been evaluated as a thrombophilic disorder, reports on acute exacerbation of ITP with newly diagnosed thrombosis are limited, and the pathophysiology and association between ITP and thrombosis remain to be elucidated. Moreover, the influences of TPO-RA on thrombosis are still controversial. To our knowledge, this is the first case report describing patients with exacerbation of ITP who developed thrombosis and were treated with TPO-RA. The outcomes of our cases underscore the importance of monitoring thrombosis and not delaying the initiation of anticoagulation treatment during the use of TPO-RA.

Topics: Aged; Anticoagulants; Humans; Lower Extremity; Male; Middle Aged; Purpura, Thrombocytopenic, Idiopathic; Receptors, Thrombopoietin; Venous Thrombosis; Warfarin

A patient with trimalleolar ankle fracture was preoperatively diagnosed with deep vein thrombosis (DVT); after induction of general anesthesia, a temporary inferior vena cava filter (TIVCF) was intraoperatively placed by an anesthesiologist. This contributed to safe anesthesia management. A 65-year-old woman was scheduled to undergo surgery for a trimalleolar ankle fracture sustained in an accidental fall. Two days before surgery, leg venous ultrasonography showed DVT. On the day of surgery, after induction of general anesthesia, a TIVCF was inserted by the anesthesiologist. After surgery, the TIVCF was removed, and anesthetic management was completed. On the day after the surgery, anticoagulant treatment was administered. Approximately 3 weeks later, thrombus disappearance was confirmed, and treatment was terminated. DVT is a serious complication that may cause pulmonary thromboembolism. TIVCF is effective in the treatment of DVT, and insertion of the TIVCF used in the present study is relatively simple. TIVCF placement by anesthesiologists, who have reliable knowledge on the various approaches to veins, contributes greatly to securing perioperative patient safety. The collaboration and cooperation of several medical departments are essential for DVT treatment and enhancing perioperative patient safety.

Topics: Aged; Anesthesia, General; Anesthesia, Intravenous; Anesthesiology; Ankle Fractures; Anticoagulants; Clinical Competence; Female; Humans; Perioperative Care; Physicians; Preoperative Period; Ultrasonography; Vena Cava Filters; Venous Thrombosis; Warfarin

To evaluate the safety and clinical efficacy of warfarin anticoagulation after balloon dilation alone for the treatment of Budd-Chiari syndrome (BCS) complicated by old inferior vena cava (IVC) thrombosis.. From January 2008 to November 2013, 19 BCS patients complicated with old IVC thrombosis were treated with balloon dilation followed by oral administration of anticoagulant warfarin. Follow-up was performed at 1 week, then 1, 2, 3, 6, and 12 months after balloon dilation, and then annually thereafter. IVC patency and morphologic changes of the old thrombus were examined by ultrasound, and clinical symptoms and signs were determined by clinical examinations during follow-up.. Successful IVC balloon dilation was achieved in the 19 patients (100%). Inferior vena cavography demonstrated the patency of IVC lumen, and the size of the old thrombus was not altered. The mean pressure gradient between IVC and the right atrium was reduced from 27.5 ± 3.0 cm H2O (range, 22-35) before treatment to 5.4 ± 1.3 cm H2O (range: 2-7) after treatment (t = 41.6, P < 0.05; 1 cm H2O = 0.098 kPa). Patients were followed up as outpatients for an average of 15.9 ± 14.4 months (range, 3-66). Anticoagulation with warfarin was well tolerated in all patients after balloon dilation alone. Of the 19 patients, complete resolution of the old thrombus was achieved in 12 patients and partial resolution was achieved in 7 patients. Color Doppler ultrasound showed that 17 patients had IVC lumen patency, and 2 patients had IVC reocclusion. None of the patients had recurrence of thrombosis, symptomatic pulmonary embolism, and bleeding complications throughout the follow-up period.. Our results indicate that warfarin anticoagulation after balloon dilation alone is a safe and effective therapy for BCS patients with old IVC thrombosis.

Topics: Adult; Aged; Angioplasty, Balloon; Anticoagulants; Budd-Chiari Syndrome; Combined Modality Therapy; Diagnostic Imaging; Female; Humans; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Vascular Patency; Vena Cava, Inferior; Venous Thrombosis; Warfarin

Topics: Adult; Aged; Anticoagulants; Female; Humans; Male; Mass Screening; Morpholines; Mutation; Prothrombin; Recurrence; Risk Factors; Rivaroxaban; Thiophenes; Thrombophilia; Treatment Outcome; Venous Thrombosis; Warfarin; Women's Health

Direct oral factor inhibitors (DOFIs) are an attractive alternative to vitamin K antagonists (VKA) for the treatment of patients with antiphospholipid syndrome (APS). In the absence of prospective, randomised trial data, reports of therapeutic failures in clinical practice alert clinicians to potential limitations of DOFI therapy for this indication. Data for all cases were collected from a centralised system that contains complete medical records of all patients treated and followed at Mayo Medical Center. We present here three consecutive APS patients who had had no thromboembolism recurrence on warfarin but were switched to DOFIs. The diagnosis of APS was established according to currently recommended criteria. The three cases were as follows: A woman with primary APS developed thrombotic endocarditis with symptomatic cerebral emboli after transition to dabigatran. A second woman with primary APS experienced ischemic arterial strokes and right transverse-sigmoid sinus thrombosis after conversion to rivaroxaban. A man with secondary APS suffered porto-mesenteric venous thrombosis after switching to rivaroxaban. None of these patients had failed warfarin prior to the transition to DOFIs. Based on these three cases, we advocate caution in using DOFIs for APS patients outside of a clinical trial setting, until further data becomes available.

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Benzimidazoles; beta-Alanine; Cerebral Infarction; Dabigatran; Drug Substitution; Female; Humans; International Normalized Ratio; Lupus Erythematosus, Systemic; Male; Mesenteric Veins; Middle Aged; Morpholines; Portal Vein; Recurrence; Retrospective Studies; Rivaroxaban; Splenic Vein; Stroke; Thiophenes; Thromboembolism; Thrombophilia; Treatment Failure; Venous Thrombosis; Warfarin

Peripherally inserted central catheters (PICCs) are common in the treatment of patients with cystic fibrosis (CF). Previous reports suggest that patients with CF are at increased risk for PICC-associated deep vein thrombosis (DVT).. We assessed potential risk factors for symptomatic PICC-associated DVT with subsequent implementation of a quality improvement (QI) initiative to reduce PICC-associated DVT in patients with CF.. This was a 5-year retrospective cohort study with subsequent 21-month prospective observation following implementation of a QI intervention in adults (aged 18 yr or older) with CF. All patients with a PICC inserted from July 2006 to March 2013 at our CF Foundation-accredited center were included. Symptomatic DVT was diagnosed by Doppler ultrasound. PICC insertions were analyzed, and nine risk factors for DVT were analyzed to formulate a QI initiative to reduce risk of PICC-associated DVT. The QI program focused on staff education and included modification to PICC order entry with a 4 French (F) single-lumen (SL) catheter as standard for all patients with CF.. A total of 369 PICCs were analyzed in 117 unique patients for a total of 5,437 PICC-days of placement. Symptomatic DVT was diagnosed in 28 (7.6%) of the 369 PICCs analyzed. Using regression analysis, the strongest predictors for DVT occurrence were warfarin use (odds ratio [OR] = 9.2, P = 0.006) and history of PICC-associated DVT (OR = 2.97, P = 0.08). Insertion of a 4F SL PICC resulted in zero symptomatic DVT. Zero episodes of DVT associated with 4F PICC insertion prevented use of PICC size in regression analysis. However, univariate analysis revealed that insertion of a 4F SL PICC instead of either 5F double lumen or 6F triple lumen was associated with a reduction in PICC-associated DVT (P = 0.001). After the QI intervention, 4F SL catheter insertion substantially increased to 65.8% of all PICCs inserted, whereas 6F triple-lumen catheter insertion declined to 6.8% of PICCs inserted. The QI initiative resulted in an absolute risk reduction in DVT per PICC placed of 6.1% (P = 0.055).. To reduce risk of PICC-associated DVT in patients with CF, QI strategies should focus on insertion of smaller-diameter 4F PICCs and reduction in PICC use in high-risk patients when possible.

Topics: Adolescent; Adult; Aged; Anticoagulants; Catheterization, Peripheral; Catheters; Cohort Studies; Cystic Fibrosis; Equipment Design; Humans; Middle Aged; Quality Improvement; Regression Analysis; Retrospective Studies; Risk Factors; Ultrasonography; Venous Thrombosis; Warfarin; Young Adult

Topics: Anticoagulants; Hemorrhage; History, 20th Century; History, 21st Century; Humans; International Normalized Ratio; Ontario; Prothrombin Time; Venous Thrombosis; Vitamin K; Warfarin

Topics: Aged; Antibodies; Anticoagulants; Arthroplasty, Replacement, Knee; Atrial Fibrillation; Biomarkers; Chronic Disease; Drug Administration Schedule; Drug Monitoring; Fondaparinux; Humans; Male; Platelet Activation; Platelet Count; Polysaccharides; Predictive Value of Tests; Severity of Illness Index; Thrombocytopenia; Time Factors; Treatment Outcome; Venous Thrombosis; Warfarin

Antithrombotic treatment of splanchnic vein thrombosis (SVT) is a clinical challenge. Depending on the site of thrombosis, patients are at risk of developing liver insufficiency, portal hypertension, or bowel infarction and may experience recurrence in both the splanchnic veins and other vein segments. To prevent recurrence, anticoagulant therapy should be started as soon as possible after diagnosis and is often continued for an indefinite period of time. However, active bleeding is not infrequent at the time of SVT diagnosis, and major risk factors for bleeding, such as esophageal varices or a low platelet count, are frequently present in these patients. In real-world clinical practice, a proportion of SVT patients are left untreated because the risks associated with anticoagulant therapy are felt to exceed its benefits. However, the majority of patients receive anticoagulant drugs, with heterogeneous timing of initiation, drug choice, and dosages. Evidence to drive treatment decisions is limited because no randomized controlled trials have been carried out in these patients. This review provides practical guidance for the use of anticoagulant drugs in patients presenting with SVT, including symptomatic as well as incidentally detected events.

Topics: Aged; Anticoagulants; Female; Heparin, Low-Molecular-Weight; Humans; Male; Mesenteric Veins; Middle Aged; Portal Vein; Practice Guidelines as Topic; Propranolol; Risk Factors; Splanchnic Circulation; Splenic Vein; Treatment Outcome; Vasodilator Agents; Venous Thrombosis; Warfarin

Topics: Aged; Aged, 80 and over; Anticoagulants; Comorbidity; Female; Humans; Idiopathic Pulmonary Fibrosis; Incidence; Logistic Models; Male; Middle Aged; Proportional Hazards Models; Pulmonary Embolism; Smoking; Venous Thrombosis; Warfarin

Iliofemoral deep vein thrombosis is a medical emergency associated with pulmonary embolism, severe postthrombotic morbidity and increased rates of recurrence. We present 3 cases of iliofemoral deep vein thrombosis managed in a setting of limited resources. Results of 2-D Ultrasound scan which suggested proximal DVT was confirmed by Doppler ultrasound scan. Patients were all managed by systemic anticoagulation alone. In experienced hands, it is possible to diagnose iliofemoral DVT with 2-D Ultrasound scan and treatment with systemic anticoagulation alone still has a role. However recent studies have proved clearly the superiority of thrombectomy over systemic anticoagulation alone. There is a need to improve the infrastructure and expertise of clinicians managing these conditions in underdeveloped settings to enable them offer the best to their patients.

Topics: Adolescent; Adult; Anticoagulants; Developing Countries; Drug Therapy, Combination; Enoxaparin; Femoral Vein; Fibrinolytic Agents; Humans; Iliac Vein; Male; Middle Aged; Nigeria; Pulmonary Embolism; Ultrasonography; Venous Thrombosis; Warfarin; Young Adult

With the advent of new treatment options for venous thromboembolism (VTE), it is valuable to gain insights into current clinical practices.. Assess treatment patterns and recurrence among patients hospitalized for VTE.. This retrospective study evaluated patients hospitalized with an incident VTE diagnosis (index) from 2008 to 2012 in a de-identified electronic health record database. Patients were further required to receive anticoagulant treatment and/or a VTE-related procedure for study inclusion. Patients were excluded if they: (1) did not have a medical encounter in the 6 months before index (baseline); (2) had a prior VTE diagnosis or used an anticoagulant during the baseline period; or (3) had a diagnosis of atrial fibrillation/flutter, cardiomyopathy, or a coagulation disorder during baseline or the year after index (follow-up). Hospitalization for recurrent VTE and bleeding were evaluated.. A total of 2060 patients were identified (mean age, 60.9 years; 53.0% women), with a mean length of stay of 8.1 days. Of the VTE types, acute DVT was the most common (41.9%), followed by PE (33.3%), and DVT + PE (24.7%). Almost all patients (96.9%) received anticoagulants, of which 94.3% received heparin and 76.5% received warfarin. Although 77.4% of warfarin users were prescribed it at discharge, only (40.2%) had a warfarin prescription within 30 days of discharge. Overall 30 day, 90 day and 1-year VTE recurrence rates were 2.0%, 4.2%, and 7.5%, respectively, and the major bleeding rate was 6.8%.. In a real-world population of hospitalized VTE patients, heparin treatment in combination with warfarin was common. However, continuation of warfarin post-discharge was challenging. Initiatives to improve continuation of therapy may be important to reduce VTE recurrence.

Topics: Adult; Aged; Anticoagulants; Electronic Health Records; Female; Hemorrhage; Heparin; Hospitalization; Humans; Male; Middle Aged; Practice Patterns, Physicians'; Recurrence; Retrospective Studies; Treatment Outcome; United States; Venous Thrombosis; Warfarin

Topics: Anesthesia, Conduction; Anticoagulants; Heparin; Humans; Nerve Block; Platelet Aggregation Inhibitors; Postoperative Complications; Practice Guidelines as Topic; Pulmonary Embolism; Venous Thrombosis; Warfarin

A 63-year-old man who had been admitted to another institute with sepsis and renal failure was referred to our hospital after computed tomography (CT) findings showed thickening of the walls in the sigmoid colon and a defect in contrast enhancement in the portal and inferior mesenteric veins. Emergency sigmoid colon resection with D2 lymphadenectomy was performed after detection of perforation due to sigmoid colon cancer. The histopathological diagnosis was adenosquamous carcinoma, pSS, int, INF b, ly1, v0, pN2, pStage IIIband inferior mesenteric vein thrombosis. He was discharged on day 12, and we administered anticoagulant warfarin therapy.

Topics: Aged; Anticoagulants; Carcinoma, Adenosquamous; Humans; Male; Mesenteric Veins; Sigmoid Neoplasms; Tomography, X-Ray Computed; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Heparin; Humans; Male; Middle Aged; Proteinuria; Renal Veins; Severity of Illness Index; Tomography, X-Ray Computed; Treatment Outcome; Venous Thrombosis; Warfarin

Topics: Administration, Oral; Anticoagulants; Antithrombins; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Dabigatran; Humans; Pulmonary Embolism; Treatment Outcome; Venous Thrombosis; Warfarin

To assess the safety and efficacy of low-molecular-weight heparin (LMWH) in pregnancy and puerperium in women with previous acute iliofemoral deep venous thrombosis (DVT) treated with catheter-directed thrombolysis (CDT).. Consecutive patients treated for acute iliofemoral DVT using CDT between June 1999 and June 2009 were followed yearly by colour duplex ultrasound scanning. A subgroup of these patients who became pregnant during the follow-up period, three months to 10 years after CDT, was included in the present study. During pregnancy, thromboprophylaxis using LMWH was prescribed according to individual risk assessment, and the women were regularly assessed for adverse events. Women on warfarin had this treatment discontinued before the sixth week of pregnancy in order to prevent potential teratogenic adverse effects. Administration of LMWH was started at international normalized ratio ≤ 2.0, and continued during pregnancy, delivery and puerperium. Postnatal, the anticoagulation treatment was converted back to warfarin and LMWH discontinued after a bridging period. Women, who, prior to pregnancy, had discontinued anticoagulation treatment after CDT, were prescribed anticoagulation treatment using LMWH as early in pregnancy as practical. LMWH was continued during pregnancy, delivery and for six weeks postpartum. All women were prescribed graduated compression stockings.. A total of 33 women completed 45 pregnancies, 44 singletons and 1 gemelli. In 24 (53%) of the cases, the mother had been treated with adjunctive stenting immediately following the CDT. In nine (21%) of the pregnancies, the mother had been on long-time anticoagulation treatment using warfarin prior to conception due to permanent severe risk factors. Thrombophilia was demonstrated in 31 (69%) of the pregnancies, and in 29 (64%) of the patients, the previous DVT was oestrogen-related. Thromboprophylaxis using tinzaparin was given in 41 (91%) and using dalteparin in four (9%) of the pregnancies. Doses of LMWH during pregnancy were adjusted according to risk assessment. One pregnancy was terminated by induced delivery at week 22 due to fetal malformations, and two of the pregnancies (4%) were complicated by intrauterine fetal death, one in week 39 due to severe fetal infection and one in week 23 due to intrauterine fetal growth restriction caused by severe antiphospholipid syndrome. All but one of the pregnancies was carried out without recurrence of DVT or maternal pulmonary embolism and the mother remained having patent deep veins postnatal. The mother with the antiphospholipid syndrome had a recurrent DVT complicated by iliac stent occlusion. This mother was prior to pregnancy on long-time treatment using warfarin. During pregnancy, she was erroneously treated with LMWH in standard prophylaxis doses instead of therapeutic doses and without adding aspirin.. After CDT for acute iliofemoral DVT including adjunctive stenting, pregnancy can be carried out almost uneventful even in women at high risk of thromboembolism. Thromboprophylaxis during pregnancy, using LMWH in a dosage adjusted to individual risk assessment, is essential.

Topics: Acute Disease; Adolescent; Adult; Anticoagulants; Catheterization, Peripheral; Drug Administration Schedule; Drug Monitoring; Drug Substitution; Female; Femoral Vein; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Iliac Vein; International Normalized Ratio; Pregnancy; Pregnancy Complications, Cardiovascular; Risk Assessment; Risk Factors; Stents; Stockings, Compression; Thrombolytic Therapy; Time Factors; Treatment Outcome; Ultrasonography, Doppler, Color; Venous Thrombosis; Warfarin; Young Adult

Topics: Abdominal Pain; Anti-Bacterial Agents; Anticoagulants; Appendectomy; Appendicitis; Drainage; Escherichia coli Infections; Female; Heparin; Humans; Mesenteric Vascular Occlusion; Mesenteric Veins; Middle Aged; Radiography; Sclerosis; Venous Thrombosis; Warfarin

A systematic study of thrombophilia markers in a large series of patients with cerebral venous thrombosis (CVT) from India is scarce. The present study was undertaken to know the prevalence of common hereditary thrombophilia in a large series of CVT patients from India. Six hundred and twelve (354 men, 219 women and 39 children) consecutive patients with CVT admitted to various hospitals in Mumbai between 2001 and 2010 were investigated for the common thrombophilia markers, that is, protein C (PC), protein S, antithrombin (AT), and factor V Leiden (FVL) mutation. The main presenting clinical manifestations included papilledema (62%), headache (62%), hemiparesis (48%), seizures (31%), and cranial nerve palsy (7%). All the patients were managed with heparin followed by warfarin during the succeeding 6 months. Superior sagittal sinus thrombosis was the commonest site (74%) followed by cortical venous thrombosis (15%). Associated clinical pathologies were dehydration, sepsis, pregnancy and puerperium, malaria, and tuberculosis; but in the majority of patients, there was no obvious cause. Eighteen percent of the patients had any of the thrombophilia markers studied; PC deficiency was the commonest thrombophilia marker followed by deficiency of protein S, FVL mutation and AT deficiency. The men below 45 years with PC deficiency (P=0.03) and women with protein S deficiency were significantly higher (P=0.04). In conclusion, CVT is not an uncommon cause of neurological deficit as was presented in earlier reports. Pregnancy and puerperium-related CVT was much less common. Thrombophilia markers accounted for approximately one-fifth of the patients. Death due to CVT has shown remarkable reduction (13%) because of early diagnosis and appropriate anticoagulation.

Topics: Adolescent; Adult; Anticoagulants; Antithrombins; Child; Child, Preschool; Factor V; Female; Heparin; Humans; India; Intracranial Thrombosis; Male; Middle Aged; Pregnancy; Protein C Deficiency; Protein S Deficiency; Thrombophilia; Venous Thrombosis; Warfarin

A woman in her late 70s presented to the acute general surgical take with a 3-day history of worsening right leg pain and swelling. She had undergone right revision total hip arthroplasty 20 months previously and reported chronic postoperative right thigh pain attributed to a femoral deep venous thrombosis for which she had been warfarinised. On examination, Grey Turner's sign (bruising of the flanks indicating retroperitoneal haemorrhage) was present, as well as a large tender mass in the right iliac fossa and pitting oedema throughout the right lower limb. Urgent CT scan with intravenous contrast revealed a right retroperitoneal haematoma secondary to a right acetabular screw protruding into the right external iliac vein. The patient was successfully managed with warfarin reversal and surgical removal of the relevant acetabular screw. At 2-month follow-up, the patient's symptoms continue to resolve.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Bone Screws; Contusions; Female; Hemorrhage; Humans; Iliac Vein; Radiography; Retroperitoneal Space; Venous Thrombosis; Warfarin

The clinical characteristics and long-term outcomes of patients presenting with acute pulmonary embolism (PE) during treatment with warfarin have not been described. Clinical details of all patients admitted to a tertiary institution from 2000-2007 with acute PE were retrieved retrospectively, baseline warfarin status and the international normalised ratio (INR) were recorded, and their outcomes tracked using a statewide death registry. Of 923 patients with clearly documented warfarin status included in this study, 83 (9%) were taking warfarin. Mean (± standard deviation) day-1 INR of those taking warfarin was 2.3 ± 0.9, with 67% of patients therapeutically anti-coagulated (INR ≥2.0) at presentation (49 patients with INR <2.5 and 34 with INR ≥2.5). Patients taking warfarin on admission were more likely to have heart failure, atrial fibrillation and valvular heart disease, with similar prevalence of malignancy and ischaemic heart disease, compared to patients not on warfarin. Total mortality of the cohort (mean follow-up 4.0 ± 2.5 years) was 31.6% (in-hospital mortality 1.5%), and was similar between warfarin and no warfarin groups. There was however a greater than four-fold increased risk of post-discharge death due to recurrent PE for the patients taking warfarin on admission (hazard ratio [HR] 4.43, 95% confidence interval [CI] 1.36-14.42, p=0.01). Among patients taking warfarin on admission, day-1 INR <2.5 significantly increased long-term all-cause mortality compared to INR ≥2.5 (adjusted HR 2.51, 95% CI 1.08-5.86, p=0.03). In conclusion, patients presenting with PE during treatment with warfarin have an increased risk of death from recurrent PE. Admission INR appears to have independent long-term prognostic importance in these patients.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Female; Follow-Up Studies; Heart Diseases; Heart Failure; Humans; International Normalized Ratio; Male; Middle Aged; Prognosis; Proportional Hazards Models; Pulmonary Embolism; Recurrence; Retrospective Studies; Time Factors; Treatment Outcome; Venous Thrombosis; Warfarin

Topics: Brain; Heparin; Humans; Male; Middle Aged; Sinus Thrombosis, Intracranial; Tomography, X-Ray Computed; Treatment Outcome; Venous Thrombosis; Warfarin

The incidence of pulmonary embolism (PE) rises markedly with age, and only a few cases have been reported in younger adults. Thrombophilia has been reported as one of the predisposing factors for PE in younger adults. Here we report an extraordinary case of PE complicated with dysplasminogenemia, a rare genetic disorder resulting in hypercoagulability, in a young male. An 18-yr-old male visited an emergency room in the United States complaining chest discomfort. He was diagnosed as PE with deep vein thrombosis without apparent risk factors. Anticoagulation therapy with warfarin had been initiated and discontinued after 6 months of treatment. After returning to Korea he was tested for thrombophilia which revealed decreased activity of plasminogen and subsequent analysis of PLG gene showed heterozygous Ala620Thr mutation. He was diagnosed with PE complicated with dysplasminogenemia. Life-long anticoagulation therapy was initiated. He is currently under follow-up without clinical events for 2 yr.

Topics: Acute Disease; Adolescent; Anticoagulants; Conjunctivitis; Heterozygote; Humans; Male; Plasminogen; Polymorphism, Single Nucleotide; Pulmonary Embolism; Risk Factors; Skin Diseases, Genetic; Tomography, X-Ray Computed; Venous Thrombosis; Warfarin

Ehlers-Danlos syndrome (EDS) comprises a group of hereditary connective tissue disorders in which collagen synthesis and fibrogenesis are impaired. Patients with EDS type III have a bleeding tendency manifested by ecchymoses and haematomas. However, thrombotic events are rare in this entity. Herein, we present a 48-year-old Hispanic man with EDS type III who had recurrent cephalic vein thrombophlebitis and thrombosis, and brachial vein thrombosis. Tests for hypercoagulable disorders including antithrombin III activity, protein C activity, protein S activity, anticardiolipin antibodies, homocysteine levels, factor V Leiden mutation and prothrombin gene mutation were negative. The patient required long-term anticoagulation with warfarin. After 3 years follow-up, he did not present further thrombotic events. Clinicians should be aware that patients with EDS might be at risk for hypercoagulable disorders.

Topics: Anticoagulants; Arm; Ehlers-Danlos Syndrome; Humans; Male; Middle Aged; Secondary Prevention; Thrombophlebitis; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Creatinine; Female; Fibrinolytic Agents; Heparin; Humans; International Normalized Ratio; Neoplasms; Platelet Count; Pregnancy; Pulmonary Embolism; Venous Thrombosis; Warfarin

Some patients show warfarin resistance needing more than 70 mg of warfarin per week. In this study, we examined if C3435T polymorphism of MDR1 gene could be a factor of warfarin resistance.. We examined 196 blood specimens from the patients who took warfarin more than 42 mg/week for at least 1 year. The subjects consisted of 74 European Americans, 59 African Americans, 42 Hispanic Americans and 21 Asian Americans. Genotype of C3435T polymorphism was determined by using real-time polymerase chain reaction (PCR).. Ninety (45.9%) of the 196 patients had C3435T genotype and the remaining patients had C3435C genotype (35.7%) and T3435T genotype (18.4%). Mean dose of warfarin of patients with C3435C, C3435T and T3435T genotypes were 59.5mg/week, 56.9 mg/week and 55.6 mg/week, respectively. There was no statistical difference in the dose of warfarin between the 3 genotypes within each race.. Our results suggest that C3435T polymorphism of MDR1 gene is not associated with warfarin resistance.

Topics: Adult; Aged; Anticoagulants; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Atrial Fibrillation; Drug Administration Schedule; Female; Gene Frequency; Genotype; Humans; Male; Metabolism, Inborn Errors; Middle Aged; Polymorphism, Single Nucleotide; Pulmonary Embolism; Racial Groups; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Contraindications; Dalteparin; Dyspnea; Female; Fibrinolytic Agents; Humans; Middle Aged; Popliteal Vein; Prognosis; Pulmonary Embolism; Stockings, Compression; Venous Thrombosis; Warfarin

We present the result of right atrial thrombectomy in a paediatric patient suffering from a right atrial thrombus due to amoebic liver abscess under total circulatory arrest. A 2-year old boy with amoebic liver abscess complicated by inferior vena cava (IVC) thrombus extending up to the right atrium (RA) was operated on in our institute. During the surgery, the thrombus was removed from the IVC and the RA under deep hypothermic circulatory arrest. After chest closure, open drainage of the abscess was performed. Metronidazole was given postoperatively for 2 weeks. The postoperative period was uneventful. There was rapid convalescence with complete resolution of the abscess. Anticoagulation with warfarin was started on the day following surgery and continued for 6 weeks. There was no recurrence of thrombosis or embolic events in the follow-up period. Extension of thrombus into the right atrium mandates an aggressive surgical approach which may prove life saving. It is crucial in the prevention of pulmonary embolism or Budd-Chiari syndrome, which may have an overall poor outcome.

Topics: Anticoagulants; Child, Preschool; Circulatory Arrest, Deep Hypothermia Induced; Drainage; Heart Diseases; Humans; Liver Abscess, Amebic; Male; Thrombectomy; Thrombosis; Treatment Outcome; Vena Cava, Inferior; Venous Thrombosis; Warfarin

There is considerable controversy regarding the best method to prevent venous thromboembolism. In 2008, the American College of Chest Physicians (ACCP) published specific guidelines recommending the use of ow-molecular-weight heparin or warfarin, and a target international normalised ratio of 2.0-3.0 for a duration of at least 7-10 days, after elective knee arthroplasties. Many orthopaedic surgeons believe that these recommendations are biased toward reducing deep venous thrombosis (DVT), but neglect the implicated possibility of a higher incidence of wound complications. In order to enable an objective evaluation of the fit of the ACCP recommendations to the needs of our local cohort of patients, we aimed to look at the incidence of DVT in our local population.. This study was a prospective observational study involving existing local patients in Singapore General Hospital, Singapore, who underwent total knee arthroplasty (TKA) and were on a short course of chemothromboprophylaxis (< 7 days) after the operation. The incidence of DVT in patients was evaluated using DVT imaging 4-6 days after the operation and at one month after the operation.. In our study cohort, the prevalence of DVT during the period between postoperative Days 4 and 6 was 12% (11% were distal DVT and 1% was proximal DVT). Only 9% of the patients had DVT one month after the operation. Using chi-square analysis, we found that there was no significant increase in the number of DVT and pulmonary embolism cases 4-6 days and 1 month after the operation (p > 0.05).. Contrary to the ACCP guidelines, a short course of chemothromboprophylaxis post TKA, lasting no more than 7 days, is safe and adequate in the low-risk Asian population.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Knee; Drug Administration Schedule; Female; Follow-Up Studies; Heparin, Low-Molecular-Weight; Humans; Incidence; Male; Middle Aged; Osteoarthritis, Knee; Postoperative Complications; Prognosis; Prospective Studies; Singapore; Treatment Outcome; Venous Thrombosis; Warfarin

We describe here the case of 41 yrs old male patient, who was admitted to the emergency department complaining for abdominal pain lasting for two days. The patient self-reported a history of idiopathic deep vein thrombosis five yrs before the visit. A subcutaneous cordlike induration, tender and painful, was clearly palpable in the left lower abdominal quadrant. Routine blood tests did not reveal any substantial abnormality, except increased D-dimer concentration. Ultrasound evaluation of the abdominal wall revealed diffuse thrombosis of the left superficial inferior epigastric vein, involving several small tributaries branches, extended until 1.5 cm from the confluence with the common femoral vein, which was finally classified as an atypical case of Abdominal Mondor's disease. Complete thrombophilia screening was negative. The patient was discharged with warfarin therapy 48 hours from admission. At 30 days follow-up, the patient self-reported a nearly complete recovery.

Topics: Abdominal Pain; Humans; Thrombophlebitis; Venous Thrombosis; Warfarin

Hormone replacement therapy increases risk of deep venous thrombosis (DVT) mainly in the extremities and lungs. There are reports of mesenteric ischemia secondary to oral contraceptive pills but no reports on hormone replacement therapy and mesenteric thrombosis. The authors present a case of a 44-year-old obese (BMI 32) woman, on long-term hormone replacement therapy, presented with thrombosis of portal, splenic and superior mesenteric veins. She underwent surgical resection of ischemic bowel and planned re-look laparotomies with further resections and jejuno-ileal anastomosis at final laparotomy. Thorough haematological investigations were normal. The authors conclude that hormone replacement therapy in obese patients with no other risk factors can cause a catastrophic mesenteric thrombosis. Aggressive surgical resection with re-look laparotomies and further resections can be lifesaving.

Topics: Abdominal Pain; Adult; Anticoagulants; Body Mass Index; Female; Hormone Replacement Therapy; Humans; Laparotomy; Mesenteric Veins; Obesity; Portal Vein; Tomography, X-Ray Computed; Treatment Outcome; Venous Thrombosis; Warfarin

A 87-year-old man presented to the emergency department (ED) with right-sided abdominal and thigh pain which had been present for the last 3 days and was getting worse. He had been diagnosed with a deep venous thrombosis of the left common femoral and superficial veins 10 days previously and had been discharged on a loading dose of warfarin and low-molecular weight heparin (dalteparin) injections. Despite his international normalised ratio being only 2.4, an ED ultrasound showed an unusual mass in the right iliac fossa, partly cystic and partly solid. A CT scan was performed which showed the lesion was a haematoma in the right iliopsoas muscle mass.

Topics: Aged, 80 and over; Anticoagulants; Drug Therapy, Combination; Femoral Artery; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Male; Psoas Muscles; Tomography, X-Ray Computed; Ultrasonography; Venous Thrombosis; Warfarin

Topics: Aged; Anticoagulants; Antipsychotic Agents; Dementia; Dibenzothiazepines; Drug Therapy, Combination; Hemorrhage; Humans; International Normalized Ratio; Male; Quetiapine Fumarate; Venous Thrombosis; Warfarin

A young woman leading a sedentary life, travelled on foot for a distance of 25 km in a day. The following day she noticed pain and swelling of left foot and left leg. She got no relief with analgesics and her orthopaedic evaluation was normal. Her clinical examination was normal except for local swelling, oedema and tender calf. Her haematological and biochemical examination was normal except for mild elevation of creatine phosphokinase. A Doppler ultrasound revealed the thrombosis of anterior tibial vein and popliteal vein.

Topics: Adult; Anticoagulants; Enoxaparin; Female; Humans; Leg; Motor Activity; Physical Exertion; Popliteal Vein; Ultrasonography; Venous Thrombosis; Warfarin

Topics: Administration, Oral; Anticoagulants; Hemorrhage; Humans; Pulmonary Embolism; Pyridines; Randomized Controlled Trials as Topic; Secondary Prevention; Thiazoles; Venous Thrombosis; Vitamin K; Warfarin

Mesenteric venous thrombosis (MVT) is a rare but life threatening form of bowel ischemia. It is implicated in 6%-9% of all cases of acute mesenteric ischemia. The proportion of patients with primary (or idiopathic) MVT varies from 0% to 49%, with a decrease in frequency secondary to more recent availability of newer investigations for hypercoagulability. The presence of factor V Leiden (FVL) and prothrombin G20210A mutations (PGM) have been well documented in these cases. However, there have been scarce case reports describing MVT in heterozygotes of both these mutations occurring simultaneously and its implications on long term management. Our case describes acute MVT in a previously asymptomatic young patient with no prior history of venous thromboembolism. The patient was found to be heterozygous for FVL and PGM and treated with lifelong anticoagulation with warfarin (goal international normalized ratio: 2-3) and avoidance of hormonal contraceptives.

Topics: Activated Protein C Resistance; Anticoagulants; Blood Coagulation; DNA Mutational Analysis; Factor V; Female; Genetic Predisposition to Disease; Heterozygote; Humans; International Normalized Ratio; Ischemia; Mesenteric Ischemia; Mesenteric Vascular Occlusion; Mesenteric Veins; Mutation; Phenotype; Phlebography; Prothrombin; Tomography, X-Ray Computed; Vascular Diseases; Venous Thrombosis; Warfarin; Young Adult

Topics: Anti-Bacterial Agents; Anticoagulants; Diagnosis, Differential; Drug Therapy, Combination; Female; Gentamicins; Heparin; Humans; Jugular Veins; Middle Aged; Renal Dialysis; Vancomycin; Venous Thrombosis; Warfarin

A 46-year-old woman presented with loss of consciousness and was diagnosed with acute cerebral embolism. She had undergone left upper lobectomy for primary lung cancer 6 months before this event. Transesophageal echocardiography and computed tomography showed a large mobile thrombus in the left upper pulmonary vein (LSPV). An emergent operation was performed through a median sternotomy. Cardiopulmonary bypass was performed and the heart was arrested, and the LSPV was incised. A fresh thrombus had formed in the stump of the LSPV and was removed successfully. The postoperative course was uneventful. During a 1 year of follow-up, there was no recurrence of the thrombus.

Topics: Acute Disease; Anticoagulants; Diagnosis, Differential; Echocardiography, Transesophageal; Female; Humans; Intracranial Embolism; Lung Neoplasms; Magnetic Resonance Imaging; Middle Aged; Pneumonectomy; Pulmonary Embolism; Pulmonary Veins; Thrombectomy; Thrombolytic Therapy; Tomography, X-Ray Computed; Venous Thrombosis; Warfarin

We present a case report of a young man with spontaneous deep venous thrombosis. He tested positive for heterozygote factor V Leiden mutation and was treated with warfarin. However, he turned out to be resistant to warfarin, and another venous thrombosis occurred during the insufficient treatment. The antithrombotic treatment was then successfully replaced by phenprocoumon. This case report emphasizes the importance of critically evaluating the efficacy of a treatment and substitute if proven insufficient.

Topics: Activated Protein C Resistance; Adult; Anticoagulants; Humans; Male; Metabolism, Inborn Errors; Thrombophilia; Venous Thrombosis; Warfarin

We report an Indian adult female patient with Deep Vein Thrombosis (DVT), in whom it was difficult to achieve and maintain target INR on warfarin (oral anticoagulant) by conventional doses. Pharmacogenomics study for warfarin revealed that she had Homozygous mutant for CYP2C9 *3(CYP2C9 *3/*3) and Heterozygous mutant for VKORC 1(1639G >A) {genetic polymorphism double defect}. This conferred a greater sensitivity to her warfarin therapy in an otherwise conventional dose regime used in most patients, making her management challenging. This sensitivity (or resistance in other cases) can be assessed by this evidence based test and warfarin dosing could be individualised to avoid toxicity.

Topics: Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP2C9; Female; Humans; International Normalized Ratio; Middle Aged; Mutation; Venous Thrombosis; Vitamin K Epoxide Reductases; Warfarin

VKORC1, CYP2C9, and CYP4F2 are known to be responsible for the metabolism of warfarin. The aim was to explore the frequencies of these genotypes in the Russian population and compare the results with those for other populations.. In total, 91 Caucasian subjects with a mean age of 66.17 years (SD, 10.9) were recruited into the study. Of them, 40 patients (48.2%) were men. In order to obtain necessary clinical data, the medical records of the patients were reviewed. Blood (5 mL) was taken from each subject, and DNA was isolated and used for identification of the CYP2C9 allele *1, *2, *3, -1639G/A VKORC1, and CYP4F2 V433M rs2108622 C>T, using the real-time polymerase chain reaction-restriction fragment length polymorphism assay.. The CYP2C9*1/*1 genotype was detected in 67.0%, CYP2C9*1/*2 in 9.9%, CYP2C9*1/*3 in 11.0%, CYP2C9*2/*2 in 2.2%, CYP2C9*2/*3 in 8.8%, and CYP2C9*3/*3 in 1.1% of the patients. The results for VKORC1 were as follows: 49.5% (GG), 28.6% (GA), and 22.0% (AA); meanwhile, those for the genotype CYP4F2 were 57.1% (CC), 34.1% (CT), and 7.7% (TT). No significant deviations from the Hardy-Weinberg equilibrium were observed. The frequency of the polymorphisms in the Russian population was found to differ from Asian and close to Caucasian. There were no significant interethnic variations in the frequency of CYP4F2 among Russian, Asian, and Caucasian populations.. The frequency of CYP2C9, CYP4F2, and VKORC1 polymorphisms in Russian patients is comparable with other European ethnic groups.

Topics: Aged; Alleles; Anticoagulants; Cytochrome P-450 CYP2C9; Cytochrome P-450 Enzyme System; Cytochrome P450 Family 4; Female; Gene Frequency; Genotype; Humans; Male; Middle Aged; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Real-Time Polymerase Chain Reaction; Risk; Russia; Venous Thrombosis; Vitamin K Epoxide Reductases; Warfarin

Venous thrombotic events (VTE) occur at high ratesin HIV/AIDS patients and are likely under-diagnosed in rural sub-Saharan Africa.. To describe clinical presentations and challenges in the management of VTE in patients with advanced HIV/AIDS.. Case series from patients enrolled in a prospective observational cohort study.. A clinical research centre in rural Kericho, Kenya.. Two hundred patients with median age 38 (30-47) years, BMI 16.9 (12.4-20.3) kg/m2, haemoglobin 9.3 (6.8-13.4) g/dL, CD4+ T-cell count 27 (4-77) cells/mm and plasma HIV RNA 5.23 (3.70-5.88) log10 copies/mL.. VTE cases were diagnosed by clinical presentation and Doppler/ radiographic confirmation. Anti-coagulation therapy was managed by a multidisciplinary team; patients were initiated on enoxaparin or heparin followed by warfarin.. Over two years,11patients (5.5%) experienced VTE. All but one (10/11,90.9%) case occurred within six months of starting ART. Nine patients had peripheral VTE (five popliteal, four femoral) and two had cerebral sinus thromboses. VTE was diagnosed 52 (1-469) days after ART initiation, and 81.8% of cases were outpatients at presentation. All patients received at least one concomitant medication that could significantly interact with warfarin (efavirenz, nevirapine, lopinavir/ritonavir, rifampicin, trimethoprim-sulfamethoxazole, and fluconazole). A median of 39 (10-180) days and eight (4-22) additional clinic visits were required to achieve/maintain a therapeutic INR of 2-3. Two minor bleeding complications occurred. No recurrent VTE cases were observed.. Consideration of VTE and preparedness for management in patients with advanced HIV/AIDS starting ART is critical in sub-Saharan Africa. Overcoming challenges in anti-coagulation is possible in rural settings using a multidisciplinary team approach.

Topics: Adult; Anticoagulants; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Disease Management; Drug Interactions; Drug Monitoring; Female; HIV Infections; Humans; International Normalized Ratio; Kenya; Male; Middle Aged; Patient Acuity; Patient Care Team; Rural Population; Ultrasonography, Doppler, Duplex; Venous Thrombosis; Warfarin

Deep venous thrombosis (DVT) is uncommonly seen in children and adolescents. A distal femoral osteochondroma causing isolated lower limb DVT is even rarer and to our knowledge only four such cases have been reported in the literature. We report a case of a solitary distal femoral osteochondroma in a 15-year-old adolescent presenting as isolated DVT. We highlight the potential of coexistence of DVT and osteochondroma in young patients. We also emphasize the importance of timely diagnosis and outline the plan of management when faced with such a rare condition.

Topics: Adolescent; Anticoagulants; Femoral Neoplasms; Humans; Magnetic Resonance Angiography; Male; Osteochondroma; Popliteal Vein; Tomography, X-Ray Computed; Venous Thrombosis; Warfarin

The prevalence of portal vein thrombosis (PVT) increases with the severity of liver disease. Development of PVT is often accompanied by increased rate of morbidity and mortality and may affect patient candidacy for liver transplant. There is limited data regarding the role of anticoagulation therapy in patients with PVT and liver cirrhosis.. The aims of this study were to describe the prevalence of hypercoagulable disorders in patients with liver cirrhosis and PVT, and to describe the outcome of anticoagulation in patients with liver cirrhosis and PVT.. A retrospective chart review was conducted of patients with liver cirrhosis awaiting liver transplant who were diagnosed with PVT between January 2005 and November 2011.. During the study period, 537 patients were evaluated for liver transplant. Sixty-nine (13 %) patients were diagnosed with portal vein thrombosis. Chronic hepatitis C was the cause of liver disease in 24/69 (35 %) patients, and hepatocellular carcinoma was present in 39 % of patients. In 22 patients screened for hypercoagulable disorders, hypercoagulable disorder was diagnosed in one patient (5 %). Twenty-eight (28/69) patients were treated during the study period with warfarin: PVT resolved in 11/28 (39 %), no change in 5/28 (18 %), and 12/28 (43 %) patients showed partial resolution of thrombus. Eight patients received liver transplant while on anticoagulation, and operative notes confirmed patency of PV in all eight patients.. PVT is frequently seen in patients with end stage liver disease with prevalence of 13 %. Hypercoagulable disorder was detected in 5 % of the patients screened. Careful use of anticoagulation is safe and effective in patients with PVT.

Topics: Administration, Oral; Adult; Aged; Anticoagulants; Drug Administration Schedule; End Stage Liver Disease; Female; Humans; Liver Transplantation; Male; Middle Aged; Portal Vein; Prevalence; Retrospective Studies; Thrombophilia; Treatment Outcome; Venous Thrombosis; Waiting Lists; Warfarin

Topics: Administration, Oral; Anticoagulants; Drug Administration Schedule; Humans; Infant, Newborn; Pharmaceutical Solutions; Renal Veins; Venous Thrombosis; Warfarin

A patient with a history of deep vein thrombosis presented with painful bruising and blistering on his left leg 7-10 days after warfarin treatment. A complicated 2-month treatment followed, where vasculitis was originally diagnosed from histological findings before the final diagnosis of warfarin-induced skin necrosis (WISN) was made on clinical grounds. Warfarin was stopped, reversed and low molecular weight heparin started but, the lesions had progressed to full thickness necrosis. This was originally treated with conventional surgical debridement before introducing maggot debridement therapy (MDT) in an effort to try to salvage the limb.

Topics: Aged; Animals; Anticoagulants; Debridement; Diagnosis, Differential; Humans; Larva; Male; Necrosis; Skin; Venous Thrombosis; Warfarin

Klinefelter's syndrome is the most common cause of primary testicular failure. Previous reports have associated Klinefelter's syndrome with increased risk of thrombosis. The exact cause for this association is unknown, but hypoandrogenism affecting fibrinolysis has been implicated. The authors described a unique patient with Klinefelter's syndrome who presented with deep vein thrombosis of the leg and underlying mutations of MTHFR gene, increased factor VIII coagulant activity and an elevated anticardiolipin antibody. To the authors' knowledge, this combination of hypercoagulability risk factors in such a patient has not been previously reported. The authors also reviewed previously published reports of similar patients and discuss potential genetic mutations that may in part predispose this group of patients to venous thrombosis.

Topics: Adult; Antibodies, Anticardiolipin; Anticoagulants; Enoxaparin; Factor VIII; Gene Expression Regulation; Humans; Immunoglobulin M; Klinefelter Syndrome; Male; Methylenetetrahydrofolate Reductase (NADPH2); Mutation; Venous Thrombosis; Warfarin

Extrahepatic portal vein obstruction (EHPVO) is an important cause of chronic portal hypertension in children. Although usually idiopathic in etiology, genetic and acquired thrombophilia have been implicated in EHPVO. Meso-Rex bypass is increasingly used to treat EHPVO in children.. The objective of this study is to assess the relationship of postoperative anticoagulation strategies and thrombophilic risk factors to the development of bypass thrombosis following the meso-Rex bypass.. Records of children who underwent meso-Rex bypass for EHPVO at a single institution from 1999 to 2009 were reviewed, and preoperative thrombophilia testing, perioperative anticoagulation strategies, and postoperative bypass patency based on imaging at last follow-up were examined.. Sixty-five children with EHPVO underwent a first time meso-Rex bypass during the study period, and 9 of 65 (14 %) developed bypass thrombosis. The use of warfarin in the postoperative period was more common among children with thrombosed shunts than among those with open shunts [63 % vs. 20 %; OR, 6.5 (95 % CI, 1.3-31.5), p = 0.022]. The contribution of genetic or acquired thrombophilia to shunt thrombosis was inconclusive given variability in testing.. Choice of anticoagulation following meso-Rex bypass may affect postoperative incidence of bypass thrombosis. Role of thrombophilic risk factors in the development of shunt thrombosis remains unclear.

Topics: Anticoagulants; Chi-Square Distribution; Child, Preschool; Female; Humans; Hypertension, Portal; Infant; Male; Postoperative Complications; Retrospective Studies; Risk Factors; Thrombophilia; Treatment Outcome; Venous Thrombosis; Warfarin

In this report, we describe a patient who developed severe headache following epidural analgesia for labor and delivery. Although the epidural puncture had been reported to be uneventful, headache was initially suspected to result from an accidental dural puncture. After the headache worsened, a sinus venous thrombosis was suspected and subsequently confirmed by magnetic resonance imaging. This case highlights the difficulty of differential diagnosis of headache in the postnatal period in patients after EDA and stresses the necessity of considering alternative pathologies.

Topics: Adult; Analgesia, Epidural; Analgesics; Anticoagulants; Diagnosis, Differential; Female; Fibrinolytic Agents; Heparin; Humans; Magnetic Resonance Imaging; Post-Dural Puncture Headache; Postpartum Period; Pregnancy; Puerperal Disorders; Severity of Illness Index; Treatment Outcome; Venous Thrombosis; Warfarin

Warfarin responsiveness is characterized by marked interindividual variability. A major portion of this variability is attributed to CYP2C9 and VKORC1 polymorphisms, but almost 50% is still unaccounted for. This paper reports the first prospective study on the association between factor VII R353Q polymorphism and warfarin responsiveness during induction.. Genotyping for factor VII R353Q and 323D/I polymorphisms was performed in a cohort consisting of 374 patients (198 CYP2C9*1/*1) treated with warfarin who were prospectively followed from warfarin initiation.. Compared with *1/*1-R/R and *1/*1-R/Q genotype carriers, *1/*1-Q/Q homozygotes achieved higher International Normalized Ratio (INR) values while consuming lower warfarin doses. The greater sensitivity was illustrated by 82.1% higher Warfarin Sensitivity Index During Induction (WSIDI) (0.14 ± 0.11 vs. 0.08 ± 0.50 mg⁻¹ Mann-Whitney, P = 0.043). Multiple regression analysis consisting of both genetic and nongenetic factors explained 26% of WSIDI variability, with R353Q genetic polymorphism having a modest yet significant effect and accounting for 1.7% of the overall variability. Moreover, the incidence of overanticoagulation (i.e., INR > 4) was 6.94-fold higher among *1/*1-Q/Q vs. *1/*1-R/R&R/Q carriers during warfarin induction (Pearson chi-square, P = 0.005). These findings were not accounted for by a chance difference in the distribution of VKORC1 genotypes. Analysis of these parameters among the entire cohort, including CYP2C9*2 and CYP2C9*3 variant allele carriers, did not reach statistical significance. Warfarin responsiveness during induction was unrelated to factor VII 323D/I genetic polymorphism.. The response to warfarin during induction is influenced by factor VII R353Q polymorphism. The prospective use of this polymorphism, along with CYP2C9 and VKORC1, may enhance the accuracy of warfarin loading. However, the impact of R353Q polymorphism on overall warfarin response is subtle, and it is therefore unlikely that its use would be of clinical importance.

Topics: Adult; Aged; Aged, 80 and over; Amino Acid Substitution; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Atrial Fibrillation; Cohort Studies; Cytochrome P-450 CYP2C9; Drug Monitoring; Drug Resistance; Factor VII; Female; Genetic Association Studies; Humans; Israel; Male; Middle Aged; Polymorphism, Genetic; Prospective Studies; Pulmonary Embolism; Venous Thrombosis; Warfarin; Young Adult

Warfarin is widely used as an oral anticoagulant for the prevention and long-term treatment of venous thromboembolism and for the prevention of thromboembolic complications associated with atrial fibrillation, heart valve replacement and myocardial infarction. Warfarin exerts its anticoagulation effect by inhibiting the enzymes responsible for the cyclic interconversion of vitamin K in the liver. Vitamin K serves as a cofactor required for the carboxylation of the vitamin K-dependent coagulation proteins. By inhibiting the supply of vitamin K in the production of these proteins, warfarin indirectly slows their rate of synthesis. The authors describe a 46-year-old patient readily anticoagulated for a deep venous thrombosis who then required large doses of warfarin after initiation of total parenteral nutrition, which included lipid preparation that contained vitamin K, in addition to vitamin K required for the daily parenteral nutrition. The effect of total parenteral nutrition with vitamin K on anticoagulation is discussed.

Topics: Anticoagulants; Drug Resistance; Female; Humans; International Normalized Ratio; Middle Aged; Parenteral Nutrition; Serum Albumin; Venous Thrombosis; Vitamin K; Warfarin

Congenital anomalies of the inferior vena cava (IVC) are rare, but recognized, causing deep venous thrombosis. We present a case of a 50-year-old patient with trauma who suffered an intracranial hemorrhage secondary to a fall while on anticoagulation for deep vein thromboses. Venous return from the lower extremities was determined to be through dilated lumbar venous collaterals into the azygous and hemiazygous systems. A second interesting anatomic finding was a hypoplastic left kidney.

Topics: Accidental Falls; Acute Kidney Injury; Anticoagulants; Azygos Vein; Collateral Circulation; Dilatation, Pathologic; Humans; Intracranial Hemorrhage, Traumatic; Kidney; Magnetic Resonance Angiography; Male; Middle Aged; Phlebography; Regional Blood Flow; Vascular Malformations; Vena Cava, Inferior; Venous Thrombosis; Warfarin

Topics: Adult; Anti-Bacterial Agents; Anticoagulants; Bacteremia; Brachiocephalic Veins; Defibrillators, Implantable; Drug Therapy, Combination; Echocardiography, Transesophageal; Endocarditis, Bacterial; Furunculosis; Humans; Jaw; Jugular Veins; Male; Nafcillin; Pulmonary Embolism; Reoperation; Risk Factors; Tomography, X-Ray Computed; Treatment Outcome; Venous Thrombosis; Warfarin

Gonadal vein thrombosis is a rare but well recognized entity which predominantly occurs in the post partum period. It is also associated with gynecological malignancies, cesarean deliveries, abortions, hypercoagulability and pelvic inflammatory disease. Prompt diagnosis and treatment is warranted to avoid serious complications. We report the rare case of idiopathic, unprovoked gonadal vein thrombosis.

Topics: Aged; Anticoagulants; Female; Humans; Incidental Findings; Ovary; Phlebography; Predictive Value of Tests; Treatment Outcome; Venous Thrombosis; Warfarin

The manifestation and management of spontaneous axillosubclavian vein thrombosis in patients with gastrointestinal stromal tumour (GIST) undergoing oral chemotherapy have never been described. We report a patient with a recurrent GIST who was receiving maintenance imatinib yet developed a right axillosubclavian vein thrombotic occlusion. The occluded vein was unresponsive to systemic anticoagulation but was reopened by percutaneous rheolytic thrombectomy and has shown good long-term patency. Thus, for patients with recurrent GIST undergoing imatinib therapy, axillosubclavian vein thrombosis might manifest as a complication and could be managed with rheolytic thrombectomy, which thoroughly removes intravascular thrombus and effectively re-vascularizes the thrombosed vessel uneventfully.

Topics: Angiography; Benzamides; Gastrointestinal Stromal Tumors; Humans; Imatinib Mesylate; Male; Middle Aged; Neoplasm Recurrence, Local; Phlebography; Piperazines; Pyrimidines; Subclavian Vein; Thrombectomy; Thrombolytic Therapy; Venous Thrombosis; Warfarin

Topics: Adult; Anticoagulants; Black or African American; Case Management; Female; Fibrin Fibrinogen Degradation Products; Genetic Predisposition to Disease; Humans; Obesity; Pulmonary Embolism; Risk; Sickle Cell Trait; Thrombophilia; Thrombophlebitis; Ultrasonography; Venous Thrombosis; Warfarin

Venous thromboembolism is a rarely described complication of diabetic ketoacidosis (DKA). We describe a 21-year-old male patient with poorly controlled type 1 diabetes mellitus who was admitted with DKA, presumably secondary to noncompliance, whose clinical picture was complicated by generalized thrombosis involving multiple venous locations including renal vein, pulmonary vasculature, external iliac and common iliac veins. The patient had no family history of any coagulation disorders and a hypercoagulabilty work-up remained negative. The patient was subsequently anticoagulated with heparin and discharged home on warfarin. To the best of our knowledge, this is the first reported case of multiple venous thromboses occurring as a complication of DKA with no other risk factors. We also reiterate that although rare, venous thrombosis should always be considered as a potential complication of DKA.

Topics: Anticoagulants; Diabetic Ketoacidosis; Heparin; Humans; Iliac Vein; Male; Patient Compliance; Pulmonary Veins; Renal Veins; Risk Factors; Venous Thrombosis; Warfarin; Young Adult

A 58-year-old Japanese man with a 2-year history of multidrug therapy for borderline lepromatous leprosy presented with skin lesions suggestive of erythema nodosum leprosum (ENL) and was treated with an oral corticosteroid. As attempts to taper the oral corticosteroid resulted in the appearance of new lesions, thalidomide was added along with cyclosporin. Two months after the introduction of thalidomide, deep venous thrombosis (DVT) occurred in both legs and anticoagulant therapy was started without cessation of thalidomide. Pulmonary embolism developed 1 month after the appearance of DVT, and these thromboembolic events were believed to be due to thalidomide. This case highlights the need for vigilance against venous thromboembolism when corticosteroid and thalidomide are co-administrated for the treatment of ENL.

Topics: Adrenal Cortex Hormones; Cyclosporine; Humans; Leprostatic Agents; Leprosy; Male; Middle Aged; Pulmonary Embolism; Radiography; Thalidomide; Treatment Outcome; Venous Thrombosis; Warfarin

Persistently elevated antiphospholipid antibodies and positive lupus anticoagulant (LAC) are associated with an increased risk of thrombosis. The objective of this study was to explore whether antiphospholipid antibody and/or LAC positivity were associated with the traditional risk factors for thrombosis or with medication use in patients without autoimmune diseases hospitalised with arterial or venous thrombosis.. Cross-sectional study.. Montefiore Medical Center, a large urban tertiary care centre.. 270 patients (93 with deep vein thrombosis (DVT) or pulmonary embolism (PE), and 177 with non-haemorrhagic stroke (cerebrovascular accident (CVA)) admitted between January 2006 and December 2010 with a discharge diagnosis of either DVT, PE or CVA, who had LAC and antiphospholipid antibodies measured within 6 months from their index admission. Patients with lupus or antiphospholipid syndrome were excluded.. The main dependent variable was antiphospholipid antibodies of 40 units or greater (antiphospholipid antibody positivity) and/or LAC positivity. Independent variables were traditional thrombosis risk factors, statin use, aspirin use and warfarin use.. 31 (11%) patients were LAC positive and/or antiphospholipid antibody positive. None of the traditional risk factors at the time of DVT/PE/CVA was associated with antiphospholipid antibody positivity. Current statin use was associated with an OR of 3.2 (95% CI 1.3 to 7.9, p=0.01) of antiphospholipid antibody positivity, adjusted for age, ethnicity and gender. Aspirin or warfarin use was not associated with antiphospholipid antibody levels.. If statin therapy reflects the history of previous hyperlipidaemia, high levels of antiphospholipid antibodies may be a marker for earlier endothelial damage caused by hyperlipidaemia.

Topics: Aged; Antibodies, Antiphospholipid; Aspirin; Biomarkers; Chronic Disease; Cross-Sectional Studies; Endothelium, Vascular; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Lupus Coagulation Inhibitor; Male; Middle Aged; Pulmonary Embolism; Risk Factors; Stroke; Venous Thrombosis; Warfarin

An elevated factor VIII level has been shown to be an independent risk factor for venous thrombosis. However, physicians screen for this factor far less frequently than they screen for other coagulopathies. The causes of increased factor VIII levels are likely a combination of genetic and acquired variables. The authors describe a case of a healthy 48-year-old woman found to have a cerebral venous thrombosis, with her only identifiable risk factor being an elevated factor VIII level.

Topics: Anticoagulants; Cerebral Veins; Factor VIII; Female; Humans; Middle Aged; Risk Factors; Venous Thrombosis; Warfarin

Only few studies are available on the comparison of the efficacy and safety of the acenocoumarol and warfarin. The authors treated patients with deep vein thrombosis according to latest recommendations using D-dimer measurements and duplex ultrasound exams.. To examine the efficacy and safety of the two anticoagulants in patients with lower limb deep vein thrombosis.. The authors included 100 consecutive patients with lower limb dee deep vein thrombosis. The patients were treated with acenocoumarol or warfarin in doses to achieve INR values between 2 and 3.5 for six months. After 6 months the authors performed physical examination, D-dimer measurements and ultrasound exams, and determined the rate of unchanged thrombotic process, as well as the rate of complete and incomplete recanalisations.. There was no significant difference in the number of INR determinations during treatment between the two groups (acenocoumarol group 442, warfarin group 416). The INR values were in the therapeutic range in 71.2% and 75.4% of patients in the acenocoumarol and warfarin groups, respectively. Dose adjustment was necessary in 129 and 84 times in the acenocoumarol and warfarin groups, respectively (p = 0.0025). The therapy was optimally effective (INR value was within the therapeutic range throughout the treatment period) in 46% and 52% of patients in the acenocoumarol and warfarin groups, respectively. The thrombotic vein was completely recanalised in 91.9% of patients treated optimally, and only 80.4% of patients treated not optimally. There were 3 minor bleedings in the acenocoumarol and 4 minor bleedings in the warfarin groups, while one major bleedings occurred in both groups.. The INR values were more stable in the warfarin group than in the acenocumarole group. In both groups the rate of complete vein recanalization was related to the rate of optimally stable INR values within the therapeutic range.

Topics: Acenocoumarol; Adult; Aged; Anticoagulants; Drug Administration Schedule; Female; Fibrin Fibrinogen Degradation Products; Hemorrhage; Humans; International Normalized Ratio; Lower Extremity; Male; Middle Aged; Treatment Outcome; Venous Thrombosis; Warfarin

Multimodal thromboprophylaxis includes preoperative thromboembolic risk stratification and autologous blood donation, surgery performed under regional anaesthesia, postoperative rapid mobilisation, use of pneumatic compression devices and chemoprophylaxis tailored to the patient's individual risk. We determined the 90-day rate of venous thromboembolism (VTE), other complications and mortality in patients who underwent primary elective hip and knee replacement surgery with multimodal thromboprophylaxis.. A total of 1,568 consecutive patients undergoing hip and knee replacement surgery received multimodal thromboprophylaxis: 1,115 received aspirin, 426 received warfarin and 27 patients received low molecular weight heparin and warfarin with or without a vena cava filter.. The rate of VTE, pulmonary embolism, proximal deep vein thrombosis (DVT) and distal DVT was 1.2, 0.36, 0.45 and 0.36 %, respectively, in patients who received aspirin. The rates in those who received warfarin were 1.4, 0.9, 0.47 and 0.47 %, respectively. The overall 90-day mortality rate was 0.2 %.. Multimodal thromboprophylaxis in which aspirin is administered to low-risk patients is safe and effective following primary total joint replacement.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Arthroplasty, Replacement; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Clinical Protocols; Combined Modality Therapy; Elective Surgical Procedures; Female; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; New York City; Patient Readmission; Platelet Aggregation Inhibitors; Postoperative Complications; Pulmonary Embolism; Retrospective Studies; Survival Rate; Thromboembolism; Treatment Outcome; Venous Thrombosis; Warfarin; Young Adult

Henoch-Schönlein Purpura (HSP) is a small vessel-vasculitis that usually affects children and adolescents; its onset in adults is uncommon.We describe a case of HSP complicated with nephritis and extensive deep vein thrombosis in an 81-year-old Caucasian woman, successfully treated with oral corticosteroids. Even at the extremes of age, HSP should be considered in the differential diagnosis of leukocytoclastic vasculitis, with a particular attention to renal involvement, because of its potential morbidity and mortality in the elderly; in addition, ruling out an occult thrombotic event in course of HSP is mandatory, especially in the presence of additional thrombotic risk factors.

Topics: Administration, Oral; Adrenal Cortex Hormones; Aged, 80 and over; Anticoagulants; Diagnosis, Differential; Female; Humans; IgA Vasculitis; Risk Factors; Skin; Thrombosis; Venous Thrombosis; Warfarin

To determine the indications for, rates of therapeutic anticoagulation during, and complications of warfarin therapy in HIV-infected individuals, in whom long-term anticoagulation is frequently indicated. To identify risk factors for nonoptimal anticoagulation and to determine if warfarin dosing is differentially affected by specific antiretroviral agents. Retrospective study of a dedicated anticoagulation program at one of the largest clinics for HIV-infected individuals in the United States. Seventy-three HIV-infected individuals on warfarin were followed for a total of 911 visits. The rate of therapeutic internation normalized ratio (INR) levels was 34.5% when including only visits at which patients were assessed to be adherent with warfarin. In multivariable analysis, injection drug use at baseline was an independent risk factor for subtherapeutic INR (odds ratio [OR] 2.4, 95% confidence interval [CI] 1.3-4.7, p=0.01). Additionally, warfarin adherence was protective of both subtherapeutic (OR 0.4, 95% CI 0.2-0.6, p<0.0001) and supratherapeutic (OR 0.5, 95% CI 0.3-0.9, p=0.02) INR status. Efavirenz-based antiretroviral regimens were associated with lower weekly warfarin doses (46 mg) to maintain therapeutic INR compared to lopinavir/ritonavir-based regimens (68 mg; p=0.01) and atazanavir/ritonavir-based regimens (71 mg; p=0.007). Consistently therapeutic warfarin therapy is difficult to achieve in HIV-infected individuals, even with a dedicated anticoagulation program. Adherence to warfarin therapy is important but rates of therapeutic INR levels are nonetheless low. Lower warfarin dosing was required for efavirenz compared to two commonly used protease inhibitor-based regimens. Because of these factors, the emergence of new oral anticoagulants is an important development for HIV-infected individuals who require long term anticoagulation therapy.

Topics: Adult; Alkynes; Anti-HIV Agents; Anticoagulants; Benzoxazines; Cyclopropanes; Drug Administration Schedule; Drug Interactions; Female; HIV Seropositivity; Humans; International Normalized Ratio; Lopinavir; Male; Medication Adherence; Patient-Centered Care; Retrospective Studies; Ritonavir; Thromboembolism; Treatment Outcome; United States; Venous Thrombosis; Warfarin

Thrombotic risk is increased in patients with cancer and there are important implications for those who suffer a venous thromboembolism (VTE). We undertook this study to determine the frequency, clinical patterns, and outcome of VTE in Saudi patients with cancer.. Cancer (solid tumors and lymphoma) patients who developed VTE from January 2004 to January 2009 were studied retrospectively. Demographics and clinical characteristics related to thrombosis and cancer were evaluated.. A total of 701 patients with cancer were seen during the study period. VTE was diagnosed in 47 (6.7%) patients (median age 52, range 18-80 years). Lower limb DVT was the most common type, seen in 47% patients, followed by PE in 19%, and 19% patients had both DVT and PE. Thrombosis was symptomatic in 72% patients while it was an incidental finding on routine workup in 28% . Cancer and VTE were diagnosed at the same time in 38% of patients, and 47% patients developed VTE during the course of disease after the cancer diagnosis. The majority of VTE post cancer diagnoses occurred during the first year (median 4 months, range 1-14). Additional risk factors for VTE were present in 22 (47%) patients and 14 (30%) of these patients were receiving chemotherapy at the time of thrombosis. Only 5 (10.6%) patients were receiving thrombo-prophylaxis at the time of VTE diagnosis. Most common types of tumors associated with thrombosis were breast cancer, non-Hodgkin's lymphoma and lung cancer. The majority of the affected patients (79%) had advanced stage of cancer. After a median follow-up of 13 (range 0.5-60) months, 38 (81%) patients had died. There was no difference in the mortality of patients with symptomatic or asymptomatic thrombosis (82% vs 78.6%).. Thrombotic complications can develop in a significant number of patients with cancer, and almost half of the patients have additional risk factors for VTE. Thrombosis is usually associated with advanced disease and can be asymptomatic in more than a quarter of cases. Thromboprophylaxis in cancer patients is under-utilized. Community based studies are needed to accurately define the extent of this problem and to develop effective prophylactic strategies.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Female; Heparin, Low-Molecular-Weight; Humans; Lymphoma; Male; Middle Aged; Neoplasm Staging; Neoplasms; Pulmonary Embolism; Retrospective Studies; Saudi Arabia; Venous Thromboembolism; Venous Thrombosis; Warfarin; Young Adult

Anticoagulation management of a patient complicated by heparin-induced thrombocytopenia is one of the challenging situations in open heart surgery. A 40-year old male receiving warfarin for anticoagulation was admitted to our clinic with a history of heparin-induced thrombocytopenia and a diagnosis of inferior caval thrombosis. He was scheduled for inferior vena cava thrombectomy via the inflow occlusion technique on the beating heart. Warfarin sodium was stopped three days prior to the operation while fondaparinux sodium was begun twice a day. The operation was successfully performed and no postoperative complications were observed.

Topics: Adult; Anticoagulants; Drug Administration Schedule; Drug Substitution; Fondaparinux; Heparin; Humans; Male; Polysaccharides; Thrombectomy; Thrombocytopenia; Treatment Outcome; Vena Cava, Inferior; Venous Thrombosis; Warfarin

Patients with central nervous system (CNS) malignancies have a substantial risk for developing both thrombotic and bleeding disorders. The risk of venous thromboembolism (VTE) is substantially higher in these patients, both in the perioperative period and throughout their disease course. Patients with CNS malignancy harbor a latent hypercoagulability, which predisposes to VTE, as do postoperative immobility, hemiparesis, and other factors. The management of VTE in these patients is complex, given the significant morbidity and mortality associated with intratumoral hemorrhage. In the past, the perceived risk of intracranial hemorrhage limited the use of anticoagulation for the management of VTE with many favoring nonpharmacologic methods for prophylaxis and treatment. Inferior vena cava (IVC) filters have since lost favor at many centers given significant complications, which appear to be more frequent in patients with CNS malignancy. Recent studies have demonstrated safe and efficacious use of anticoagulation in these patients with a low incidence of intracranial hemorrhage. Treatment of established VTE is now recommended in this population with many centers favoring low-molecular-weight heparin (LMWH) versus oral warfarin for short- or long-term treatment. We advocate a multimodality approach utilizing compression stockings, intermittent compression devices, and heparin in the perioperative setting as the best proven method to reduce the risk of VTE. In the absence of a strict contraindication to systemic anticoagulation, such as previous intracranial hemorrhage or profound thrombocytopenia, we recommend LMWH in patients with newly diagnosed VTE and a CNS malignancy.

Topics: Antibodies, Monoclonal, Humanized; Anticoagulants; Arginine; Bevacizumab; Central Nervous System Neoplasms; Fondaparinux; Glioblastoma; Glioma; Hemorrhage; Heparin, Low-Molecular-Weight; Hirudins; Humans; Pipecolic Acids; Polysaccharides; Postoperative Complications; Pulmonary Embolism; Recombinant Proteins; Sulfonamides; Thrombocytopenia; Vena Cava Filters; Venous Thromboembolism; Venous Thrombosis; Warfarin

Topics: Abdomen; Aged; Aged, 80 and over; Anticoagulants; Cohort Studies; Female; Gastrointestinal Neoplasms; Gastrointestinal Tract; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors; Veins; Venous Thrombosis; Viscera; Warfarin

Risk factors for post-thrombotic syndrome (PTS) remain poorly understood.. In this multinational multicenter study, we evaluated whether subtherapeutic warfarin anticoagulation was associated with the development of PTS.. Patients with a first unprovoked deep venous thrombosis (DVT) received standard anticoagulation for 5-7 months and were then assessed for PTS. The time in the therapeutic range was calculated from the international normalized ratio (INR) data. An INR below 2, more than 20% of the time, was considered as subtherapeutic anticoagulation.. Of the 349 patients enrolled, 97 (28%) developed PTS. The overall frequency of PTS in patients with subtherapeutic anticoagulation was 33.5%, compared with 21.6% in those with an INR below two for ≤ 20% of the time (P = 0.01). During the first 3 months of therapy, the odds ratio (OR) for developing PTS if a patient had subtherapeutic anticoagulation was 1.78 (95% confidence interval [CI] 1.10-2.87). After adjusting for confounding variables, the OR was 1.84 (95% CI 1.13-3.01). Corresponding ORs for the full period of anticoagulation were 1.83 (95% CI 1.14-3.00) [crude] and 1.88 (95% CI 1.15-3.07) [adjusted].. Subtherapeutic warfarin anticoagulation after a first unprovoked DVT was significantly associated with the development of PTS.

Topics: Adult; Aged; Anticoagulants; Blood Coagulation; Canada; Europe; Female; Humans; International Normalized Ratio; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Postthrombotic Syndrome; Predictive Value of Tests; Prospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Venous Thrombosis; Warfarin

The objective of our present study was to develop a warfarin dosing algorithm for the Omani patients, as performances of warfarin dosing algorithms vary across populations with impact on the daily maintenance dose. We studied the functional polymorphisms of CYP2C9, CYP4F2 and VKORC1 genes to evaluate their impact on the warfarin maintenance dose in an admixed Omani patient cohort with Caucasian, African and Asian ancestries. We observed a 64-fold inter-patient variability for warfarin to achieve stable international normalized ratio in these patients. Univariate analysis revealed that age, gender, weight, atrial fibrillation, deep vein thrombosis/pulmonary embolism and variant genotypes of CYP2C9 and VKORC1 loci were significantly associated with warfarin dose in the studied patient population. However, multiple regression model showed that only the atrial fibrillation, and homozygous CYP2C9 variant genotypes (*2/*3 and *3/*3) and VKORC1 GA and AA genotypes remained significant. A multivariate model, which included demographic, clinical and pharmacogenetic variables together explained 63% of the overall inter-patient variability in warfarin dose requirement in this microgeographically defined, ethnically admixed Omani patient cohort on warfarin. This locally developed model performed much better than the International Warfarin Pharmacogenetics Consortium (IWPC) model as the latter could only explain 34% of the inter-patient variability in Omani patients. VKORC1 3673G>A polymorphism emerged as the single most important predictor of warfarin dose variability, even in this admixed population (partial R(2)=0.45).

Topics: Adult; Aged; Algorithms; Aryl Hydrocarbon Hydroxylases; Atrial Fibrillation; Cytochrome P-450 CYP2C9; Cytochrome P-450 Enzyme System; Cytochrome P450 Family 4; Drug Dosage Calculations; Ethnicity; Female; Genetic Association Studies; Genetic Loci; Genetics, Population; Genotype; Humans; Linear Models; Linkage Disequilibrium; Male; Middle Aged; Mixed Function Oxygenases; Oman; Pharmacogenetics; Polymorphism, Genetic; Prospective Studies; Venous Thrombosis; Vitamin K Epoxide Reductases; Warfarin

Heparin-induced thrombocytopenia (HIT) is a well described side effect of heparin therapy. A 12-year-old boy developed deep-vein thrombosis. Risk factors for initial thrombosis are antiphospholipid syndrome and heterozygous mutation for prothrombin G20210A. Anticoagulant therapy with warfarin for 12 months was effective, but discontinuation of warfarin after 12 months resulted in recurrence of thrombosis. Unfractionated heparin (UFH) was initiated during the acute period, but heparin-induced thrombocytopenia developed. Transition from UFH to fondaparinux resulted in successful anticoagulation for a period of platelet recovery. We report a case of HIT developing with a background of prothrombotic genetic risk factors and antiphospholipid syndrome. This case study highlights several difficulties in pediatric HIT cases.

Topics: Anticoagulants; Antiphospholipid Syndrome; Child; Drug Substitution; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Male; Mutation; Polysaccharides; Prothrombin; Risk Factors; Thrombocytopenia; Venous Thrombosis; Warfarin

Topics: Aged; Anticoagulants; Antifibrinolytic Agents; Hemorrhage; Humans; Kidney Diseases; Male; Rest; Tomography, X-Ray Computed; Treatment Outcome; Venous Thrombosis; Vitamin K 2; Warfarin

To report a probable drug interaction between the antiretroviral TRIO regimen (ritonavir-boosted darunavir, etravirine, and raltegravir) and warfarin in an HIV-infected patient.. In January 2010, a 50-year-old transgender female with HIV infection and recurrent deep vein thrombosis began treatment with the TRIO study regimen. Treatment had been maintained with warfarin for the past 5 years and emtricitabine monotherapy for the preceding 22 months. Emtricitabine was discontinued when the TRIO regimen was started. The mean weekly warfarin dose while the patient was receiving emtricitabine monotherapy was 13.3 mg (95% CI 12.7 to 13.8), with a mean international normalized ratio (INR) of 2.8 (95% CI 2.5 to 3.1). Following the initiation of the TRIO regimen, the mean weekly warfarin dose was increased to 19.3 mg (95% CI 18.5 to 20.1) and was maintained over the ensuing 71 weeks with a mean INR of 2.6 (95% CI 2.2 to 3.0).. Information on the effect of newer antiretrovirals on warfarin metabolism, as well as the collective contribution of combination antiretroviral therapy including multiple agents that may alter warfarin metabolism, is limited. We predicted that warfarin dose requirements would change upon initiation of the TRIO regimen. Given the variability in INR that can occur with chronic warfarin treatment, weekly warfarin doses were averaged during emtricitabine monotherapy (90 weeks) and TRIO regimen (71 weeks) periods. Mean weekly warfarin doses increased by 45% (p < 0.001) following initiation of the TRIO regimen. Mean INR results for the 2 time periods were not significantly different, demonstrating that stable anticoagulation was maintained. The Horn drug interaction probability scale score to assess causation indicated a probable interaction.. An increased weekly warfarin dose requirement is predicted when warfarin is used concurrently with the antiretroviral TRIO regimen. Increased INR monitoring is prudent when the combination is administered.

Topics: Anticoagulants; Darunavir; Drug Interactions; Female; HIV Infections; HIV Protease Inhibitors; Humans; International Normalized Ratio; Middle Aged; Nitriles; Pyridazines; Pyrimidines; Reverse Transcriptase Inhibitors; Sulfonamides; Venous Thrombosis; Warfarin

Venous complications in patients with acute pancreatitis typically occur as a form of splenic, portal, or superior mesenteric vein thrombosis and have been detected more frequently in recent reports. Although a well-organized protocol for the treatment of venous thrombosis has not been established, anticoagulation therapy is commonly recommended. A 73-year-old man was diagnosed with acute progressive portal vein thrombosis associated with acute pancreatitis. After one month of anticoagulation therapy, the patient developed severe hematemesis. With endoscopy and an abdominal computed tomography scan, hemorrhages in the pancreatic pseudocyst, which was ruptured into the duodenal bulb, were confirmed. After conservative treatment, the patient was stabilized. While the rupture of a pseudocyst into the surrounding viscera is a well-known phenomenon, spontaneous rupture into the duodenum is rare. Moreover, no reports of upper gastrointestinal bleeding caused by pseudocyst rupture in patients under anticoagulation therapy for venous thrombosis associated with acute pancreatitis have been published. Herein, we report a unique case of massive upper gastrointestinal bleeding due to pancreatic pseudocyst rupture into the duodenum, which developed during anticoagulation therapy for portal vein thrombosis associated with acute pancreatitis.

Topics: Acute Disease; Aged; Anticoagulants; Duodenal Diseases; Gastrointestinal Hemorrhage; Hematemesis; Humans; Intestinal Fistula; Male; Pancreatic Pseudocyst; Pancreatitis, Alcoholic; Portal Vein; Risk Factors; Rupture, Spontaneous; Tomography, X-Ray Computed; Treatment Outcome; Venous Thrombosis; Warfarin

We report a case of an incidental finding of congenital absence of the intrahepatic segment of the inferior vena cava (IVC) complicated by extensive bilateral deep venous thrombosis (DVT) with significant oedema following a long-distance road trip. Initially the patient failed treatment with standard anticoagulation therapy with enoxaparin and warfarin. However, he has responded to the new oral antifactor-Xa anticoagulant (rivaroxaban). Within a few days, rivaroxaban improved the oedema and DVT. The significant features of this case are the unusual presentation, the poor response to initial standard anticoagulation therapy and the beneficial outcomes when managed with the novel new anticoagulant. The patient has continued the new treatment regularly for the last 12 months with good toleration and without side effects. This report presents the findings, management and outcomes in a case of extensive bilateral DVT in a previously healthy young man who was found to have a congenital short IVC.

Topics: Adult; Anticoagulants; Edema; Enoxaparin; Humans; Iliac Vein; Incidental Findings; Male; Morpholines; Rivaroxaban; Thiophenes; Tomography, X-Ray Computed; Travel; Vena Cava, Inferior; Venous Thrombosis; Warfarin; Young Adult

An extrahepatic arterioportal fistula (APF) involving the gastroduodenal artery and superior mesenteric vein is rare and mostly results from iatrogenic injuries. The clinical symptoms associated with APFs may include abdominal pain, gastrointestinal bleeding, ascites, nausea, vomiting, diarrhea, or even congestive heart failure. We present the case of a 70-year-old man who presented with chronic abdominal pain and gastrointestinal bleeding secondary to APF and portal vein thrombosis. The endovascular embolization of APF was accomplished successfully, and symptoms of portal hypertension resolved immediately after intervention. Unfortunately, the patient did not respond well to anticoagulation therapy with warfarin. Therefore, the patient underwent implantation of a transjugular intrahepatic portosystemic shunt, and the complications of portal hypertension resolved. In conclusion, the embolization of APF is technically feasible and effective and can be considered the first-choice therapy in selected patients.

Topics: Abdominal Pain; Aged; Aneurysm; Anticoagulants; Arteriovenous Fistula; Duodenum; Embolization, Therapeutic; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Male; Mesenteric Veins; Phlebography; Portal Vein; Portasystemic Shunt, Surgical; Tomography, X-Ray Computed; Treatment Outcome; Venous Thrombosis; Warfarin

The main objective of this study was to compare clinical and laboratory data obtained from patients with primary antiphospholipid syndrome (PAPS) with and without Sneddon's syndrome (SS). A transverse study with 54 (85.2% female) PAPS patients (Sapporo criteria) was performed. Demographic, drug use, and antiphospholipid antibodies data were evaluated, as well as clinical and laboratory findings of SS. Patients were subdivided into one of two groups: PAPS with SS and PAPS without SS. Both groups were similar with respect to age (p = 0.05), gender (p = 0.34), race (p = 0.31), weight (p = 0.93), height (p = 0.27), and body mass index (p = 0.75); however, the SS group exhibited higher disease duration (96.0 ± 54.9 vs. 55.2 ± 52.0 months, p = 0.01). By definition, all PAPS with SS patients suffer from stroke, an arterial event; the frequency of stroke events (28.5 vs. 7.5%, p = 0.04), as well as of limb ischemia (100 vs. 30.0%, p < 0.0001) was higher in this group than in the PAPS without SS group. On the other hand, patients in the PAPS without SS group had more venous events, such as deep venous thrombosis, than those in the PAPS with SS group (80.0 vs. 50.0%, p = 0.03). In conclusion, an understanding of the relationship between APS and SS is important in order to identify a subgroup for which more rigorous accompaniment and therapy may be necessary.

Topics: Adult; Antiphospholipid Syndrome; Aspirin; Autoantibodies; Chloroquine; Female; Glucocorticoids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Prevalence; Sneddon Syndrome; Treatment Outcome; Venous Thrombosis; Warfarin

A 39-year-old Afro-Caribbean man with Crohn disease with recurrent deep vein thromboses and pulmonary emboli was commenced on lifelong warfarin treatment. The patient required high-dose warfarin (>140 mg/wk), which increased further during azathioprine treatment. Cessation of azathioprine resulted in an increase in the international normalized ratio (INR). Mutation analysis identified a Val66Met substitution in vitamin K epoxide reductase complex subunit 1 (VKORC1), consistent with severe warfarin resistance. This report is the first presentation where the patient had a defined hereditary resistance to warfarin, which was aggravated by concomitant azathioprine. It is important for clinicians to be aware of the interaction between warfarin and azathioprine, to monitor clinical response closely, and to manage the doses of both drugs accordingly.

Topics: Adult; Amino Acid Substitution; Anticoagulants; Antimetabolites; Azathioprine; Crohn Disease; Drug Resistance; Humans; Male; Mixed Function Oxygenases; Mutation, Missense; Venous Thrombosis; Vitamin K Epoxide Reductases; Warfarin

We describe a 17-year-old Caucasian adolescent with ulcerative colitis who presented with cerebral venous sinus thrombosis. Laboratory investigation revealed low protein S levels. With successful management the patient remained without neurologic sequalae. Although there may be an association between ulcerative colitis and cerebral venous sinus thrombosis, the exact pathophysiologic mechanism remains unknown.

Topics: Adolescent; Anticoagulants; Colitis, Ulcerative; Humans; Intracranial Thrombosis; Magnetic Resonance Imaging; Male; Protein S; Venous Thrombosis; Warfarin

Bilateral optic neuritis is an extremely uncommon complication of pediatric systemic lupus erythematosus and sporadic cases are reported in the literature. The authors describe an 11-yr-old girl who presented with fever and progressively increasing pallor for 4 months, headache for 7 days, severe anemia and hepatosplenomegaly. Soon after admission, she developed rapid deterioration of vision, worsening to no perception of light with afferent pupillary defect. Fundoscopy showed bilateral optic neuritis. Investigations revealed autoimmune hemolytic anemia and thrombocytopenia. Anti-dsDNA and anti-phospholipid antibodies were positive. Magnetic resonance venography showed multiple thrombi in the cerebral venous sinuses, for which anticoagulant therapy was initiated. She was managed with intravenous methylprednisolone followed by cyclophosphamide pulse therapy for 6 months along with oral prednisolone. Though she went into remission, visual outcome has been dismal, with development of bilateral optic atrophy, and absence of perception of light.

Topics: Anemia, Hemolytic, Autoimmune; Anti-Inflammatory Agents; Anticoagulants; Antiphospholipid Syndrome; Cerebral Veins; Child; Cyclophosphamide; Female; Heparin; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Methylprednisolone; Optic Neuritis; Prednisolone; Thrombocytopenia; Treatment Outcome; Venous Thrombosis; Warfarin

Anticoagulation consultations provided by a pharmacist-staffed inpatient service, similar to the experience reported in outpatient anticoagulation clinics, can potentially improve anticoagulation control and outcomes. At Tan Tock Seng Hospital, a 1200-bed acute care teaching hospital in Singapore, pharmacist-managed anticoagulation clinics have been in place since 1997. Pharmacist-managed services were extended to inpatient consultations in anticoagulation management from April 2006. Our objective was to assess the effect of implementing a pharmacist-managed inpatient anticoagulation service.. This was a single-centre cohort study. Baseline data from 1 January 2006 to 31 March 2006 were collected and compared with post-implementation data from 1 April 2006 to 31 March 2007. Patients newly started on warfarin for deep vein thrombosis, pulmonary embolism or atrial fibrillation in general medicine and surgery departments were included. The three endpoints were as follows: (i) percentage of international normalized ratios (INRs) achieving therapeutic range within 5 days, (ii) INRs more than 4 during titration and (iii) subtherapeutic INRs on discharge.. A total of 26 patients in the control period were compared with 144 patients who had received dosing consultations by a pharmacist during the initiation of warfarin. The provision of pharmacist consult resulted in 88% compared to 38% (P < 0·001) of INR values achieving therapeutic range within 5 days. There was a reduction in INR values of more than 4 during titration from 27% to 2% (P < 0·001), and subtherapeutic INR values on discharge without low molecular weight heparin from 15% to 0% (P < 0·001). The mean time to therapeutic INR was reduced from 6·5 to 3·9 days (P < 0·001) and mean length of stay after initiation of warfarin from 11 to 7·7 days (P = 0·004).. Inpatient anticoagulation care and outcomes were significantly improved by a pharmacist-managed anticoagulation service. The time to therapeutic INR was achieved appropriately and efficiently without compromising patient's safety.

Topics: Adult; Aged; Aged, 80 and over; Ambulatory Care Facilities; Anticoagulants; Atrial Fibrillation; Cohort Studies; Dose-Response Relationship, Drug; Drug Monitoring; Female; Heparin, Low-Molecular-Weight; Hospital Departments; Hospitalization; Hospitals, Teaching; Humans; Inpatients; International Normalized Ratio; Male; Middle Aged; Nomograms; Patient Discharge; Pharmaceutical Services; Pharmacists; Pulmonary Embolism; Referral and Consultation; Retrospective Studies; Sample Size; Venous Thrombosis; Warfarin; Workforce

Warfarin exhibits wide interpatient variability in dosing requirements. Recent studies have shown a novel polymorphism (rs2108622, V433M) in the CYP4F2 gene to be associated with variability in warfarin requirements in Caucasians. The purpose of this study was to evaluate the impact of rs2108622 on warfarin dose requirements in the Asian population. The mean warfarin dose was found to be significantly lower in patients carrying homozygous wild-type allele CC when compared with patients carrying variant alleles CT and TT (CC vs CT+TT: 3.0 mg/day vs 3.75 mg/day, p = 0.033). In patients harboring VKORC1 diplotypes associated with low warfarin requirements, a linear regression model which included age, weight, CYP2C9 and CYP4F2 variants accounted for 38% of the variability in warfarin dose. Approximately 11% of the dose variation was explained by CYP4F2 rs2108622 (p = 0.004). The influence of rs2108622 in patients harboring VKORC1 diplotypes associated with high warfarin requirements was not significant. This study suggests that CYP4F2 rs2108622 may significantly affect warfarin dose requirements in carriers of VKORC1 low-dose-associated diplotypes.

Topics: Adult; Aged; Aged, 80 and over; Alleles; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Asian People; Atrial Fibrillation; Cytochrome P-450 CYP2C9; Cytochrome P-450 Enzyme System; Cytochrome P450 Family 4; Dose-Response Relationship, Drug; Female; Genotype; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Pharmacogenetics; Polymorphism, Single Nucleotide; Pulmonary Embolism; Venous Thrombosis; Warfarin

To report a case of increased international normalized ratio (INR) in a patient established on warfarin therapy who was then initiated on atovaquone therapy.. A 53-year-old African American male with HIV was prescribed warfarin 5 mg/day for 12 months after diagnosis of idiopathic deep vein thrombosis and bilateral pulmonary emboli (target INR 2.5 [range 2.0-3.0]). The patient required Pneumocystis jiroveci pneumonia prophylaxis and was prescribed atovaquone instead of trimethoprim/sulfamethoxazole therapy because of the latter drug's known interaction with warfarin. The patient's INR rose by greater than 50% (from 2.3 to 3.5) after 7 days of concomitant warfarin and atovaquone. In response, the patient's total weekly warfarin dose was decreased by 5%. Eight days later, the patient's INR was still supratherapeutic at 3.1. Approximately 4 weeks later, his INR was 4.2. One dose of warfarin was withheld and then the total weekly warfarin dosage was decreased by another 10%. Eight days later, the patient discontinued atovaquone therapy but continued on warfarin as prescribed. One day after atovaquone discontinuation, his INR decreased to 1.7. Due to this subtherapeutic INR level, 8 days later the total weekly warfarin dose was increased by 5%. Although a follow-up appointment was scheduled, no further INR values were obtained because the patient's 12-month course of anticoagulation therapy was completed and warfarin was discontinued. The patient did not report any adverse effects or signs or symptoms of hemorrhage while his INR values were supratherapeutic.. Warfarin's potential for interactions with other highly protein-bound drugs, such as atovaquone, can result in displacement from protein binding sites and increased serum concentrations of warfarin. Based on a search of MEDLINE/PubMed, International Pharmaceutical Abstracts, and the Food and Drug Administration MedWatch Adverse Event Reporting Program (all through July 31, 2010), no cases were found of an interaction between atovaquone and warfarin. The Horn Drug Interaction Probability Scale calculated this to be a probable interaction between warfarin and atovaquone.. Although current medication references do not report an interaction between atovaquone and warfarin, knowledge of their pharmacodynamic properties can enable practitioners to anticipate the consequences of a possible transient increase in warfarin serum concentration, such as that seen in our patient, when given concomitantly.

Topics: AIDS-Related Opportunistic Infections; Anticoagulants; Antifungal Agents; Atovaquone; Drug Interactions; Drug Monitoring; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Pulmonary Embolism; Risk Factors; Venous Thrombosis; Vitamin K; Warfarin

Topics: Accidents, Traffic; Anticoagulants; Female; Heparin; Humans; Middle Aged; Phlebography; Tomography, X-Ray Computed; Treatment Outcome; Vascular System Injuries; Vena Cava, Inferior; Venous Thrombosis; Warfarin

Thrombophilic disorders that predispose patients to develop blood clots can be life-threatening and result in a large economic burden on healthcare expenditures. Venous Thromboembolism(VTE) (deep vein thrombosis and pulmonary embolism) are the third leading cause of death in the United States. Protein C deficiency is a common thrombophilic condition that affects an estimated 1 in 400 Americans. Zymogen Protein C (ZPC) is the precursor to Activated Protein C (APC), a pivotal endogenous anticoagulant in human blood. Patients with protein C deficiency who have roughly half the normal level of protein C are estimated to be at 10-fold increased risk of VTE. We describe the use of protein C concentrate (Ceprotin®, Baxter, Deerfield, IL) in a patient with protein C deficiency and with a previous pulmonary embolism who developed a life-threatening gastrointestinal bleed after polypectomy. The patient is a 75-year-old male at very high risk for deep vein thrombosis and possible lung emboli. He has heterozygous Protein C deficiency (50%) and heterozygosity for the prothrombin gene G20210A mutation. During a routine colonoscopy, a large 3 cm cecal polyp was identified and resected. Eight days post-procedure while performing abdominal exercise he developed a life-threatening GI bleed originating from the polypectomy site as his warfarin was becoming therapeutic on a Low Molecular Weight Heparin (LMWH) periprocedural bridge. The patient's warfarin was reversed with vitamin K, and LMWH and warfarin were discontinued. To prevent thrombosis, he was started on ZPC until anticoagulation could be safely restarted. During endoscopy, the bleeding site was treated with an injection of 1:10,000 dilution of epinephrine, followed by cauterization and placement of endoclips (4 metal staples). Three days after endoscopic repair LMWH was restarted with warfarin. Sixteen months post-bleed, the patient remains on life-long warfarin without further episodes of bleeding or thrombosis. Zymogen Protein C concentrate (Ceprotin®, Baxter Deerfield, IL) should be strongly considered for peri-procedural management of any patient with protein C deficiency and previous thromboembolism.

Topics: Aged; Anticoagulants; Blood Coagulation; Enzyme Precursors; Gastrointestinal Diseases; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Protein C; Protein C Deficiency; Pulmonary Embolism; Secretory Vesicles; Venous Thrombosis; Warfarin

To assess the effectiveness and clinical outcomes of catheter-directed thrombolysis in patients with atresia of the inferior vena cava (IVC) and acute iliofemoral deep vein thrombosis (DVT).. From 2001 to 2009, 11 patients (median age, 32 y) with atresia of the IVC and acute iliofemoral DVT in 13 limbs were admitted for catheter-directed thrombolysis. Through a multiple-side hole catheter inserted in the popliteal vein, continuous pulse-spray infusion of tissue plasminogen activator and heparin was performed. Thrombolysis was terminated when all thrombus was resolved and venous outflow through the paravertebral collateral vessels was achieved. After thrombolysis, all patients received lifelong anticoagulation and compression stockings and were followed up at regular intervals.. Ultrasound or computed tomography revealed absence of the suprarenal segment of the IVC in two patients, and nine were diagnosed with absence of the infrarenal segment of the IVC. Median treatment time was 58 hours (range, 42-95 h). No deaths or serious complications occurred. Overall, complications were observed in four patients, one of whom required blood transfusion. Three patients were diagnosed with thrombophilia. Median follow-up was 37 months (range, 51 d to 96 mo). All patients had patent deep veins and one developed reflux in the popliteal fossa after 4 years. No thromboembolic recurrences were observed during follow-up.. Catheter-directed thrombolysis of patients with acute iliofemoral DVT and atresia of the IVC is a viable treatment option, as reasonable clinical outcomes can be obtained.

Topics: Acute Disease; Adolescent; Adult; Anticoagulants; Catheterization, Peripheral; Denmark; Female; Femoral Vein; Fibrinolytic Agents; Heparin; Humans; Iliac Vein; Male; Middle Aged; Phlebography; Popliteal Vein; Retrospective Studies; Stockings, Compression; Thrombolytic Therapy; Time Factors; Tissue Plasminogen Activator; Tomography, X-Ray Computed; Treatment Outcome; Ultrasonography; Vascular Malformations; Vena Cava, Inferior; Venous Thrombosis; Warfarin; Young Adult

A retrospective cohort study of 2,218 patients with deep vein thrombosis or pulmonary embolism during a 25-year period from 1966-1990 in Minnesota showed an annual incidence of venous thromboembolism of 117 per 100,000 (deep vein thrombosis, 48 per 100,000; pulmonary embolism, 69 per 100,000). Higher rates were found in males than females (130 vs 110 per 100,000, respectively) after adjusting for age. Early diagnosis and appropriate treatment of DVT and PE have been shown to significantly reduce mortality and morbidity. Risk factors for venous thromboembolism include alterations in blood flow (surgery, injury or long-distance air travel, pregnancy, obesity), hypercoagulability (factor V Leiden mutation, prothrombin mutation, protein C deficiency, protein S deficiency, antithrombin deficiency, hyperhomocysteinemia, antiphospholipid syndrome, nephrotic syndrome, paroxysmal nocturnal hemoglobinuria) and vessel wall abnormalities. Eighty percent of deep venous thrombosis resolves spontaneously and less than 15% embolize to pulmonary arteries.

Topics: Anticoagulants; Blood Coagulation; Clinical Competence; Critical Pathways; Diagnosis, Differential; Drug Dosage Calculations; Enoxaparin; Female; Humans; International Normalized Ratio; Male; Middle Aged; Pulmonary Embolism; Radiography; Risk Factors; Thrombophilia; Treatment Outcome; Venous Thrombosis; Warfarin

As both cancer and major orthopaedic surgery are risk factors for venous thromboembolism, patients undergoing lower-extremity oncologic endoprosthetic arthroplasty for neoplastic processes are at substantial risk of the development of symptomatic venous thromboembolism. Therefore, the primary purpose of this study was to determine the incidence of symptomatic venous thromboembolism in patients undergoing lower-extremity oncologic endoprosthetic arthroplasty. Secondary purposes were to assess whether chemoprophylaxis influenced the incidence of venous thromboembolism, surgical complications, or the incidence of local sarcoma recurrence. We also sought to determine whether any known risk factors for venous thromboembolism could be identified in this patient population.. We performed a retrospective comparative review of 423 patients who had undergone mega-endoprosthetic reconstruction following cancer resection. Univariate analysis was used to assess the association between chemoprophylaxis and the incidence of venous thromboembolism, to postulate the surgical complications associated with chemoprophylaxis, and to assess the rate of recurrence of local sarcoma as well the association between risk factors and venous thromboembolism.. Seventeen patients (4.0%) (95% confidence interval: 2.5% to 6.3%) had a venous thromboembolic event, ten with deep venous thrombosis and seven with nonfatal pulmonary embolism. Risk factors and chemoprophylactic regimens were not statistically associated with the occurrence of venous thromboembolism.. The incidence of symptomatic venous thromboembolism in our group of cancer patients who underwent lower-extremity endoprosthetic arthroplasty was lower than anticipated. A significant difference was not identified between the use of any or no chemoprophylactic agent and the incidence of venous thromboembolism or complication rates. No risk factors were associated with the incidence of symptomatic venous thromboembolism.

Topics: Adolescent; Adult; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Bone Neoplasms; Femoral Neoplasms; Heparin, Low-Molecular-Weight; Humans; Limb Salvage; Neoplasm Recurrence, Local; Pulmonary Embolism; Tibia; Venous Thromboembolism; Venous Thrombosis; Warfarin

Topics: Acute Disease; Antithrombins; Cardiology; False Positive Reactions; Guidelines as Topic; Humans; Protein C; Protein S; Reproducibility of Results; Venous Thrombosis; Warfarin

In anticoagulation treatment with warfarin, the risk of thrombo-embolic events must be weighed against the risk of bleeding. Time in therapeutic range (TTR) is an important tool to assess the quality of anticoagulation treatment, and has been shown to correlate with less bleeding and thrombo-embolic complications. AuriculA, the Swedish national quality registry for atrial fibrillation and anticoagulation, is used for follow-up and dosage control of warfarin. This is the first report of TTR in AuriculA and, in a subgroup of two centres, bleeding and thrombo-embolic complications during 2008.. Prothrombin complex (International normalized ratio) values from 18 391 patients in 67 different centres were analysed. The mean (SD) age was 70 (12) years. The main indications for warfarin treatment were: atrial fibrillation (64%), venous thromboembolism (19%), and heart valve dysfunction (13%). Time in therapeutic range for all patients was 76.2%. The mean weekly dose of warfarin decreased with age and TTR increased with age. In 4273 patients from two centres in AuriculA, the frequency of major bleedings and venous/arterial thrombo-embolism were 2.6 and 1.7% and for atrial fibrillation, 2.6 and 1.4%, per treatment year, respectively. A correlation between age and the risk of major bleeding (P< 0.001), but not thrombo-embolic complications (P= 0.147), was seen.. Compared with prospective randomized trials of warfarin treatment, TTR in the AuriculA population was higher. Complications were low, probably due to the organization of anticoagulation treatment in Sweden. Use of the AuriculA dosing programme could have contributed to the results by keeping dosing regimens consistent over all centres.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Heart Valve Diseases; Hemorrhage; Humans; International Normalized Ratio; Middle Aged; Prospective Studies; Registries; Sweden; Thromboembolism; Venous Thrombosis; Warfarin

Topics: Accidental Falls; Acute Disease; Anticoagulants; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Male; Subclavian Vein; Venous Thrombosis; Warfarin; Young Adult

Topics: Adult; Anticoagulants; Humans; Male; Protein S Deficiency; Pulmonary Embolism; Tomography, Spiral Computed; Venous Thrombosis; Warfarin

Topics: Adult; Anticoagulants; Duodenal Diseases; Duodenoscopy; Duodenum; Endosonography; Female; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Portal Vein; Varicose Veins; Venous Thrombosis; Warfarin

Topics: Acute Kidney Injury; Anti-Inflammatory Agents; Anticoagulants; Biopsy; Cyclophosphamide; Diagnosis, Differential; Female; Heparin, Low-Molecular-Weight; Humans; Immunoglobulin A; Immunosuppressive Agents; Kidney Tubules; Methylprednisolone; Middle Aged; Necrosis; Nephrotic Syndrome; Prednisone; Radiography; Renal Veins; Venous Thrombosis; Warfarin

Pregnant women have a fourfold to fivefold increased risk of thromboembolism compared with nonpregnant women (1, 2). Approximately 80% of thromboembolic events in pregnancy are venous (3), with a prevalence of 0.5–2.0 per 1,000 pregnant women (4–9). Venous thromboembolism, including pulmonary embolism, accounts for 1.1 deaths per 100,000 deliveries (3), or 9 % of all maternal deaths in the United States (10). In the developing world, the leading cause of maternal death is hemorrhage (11); however, in developed nations, where hemorrhage is more often successfully treated and prevented, thromboembolic disease is one of the leading causes of death (12). The prevalence and severity of this condition during pregnancy and the peripartum period warrant special consideration of management and therapy. Such therapy includes the treatment of acute thrombotic events and prophylaxis for those at increased risk of thrombotic events. The purpose of this document is to provide information regarding the risk factors, diagnosis, management, and prevention of thromboembolism, particularly venous thromboembolism in pregnancy.

Topics: Anticoagulants; Blood Coagulation; Contraceptives, Oral; Contraindications; Drug Hypersensitivity; Drug Monitoring; Female; Heparin; Heparin, Low-Molecular-Weight; Humans; Patient Selection; Postpartum Period; Pregnancy; Pregnancy Complications, Cardiovascular; Pulmonary Embolism; Risk Factors; Thromboembolism; Venous Thrombosis; Warfarin

Topics: Aged; Anticoagulants; Fondaparinux; Humans; Leg; Male; Polysaccharides; Stroke; Stroke Rehabilitation; Venous Thrombosis; Warfarin

To report 2 cases of a probable interaction between cisplatin and warfarin.. Two cases of transient elevation of international normalized ratio (INR) during irinotecan (60 mg/m2 on days 1, 8, and 15) plus cisplatin (60 mg/m2 on day 1) chemotherapy with concomitant warfarin are presented. In both cases, warfarin dosages were stable at the therapeutic target range prior to initiation of chemotherapy. Granisetron hydrochloride (3 mg on days 1, 8, and 15) and dexamethasone (13.2 mg on day 1 and 6.6 mg on days 2, 3, 8, and 15) were used prior to irinotecan administration in both patients. In addition, aprepitant was administered to both patients for 3-5 days with cisplatin. One of these patients also received aprepitant with irinotecan on days 8 and 15. During chemotherapy, INR was transiently elevated almost 1.5-fold over baseline level on day 3. This variation did not occur in subsequent irinotecan cycles on days 8 and 15. The timing of these increases was similar in each of the cycles.. Cisplatin was the common drug in the cases presented and therefore could be related to the INR elevations. To our knowledge, these are the first reports of an interaction between warfarin and irinotecan-cisplatin chemotherapy, but reports of a similar interaction with chemotherapy including platinum derivatives exist. Use of the Horn Drug Interaction Probability Scale indicated a probable interaction between warfarin and cisplatin.. Cisplatin might affect the anticoagulation function of warfarin. Careful INR monitoring is necessary during antineoplastic chemotherapy with cisplatin in patients taking warfarin.

Topics: Anticoagulants; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Drug Interactions; Drug Monitoring; Female; Genital Neoplasms, Female; Humans; International Normalized Ratio; Irinotecan; Middle Aged; Thromboembolism; Treatment Outcome; Venous Thrombosis; Warfarin

To test recommended anticoagulation measures as predictors of 180-day venous thromboembolism (VTE) recurrence, we identified all Olmsted County, MN residents with incident VTE over the 14-year period of 1984-1997, and followed each case (N = 1166) forward in time for VTE recurrence. We tested the activated partial thromboplastin time (APTT), international normalized ratio (INR), and other measures of heparin and warfarin anticoagulation as predictors of VTE recurrence while controlling for baseline and time-dependent characteristics using Cox proportional hazards modeling. Overall, 1026 (88%) and 989 (85%) patients received heparin and warfarin, respectively, and 85 (8%) developed VTE recurrence. In multivariable analyses, increasing proportions of time on heparin with an APTT ≥ 0.2 anti-X(a) U/mL and on warfarin with an INR ≥ 2.0 were associated with significant reductions in VTE recurrence, while the hazard with active cancer was significantly increased. Time from VTE onset to heparin start, duration of overlapping heparin and warfarin, and inferior vena cava (IVC) filter placement were not independent predictors of recurrence. At a heparin dose ≥ 30 000 U/d, the median proportion of time with an APTT ≥ 0.2 anti-X(a) U/mL was 92%, suggesting that routine APTT monitoring and heparin dose adjustment may be unnecessary. In summary, lower-intensity heparin and standard-intensity warfarin anticoagulation are effective in preventing VTE recurrence.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Biomarkers, Pharmacological; Blood Coagulation; Child; Child, Preschool; Cohort Studies; Dose-Response Relationship, Drug; Female; Heparin; Humans; Infant; Infant, Newborn; Male; Middle Aged; Population; Prognosis; Pulmonary Embolism; Recurrence; Venous Thrombosis; Warfarin; Young Adult

To evaluate the impact of stopping anticoagulant medications prior to transurethral resection of the prostate on peri-operative cardiovascular complications.. Retrospective series (305 patients) undergoing TURP at a tertiary hospital between 2006 and 2010. All men were evaluated in preadmission clinics with defined protocols, with a low threshold for cardiovascular investigation. Incidence of postoperative bleeding and cardiovascular and cerebrovascular events was determined for 3 patient cohorts: group A--where anticoagulants were ceased preoperatively; group B--who were not receiving any anticoagulants; and group C--who underwent TURP while taking aspirin.. Of 305 patients, 194 (64%) did not receive anticoagulation therapy, 108 (35%) stopped receiving anticoagulation therapy pre-TURP, and 3 (0.98%) underwent TURP while taking aspirin. Anticoagulants used were aspirin (22.6%), warfarin (4.9%), antiplatelets (4.9%), and combination treatments (3.9%). Incidence of postoperative hemorrhage (early and delayed) was not significant (P = .69) between group A (10/108) and group B (7/194). Transfusion rate was 0.6% (2/305). Overall incidence of cardiovascular events was 0.98% (group A, n = 1 vs group B, n = 2), and incidence of deep vein thrombosis (0.32%; group A, n = 0 vs group B, n = 1) was not statistically significant (P = .30 and P = .37, respectively). Overall incidence of cerebrovascular events (0.65%; group A, n = 1 vs group B, n = 1) was not significant (P = 1.00). There were no deaths.. Men who have discontinue anticoagulation therapy before TURP do not appear to have a higher incidence of cardiovascular or cerebrovascular events, or bleeding-associated morbidity. It is possible that the morbidity attributed to discontinuing anticoagulation in this population may be overemphasized. Larger prospective studies are needed to better evaluate this clinical problem.

Topics: Aged; Angina Pectoris; Anticoagulants; Arrhythmias, Cardiac; Aspirin; Blood Transfusion; Humans; Ischemic Attack, Transient; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Postoperative Hemorrhage; Preoperative Care; Prostatectomy; Retrospective Studies; Stroke; Venous Thrombosis; Warfarin

Darexaban (YM150) is an oral factor Xa inhibitor developed for the prophylaxis of venous and arterial thromboembolic disease. This study was conducted to investigate the biochemical and pharmacological profiles of darexaban and its active metabolite darexaban glucuronide (YM-222714), which predominantly determines the antithrombotic effect after oral administration of darexaban. In vitro activity was evaluated by enzyme and coagulation assays, and a prothrombin activation assay using reconstituted prothrombinase or whole blood clot. In vivo effects were examined in venous thrombosis, arterio-venous (A-V) shunt thrombosis, and bleeding models in rats. Both darexaban and darexaban glucuronide competitively and selectively inhibited human factor Xa with Ki values of 0.031 and 0.020 μM, respectively. They showed anticoagulant activity in human plasma, with doubling concentrations of darexaban and darexaban glucuronide for prothrombin time of 1.2 and 0.95 μM, respectively. Anticoagulant activity was independent of antithrombin. Darexaban and darexaban glucuronide inhibited the prothrombin activation induced by prothrombinase complex or whole blood clot with similar potency to free factor Xa. In contrast, prothrombinase- and clot-induced prothrombin activation were resistant to inhibition by enoxaparin. In venous and A-V shunt thrombosis models in rats, darexaban strongly suppressed thrombus formation without affecting bleeding time, with ID₅₀ values of 0.97 and 16.7 mg/kg, respectively. Warfarin also suppressed thrombus formation in these models, but caused a marked prolongation of bleeding time at antithrombotic dose. In conclusion, darexaban is a selective and direct factor Xa inhibitor and a promising oral anticoagulant for the prophylaxis and treatment of thromboembolic diseases.

Topics: Administration, Oral; Animals; Anticoagulants; Azepines; Benzamides; Bleeding Time; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Enoxaparin; Factor Xa Inhibitors; Glucuronides; Humans; Macaca fascicularis; Male; Mice; Mice, Inbred ICR; Prothrombin Time; Rabbits; Rats; Rats, Sprague-Dawley; Thrombosis; Venous Thrombosis; Warfarin

Warfarin is a key element in therapy for atrial fibrillation, deep venous thrombosis (DVT), stroke (cerebrovascular accident) and cardiac valve replacement. Often, patients' warfarin blood levels are not tightly controlled with regard to accepted therapeutic ranges, by virtue of the drug's unpredictable nature.. The authors searched 16,017 active clinical charts for active patients of record from the three campuses of the School of Dentistry, Marquette University (MU), Milwaukee, for the years 2009 and 2010. Dental records of 315 patients contained entries including "INR," the abbreviation for the term "international normalized ratio." Only 247 of those records contained an indication of whether the patient's INR values were within therapeutic range. The authors found that 1.96 percent of the total MU dental clinic patient population had a history of warfarin use.. When the authors compared the INR values for patients with diagnoses of atrial fibrillation, DVT, stroke and cardiac valve replacement, they found that INR values for 107 of the 247 patients (43.3 percent) were not within therapeutic range for the respective diagnoses. For example, only 50 percent of the patients being treated for atrial fibrillation presented themselves for surgical dental treatment while their INR values were in tight control.. The INR values for a significant number of dental patients are not within the therapeutic range for their medical conditions. These patients need to seek follow-up care from their medical care providers.. Screening for INR in the dental office-especially before invasive dental treatment such as periodontal surgery, tooth extraction and dental implant placement-can help prevent postoperative complications. It also can aid the clinician in evaluating whether a patient's INR is within therapeutic range and, subsequently, whether the patient's physician needs to adjust the warfarin dosage.

Topics: Anticoagulants; Atrial Fibrillation; Dental Care for Chronically Ill; Heart Valve Prosthesis; Hemorrhage; Humans; International Normalized Ratio; Oral Surgical Procedures; Point-of-Care Systems; Reagent Strips; Referral and Consultation; Retrospective Studies; Stroke; Thromboembolism; Venous Thrombosis; Warfarin

Following the landmark study by Barritt and Jordan in 1960, in which patients with venous thromboembolism (VTE) were randomized to no treatment or a combination of heparin and warfarin, antithrombotic therapy for this disease became widely accepted. This study was stopped prematurely because half of the non-treated patients had recurrent pulmonary embolism (PE), or died. It was subsequently found that after a VTE, patients given warfarin alone had a 3-4-fold higher incidence of recurrent VTE than patients given both heparin and warfarin. Since the 1990 s, standard therapy for VTE has comprised an initial 5-7 day course of parenteral anticoagulant plus warfarin continued for at least 3 months. Recently, several orally active small molecules have been evaluated in the treatment of VTE, including a direct thrombin inhibitor and direct Factor Xa inhibitors. Other novel oral agents are also in development for VTE treatment. Although the DTI ximelagatran, the first oral agent to be introduced since warfarin was withdrawn from the market in Europe because of hepatotoxicity, evidence from clinical trial evaluating other single target-specific oral agents in the treatment of VTE is encouraging. It is therefore likely that use of warfarin in the treatment and secondary prevention of VTE will decrease should these novel oral agents be introduced for these indications. Additionally, there will be less distinction between initial and long-term therapy, and a great majority of patients will be treated on an outpatient basis for prolonged periods of time. Recently these expectations were fulfilled by the results of two Phase III studies in patients with VTE. The Recover I study indicated that Dabigatran (150 mg b.d.) following an initial course of LMWH was non-inferior to the standard treatment of LMWH plus warfarin, with also a similar safety profile. The Einstein DVT study revealed that Rivaroxaban as a single agent can safely replace the standard treatment in patients with DVT. Taken together these studies and a few others that have or are about to be completed will indeed introduce a paradigm shift in the way patients with VTE will be treated.

Topics: Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Heparin; Humans; Morpholines; Pulmonary Embolism; Rivaroxaban; Secondary Prevention; Thiophenes; Venous Thrombosis; Warfarin

Hypothyroidism is a procoagulant state; hypothyroid females have greater risk of DVT than hypothyroid males. We present a case of primary hypothyroidism who presented with euvolemic hyponatremia and DVT that required thyroxine replacement and correction of hyponatremia. This highlights that hypothyroidism can present as euvolemic hyponatremia and deep vein thrombosis.

Topics: Diagnosis, Differential; Female; Fibrinolytic Agents; Heparin; Humans; Hyponatremia; Hypothyroidism; Leg; Lost to Follow-Up; Middle Aged; Thyroxine; Treatment Outcome; Ultrasonography, Doppler, Duplex; Venous Thrombosis; Warfarin

A 41-year-old patient with schizophrenia was admitted to hospital following episodes of unexplained collapse attacks and on and off episodes of frontal headaches for 3 months. After three such episodes of loss of consciousness in 2 weeks duration and subsequent spontaneous recovery, his evaluation which included MRI scan of head revealed extensive cortical venous thrombosis. He was on zuclopenthixol (thioxanthene group) for several months for schizophrenia and was under regular psychiatric evaluation. He was treated for simple lower respiratory infection a week prior to admission. Other causes for any clotting disorders including vasculitic and thrombophilic screen were negative. There was no evidence of focal neurology on examination. Systemic examination was otherwise unremarkable. He was treated initially with unfractionated heparin and subsequently changed to warfarin with target international normalised ratio between two and three for at least 6 months and psychiatrist was advised to stop zuclopenthixol.

Topics: Adult; Anticoagulants; Antipsychotic Agents; Cerebral Veins; Clopenthixol; Heparin; Humans; Magnetic Resonance Imaging; Male; Schizophrenia; Venous Thrombosis; Warfarin

Topics: Adult; Brain; Female; Fibrinolytic Agents; Heparin; Humans; Magnetic Resonance Imaging; Tomography, X-Ray Computed; Venous Thrombosis; Warfarin

Cerebral venous thrombosis is an uncommon and diverse entity accounting for less than 1% of strokes. It can present with a variety of clinical symptoms ranging from isolated headaches to deep coma making the clinical diagnosis difficult. We present a rare case of cerebral venous thrombosis secondary to dehydration and inflammatory bowel disease.

Topics: Anticoagulants; Dehydration; Heparin; Humans; Inflammatory Bowel Diseases; Intracranial Thrombosis; Male; Middle Aged; Risk Factors; Stroke; Venous Thrombosis; Warfarin

Agenesis of the inferior vena cava (IVC) is an uncommon congenital vascular malformation. We report a case in a teenage female recently started on oral contraception.. Because of menorrhagia, the patient had begun an oral contraceptive pill (OCP) 1(1/2) months prior to presentation. She initially presented with pelvic and lower back pain, and imaging showed a pelvic deep venous thrombosis (DVT) and an interrupted IVC. Anticoagulation was started, the OCP was discontinued, and a discussion occurred regarding the treatment options for her menorrhagia following her recent diagnosis.. The case presented shows the rare occurrence of the congenital absence of an IVC with pelvic thrombosis in a young female with a history of menorrhagia and new onset of pelvic pain. The evaluation of this case report leads to a comprehensive review in the treatment choice for menorrhagia with the preceding history of a thrombotic event.

Topics: Adolescent; Anticoagulants; Contraceptives, Oral; Contraindications; Female; Humans; Magnetic Resonance Imaging; Menorrhagia; Pelvic Pain; Tomography, X-Ray Computed; Vena Cava, Inferior; Venous Thrombosis; Warfarin

The purpose of this investigation is to show trends in the duration of hospitalization of patients with pulmonary embolism (PE) and deep venous thrombosis (DVT). The number of patients discharged from short-stay non-Federal hospitals throughout the United States with a primary diagnostic code for PE or DVT from 1979 through 2005 was obtained from the National Hospital Discharge Survey. By 2005, 13% of patients with PE were discharged in 1 to 2 days, 30% in 3 to 4 days, 26% in 5 to 6 days, and 31% in > or =7 days. Regarding DVT, by 2005, 26% of patients with DVT were discharged in 1 to 2 days, 34% were discharged in 3 to 4 days, 20% were discharged in 5 to 6 days, and 19% were discharged in > or =7 days. The data indicate that large proportions of patients with a primary diagnosis of PE and of DVT are being discharged before adequate heparin can be administered and before warfarin can become antithrombotic. Others have reported an increased mortality among patients with PE discharged in < or =4 days. If patients are to be discharged before adequate heparin can be administered, outpatient treatment with low-molecular-weight heparin (LMWH) for at least 5 days and until the international normalized ratio (INR) is > or =2.0 for 24 hours is recommended or extended outpatient treatment with LMWH may be considered.

Topics: Anticoagulants; Cost Savings; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Length of Stay; Patient Discharge; Patient Selection; Polysaccharides; Pulmonary Embolism; United States; Venous Thrombosis; Warfarin

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation; Female; Genetic Predisposition to Disease; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Kaplan-Meier Estimate; Male; Middle Aged; Postthrombotic Syndrome; Proportional Hazards Models; Retrospective Studies; Risk Assessment; Risk Factors; Thrombophilia; Time Factors; Treatment Outcome; Venous Thrombosis; Warfarin; Young Adult

Topics: Anticoagulants; Female; Follow-Up Studies; Heparin, Low-Molecular-Weight; Humans; Male; Mesenteric Veins; Middle Aged; Thrombolytic Therapy; Venous Thrombosis; Warfarin

The purpose of this study was to determine the frequency of bleeding complications after invasive dental procedures in patients on low-molecular-weight heparin (LMWH) therapy.. A chart review of patients who underwent invasive dental procedures while on LMWH therapy was conducted. The following information was obtained: demographics, medical history, social history, medications, relevant laboratory values, postoperative bleeding events, and use of local hemostatic agents and blood products.. Forty-one patients (21 men) were identified with 42 dental appointments. The mean age was 48 years (range, 16 to 78 years). Thirty-seven patients (90%) were on LMWH therapy for deep venous thrombosis prophylaxis. Thirty-one patients (76%) were on concomitant medications that may potentiate bleeding. Multiple dental extractions (range, 2 to 14 teeth) were performed during 19 dental appointments. Twenty-one appointments were for single-tooth extraction and 2 were for soft tissue biopsies. Three patients (7%) had postextraction bleeding events. All 3 patients were on LMWH (enoxaparin) and warfarin therapy concurrently. One patient had persistent bleeding after extraction of 4 teeth (international normalized ratio, 1.6), which was successfully controlled with topical thrombin, administration of vitamin K and fresh frozen plasma, and discontinuation of enoxaparin and warfarin. Postoperative bleeding in the other 2 patients was managed successfully with local hemostatic measures and home care instructions.. Our study suggests that, although postoperative bleeding in patients on LMWH therapy alone is rare to nonexistent, patients on warfarin and LMWH may be at increased risk of bleeding after invasive dental procedures.

Topics: Adolescent; Adult; Aged; Anticoagulants; Antifibrinolytic Agents; Aspirin; Enoxaparin; Female; Gelatin Sponge, Absorbable; Hemostatic Techniques; Hemostatics; Humans; Male; Middle Aged; Oral Hemorrhage; Oral Surgical Procedures; Plasma; Platelet Aggregation Inhibitors; Postoperative Hemorrhage; Retrospective Studies; Sutures; Thrombin; Tooth Extraction; Venous Thrombosis; Vitamin K; Warfarin; Young Adult

Only few small studies have assessed rates of recanalization and impact of recanalization on outcome in patients after cerebral vein thrombosis (CVT).. In this retrospective cohort study, we included 91 consecutive patients-treated in Helsinki University Central Hospital-who had non-invasively verified CVT and follow-up imaging at 4 months or later, or autopsy. We categorized vessel status at follow-up as complete, partial, or no recanalization. A complete recovery was defined as a score of 0 on the modified Rankin Scale.. Of the 91 patients (median age, 36 years; 70% females), 43 (47%) achieved complete recanalization, in 31 (34%) patients recanalization was partial, and 17 (19%) had no recanalization. Males, patients aged > or =37 years, and those with no identified risk factors for CVT had more frequently partial or no recanalization. Patients aged > or =37 years, those with chronic onset of symptoms (>30 days), and those with no recanalization had worse outcome in univariate analysis. Only increasing age associated with no recanalization (OR, 1.04; 95% CI, 1.01-1.08) when adjusted for age, sex, and number of causes for CVT. Increasing age (OR 1.05; 95% CI 1.01-1.09) and chronic mode of onset (OR 9.41; 95% CI 1.02-87.07) predicted incomplete recovery or death when adjusted for age, sex, mode of onset, and status of recanalization. Headache was more common in patients with no recanalization (44%).. Half of the patients after CVT had complete recanalization. Despite the univariate association, recanalization did not associate with poor outcome in multivariate analysis. However, residual headache was more common in those with no recanalization.

Topics: Adolescent; Adult; Age Factors; Aged; Anticoagulants; Cohort Studies; Female; Heparin; Humans; Intracranial Thrombosis; Magnetic Resonance Imaging; Male; Middle Aged; Radiography; Retrospective Studies; Sex Factors; Treatment Outcome; Venous Thrombosis; Warfarin

To discuss the efficacy of anticoagulation on patency post-permanent inferior vena caval filter (IVCF) placements.. The patients with deep vein thrombosis (DVT) of the lower extremity who were accepted permanent IVCF placement from December 2001 to December 2007 were reviewed retrospectively. Data on vital status, filter thromboembolism, anticoagulation time, and so on were obtained through follow-up. One hundred and thirty eight patients (75 male and 63 female) with a mean age of 65 years were enrolled in the study. All the patients were divided into non-anticoagulation group, anticoagulation group A with taking warfarin less than 6 months, or anticoagulation group B with taking warfarin more than 6 months. chi(2) test, t test, Kaplan-Meier survival curve, Log-rank test were used for statistics analysis.. Sixteen patients died, and 1 of them died of pulmonary embolism. Including the 1 patient mentioned before, there were 19 patients (13.8%) suffered from filter thromboembolism. Upon chi(2) test, there were no significant differences (P = 0.288) on the patency rates between non-anticoagulation, anticoagulation group A and anticoagulation group B (87.8%, 75.0%, and 88.3% respectively). Upon Kaplan-Meier survival analysis, there were still no significant differences (P = 0.227) on the mean patency time and the cumulate rates of patency at the 1st or 3rd year between the 3 groups (87.1%, 80.0%, 94.8% and 87.1%, 74.3%, 85.4% respectively).. Anticoagulation has no efficacy on patency post-permanent IVCF placements.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Equipment Failure; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pulmonary Embolism; Retrospective Studies; Vena Cava Filters; Venous Thrombosis; Warfarin

We present a 55-year-old man with acute migrating thrombophlebitis and deep vein thrombosis of muscle veins in both calves indicating occurrence of acute myelomonocytic leukemia. Thrombosis of superficial and deep veins of the lower limbs arose in spite of the adequate anticoagulation therapy with warfarin.

Topics: Anticoagulants; Humans; Leukemia, Myelomonocytic, Acute; Male; Middle Aged; Muscles; Thrombophlebitis; Ultrasonography; Veins; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Cytochrome P-450 Enzyme System; Dose-Response Relationship, Drug; Female; Humans; Polymorphism, Single Nucleotide; Postpartum Period; Venous Thrombosis; Warfarin

Mesenteric vein thrombosis is a rare disorder that is often the first manifestation of a systemic condition such as a hypercoagulable state or cancer. In particular, myeloproliferative disorders can present as mesenteric vein thrombosis even in the setting of relatively normal peripheral blood counts. A recent novel mutation in the Janus activated kinase 2 gene involving a gain-of-function substitute of valine to phenylalanine at position 617 (JAK2 V617F) has been discovered to be prevalent in patients with mesenteric vein thrombosis and myeloproliferative disorders. This article reports a patient who presented with mesenteric vein thrombosis and relatively normal peripheral blood counts. He was diagnosed with essential thrombocythemia after he tested positive for the JAK2 V617F mutation.

Topics: Aged; Anticoagulants; DNA Mutational Analysis; Genetic Predisposition to Disease; Genetic Testing; Humans; Janus Kinase 2; Male; Mesenteric Vascular Occlusion; Mesenteric Veins; Point Mutation; Thrombocythemia, Essential; Tomography, X-Ray Computed; Venous Thrombosis; Warfarin

Unanticipated elevation of the INR is common in patients receiving warfarin. We performed a prospective cohort study of 107 warfarin-treated patients with INR values of more than 10 who received a single 2.5 mg dose of oral vitamin K. During the first week, one patient experienced major bleeding, and one died. In the first 90 days after enrolment four patients had major bleeding (3.7%, 1.0% to 9.3%), eight patients (7.5%, 3.3% to 14.2%) died and two had objectively confirmed thromboembolism. Based on our low rate of observed major bleeding we conclude that 2.5 mg of oral vitamin K is a reasonable treatment for patients with INR values of more than 10 who are not actively bleeding.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Female; Follow-Up Studies; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Prospective Studies; Venous Thrombosis; Vitamin K; Warfarin

Patients with inflammatory bowel disease (IBD) are known to have an increased propensity for thromboembolic events. Like any patient with a high risk of event recurrence, most of these patients can be managed successfully with long-term warfarin therapy. We present the case of a 66-year-old woman with Crohn's disease who, despite careful attention to the management of her international normalized ratio, developed a new deep vein thrombosis and required inferior vena cava filter placement in addition to ongoing warfarin therapy to prevent recurrent pulmonary emboli. This report serves as a reminder to physicians to have a low threshold for diagnosing thromboembolic events in patients with IBD, even if they are presumed to be adequately anticoagulated. Known and theoretical contributing factors to this increased clotting tendency are also reviewed.

Topics: Aged; Anticoagulants; Crohn Disease; Female; Humans; Pulmonary Embolism; Recurrence; Vena Cava Filters; Venous Thrombosis; Warfarin

The prevalence and clinical spectrum of acute mesenteric venous thrombosis (AMVT) in Pakistan is largely unknown. The authors report two patients with acute mesenteric, portal and inferior vena cava venous thrombosis confirmed on CT imaging. The diagnoses were established within 24 hours of presentation and both patients were successfully treated with therapeutic heparin during hospital admission and continued on oral warfarin because of hypercoagulable state. The protocol that we currently use is evidence based and is leading to optimal outcome.

Topics: Acute Disease; Adult; Anticoagulants; Female; Heparin; Humans; Liver; Mesenteric Vascular Occlusion; Mesenteric Veins; Peritoneal Diseases; Tomography, X-Ray Computed; Treatment Outcome; Vena Cava, Inferior; Venous Thrombosis; Warfarin

At the turn of the century, only 300 cases of warfarin-induced skin necrosis (WISN) had been reported. WISN is a rare but potentially fatal complication of warfarin therapy. There are no published reports of WISN occurring in patients with HIV-1 infection or tuberculosis (TB).. We retrospectively reviewed cases of WISN presenting from April 2005 to July 2008 at a referral hospital in Cape Town, South Africa.. Six cases of WISN occurred in 973 patients receiving warfarin therapy for venous thrombosis (0.62%, 95% CI 0.25 - 1.37%). All 6 cases occurred in HIV-1-infected women (median age 30 years, range 27 - 42) with microbiologically confirmed TB and venous thrombosis. All were profoundly immunosuppressed (median CD4+ count at TB diagnosis 49 cells/microl, interquartile range 23 - 170). Of the 3 patients receiving combination antiretroviral therapy, 2 had TB-IRIS (immune reconstitution inflammatory syndrome). The median interval from initiation of antituberculosis treatment to venous thrombosis was 37 days (range 0 - 150). The median duration of parallel heparin and warfarin therapy was 2 days (range 1 - 6). WISN manifested 6 days (range 4 - 8) after initiation of warfarin therapy. The international normalised ratio (INR) at WISN onset was supra-therapeutic, median 6.2 (range 3.8 - 6.6). Sites of WISN included breasts, buttocks and thighs. Four of 6 WISN sites were secondarily infected with drug-resistant nosocomial bacteria (methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter, extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae) 17 - 37 days after WISN onset. In 4 patients, the median interval from WISN onset to death was 43 days (range 25 - 45). One of the 2 patients who survived underwent bilateral mastectomies and extensive skin grafting at a specialist centre.. This is one of the largest case series of WISN. We report a novel clinical entity: WISN in HIV-1 infected patients with TB and venous thrombosis. The occurrence of 6 WISN cases in a 40-month period may be attributed to (i) hypercoagulability, secondary to HIV-1 and TB: (ii) short concurrent heparin and warfarin therapy; and (iii) high loading doses of warfarin. Active prevention and appropriate management of WISN are likely to improve the dire morbidity and mortality of this unusual condition.

Topics: Adult; Anticoagulants; Comorbidity; Female; HIV Infections; Humans; Necrosis; Retrospective Studies; Skin; Tuberculosis; Tuberculosis, Pulmonary; Venous Thrombosis; Warfarin

Tender lumps in the inguinal region are often explored emergently to treat suspected hernial strangulation. We discuss the case of an adult male who presented acutely with a tender inguinal swelling and raised inflammatory markers and was therefore deemed as requiring surgical exploration. However preoperative abdominal computerized tomography (CT) revealed an extensive thrombosing congenital venous malformation of portosystemic origin with extension into the symptomatic inguinal canal. A potentially lethal exsanguination from surgery was thus avoided.

Topics: Adult; Anticoagulants; Azygos Vein; Diagnosis, Differential; Hernia, Inguinal; Humans; Magnetic Resonance Angiography; Male; Phlebography; Portal Vein; Tomography, X-Ray Computed; Treatment Outcome; Vascular Malformations; Vena Cava, Inferior; Venous Thrombosis; Warfarin

Iliac vein compression syndrome (CS) is a rare cause of deep venous thrombosis. It is caused by an anatomic anomaly in which the right common iliac artery overlies the left common iliac vein causing mechanical compression. Subsequent endothelial changes within the vessels have the potential to spur thrombus formation. Aggressive diagnostic and therapeutic interventions must be implemented upon suspicion to avoid long-term complications. We report on a 19 year old male who presented with ICS. We discuss the clinical presentation, diagnosis, and current treatment options.

Topics: Anticoagulants; Clopidogrel; Constriction, Pathologic; Heparin; Humans; Iliac Vein; Lower Extremity; Male; Platelet Aggregation Inhibitors; Syndrome; Thrombectomy; Thrombolytic Therapy; Ticlopidine; Venous Thrombosis; Warfarin; Young Adult

Topics: Emergencies; Exanthema; Female; Humans; Leg; Middle Aged; Necrosis; Skin; Venous Thrombosis; Warfarin

Pulmonary embolism (PE) is one of the major complications after percutaneous balloon angioplasty (PTBA) for Budd-Chiari's syndrome (BCS). The purpose of this study was to investigate the role of warfarin pre-treatment in the prevention of PE after PTBA in patients with large inferior vena cava (IVC) thrombus.. From October 2002 to December 2009, 16 patients with symptomatic membranous or segmental IVC occlusion and large thrombus were treated with warfarin before PTBA. Eleven patients were men and 5 were women. The median age was 36 years, ranging from 21 to 52 years. The median duration of warfarin treatment before PTBA was 7 months, ranging from 3 to 12 months. Fourteen patients had membranous IVC occlusion and 2 had segmental occlusion. All 16 patients had significant thrombi underneath the obstructive lesions. PE diagnosis was based on clinical presentation and pulmonary computerized tomographic angiogram, if indicated.. In 14 of 16 patients, IVC thrombus was completely or near-completely resolved based on follow-up cavogram and PTBA was performed. In the other 2 patients, residual thrombus was demonstrated by cavogram at 12 months. PTBA and stent placement were carried out. IVC patency in the 16 patients was confirmed by completion cavogram. No major bleeding complication during warfarin pre-treatment aimed to keep international normalized ratio (INR) 2 to 3. There was no clinically significant PE or death in this group during follow-up, ranging from 6 to 40 months (median 21 months).. Spontaneous fibrinolysis of IVC thrombus occurs within 1 year in the majority of the patients treated with warfarin. Pre-treatment with warfarin prevents PE after PTBA in the patients with BCS with IVC membranous or segmental occlusion and large thrombus.

Topics: Adult; Angioplasty, Balloon; Anticoagulants; Budd-Chiari Syndrome; China; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Phlebography; Pulmonary Embolism; Stents; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Vena Cava, Inferior; Venous Thrombosis; Warfarin; Young Adult

Few studies have investigated current practices in the USA relating to warfarin use and monitoring, or the effects of warfarin discontinuation on risk of venous thromboembolism (VTE) and bleeding complications. This study investigated the effect of warfarin discontinuation on rates of VTE recurrence in a real-world setting.. Integrated Healthcare Information Services database records from January 2003 to September 2007 from patients aged at least 18 years, hospitalized for VTE, and with at least two prescriptions or 60 days of warfarin treatment were reviewed, with warfarin discontinuation and international normalized ratio (INR) data collated.. A total of 1027 of 8380 (12.3%) patients discontinued warfarin within 3 months. Overall, 1656 (19.8%) patients had no INR monitoring, with 38.1% of INR values being inside the therapeutic range (INR 2-3). Recurrent VTE was observed in 915 (10.9%) patients. Significant predictors of recurrent VTE (at any time) included discontinuation of warfarin within 3 months, time from index VTE to warfarin initiation, previous VTE-related hospitalization, and duration of index hospitalization.. This study found that in a real-world population, less than 50% of warfarin patients achieved INR values within the therapeutic range. Warfarin discontinuation within 3 months was associated with a higher rate of recurrent VTE.

Topics: Adult; Aged; Anticoagulants; Comorbidity; Databases, Factual; Diagnosis-Related Groups; Drug Monitoring; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Medication Therapy Management; Middle Aged; Patient Readmission; Pulmonary Embolism; Retrospective Studies; Risk Assessment; Secondary Prevention; Time Management; Treatment Outcome; United States; Venous Thromboembolism; Venous Thrombosis; Warfarin; Young Adult

Via generation of vitamin K-dependent proteins, gamma-glutamyl carboxylase (GGCX) plays a critical role in the vitamin K cycle. Single nucleotide polymorphisms (SNPs) in GGCX, therefore, may affect dosing of the vitamin K antagonist, warfarin. In a multi-centered, cross-sectional study of 985 patients prescribed warfarin therapy, we genotyped for two GGCX SNPs (rs11676382 and rs12714145) and quantified their relationship to therapeutic dose. GGCX rs11676382 was a significant (p=0.03) predictor of residual dosing error and was associated with a 6.1% reduction in warfarin dose (95% CI: 0.6%-11.4%) per G allele. The prevalence was 14.1% in our predominantly (78%) Caucasian cohort, but the overall contribution to dosing accuracy was modest (partial R2 = 0.2%). GGCX rs12714145 was not a significant predictor of therapeutic dose (p = 0.26). GGCX rs11676382 is a statistically significant predictor of warfarin dose, but the clinical relevance is modest. Given the potentially low marginal cost of adding this SNP to existing genotyping platforms, we have modified our non-profit website (www.WarfarinDosing.org) to accommodate knowledge of this variant.

Topics: Aged; Biomarkers, Pharmacological; Carbon-Carbon Ligases; Clinical Protocols; Female; Genotype; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Prognosis; Venous Thrombosis; Vitamin K; Warfarin

Cardiopulmonary bypass during pregnancy is associated with a high fetal and maternal mortality. We report a successful pulmonary embolectomy in a woman at the 27th week of pregnancy; we performed surgical pulmonary embolectomy under cardiopulmonary bypass to restore adequate hemodynamic stability and to relieve right ventricle strain. We discuss the decision made for the preferred anticoagulation drug in the setting of heparin-induced thrombocytopenia in the gravida. The pregnancy was carried to term and she delivered a healthy boy at 38 weeks of gestation.

Topics: Adult; Anticoagulants; Cardiopulmonary Bypass; Echocardiography, Transesophageal; Embolectomy; Enoxaparin; Female; Fondaparinux; Heart Arrest, Induced; Heparin; Humans; Infant, Newborn; Live Birth; Male; Polysaccharides; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Trimester, Second; Pulmonary Embolism; Thrombocytopenia; Tirofiban; Treatment Outcome; Tyrosine; Venous Thrombosis; Warfarin

Venous thromboembolism remains the most common cause of hospital readmission and death after total joint arthroplasty. The 2008 American College of Chest Physicians (ACCP) guidelines, based on prospective randomized clinical trials with a venography endpoint, endorse the use of low-molecular-weight heparin, fondaparinux, or adjusted dose warfarin (target international normalized ratio, 2.5; range, 2-3) for up to 35 days after total hip arthroplasty (THA) and total knee arthroplasty (TKA). In the past, the ACCP has recommended against the use of aspirin, graduated compression stockings, or venous compression devices as the sole means of prophylaxis, but in 2008 they first recommended the "optimal use of mechanical thromboprophylaxis with venous foot pumps or intermittent pneumatic compression devices" in patients undergoing total joint arthroplasty who "have a high risk of bleeding." When the high risk subsides, pharmacologic thromboprophylaxis is substituted for, or added to, mechanical methods. Fractionated heparins and pentasaccharide are the most effective agents in reducing venographic deep venous thrombosis (DVT) after total joint arthroplasty with residual clot rates <5% after THA and 20% after TKA, but major or clinically meaningful bleeding occurs in 3% to 5% of patients. Newer Xa and thrombin inhibitors enjoy greater efficacy with equal or higher bleeding rates. Low-intensity warfarin (target international normalized ratio, 2.0) combines safety (bleeding rates <1%) with efficacy (readmission for clinical DVT or pulmonary embolism 0.2%) after total joint arthroplasty. Warfarin represents a therapeutic compromise by preventing clinical events in exchange for a lower bleeding rate; genetic testing will likely simplify warfarin use and reduce outlier responders.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Chemoprevention; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Intermittent Pneumatic Compression Devices; Patient Readmission; Platelet Aggregation Inhibitors; Polysaccharides; Postoperative Hemorrhage; Practice Guidelines as Topic; Pulmonary Embolism; Venous Thrombosis; Warfarin

This article describes a case of a 26-year-old man presenting with left knee pain of 1 week's duration, fever, and acute onset of shortness of breath the day of admission. An arthrocentesis of the knee joint was grossly positive for methicillin-resistant Staphylococcus aureus. A left lower extremity venous duplex showed thrombosis of the superficial femoral, popliteal, posterior tibial, peroneal, and gastrocnemius veins. Pulmonary computed tomography-angiography was positive for acute pulmonary emboli. Initial management consisted of anticoagulation, intravenous antibiotics, and 2 arthroscopic irrigation and debridement procedures. After a normal transesophageal echocardiogram, a diagnosis of septic knee-induced deep venous thrombosis (DVT) of the left lower leg with subsequent septic pulmonary emboli was established. The patient was discharged to a long-term care facility for a 6-week monitored course of intravenous antibiotics. His DVT and pulmonary emboli were managed successfully with oral warfarin. Two months after his initial presentation, the patient returned with acute worsening knee pain. A knee arthrocentesis was unremarkable; however, radiographic imaging revealed fulminant osteomyelitis of the distal femur. He has since undergone open arthrotomy with excisional irrigation and debridement and is on a chronic oral antibiotic regimen. Sparse pediatric literature has shown an association between musculoskeletal sepsis and thrombosis. Only 1 case of septic knee-induced DVT exists in the adult literature, and it was not associated with pulmonary emboli. Our case provides evidence that DVT must be considered by the treating physician as a possible and devastating complication of septic arthritis.

Topics: Adult; Anti-Bacterial Agents; Anticoagulants; Arthritis, Infectious; Debridement; Femur; Humans; Injections, Intravenous; Knee Joint; Male; Methicillin-Resistant Staphylococcus aureus; Osteomyelitis; Staphylococcal Infections; Therapeutic Irrigation; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Cardiopulmonary Bypass; Embolectomy; Enoxaparin; Female; Fondaparinux; Heart Arrest, Induced; Heparin; Humans; Polysaccharides; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Trimester, Second; Pulmonary Embolism; Risk Assessment; Thrombocytopenia; Tirofiban; Treatment Outcome; Tyrosine; Ultrasonography; Venous Thrombosis; Warfarin

Topics: Administration, Oral; Ambulatory Care; Anticoagulants; Blood Coagulation; Compression Bandages; Drug Administration Schedule; Drug Therapy, Combination; Enoxaparin; Fibrinolytic Agents; Hemorrhage; Humans; Injections, Subcutaneous; Lower Extremity; Outpatients; Risk Assessment; Time Factors; Treatment Outcome; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Treatment Outcome; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Echocardiography, Transesophageal; Heart Atria; Heart Diseases; Heart Ventricles; Humans; Male; Middle Aged; Thrombolytic Therapy; Thrombosis; Treatment Outcome; Venous Thrombosis; Warfarin

Due to the importance of anticoagulation use along with the complications that deep vein thrombosis (DVT) and pulmonary embolism (PE) may bring about for the patients, in this study we decided to carry out a drug utilization evaluation on anticoagulants that are routinely administered in a tertiary teaching hospital.. Anticoagulants utilization was evaluated in 400 patients from 4 wards (infectious disease, cardiology, nephrology, and cardiac care unit) of a tertiary teaching hospital in a cross-sectional, prospective study.. According to the risk stratification, 220 (55%) of the evaluated patients have indication to receive anticoagulants as deep venous thrombosis prophylaxis. With definite diagnosis of DVT or PE, 169 (42.3%) patients have received anticoagulant therapy. In 11 (2.8%) cases, anticoagulants has been ordered inappropriately. In assessment of the anticoagulants regimens that were used as DVT prophylaxis doses of heparin and enoxaparin were appropriate in 75% and 79% of patients, respectively.. Despite the existence of comprehensive guidelines for the prevention and treatment of DVT and PE, it is not performed accurately.

Topics: Adult; Aged; Anticoagulants; Cross-Sectional Studies; Drug Monitoring; Drug Utilization Review; Enoxaparin; Female; Heparin; Hospitals, Teaching; Humans; Male; Middle Aged; Prospective Studies; Pulmonary Embolism; Risk; Thrombocytopenia; Venous Thrombosis; Warfarin; Young Adult

Antiphospholipid syndrome is an autoimmune disease that presents with recurrent arteriovenous thrombosis, repeated pregnancy loss and elevated titres of antiphospholipid antibodies in the blood. It is a common cause of acquired thrombosis and can manifest within any part of the vascular tree. Inferior Venacava thrombosis at outset, however, is not a common manifestation of systemic lupus erythematosus associated-antiphospholipid syndrome particularly in children. Here, we present a 14-year old girl who developed antiphospholipid syndrome as a presenting manifestation of systemic lupus erythematosus.

Topics: Adolescent; Antihypertensive Agents; Antiphospholipid Syndrome; Female; Glucocorticoids; Heparin; Humans; Hydrochlorothiazide; Lupus Erythematosus, Systemic; Prednisone; Vena Cava, Inferior; Venous Thrombosis; Warfarin

Warfarin is a widely used anticoagulant in the treatment and prevention of thrombosis, in the treatment for chronic atrial fibrillation, mechanical valves, pulmonary embolism, and dilated cardiomyopathy. It is tasteless and colorless, was used as a poison, and is still marketed as a pesticide against rats and mice. Several long-acting warfarin derivatives-superwarfarin anticoagulants-such as brodifacoum, diphenadione, chlorophacinone, bromadiolone, are used as pesticides and can produce profound and prolonged anticoagulation. Several factors increase the risk of warfarin toxicity. However, polymorphisms in cytochrome P450 genes and drug interactions account for most of the risk for toxicity complications. Each person is unique in their degree of susceptibility to toxic agents. The toxicity interpretation and the health risk of most toxic substances are a subject of uncertainty. Genetically determined low metabolic capacity in an individual can dramatically alter the toxin and metabolite levels from those normally expected, which is crucial for drugs with a narrow therapeutic index, like warfarin. Personalized approaches in interpretation have the potential to remove some of the scientific uncertainties in toxicity cases.

Topics: Anticoagulants; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP2C9; Cytochrome P-450 Enzyme System; Female; Genetic Predisposition to Disease; Genotype; Humans; International Normalized Ratio; Middle Aged; Pharmacogenetics; Polymorphism, Genetic; Venous Thrombosis; Warfarin

A 60-year-old man presented to the accident and emergency department with a 4-day history of abdominal pain following blunt abdominal trauma. An initial CT scan showed thickened walls of the proximal jejunum and thromboses in the portal, splenic and superior mesenteric veins. He was given warfarin and the abdominal pain resolved. A repeat CT scan 1 week later revealed significant resolution of the mural thickening and the portal vein thrombosis. A subsequent thrombophilia screen was negative and he continued taking oral anticoagulants for a total of 6 months. A repeat CT scan 3 months after presentation revealed complete recanalisation the portal venous system.

Topics: Abdominal Injuries; Abdominal Pain; Anticoagulants; Follow-Up Studies; Humans; Male; Middle Aged; Portal System; Portal Vein; Rare Diseases; Risk Assessment; Severity of Illness Index; Splenic Vein; Tomography, X-Ray Computed; Treatment Outcome; Venous Thrombosis; Warfarin; Wounds, Nonpenetrating

We present an unusual case of a 31-year-old nulliparous woman who was in her normal state of health until 3 weeks before her Emergency Department visit, when she began to have generalized abdominal pain that got acutely worse over a few days. She had a soft abdomen, but complained of excruciating pain. Her computed tomography (CT) scan revealed thrombosis in the superior mesenteric, splenic, and portal veins. Her hematological work-up detected a protein S deficiency, which is associated with recurrent venous thrombosis. The finding of mesenteric venous thrombosis associated with protein S deficiency is rare. The most important factor in survival is early diagnosis and prompt treatment with anticoagulants. Properly treated, patients with mesenteric venous thrombosis should have a good long-term prognosis. Past medical or family history of thrombosis in combination with abdominal symptoms should increase the suspicion for the disease.

Topics: Abdominal Pain; Adult; Anticoagulants; Female; Humans; Mesenteric Vascular Occlusion; Mesenteric Veins; Portal Vein; Prognosis; Protein S Deficiency; Splenic Vein; Venous Thrombosis; Warfarin

This case report describes a young man presenting with iliac fossa pain secondary to iliac vein thrombus due to inferior vena cava aplasia. No other identifiable risk factor or cause for deep vein thrombosis was demonstrated.

Topics: Abdominal Pain; Angiography; Anticoagulants; Humans; Iliac Vein; Magnetic Resonance Imaging; Male; Tomography, X-Ray Computed; Vena Cava, Inferior; Venous Thrombosis; Warfarin; Young Adult

May-Thurner syndrome is characterized by left common iliac obstruction secondary to compression of the left iliac vein by the right common iliac artery against the fifth-lumbar vertebra. This anatomic variant results in an increased incidence of left-sided deep venous thrombosis (DVT). Furthermore, while a preponderance of left-sided DVT has been demonstrated in women during pregnancy and oral contraceptive use, patients are not typically screened for this condition after developing a left-sided DVT. As anticoagulation alone is ineffective for DVT treatment in the setting of May-Thurner anatomy, more aggressive treatment is warranted. Failure to diagnosis this condition predisposes these women to the unnecessary risks of recurrent DVT and post-thrombotic syndrome.. We present the occurrence of 7 adolescent patients with previously undiagnosed May-Thurner syndrome who presented with DVT after the initiation of oral contraceptive steroids (OCP) use. All 7 patients elected to proceed with mechanical thrombolysis/catheter based thrombolysis followed by endovascular stenting and were postoperatively treated with 6 months of warfarin.. Mean patient age was 18.3 +/- 3.3 years (range, 16-24 years). Mean time to presentation after initiation of OCP was 5 weeks (range, 2-10 weeks). Mean time to intervention was 16.8 days (range, 10-24 days). All patients were treated with mechanical thrombectomy. Our rate of intraoperative clot resolution was 100%. All 7 patients were treated with self expanding nitinol stents after angioplasty of the iliac vein stenosis with resolution of the stenotic segment. Primary stent patency is 100% (7/7). Mean follow-up time is 13 +/- 13.84 months (range, 6-42 months). There have been no long-term complications related to surgical treatment or anticoagulation. All 7 patients have experienced resolution of left leg swelling and pain and have no evidence of post-thrombotic syndrome or DVT recurrence to date.. Women on OCPs presenting with left-sided iliofemoral DVT should be screened for hypercoagulable disorders and underlying May-Thurner anatomy. Treatment of May-Thurner syndrome should include thrombolysis/thrombectomy and anticoagulation for current DVT in addition to angioplasty and stenting of the underlying obstruction.

Topics: Adolescent; Angioplasty; Anticoagulants; Combined Modality Therapy; Constriction, Pathologic; Contraceptives, Oral, Hormonal; Female; Femoral Vein; Humans; Iliac Artery; Iliac Vein; Peripheral Vascular Diseases; Phlebography; Retrospective Studies; Stents; Syndrome; Thrombectomy; Thrombolytic Therapy; Time Factors; Treatment Outcome; Ultrasonography, Doppler, Color; Venous Thrombosis; Warfarin; Young Adult

The authors evaluated the prophylactic protocols with unfractionated heparin (UFH) and warfarin in Japanese patients who underwent total knee arthroplasty (TKA) for osteoarthritis knee in regard to bleeding complications. Fifty-six patients who underwent TKA for osteoarthritis knee with the use of methylmethacrylate were included. Subcutaneous UFH and warfarin were administered for thromboprophylaxis to the first group of 26 patients. The second group of 30 patients did not receive any pharmacological thromboprophylaxis and were used as controls. No significant differences were found between the 2 groups for operative and postoperative blood loss. There were no cases with major bleeding as a complication, but for 2 cases, the international normalized ratio high value exceeded the remedy limits, and temporary dosage discontinuance was required. There were no clinically important bleeding events in the 2 groups. No heparin-induced thrombocytopenia or warfarin-induced skin necrosis occurred. The authors conclude that the protocol with UFH and warfarin is safe for thromboprophylaxis against deep venous thrombosis and pulmonary embolism after TKA in Japanese patients, but its efficacy can only be resolved with further studies.

Topics: Aged; Aged, 80 and over; Arthroplasty, Replacement, Knee; Blood Loss, Surgical; Female; Heparin; Humans; Male; Middle Aged; Osteoarthritis, Knee; Postoperative Complications; Prospective Studies; Pulmonary Embolism; Venous Thrombosis; Warfarin

It is known that warfarin treatment is problematic, due to its narrow therapeutic range and to the great interindividual variability. Numerous papers have shown the important contribution of CYP2C9 and VKORC1 genetic variants to this variability. Recently, a new SNP within the CYP4F2 gene was found associated with warfarin dose in the USA.. The aim of our work was to replicate this study in the Italian population and to assess the new CYP4F2 variant relative contribution in explaining warfarin dose variability with respect to CYP2C9 and VKORC1 genetic variants together with age and weight.. CYP4F2 rs2108622 genotyping was performed by allelic discrimination assay by TaqMan technology. Analysis of variance and multiple linear regression analyses were carried out to examine the contribution of genetic and nongenetic factors.. Our TT patients require 5.49 mg/day versus 2.93 mg/day of our CC patients. Analysis of variance indicates that about 7% of mean weekly warfarin dose variance is explained by CYP4F2 genotype. Our linear regression model including CYP4F2, CYP2C9 and VKORC1 genetic variants, age and weight, explains 60.5% of the interindividual variability.. Our data confirm and strengthen the role of this variant.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cohort Studies; Cytochrome P-450 Enzyme System; Cytochrome P450 Family 4; DNA; Dose-Response Relationship, Drug; Female; Genetic Variation; Genotype; Heart Valve Prosthesis Implantation; Humans; Italy; Male; Mixed Function Oxygenases; Rome; Venous Thrombosis; Vitamin K Epoxide Reductases; Warfarin

Topics: Anticoagulants; Antineoplastic Agents; Catheterization, Central Venous; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Neoplasms; Randomized Controlled Trials as Topic; Venous Thrombosis; Vitamin K; Warfarin

Topics: Aged; Antibodies, Anticardiolipin; Anticoagulants; Arginine; Catheterization; Contraindications; Drug Therapy, Combination; Femoral Vein; Heparin; Humans; Iliac Vein; Infusions, Intravenous; Ischemia; Kidney; Kidney Transplantation; Male; Pipecolic Acids; Popliteal Vein; Postoperative Complications; Protein S Deficiency; Purpura, Thrombocytopenic, Idiopathic; Renal Veins; Sulfonamides; Thrombolytic Therapy; Thrombophilia; Tissue Plasminogen Activator; Vena Cava Filters; Venous Thrombosis; Warfarin

Topics: Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Infant, Newborn; Infusions, Intravenous; Magnetic Resonance Angiography; Male; Renal Insufficiency; Renal Veins; Thrombolytic Therapy; Tissue Plasminogen Activator; Vena Cava, Inferior; Venous Thrombosis; Warfarin

Topics: Activated Protein C Resistance; Adult; Androgens; Anticoagulants; Causality; Erectile Dysfunction; Factor V; Gynecomastia; Humans; Hypogonadism; International Normalized Ratio; Klinefelter Syndrome; Male; Medication Adherence; Pulmonary Embolism; Testis; Testosterone; Ultrasonography; Venous Thrombosis; Warfarin

For patients on warfarin therapy, an international normalized ratio (INR) recall interval not exceeding 4 weeks has traditionally been recommended. Less frequent INR monitoring may be feasible in stable patients. We sought to identify patients with stable INRs (defined as having INR values exclusively within the INR range) and comparator patients (defined as at least one INR outside the INR range) in a retrospective, longitudinal cohort study. Occurrences of thromboembolism, bleeding, and death were compared between groups. Multivariate logistic regression models were used to identify independent predictors of stable INR control. There were 2504 stable and 3569 comparator patients. The combined rates of bleeding and thromboembolism were significantly lower in stable patients. Independent predictors of stable INR control were age older than 70 years and the absence of comorbid heart failure and diabetes. Stable patients were significantly less likely to have target INR of 3.0 or higher or chronic diseases. We hypothesize that many patients demonstrating stable INR control could be safely treated with INR recall intervals greater than the traditional 4 weeks.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Cohort Studies; Colorado; Comorbidity; Diabetes Mellitus; Drug Monitoring; Female; Heart Failure; Heart Valve Diseases; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Retrospective Studies; Thrombophilia; Treatment Outcome; Venous Thrombosis; Warfarin

We present two cases of clinically extensive bilateral DVTs associated with inferior vena caval thrombosis. Young patients presenting with symptoms of DVT should be investigated not only to establish any thrombophilic pre-disposition, but to ascertain the proximal extent of thrombus which may itself influence treatment.

Topics: Adult; Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Male; Vena Cava, Inferior; Venous Thrombosis; Warfarin

Air travel is implicated as a predisposing factor for thromboembolism, which at times can have catastrophic consequences. We present three cases who developed deep vein thrombosis (DVT) and subsequent pulmonary thromboembolism (PTE) after transatlantic air travel.

Topics: Adult; Aircraft; Anticoagulants; Enoxaparin; Humans; Male; Middle Aged; Pulmonary Embolism; Risk Factors; Syndrome; Thromboembolism; Travel; Venous Thrombosis; Warfarin

To my knowledge, no published reports have described an interaction between pomegranate juice and warfarin. Investigators from previous animal and in vitro studies have reported a potential for pomegranate juice to inhibit metabolism involving the cytochrome P450 system, an effect that could translate into a clinical drug-diet interaction with warfarin. This case report describes a 64-year-old Caucasian woman who was treated with warfarin for recurrent deep vein thrombosis. She had been receiving a relatively stable dosage of warfarin 4 mg/day for several months, with stable international normalized ratios (INRs). During that time, the patient was consuming pomegranate juice 2-3 times/week. She stopped drinking the juice, and her INRs became subtherapeutic. Her dosage of warfarin was increased to maintain therapeutic anticoagulation. No rechallenge with pomegranate juice was performed. Use of the Drug Interaction Probability Scale indicated a possible relationship between the patient's subtherapeutic INR and the pomegranate juice. Although this potential interaction needs to be explored further, clinicians should be aware of the interaction and thoroughly interview and closely monitor their patients who are receiving warfarin.

Topics: Anticoagulants; Female; Food-Drug Interactions; Fruit; Humans; Lythraceae; Middle Aged; Venous Thrombosis; Warfarin

Topics: Emergency Service, Hospital; Female; Humans; Medical Errors; Risk Management; United Kingdom; Venous Thrombosis; Warfarin

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Arthroplasty, Replacement; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Heparin, Low-Molecular-Weight; Humans; Practice Guidelines as Topic; Pulmonary Embolism; Venous Thromboembolism; Venous Thrombosis; Warfarin

We present a case of acute intestinal infarction in a pregnant woman with chronic idiopathic mesenteric vein thrombosis (MVT) under regular anticoagulation treatment.. The condition of the 26-year-old woman who was diagnosed with chronic idiopathic MVT after detailed investigation was stable after receiving regular anticoagulation with warfarin. One year later, she presented with a 7-day episode of intermittent epigastric pain. Acute intestinal infarction and concomitant 7-week pregnancy were diagnosed. To preserve her life, a dilation and curettage procedure and emergency laparotomy with bowel resection were performed. Ten days later, she was discharged, having made a good recovery.. Although pregnancy was not the primary cause of chronic MVT, it did play a role in inducing the acute intestinal infarction. This case indicates that pregnant patients with known chronic idiopathic MVT should be counseled about the high risk of acute mesenteric thrombosis. This case also serves to remind physicians that there should always be a high level of suspicion of intestinal infarction in patients with an acute abdomen who are in a hypercoagulable state.

Topics: Adult; Anticoagulants; Female; Humans; Jejunum; Mesenteric Vascular Occlusion; Mesenteric Veins; Pregnancy; Pregnancy Complications, Cardiovascular; Venous Thrombosis; Warfarin

Topics: Acenocoumarol; Aged, 80 and over; Anticoagulants; Drug Resistance; Genotype; Humans; Male; Venous Thrombosis; Warfarin

A case of malabsorption- associated warfarin resistance is reported.. A 42-year-old, 111-kg, Caucasian man arrived at the emergency department with atypical pleuritic chest pain. The chest pain was associated with shortness of breath, diaphoresis, nausea, vomiting, and tachycardia. The patient's medical history was significant for multiple episodes of deep venous thrombosis (DVT) in the left upper extremity and both lower extremities, a right above-the-knee amputation due to complications of a previous DVT, insertion of a vena cava filter, pulmonary embolism (PE), asthma, hypertension, and multiple myocardial infarctions. During admission, he was diagnosed presumptively with PE. All potential causes of interference with warfarin absorption were investigated and ruled out. I.V. warfarin therapy at a conventional initial dosage of 5 mg once daily was started on hospital day 2. The International Normalized Ratio (INR) reached the therapeutic range after increasing the i.v. warfarin dosage to 7.5 mg once daily on hospital day 6. The ability to obtain a therapeutic INR on a relatively low dosage of i.v. warfarin but not high dosages of oral warfarin strongly suggests an inherent warfarin malabsorption defect in this patient.. A 42-year-old man with a history of recurrent thromboembolisms demonstrated resistance to oral warfarin therapy due to warfarin malabsorption.

Topics: Adult; Anticoagulants; Chest Pain; Drug Resistance; Humans; Injections, Intravenous; International Normalized Ratio; Malabsorption Syndromes; Male; Obesity; Pulmonary Embolism; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Heparin; Humans; Intraoperative Period; Kidney Transplantation; Male; Middle Aged; Oliguria; Preoperative Period; Renal Veins; Ultrasonography, Doppler, Duplex; Venous Thrombosis; Warfarin

Deep venous thrombosis is common in the elderly. Diagnosis and management are now a part of office practice. As signs and symptoms are inconsistent and nonspecific, diagnostic testing is necessary. For patients with a low clinical probability, a normal D-dimer result can rule out disease. For patients with a high clinical suspicion or an elevated D-dimer, duplex ultrasonography may confirm the diagnosis. Anticoagulation, usually with low-molecular-weight heparin, should begin on suspicion and continue, along with warfarin, until the international normalized ratio is therapeutic. Arrangements for the initial daily injections can be made with a visiting nurse. Treatment should continue for at least 3 months, when a risk-versus-benefit analysis for continuing anticoagulation should be undertaken. Therapy may be discontinued for thromboses associated with a reversible risk factor or for patients in whom anticoagulant management was unstable or complicated by bleeding. A persistently high D-dimer result or evidence of residual clot on repeat duplex ultrasonography may support continuation. For all patients, the use of compression stockings to prevent the post-thrombotic syndrome is recommended.

Topics: Age Factors; Aged; Aged, 80 and over; Ambulatory Care; Biomarkers; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fibrin Fibrinogen Degradation Products; Follow-Up Studies; Heparin, Low-Molecular-Weight; Humans; Male; Office Visits; Pulmonary Embolism; Risk Assessment; Severity of Illness Index; Treatment Outcome; Ultrasonography, Doppler; Venous Thrombosis; Warfarin

A 13-year-old boy with Mycoplasma pneumoniae pulmonary infection developed deep vein thrombosis and pulmonary embolism. He was found to have protein S deficiency and transient antiphospholipid antibodies. Though uncommon, it is important to consider venous thromboembolic disease in children whose clinical course is atypically severe.

Topics: Adolescent; Anticoagulants; Antiphospholipid Syndrome; Heparin; Humans; Lupus Erythematosus, Systemic; Male; Pneumonia, Mycoplasma; Protein S Deficiency; Pulmonary Embolism; Venous Thrombosis; Warfarin

Microparticles (MPs) are blebs released from cellular surfaces during activation/apoptosis. They are procoagulant, pro-inflammatory and could contribute to pathogenesis of deep venous thrombosis (DVT). This study compared the number, cellular origin and procoagulant activity of MPs on DVT patients in different clinical situations: at diagnosis (n = 9, 5F/4M; mean age = 41.11), 1-3 years after warfarin withdrawal (n = 10, 7F/3M; mean age = 32.90), associated to antiphospholipid syndrome (APS; n = 11, 9F/2M; mean age = 33.82), or asymptomatic carriers of Factor V Leiden (FVL; n = 7, 7F/0M; mean age = 34.00) vs healthy controls (CTR). The quantification and characterization were performed by flow cytometry using CD235, CD61, CD45, CD31, CD14, CD45, anti-TF and Annexin V. The plasmatic procoagulant activity was investigated by prothrombin fragment 1 + 2 (F1 + 2) determination. The MPs procoagulant activity was analyzed by D-dimer (DD2) and Thrombin Generation Test (TGT) on a healthy pool of plasmas adjusted or not by their number (10,000 MPs). The MPs percentages were not different between the groups, but absolute number was increased in patients 1-3 years after warfarin withdrawal vs CTR (P = 0.02). There was no difference of the MPs cellular origin comparing patients to controls. TGT using 10,000 MPs was lower on these patients (P = 0.01). APS patients showed a reduction of plasmatic procoagulant activity (P = 0.004), but they were under warfarin therapy. DD2 in the presence of MPs, independently of its number, was higher in patients with DVT at diagnosis (P < 0.0001). MPs of patients with spontaneous DVT at diagnosis can promote coagulation activation demonstrated by increased DD2. Even the increased MPs from patients 1-3 years after thrombotic episode generated lower amount of thrombin, they can have a protective effect by activation of Protein C anticoagulant pathway.

Topics: Adult; Antiphospholipid Syndrome; Blood Coagulation Tests; Case-Control Studies; Factor V; Female; Fibrin Fibrinogen Degradation Products; Flow Cytometry; Humans; Lipoproteins; Male; Particle Size; Substance Withdrawal Syndrome; Thrombin; Thrombosis; Venous Thrombosis; Warfarin

To compare efficacy and safety of warfarin and enoxaparin used in the first month of treatment of patients with an episode of deep vein thrombosis (DVT) and/or pulmonary artery thromboembolism (PATE).. Sixty patients (34 males, 26 females, age 18-76 years) after the DVT/PATE episode were divided into two groups. Patients of group 1 received standard therapy (non-fractionated heparin -NFH followed by warfarin), patients of group 2 instead of NFH received enoxaparin (1 mg/kg each 12 hours for at least 30 days). Ultrasonic scanning of the limbs and determination of D-dimer were conducted before and after 1 month of treatment. End points were the following: recurrent DVT/PATE, death due to PATE, hemorrhagic complications.. Improvement of deep vein patency after 1 month of anticoagulant treatment was observed in both the groups. Enoxaparin proved more effective in relation to reduction of the number of venous occlusions (9 and 50, respectively, after 1 month treatment (p < 0.001). Hemorrhagic complications were seen in both the groups with equal frequency (13.4%). These hemorrhagic episodes did not require discontinuation of the drugs. Baseline D-dimer was significantly higher in the enoxaparin group--1.51 (0.73-2.44) mcg/ml vs 0.93 (0.42-1.33) mcg/ml (p = 0.019). After treatment D-dimer level and number of patients with high D-dimer diminished in both groups.. Enoxaparin proved more effective than warfarin in the first treatment month. In the same safety and prophylactic effect enoxaparin is more effective in recanalization of occusions in the deep veins.

Topics: Adolescent; Adult; Aged; Anticoagulants; Enoxaparin; Female; Humans; Male; Middle Aged; Venous Thrombosis; Warfarin; Young Adult

Venous thrombosis and thromboembolism appear to occur more often in patient with inflammatory bowel disease (IBD). The cause of thrombotic complications in IBD is generally considered to be associated with hypercoagulable conditions. Its prevalence rate ranges from 1% to 8% in clinical studies and rises to 39% in autopsy, but the renal vein thrombosis is very rare complication in ulcerative colitis patient. A 24-year-old man presented with intermittent abdominal pain and hematochezia for 6 months and recently developed pitting edema for few weeks. He was diagnosed as severe ulcerative colitis involving whole colon combined with thrombosis in both renal veins by colonoscopy and computed tomography scan of abdomen. We used steroid for the treatment of ulcerative colitis and both intravenous lower molecular weight heparin and warfarin for renal vein thrombosis. His symptoms were improved after treatment and maintained with mesalazine and warfarin. Follow-up abdominal CT scan showed complete resolution of both renal vein thrombosis. Currently he has been followed up for 2 years with oral mesalazine.

Topics: Anticoagulants; Colitis, Ulcerative; Colonoscopy; Heparin; Humans; Male; Protein S; Renal Veins; Tomography, X-Ray Computed; Venous Thrombosis; Warfarin; Young Adult

A daily dose of vitamin K antagonists (VKAs) may vary and its range depends on various interrelated factors. Low responsiveness to VKA (defined as a failure to achieve a target international normalized ratio [INR]) is associated with polymorphisms of the vitamin K epoxide reductase-oxidase complex gene (VKORC1). A highly prevalent promoter single-nucleotide polymorphism (VKORC1-1639 G>A, rs17878363) impairs VKORC1 expression and determines the interindividual variability of the target INR. We studied 57 patients receiving oral anticoagulation, including 50 subjects treated with acenocoumarol (mean dose: 5.7+/-2.3 mg/day) and 7 treated with warfarin (mean dose: 9.6+/-4.2 mg/day). The indications for the use of oral anticoagulant therapy were as follows: deep-vein thrombosis (N = 23); pulmonary embolism (N = 20); arterial thrombosis (N = 5); stroke (N = 4); atrial fibrillation with transient ischemic attacks (N = 2), and history of multiple thromboembolic events (N = 3). Identification of the VKORC1 genomic variation was performed using DNA sequencing methods. The prevalence of the mutated allele (VKORC1 -1639A) was 41%. The VKORC1 -1639G allele carriers required a higher daily dose of acenocoumarol (5.9+/-1.9 mg) than the noncarriers (4.1+/-3.3 mg; P < 0.001). All of 5 low responders (who failed to achieve a target INR using standard dose requirements of VKAs) were homozygous for the 1639G allele. Low responders did not differ from good responders with respect to age, gender, and body mass index. Our findings suggest the potential benefits from pharmacogenetic testing, and provide evidence that the VKORC1 -1639 G>A gene polymorphism may explain at least in part the low responsiveness to acenocoumarol.

Topics: Acenocoumarol; Adult; Alleles; Anticoagulants; Atrial Fibrillation; Base Sequence; DNA Primers; Dose-Response Relationship, Drug; Drug Resistance; Female; Gene Frequency; Humans; International Normalized Ratio; Male; Middle Aged; Mixed Function Oxygenases; Poland; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Pulmonary Embolism; Venous Thrombosis; Vitamin K; Vitamin K Epoxide Reductases; Warfarin

Topics: Anticoagulants; Drug Administration Schedule; Humans; Risk Factors; Secondary Prevention; Venous Thrombosis; Warfarin

Topics: Adult; Aged; Anticoagulants; Blood Loss, Surgical; Catheterization, Central Venous; Colectomy; Female; Fibrinolytic Agents; Heparin; Humans; Male; Middle Aged; Pregnancy; Pregnancy Complications, Cardiovascular; Pulmonary Embolism; Thrombolytic Therapy; Tissue Plasminogen Activator; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Drug Administration Schedule; Humans; Risk Assessment; Secondary Prevention; Venous Thrombosis; Warfarin

Patent foramen ovale provides a passage from venous circulation to arterial circulation. This may allow passage of a thrombus formed in the venous system into the systemic circulation. We present a case in which a thrombus was entrapped in a patent foramen ovale. A 45-year-old woman presented with complaints of atypical chest pain and pretibial edema. Transthoracic echocardiography showed normal systolic function and grade I diastolic dysfunction. Pulmonary artery pressure was 43 mmHg. There was a mobile multilobular mass in the right atrium, attached to the interatrial septum via a thin pedicle. Transesophageal echocardiography showed a biatrial mass. It was 7-10 mm thick, multilobular, homogeneously echogenic, and highly mobile. It passed through the patent foramen ovale into the left atrium. The left atrial part was 6-8 mm thick, relatively shorter, and less mobile. The patient denied any symptoms related to a cerebrovascular accident. Heparin was initiated and an urgent operation was decided. Intraoperative transesophageal echocardiography showed that the mass was a thrombus which had become smaller due to anticoagulation. She had no neurologic symptoms postoperatively. Venous Doppler examination revealed deep vein thrombosis and warfarin was started.

Topics: Anticoagulants; Chest Pain; Echocardiography, Transesophageal; Female; Foramen Ovale, Patent; Heparin; Humans; Middle Aged; Treatment Outcome; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Health Knowledge, Attitudes, Practice; Humans; Leg; Venous Thrombosis; Warfarin

The coagulation enzyme factor Xa (FXa) has been recognized as a promising target for the development of new antithrombotic agents. We previously found compound 1 to be an orally bioavailable FXa inhibitor in fasted monkeys; however, 1 showed poor bioavailability in rats and fed monkeys. To work out the pharmacokinetic problems, we focused our synthetic efforts on the chemical conversion of the 4-(imidazo[1,2- a]pyridin-5-yl)piperazine moiety of 1 to imidazolylpiperidine derivatives (fused and nonfused), which resulted in the discovery of the weakly basic imidazo[1,5- c]imidazol-3-one 3q as a potent and selective FXa inhibitor. Compound 3q showed favorable oral bioavailability in rats and monkeys under both fasted and fed conditions and antithrombotic efficacy in a rat model of venous thrombosis after oral administration, without a significant increase in bleeding time (unlike warfarin). On the basis of these promising properties, compound 3q was selected for further evaluation.

Topics: Administration, Oral; Animals; Anticoagulants; Biological Availability; Blood Coagulation; Cytochrome P-450 CYP3A Inhibitors; Eating; Factor Xa Inhibitors; Humans; Imidazoles; Macaca fascicularis; Male; Mice; Mice, Inbred ICR; Models, Molecular; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship; Sulfones; Venous Thrombosis

Pregnant women have a higher risk of developing deep vein thrombosis (DVT) and consequent thrombogenic events, including pulmonary embolisms. Low-molecular-weight heparin (LMWH) products have been shown to successfully treat DVT with few significant side effects. The purpose of this study was to compare the effects of two dose regimens of enoxaparin (a LMWH) in the management of DVT in pregnancy.. A total of 35 pregnant patients with DVT were enrolled in this study. As first-line anticoagulation therapy, patients were administered an intravenous unfractionated heparin infusion for 5 days, followed by a subcutaneous injection of enoxaparin 1 mg/kg twice a day until discharge. The enoxaparin therapy continued at home with 1 mg/kg twice a day for 18 patients (group I) and 1.5 mg/kg once a day for the other 17 patients (group II). Enoxaparin was discontinued 12-24 hours before delivery and restarted within 8-12 hours after delivery. Warfarin was given as adjuvant therapy along with enoxaparin in the post-partum period. Enoxaparin was discontinued when an international normalised ratio of 2 or above was reached. Differences between the two groups in terms of therapy response, complications and efficacy were recorded.. Thrombophilic disease was observed in three patients in each group. The iliac vein had the highest incidence of DVT in both groups. During therapy, two patients in group I were diagnosed with a mild haemorrhage; one patient (in group II) had abortion. There were no significant differences between groups in terms of recanalisation (measured by venous ultrasonography examination), post-thrombotic symptoms or safety parameters.. Enoxaparin can be used safely in DVT therapy during pregnancy. Our results indicate that therapy consisting of a single daily dose of 1.5 mg/kg enoxaparin is as effective as twice-daily administration.

Topics: Adult; Anticoagulants; Dose-Response Relationship, Drug; Enoxaparin; Female; Humans; Injections, Subcutaneous; Pregnancy; Pregnancy Outcome; Thrombophilia; Venous Thrombosis; Warfarin; Young Adult

Topics: Acute Disease; Anticoagulants; Arthroplasty, Replacement; Humans; Perioperative Care; Pulmonary Embolism; Thrombophilia; Venous Thrombosis; Warfarin

To create physician awareness of complementary and alternative medicine therapy use in patients with prostate cancer so that physicians can monitor for adverse events. Approximately one fourth to one third of patients diagnosed with prostate cancer reported complementary and alternative medicine use, and many of these patients are taking a supplement called "Dr. Donsbach's Prostasol.". We discuss the cases of 2 patients with prostate cancer who were taking Dr. Donsbach's Prostasol and developed venous thromboembolic events while taking this supplement, in the absence of other obvious risk factors. We review these 2 cases and the time-line for the development of the venous thromboembolic events and use of Dr. Donsbach's Prostasol. We compared Prostasol with PC-SPES, a similar supplement that was associated with thrombosis and was ultimately taken off the market because of patient safety concerns.. Prostasol contains phytoestrogens that could result in both the suppression of testosterone and the predisposition to thrombosis. Both patients had suppression of their testosterone to castrate levels with an associated decrease in prostate-specific antigen at the time of their thrombotic event.. These cases are suggestive of an association between Prostasol use and venous thromboembolic events. Physicians should be aware of the use of this agent in their patients, although it is not known whether it would be appropriate to prescribe prophylactic low-dose warfarin therapy. If possible, additional study of complementary and alternative medicine therapies for safety and efficacy are indicated.

Topics: Aged; Aged, 80 and over; Complementary Therapies; Dietary Supplements; Drugs, Chinese Herbal; Enoxaparin; Humans; Male; Medical Oncology; Phytoestrogens; Plant Preparations; Prostatic Neoplasms; Venous Thromboembolism; Venous Thrombosis; Warfarin

The pharmacologic effects of warfarin might be altered by various factors, including drug-drug interaction.. A 49-year-old Japanese man (height, 174 cm; weight, 68 kg) presented with a 20-month history of malignant lymphoma (diffuse large B cell lymphoma, clinical stage IV). He was treated with a combination of rituximab chemotherapy and etoposide, cisplatin, high-dose cytarabine, and methyl-prednisolone (R-ESHAP). He had been receiving warfarin for the secondary prevention of pulmonary embolism with deep venous thrombosis. When R-ESHAP was started, international normalized ratio (INR) increased from 1 to 5. This phenomenon was observed again in the second R-ESHAP. The INR was increased from 2.44 to 4.71 during chemotherapy but was returned to within the normal range (1.05; normal range: 0.81-1.009) 5 days after chemotherapy was completed.. In this patient, R-ESHAP chemotherapy might have affected warfarin anticoagulation sensitivity; thus, careful monitoring of INR is essential, particularly in patients receiving warfarin who undergo R-ESHAP chemotherapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cytarabine; Drug Interactions; Etoposide; Follow-Up Studies; Humans; Lymphoma, Large B-Cell, Diffuse; Male; Methylprednisolone; Middle Aged; Pulmonary Embolism; Venous Thrombosis; Warfarin

Priapism is a rare disorder defined as a persistent penile erection that continues hours beyond, or is unrelated to, sexual stimulation. There are two types of priapism; ischemic low-flow type or non-ischemic high flow, with differing etiologies. Priapism associated with thrombophilia is a well-recognized entity. However, the pathogenesis of this association is not fully understood. We report a rare case of recurrent (stuttering) priapism in a patient with protein C deficiency while maintained on Warfarin therapy. This therapy was also complicated by Warfarin-induced skin necrosis.

Topics: Adult; Anticoagulants; Enoxaparin; Humans; Male; Priapism; Protein C Deficiency; Pulmonary Embolism; Venous Thrombosis; Warfarin

To evaluate efficacy of 3 month therapy with warfarin in patients after an episode of deep vein thrombosis (DVT) and/or pulmonary artery thromboembolism (PATE), safety of the treatment.. 26 patients after DVT/PATE aged 18-74 were treated in the hospital with non-fractionated heparin for 10-14 days followed by warfarin. The dose was selected under the control of INR up to target values 2.0-3.0. Ultrasound angioscanning of the limbs was conducted at hospitalization, on discharge, 1 and 3 months after the discharge. D-dimer was measured at discharge, 1 and 3 months after the discharge. The patients were followed up for 3 months. The following end points were considered: recurrences of deep or surface vein thrombosis, PATE recurrence, death due to PATE, hemorrhagic complications.. By ultrasound angioscanning significant positive results were not achieved. The level of D-dimer upon discharge was elevated in 18 (69.2%) patients (0.94, 0.41-1.69 mcg/ml). 3 month therapy with warfarin resulted in complete solution of all floting thrombs, achievement of recanalization of occlusive thrombosed deep vein in 20 (80%) patients, thrombosed vein number reduced from 4.0 to 3.0, p = 0.004. Deep vein thrombs disappeared only in 3 (11.5%) patients in 3 bmonths. Warfarin lowered D-dimer content to 0.23 mcg/ml (p < 0.001) in 1 month and to 0.12 mcg/ml (p < 0.001) in 3 moths after the discharge. 23 patients reached target 2.0-3.0 values and maintained them in therapeutic ranges. In DVT recurrence no PATE and PATE-related deaths were registered. Hemorrhagic complications arose in 5 patients, but they did not lead to warfarin discontinuation.. Warfarin is effective for secondary prophylaxis of DVT/PAT, but this therapy failed to solve thrombs in the deep veins in many patients.

Topics: Adolescent; Adult; Aged; Anticoagulants; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fibrin Fibrinogen Degradation Products; Follow-Up Studies; Humans; Male; Middle Aged; Recurrence; Time Factors; Treatment Outcome; Venous Thrombosis; Warfarin

We report here the case of a 18-year-old young man with Behçet's disease who had suffered deep venous thrombosis of the right femoral and popliteal veins. Consequently, right sciatic nerve injury, drop foot and tightness of the achilles tendon also ensued. The clinical scenario was further challenged by demonstration of the agenetic inferior vena cava and epidural vein dilatations compressing the lumbar nerve roots. To the best notice of the authors, this is the first patient encompassing all these complications in the literature concerning Behçet's disease.

Topics: Adolescent; Amines; Behcet Syndrome; Colchicine; Cyclohexanecarboxylic Acids; Drug Therapy, Combination; Gabapentin; gamma-Aminobutyric Acid; Heparin; Humans; Injections, Intravenous; Interferons; Male; Nerve Compression Syndromes; Physical Therapy Modalities; Sciatic Nerve; Sciatica; Vena Cava, Inferior; Venous Thrombosis; Warfarin

To describe a complication of placement of an inferior vena cava (IVC) filter in a man with paraplegia.. Case report.. A 48-year-old man with T11 paraplegia secondary to an L1 burst fracture underwent thoracic spinal fusion. The postoperative course was complicated by deep vein thrombosis (DVT) of the right common femoral vein, which was treated with warfarin.. During rehabilitation, the hematocrit declined, and fluctuance was noted along the surgical site. Computed tomographic scan suggested a hematoma in the paraspinal and latissimus dorsi muscles. Warfarin was discontinued, and an IVC filter was placed. He subsequently developed severe leg pain, followed by hypotension, acute renal failure, and compartment syndrome in bilateral lower extremities requiring fasciotomies. Ultrasound and computed tomographic angiogram showed extensive bilateral lower extremity DVTs and pulmonary emboli. The diagnosis of cerulea dolens was made. Mechanical and pharmacological thrombectomy was aborted secondary to bleeding complications and hypotension. The patient died shortly after care was withdrawn at the family's request. The autopsy revealed multiple thrombi in IVC, bilateral pelvic and femoral veins, and left pulmonary artery embolus, consistent with phlegmasia cerulea dolens.. Inferior vena cava filters may prevent pulmonary embolism but do not affect the underlying thrombotic process. An IVC filter should be recognized as a possible thrombogenic nidus in patients with spinal cord injury who have known DVT.

Topics: Anticoagulants; Fatal Outcome; Humans; Male; Middle Aged; Paraplegia; Pulmonary Embolism; Spinal Cord Injuries; Spinal Fractures; Thrombophlebitis; Tomography, X-Ray Computed; Vena Cava Filters; Venous Thrombosis; Warfarin

A large thrombus entrapped in an atrial septal defect is a rare condition that can lead to life-threatening systemic and pulmonary embolization. The use of thrombolysis may prove dangerous to the patient. Herein, we describe the emergency surgical management that contributed to a successful outcome in a 67-year-old man who was found to have a 23-cm-long thrombus across an atrial septal defect.

Topics: Aged; Anticoagulants; Echocardiography; Heart Septal Defects, Atrial; Heparin; Humans; Male; Paraplegia; Pulmonary Embolism; Thromboembolism; Thrombosis; Vena Cava Filters; Venous Thrombosis; Warfarin

The aim of this study was to compare the efficacy of immunosuppressive therapy alone with that of combination therapy involving immunosuppressants and anticoagulation for the treatment of venous thrombosis in Behcet's disease (BD). A retrospective analysis was made of 37 patients with venous thrombosis in BD. BD patients with venous thrombosis were divided into three groups: one group (N = 16) received immunosuppressive therapy alone, another group (N = 17) received immunosuppressant and anticoagulation combination therapy, and the third group (N = 4) received anticoagulation therapy only. Clinical and laboratory parameters and the recurrence of venous thrombosis were assessed. Venous thrombosis in BD appeared to have a more diffuse pattern than idiopathic type and a predilection for lower limbs. The most commonly involved sites were the superficial and common femoral veins. Recurrence of venous thrombosis occurred in two cases in the immunosuppressant group (12.5%), one case in the combination therapy group (5.9%), and three cases in the anticoagulant group (75%). No significant difference was found between recurrence in the immunosuppressant and combination therapy groups. Acute phase reactants were elevated in all six patients at the time of venous thrombosis recurrence. Our study suggests that immunosuppressive therapy is essential and that anticoagulation therapy might not be required for the treatment of deep venous thrombosis associated with BD.

Topics: Adrenal Cortex Hormones; Adult; Anticoagulants; Behcet Syndrome; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Retrospective Studies; Venous Thrombosis; Warfarin

To determine if transitioning patients from a pharmacist- managed anticoagulation clinic after stabilization of warfarin therapy to physician-managed care alters the quality of anticoagulation care.. Retrospective medical record review.. Pharmacist-managed, urban academic medical center-based outpatient anticoagulation clinic.. Forty patients who were stabilized on warfarin therapy.. Quality of anticoagulation care was measured by percentage of international normalized ratios (INRs) in target range, anticoagulation-related health care visits, and responses to satisfaction surveys. A significant decrease in anticoagulation control was observed on transition to physician-managed care. Before transition, 76% of all INRs were in target range versus 48% after transition (p<0.0001, chi(2) test). When performing paired analysis, a median 75% of each patient's INRs were therapeutic before transition compared with 36.5% after (p<0.0001, Wilcoxon signed rank test). Thirty-two percent of first INR values measured after transition from the clinic were in target range, and the median time to first follow-up INR was 41 days. The number of INR values above 4.5 and below 1.5 increased significantly after transition from the anticoagulation clinic (p<0.0001 and p=0.01, respectively, chi(2) test). Before transition from the anticoagulation clinic, two anticoagulation-related emergency department visits were reported in one patient. After transition, 13 cases of additional medical care were reported among seven patients; seven of the 13 cases required an office visit with the physician, and six resulted in emergency room evaluation. None of these cases resulted in hospitalization. Patient satisfaction with clinical care provided by the anticoagulation clinic was significantly higher before transition.. Transition of patients from a pharmacist-managed anticoagulation clinic back to physician-managed anticoagulation care after stabilization of warfarin therapy was associated with a significant decrease in INR control, increased medical care related to anticoagulation, and decreased patient satisfaction.

Topics: Ambulatory Care; Ambulatory Care Facilities; Anticoagulants; Atrial Fibrillation; Female; Humans; International Normalized Ratio; Male; Medical Records; Patient Discharge; Patient Satisfaction; Pharmaceutical Services; Pharmacists; Physicians; Professional Role; Quality of Health Care; Retrospective Studies; Venous Thrombosis; Warfarin

To determine whether treatment guidelines for patients with lower-extremity venous thrombosis (DVT) could be applied to patients with renal vein thrombosis (RVT). The rates of recurrent venous thrombosis and survival for patients with these 2 diseases were compared.. Inception cohort of individuals was identified with their first lifetime incident of RVT. Recurrent thrombosis and survival were compared with those for patients with DVT in a case-control fashion.. All patients with a diagnosis of RVT at Mayo Clinic from 1980 to 2000.. Survival and recurrent venous thrombosis rates were compared with those for patients with DVT. Survival rates were also compared with those for US white residents.. 218 patients (mean age, 55 +/- 19 years) were included (35% women). Malignancy (66%) and nephrotic syndrome (20%) were the most common underlying causes. Warfarin was prescribed for 74 patients (46% with lifelong therapy). During a mean follow-up of 42 +/- 57 months (768 patient-years), there were 8 recurrent venous thrombotic events (1.0/100 patient-years). This recurrence rate was less than that for patients with DVT (P < 0.001). Survival was lower compared with patients with DVT or age- and sex-matched US white residents (P < 0.001). Active malignancy (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.2 to 4.7) and infection (HR, 2.4; 95% CI, 1.4 to 4.0) were associated with poor survival. Survival was influenced positively by warfarin therapy (HR, 0.53; 95% CI, 0.31 to 0.90).. Retrospective nonrandomized study.. RVT represents a distinct clinical entity with unique recurrence and survival rates. The finding of RVT should prompt a thorough evaluation for an underlying renal malignancy. Oral anticoagulation therapy may be associated with a survival advantage.

Topics: Adult; Aged; Anticoagulants; Case-Control Studies; Cohort Studies; Female; Follow-Up Studies; Humans; Kidney Neoplasms; Male; Middle Aged; Multivariate Analysis; Nephrotic Syndrome; Odds Ratio; Recurrence; Renal Veins; Retrospective Studies; Survival Analysis; Survival Rate; United States; Venous Thromboembolism; Venous Thrombosis; Warfarin; White People

Topics: Acute Disease; Anticoagulants; Arginine; Blood Coagulation; Factor Xa Inhibitors; Fondaparinux; Hemorrhage; Heparin; Hirudins; Humans; International Normalized Ratio; Pipecolic Acids; Platelet Count; Polysaccharides; Recombinant Proteins; Research Design; Sulfonamides; Thrombin; Thrombocytopenia; Treatment Outcome; Venous Thrombosis; Warfarin

In antiphospholipid syndrome (APS), there is a high prevalence of valvular heart disease which leads to increased risk of thrombo-embolic events, in particular, cerebrovascular events. We present a patient with cerebral infarction, previous deep-vein thrombosis, and miscarriages with positive lupus anticoagulant and anticardiolipin antibodies. Echocardiographic examination revealed mitral valve leaflet thickening and verrucous vegetations consistent with Libman-Sacks endocarditis, which is commonly associated with APS. In patients with combined Libman-Sacks endocarditis and antiphospholipid antibodies, anticoagulation therapy with warfarin is indicated due to high risk of valvular thrombus formation and subsequent embolization.

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Cerebral Infarction; Endocarditis; Female; Humans; Intracranial Embolism; Lupus Erythematosus, Systemic; Venous Thrombosis; Warfarin

Idiopathic mesenteric venous thrombosis is a rare entity. An early diagnosis and thrombolytic and anticoagulant therapy are very important.. We report a case of a patient, without any specific known risk factor, with small intestinal ischemia secondary to superior mesenteric vein thrombosis (SMVT).. In our case, only a computed tomography (CT) abdominal scan permitted the diagnosis of SMVT. The patient was successfully treated by resection of the infarcted bowel with primary anastomosis and immediate postoperative anticoagulation.. Diagnosis of intestinal ischemia from mesenteric venous thrombosis (MVT) is often delayed because the symptoms are nonspecific. Moreover, when there is not any known predisposing factor, the diagnosis may become even more difficult with significant morbidity and mortality. CT abdominal scan done early in case of nonspecific abdominal pain, since the patients had a previous history of venous thrombosis, may not require a surgical treatment of MVT.

Topics: Anticoagulants; Female; Humans; Mesenteric Veins; Middle Aged; Venous Thrombosis; Warfarin

Oral anticoagulation management is difficult in rural settings because of reduced patient access to pathology testing and medical management. Previous research reports the effectiveness of coordinated anticoagulation management incorporating education, point of care international normalised ratio (INR) testing, patient self care models, protocols and use of specially trained personnel. This article presents findings on the assessment of a Victorian rural program using a modified anticoagulation clinic and other strategies to improve anticoagulation management.. This program assessed multiple strategies including comprehensive patient education, protocols and point of care INR testing. These were implemented in a rural hospital and rural general practices. Specific measures for evaluation were time in the therapeutic INR range and complication rate.. Time in the therapeutic INR range was 69% for the standard range (2.0-3.0) and 81% using an expanded range (1.8-3.0). The anticoagulation related complication rate was 0.03 per patient year (95% CI: 0.01, 0.06). International normalised ratio testing every 14 days resulted in 78% of time spent in therapeutic range.. The strategies employed in the study increased time spent in therapeutic range and reduced anticoagulation related complications.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Australia; Female; Hemorrhage; Humans; Male; Patient Acceptance of Health Care; Patient Education as Topic; Prothrombin Time; Pulmonary Embolism; Rural Health Services; Thromboembolism; Venous Thrombosis; Warfarin

Topics: Antibodies, Anticardiolipin; Anticoagulants; Cryoglobulinemia; Debridement; Enoxaparin; Hepatitis C; Humans; Male; Middle Aged; Necrosis; Penis; Plastic Surgery Procedures; Vasculitis, Leukocytoclastic, Cutaneous; Venous Thrombosis; Warfarin

A case of inferior vena cava syndrome following percutaneous vertebroplasty is described herein.. To alert clinicians to the potential occurrence of inferior vena cava syndrome following percutaneous vertebroplasty.. Vertebroplasty is a less invasive treatment solution for the osteoporotic compression fracture. There complications of the cement leakage would appear to have been rather infrequent. We report a case of inferior vena cava syndrome related to the cement leakage.. A 59-year-old woman underwent percutaneous vertebroplasty for painful T11, L1, L2, and L3 compression fractures, under general anesthesia at a community hospital. A contralateral transpedicular approach was made in order to inject polymethylmethacrylate resin into the fractured vertebra.. Just subsequent to surgery, this patient developed dyspnea, arthralgia, myalgia, and progressive right lower-limb pain, redness, and swelling., conservative treatment being then undertaken, albeit in vain. One week after the attempted remediation of this patient's condition, she was transferred to our hospital for further management. After admission, radiography of the patient's lumbar spine (lateral view) revealed multiple cement leakage in the area of the posterior longitudinal ligament and also in the anterior paravertebral area. The abdominal and pelvic CT scan and venography revealed vertebroplasty cement leakage into the lumbar vein, the left renal vein, and the inferior vena cava. Thrombosis at the left common iliac vein and left femoral vein were noted with extension into the inferior part of the inferior vena cava. Intravenous heparin was then administered to our patient for the ensuing 20 days, at which time heparin was replaced by warfarin, in order to attempt to prevent progressive venous thrombosis. The patient's leg edema appeared to improve 10 weeks subsequent to her surgery, she then being able to perambulate using a rigid walker.. This case illustrates the need for clinicians to be critically aware of the potential occurrence of inferior vena cava syndrome among patients who have undergone percutaneous vertebroplasty, especially when multiple levels of vertebra are injected as part of the vertebroplasty procedure.

Topics: Anticoagulants; Bone Cements; Female; Fractures, Compression; Heparin; Humans; Lumbar Vertebrae; Middle Aged; Phlebography; Polymethyl Methacrylate; Spinal Fractures; Syndrome; Thoracic Vertebrae; Tomography, X-Ray Computed; Treatment Outcome; Vena Cava, Inferior; Venous Thrombosis; Vertebroplasty; Warfarin

Topics: Aged; Anticoagulants; Case-Control Studies; Drug Resistance; Female; Gene Frequency; Genetic Predisposition to Disease; Haplotypes; Humans; Male; Mixed Function Oxygenases; Odds Ratio; Peripheral Vascular Diseases; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Risk Assessment; Risk Factors; Venous Thromboembolism; Venous Thrombosis; Vitamin K Epoxide Reductases; Warfarin

Topics: Adult; Angiography, Digital Subtraction; Anticoagulants; Arm; Diagnosis, Differential; Humans; Male; Venous Thrombosis; Warfarin

The natural history of chronic portomesenteric (PM) and portosplenomesenteric (PSM) venous thrombosis is defined poorly. Therapeutic options are limited, and are directed at the prevention of variceal bleeding and the control of abdominal pain related to gastrointestinal hyperemia.. Patients with extensive PM and PSM thrombosis were reviewed retrospectively to evaluate the efficacy of medical therapy and to determine which clinical variables had prognostic significance regarding long-term survival.. Sixty patients, with a median age at diagnosis of 44 years (range, 18-68 y), were assessed. The median follow-up period was 3.5 years (range, 0.2-32.0 y). The overall survival rate was 73.3%, with 1- and 5-year survival rates of 81.6%, and 78.3%, respectively. One- and 5-year survival rates, excluding patients who died from malignancy-related causes, were 85.7% and 82.1%, respectively. Factors associated with improved survival included treatment with beta-blockers (P = .02; odds ratio [OR], .09; 95% confidence interval [CI], 0.01-0.70) and anticoagulation (P = .005; OR, 0.01; 95% CI, <0.01 to 0.26). Eighteen patients in total were anticoagulated, including 8 patients who had variceal bleeding, all of whom underwent endoscopic band ligation of esophageal varices before anticoagulation. By using Cox regression analysis, variables associated with reduced survival were the presence of ascites (P = .001; OR, 42.6; 95% CI, 5.03-360), and hyperbilirubinemia (P = .01; OR, 13.8; 95% CI, 1.9-100) at presentation. Six patients died of variceal hemorrhage.. Patients with chronic PM and PSM venous thrombosis without underlying malignancy have an acceptable long-term survival. Treatment with beta-blockers and anticoagulation appears to improve outcome.

Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Aged; Anticoagulants; Ascites; Chronic Disease; Esophageal and Gastric Varices; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Hyperbilirubinemia; Ligation; London; Male; Mesenteric Vascular Occlusion; Mesenteric Veins; Middle Aged; Multivariate Analysis; Serum Albumin; Survival Rate; Venous Thrombosis; Warfarin

Cerebral venous thrombosis (CVT) is rare and has a wide spectrum of symptoms, therefore it is difficult to diagnose. Thrombosis of the deep cerebral veins occurs very rarely: it has been reported that approximately 6% of patients with CVT have deep CVT, and the prognosis for patients with this condition is poor. CVT has been reported in association with dehydration, a hypercoagulable state, mastoiditis, tumour invasion of a venous sinus, use of oral contraceptives, pregnancy, puerperium, head trauma, vasculitis, and intracranial and systemic infections. However, in the literature, there are few reported cases of CVT in association with iron deficiency anaemia, especially in adults. We present here two patients with bilateral thalamic and basal ganglionic lesions due to thrombosis of the deep cerebral veins. Both of our patients had severe hypochromic microcytic anaemia due to iron deficiency, and both had a good prognosis after 2 months.

Topics: Adolescent; Adult; Anemia, Iron-Deficiency; Anticoagulants; Basal Ganglia; Blood Component Transfusion; Cerebral Veins; Erythrocytes; Female; Heparin, Low-Molecular-Weight; Humans; Intracranial Thrombosis; Thalamus; Treatment Outcome; Venous Thrombosis; Warfarin

Prolonged wound drainage following total hip or total knee arthroplasty has been associated with an increased risk of postoperative morbidity. The purpose of this study was to determine the pharmacologic, surgical, and patient-specific factors that are associated with prolonged wound drainage and the relationship of this complication to the length of hospital stay and the rate of wound infections.. We conducted a retrospective observational study of 1211 primary total hip arthroplasties and 1226 primary total knee arthroplasties. Prospectively collected data included body mass index, intraoperative blood loss, surgical time, type of prophylaxis against deep venous thrombosis, and length of hospital stay. The association of these factors with the duration of postoperative wound drainage was analyzed. An acute infection developed after fifteen primary total hip arthroplasties and ten primary total knee arthroplasties. The patients with an acute postoperative infection were compared with their uninfected counterparts, and an odds ratio was determined to estimate the risk of prolonged wound drainage resulting in a wound infection.. Morbid obesity was strongly associated with prolonged wound drainage in the total hip arthroplasty group (p = 0.001) but not in the total knee arthroplasty group (p = 0.590). An increased volume of drain output was an independent risk factor for prolonged wound drainage in both groups. Patients who received low-molecular-weight heparin for prophylaxis against deep venous thrombosis had a longer time until the postoperative wound was dry than did those treated with aspirin and mechanical foot compression or those who received Coumadin (warfarin); this difference was significant on the fifth postoperative day (p = 0.003) but not by the eighth postoperative day. Prolonged wound drainage resulted in a significantly longer hospital stay in both groups (p < 0.001). Each day of prolonged wound drainage increased the risk of wound infection by 42% following a total hip arthroplasty and by 29% following a total knee arthroplasty.. Morbid obesity, the use of low-molecular-weight heparin, and a higher drain output were associated with a prolonged time until the postoperative wound was dry following a primary total hip arthroplasty, whereas a higher drain output was the only risk factor associated with prolonged drainage following a primary total knee arthroplasty. Prolonged drainage was associated with a higher rate of infection following a primary total hip arthroplasty, whereas obesity was the only identified independent risk factor for postoperative infection following a primary total knee arthroplasty.

Topics: Aged; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Body Mass Index; Drainage; Female; Heparin, Low-Molecular-Weight; Humans; Kaplan-Meier Estimate; Length of Stay; Linear Models; Logistic Models; Male; Middle Aged; Obesity, Morbid; Postoperative Complications; Retrospective Studies; Risk Factors; Surgical Wound Infection; Venous Thrombosis; Warfarin; Wound Healing

Topics: Anticoagulants; Fibrin Fibrinogen Degradation Products; Humans; Pulmonary Embolism; Secondary Prevention; Venous Thrombosis; Warfarin

While it has long been recognized that patients with acute unprovoked deep vein thrombosis (DVT) or pulmonary embolism (PE) have a higher risk of recurrent venous thromboembolism (VTE) than that of patients with secondary thrombosis, whether other clinical parameters can help predict the development of recurrent events is controversial. The aim of this investigation was to assess the rate of recurrent VTE after withdrawal of vitamin K antagonists, and to identify clinical parameters associated with a higher likelihood of recurrence.. We followed, up to a maximum of 10 years, 1626 consecutive patients who had discontinued anticoagulation after a first episode of clinically symptomatic proximal DVT and/or PE. All patients with clinically suspected recurrent VTE underwent objective tests to confirm or rule out the clinical suspicion.. After a median follow-up of 50 months, 373 patients (22.9%) had had recurrent episodes of VTE. The cumulative incidence of recurrent VTE was 11.0% (95% CI, 9.5-12.5) after 1 year, 19.6% (17.5-21.7) after 3 years, 29.1% (26.3-31.9) after 5 years, and 39.9% (35.4-44.4) after 10 years. The adjusted hazard ratio for recurrent VTE was 2.30 (95% CI, 1.82-2.90) in patients whose first VTE was unprovoked, 2.02 (1.52-2.69) in those with thrombophilia, 1.44 (1.03-2.03) in those presenting with primary DVT, 1.39 (1.08-1.80) for patients who received a shorter (up to 6 months) duration of anticoagulation, and 1.14 (1.06-1.12) for every 10-year increase of age. When the analysis was confined to patients with unprovoked VTE the results did not change.. Besides unprovoked presentation, other factors independently associated with a statistically significant increased risk of recurrent VTE are thrombophilia, clinical presentation with primary DVT, shorter duration of anticoagulation, and increasing age.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Cohort Studies; Female; Heparin; Humans; Male; Middle Aged; Prospective Studies; Pulmonary Embolism; Secondary Prevention; Thromboembolism; Thrombophilia; Venous Thrombosis; Warfarin

To evaluate patency and clinical outcome in patients treated with catheter-directed thrombolysis and stent placement for acute extensive thrombosis affecting the iliocaval segment.. During a 10-year period (1994-2005), 37 patients with 44 limbs (26 female, median age 31 years) with acute extensive venous thrombosis affecting the iliocaval segment were treated with catheter-directed thrombolysis. Angioplasty and stent placement was performed in 36 limbs (82%) for underlying stenosis or residual thrombosis. A prospectively registered database was analyzed in combination with a telephone interview about clinical symptoms.. Technical success was achieved in all 44 limbs and clinical success in 42 of 44 (96%) limbs. Primary patency after a median imaging follow-up interval of 16 months was 34 of 44 (77%) limbs, assisted primary patency was 38 of 44 (86%) limbs, and secondary patency was 39 of 44 (89%) limbs. Thirty of 44 (68%) limbs were asymptomatic after a median clinical follow-up of 27 months, eight (18%) limbs were moderately improved, two (5%) limbs were unchanged, two (5%) limbs were moderately worse, and two (5%) limbs had no clinical follow-up. Complications occurred in six (16%) patients, three (8%) of which were major complications. No patient developed symptomatic pulmonary embolism.. Catheter-directed thrombolysis and stent placement is a safe and effective treatment for acute iliocaval thrombosis. Clinical midterm results are encouraging. Thrombolyzed and stented segments remain patent in the vast majority of patients after 16 months. Primary and aggressive stent placement in the iliocaval vein segments can prevent rethrombosis and ensure patency.

Topics: Acute Disease; Adult; Angioplasty, Balloon; Anticoagulants; Databases as Topic; Female; Follow-Up Studies; Heparin; Humans; Iliac Vein; Leg; Male; Prospective Studies; Radiography, Interventional; Stents; Stockings, Compression; Thrombolytic Therapy; Treatment Outcome; Ultrasonography, Interventional; Vascular Patency; Vena Cava, Inferior; Venous Thrombosis; Warfarin

This multicenter, prospective, open label, observational study evaluated practice patterns of physicians using tinzaparin, a low-molecular-weight heparin (LMWH), and warfarin for the treatment of deep venous thrombosis (DVT) with or without pulmonary embolism (PE). Short-term recurrence of venous thromboembolism (VTE) and safety were also evaluated. Patients with an objective diagnosis of DVT, with or without PE, were invited by their physician to participate in this study. Treatment was given according to the approved U.S. package inserts for tinzaparin (175 IU/kg SQ QD) and warfarin and the clinical judgment of the prescribing physician. Baseline patient history including demographic information and the results of tests to confirm the diagnosis of DVT, with or without PE, were collected. Follow-up information included the treatment setting in which each dose of tinzaparin was administered, medical training of the person administering tinzaparin doses, timing of initiation of warfarin with respect to that of tinzaparin, length of overlap of tinzaparin and warfarin therapy, and adverse experiences. A total of 334 patients were enrolled at 65 sites. Patients across a wide age (range 18-93 years old) and body weight (range 40-261 kg) were included. Overall, 27.3% of patients had cancer, and 50% of the overall study population reported more than one VTE risk factor. Mean duration of tinzaparin treatment was 7.61 days. Therapy at home was more common in suburban and rural settings than in urban settings. High proportions of patient, even among the small group with concurrent PE, were treated at home with self-injection. Severity of disease was the primary reason for hospitalization. Home treatment of DVT, with or without PE, with self administration of tinzaparin at 175 IU SQ once-daily was safe and resulted in an acceptably low rate of recurrent venous thromboembolism and adverse events. Home therapy in the usual practice setting should achieve substantial overall cost savings in the treatment of DVT.

Topics: Aged; Aged, 80 and over; Anticoagulants; Female; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Home Care Services; Humans; Injections, Subcutaneous; Male; Middle Aged; Outpatients; Practice Patterns, Physicians'; Prospective Studies; Pulmonary Embolism; Self Administration; Tinzaparin; Venous Thromboembolism; Venous Thrombosis; Warfarin

Limited data exist on the quality of care for patients with venous thromboembolism (VTE), and it is unknown whether the processes and outcomes of care for this illness differ between African Americans and whites.. We retrospectively studied 168 patients hospitalized for VTE in two Veterans Affairs hospitals during fiscal years 2000-2002. Patient characteristics, information about processes of care, and medical outcomes at 90 days after the index VTE event were abstracted from medical records. We used logistic regression to explore associations between race, processes of care, and the overall 90-day complication rate (i.e., death, bleeding, or recurrent VTE), adjusting for patient baseline characteristics.. Multivariable analysis demonstrated that administration of warfarin within 1 day of starting heparin (odds ratio [OR] 0.20, 95% confidence interval [CI]: 0.05-0.42) and overlap of heparin and warfarin treatment >or=4 days (OR 0.09, 95% CI: 0.02-0.50) were associated with a lower complication rate, and African American race was associated with a higher complication rate (OR 5.2, 95% CI: 1.3-21.6). Race was not significantly associated with the performance of processes of care in multivariable analysis.. Although African Americans had an increased risk of complications following VTE, race was not independently associated with the use of processes of care for VTE.

Topics: Anticoagulants; Black or African American; Female; Heparin; Humans; Male; Middle Aged; Quality of Health Care; Retrospective Studies; Risk Factors; Thromboembolism; Treatment Outcome; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Retinal Vein Occlusion; Treatment Outcome; Venous Thrombosis; Warfarin

Topics: Aged; Anticoagulants; Arm; Chest Pain; Dyspnea; Edema; Enoxaparin; Exercise; Factor V; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Mutation; Ultrasonography, Doppler; Venous Thrombosis; Warfarin

Thymomas are common mediastinal tumours. We report a rare case of thymoma invasion into the superior vena cava with resultant venous obstruction. The tumour was resected. The superior vena cava and left brachiochephalic vein were reconstructed with autologous pericardial patch.

Topics: Aged; Blood Vessel Prosthesis; Female; Follow-Up Studies; Humans; Radiography; Respiratory Paralysis; Superior Vena Cava Syndrome; Thrombectomy; Thymoma; Thymus Neoplasms; Venous Thrombosis; Warfarin

Mesenteric venous thrombosis (MVT) is an unusual site of deep venous thrombosis. Little is known about risk factors of MVT, but available data seem to confirm a pathogenetic role of acquired thrombotic risk factors as well as inherited thrombotic risk factors. However, few cases on the association of MVT with oral contraceptive use have been described. We here report a case of MVT in a woman on oral contraception with fine and complete resolution after a fast diagnosis with abdominal ultrasound imaging and prompt therapy based on low molecular weight heparin.

Topics: Administration, Oral; Adult; Anticoagulants; Contraceptives, Oral; Female; Follow-Up Studies; Heparin, Low-Molecular-Weight; Humans; Mesenteric Vascular Occlusion; Mesenteric Veins; Time Factors; Treatment Outcome; Ultrasonography; Venous Thrombosis; Warfarin; White People

To describe the clinical course of patients undergoing vitreoretinal procedures while receiving systemic anticoagulation with warfarin.. We reviewed patient demographics, ocular findings, and clinical courses for 25 patients receiving systemic anticoagulation with warfarin who subsequently underwent vitreoretinal surgery.. Patient ages ranged from 49 years to 81 years (median, 69 years). Indications for anticoagulation included atrial fibrillation, cerebrovascular disease, deep vein thrombosis, prosthetic heart valves, and hypercoagulable state. Follow-up ranged from 4 months to 36 months (median, 19.5 months). The international normalized ratio ranged from 1.5 to 3.1 (median, 2.0). Final vision after surgery ranged from 20/20 to 20/400 (median, 20/100). One patient who underwent scleral buckling and external drainage of subretinal fluid had an intraoperative subretinal hemorrhage associated with the drainage procedure. In all other patients, no intraoperative complications occurred.. Cessation of therapy with warfarin may not be necessary in patients receiving anticoagulation who are undergoing vitreoretinal procedures. Successful visual and anatomical results may be achieved after vitreoretinal surgery for patients receiving anticoagulation with warfarin. The management of anticoagulation should occur in conjunction with the patient's internist to allow a clear understanding of the potential systemic risks of cessation of warfarin treatment preoperatively.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Cryotherapy; Eye Diseases; Female; Humans; International Normalized Ratio; Male; Middle Aged; Retinal Diseases; Retrospective Studies; Scleral Buckling; Thrombophilia; Venous Thrombosis; Vitrectomy; Vitreous Body; Warfarin

Among patients treated with warfarin for venous thromboembolism (VTE), cancer patients have more thrombotic and hemorrhagic events than patients without cancer. Is this also the case when cancer patients are anticoagulated for other indications?. The objective of the study is to evaluate the effectiveness of warfarin, given for any indication, among patients with cancer in a community setting.. We identified patients with cancer from a larger prospective cohort of 6,761 patients from 101 clinical sites in the United States, matched to controls without cancer. The proportion of time spent in the therapeutic range, international normalized ration (INR) variability, and the rate of thromboembolic and major hemorrhagic events were compared between the two groups.. Ninety-five patients undergoing treatment for cancer were matched to 283 patients without cancer. The cancer group spent less time in the target INR range (54 vs 66%, P < .001) and had more variable INR values (standard deviation around the mean INR value 1.30 vs 0.71, P < .001). There were more thrombotic events in the cancer group than in the control group (5 vs 0 events, P < .001). These analyses were repeated after excluding all of the patients anticoagulated for VTE; the results were unchanged.. Compared to matched controls, cancer patients receiving warfarin spend less time in the target INR range, have more variable INR values, and have more thrombotic events. These effects are not dependent on whether the patient is anticoagulated for VTE or another indication.

Topics: Aged; Aged, 80 and over; Anticoagulants; Cohort Studies; Female; Humans; International Normalized Ratio; Male; Neoplasms; Prospective Studies; Treatment Outcome; Venous Thrombosis; Warfarin

Authors describe a case of systemic sclerosis with deep venous thrombosis. Great attention must be taken for this case because it represents the condition of hereditary thrombophilia. No similar case was reported in literature; therefore, further studies must go ahead understand the possible relation between the two pathologies.

Topics: Adult; Anticoagulants; Blood Coagulation Disorders, Inherited; Drug Therapy, Combination; Enoxaparin; Factor V; Female; Femoral Vein; Fibrinolytic Agents; Follow-Up Studies; Humans; Methylenetetrahydrofolate Reductase (NADPH2); Mutation; Popliteal Vein; Prothrombin; Saphenous Vein; Scleroderma, Systemic; Thrombophilia; Time Factors; Ultrasonography, Doppler, Color; Venous Thrombosis; Warfarin

Central venous catheters in patients with cancer are associated with development of deep vein thrombosis (DVT); however, there is no accepted standard treatment.. To assess the safety and effectiveness of a management strategy for central venous catheter-related DVT in cancer patients consisting of dalteparin and warfarin without the need for line removal.. Patients older than 18 years of age with an active malignancy and who had symptomatic, acute, objectively documented UEDVT were eligible. Patients were treated with dalteparin 200 IU kg(-1) per day for 5-7 days and warfarin with a target International Normalized Ratio of 2.0-3.0. Patients were followed for 3 months for recurrent venous thromboembolism, major hemorrhage and survival of the central venous catheter.. There were 74 patients (48 males). The average age was 58 years. There were no episodes of recurrent venous thromboembolism and three (4%) major bleeds. No lines were removed because of infusion failure or recurrence/extension of DVT.. Treatment of UEDVTs secondary to central catheters in cancer patients with standard dalteparin/warfarin can allow the central line to remain in situ with little risk of line failure or recurrence/extension of the DVT.

Topics: Aged; Anticoagulants; Catheterization, Central Venous; Cohort Studies; Dalteparin; Female; Humans; International Normalized Ratio; Male; Middle Aged; Neoplasms; Pilot Projects; Treatment Outcome; Venous Thrombosis; Warfarin

Topics: Adult; Anticoagulants; Combined Modality Therapy; Female; Fibrinolytic Agents; Heparin; Heparin, Low-Molecular-Weight; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Risk Factors; Tinzaparin; Twins; Ultrasonography, Doppler; Vacuum Extraction, Obstetrical; Vena Cava Filters; Vena Cava, Inferior; Venous Thrombosis; Warfarin

To evaluate the safety of inferior vena cava (IVC) filter retrieval in therapeutically anticoagulated patients in comparison to prophylactically or not therapeutically anticoagulated patients with respect to retrieval-related hemorrhagic complications.. This was a retrospective study of 115 consecutive attempted IVC filter retrievals in 110 patients. Filter retrievals were stratified as performed in patients who were therapeutically anticoagulated (group 1), prophylactically anticoagulated (group 2), or not therapeutically anticoagulated (group 3). The collected data included anticoagulant and antiplatelet medications (type, form and duration of administration, dosage) at the time of retrieval. Phone interviews and chart review was performed for the international normalized ratio (INR), activated partial thromboplastin time, platelet count, infusion of blood products, and retrieval-related hemorrhagic complications.. Group 1 included 65 attempted filter retrievals in 61 therapeutically anticoagulated patients by measured INR or dosing when receiving low-molecular-weight heparin (LMWH). Four retrievals were not successful. In patients receiving oral anticoagulation, the median INR was 2.35 (range, 2 to 8). Group 2 comprised 23 successful filter retrievals in 22 patients receiving a prophylactic dose of LMWH. Group 3 included 27 attempted filter retrievals in 27 patients not receiving therapeutic anticoagulation. Six retrievals were not successful. Five patients were receiving oral anticoagulation with a subtherapeutic INR (median, 1.49; range, 1.16 to 1.69). No anticoagulation medication was administered in 22 patients. In none of the groups were hemorrhagic complications related to the retrieval procedures identified.. These results suggest that retrieval of vena cava filters in anticoagulated patients is safe. Interruption or reversal of anticoagulation for the retrieval of vena cava filters is not indicated.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Blood Loss, Surgical; Cardiovascular Surgical Procedures; Child; Female; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Partial Thromboplastin Time; Platelet Count; Retrospective Studies; Risk Factors; Vena Cava Filters; Venous Thrombosis; Warfarin

Topics: Administration, Oral; Anticoagulants; Azetidines; Benzimidazoles; Benzylamines; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Dabigatran; Drug Delivery Systems; Drug Design; Enoxaparin; Factor Xa Inhibitors; Humans; Morpholines; Postoperative Hemorrhage; Pyridines; Rivaroxaban; Thiophenes; Venous Thromboembolism; Venous Thrombosis; Warfarin

Oral warfarin is the standard of care for patients requiring long-term anticoagulation due to venous thromboembolic disease. Patients with Crohn's disease may have reduced absorption in the small bowel due to loss of effective surface area secondary to chronic inflammation, ulcerative lesions, or resection. A 27-year-old Caucasian woman with end-stage Crohn's disease was hospitalized with an upper extremity thrombosis. In this complicated patient, who was resistant to oral warfarin and unable to receive subcutaneous low-molecular-weight heparin, therapeutic anticoagulation was achieved with intravenous warfarin. Intravenous warfarin provides an alternative administration route for patients who cannot receive the oral formulation and cannot be administered subcutaneous low-molecular-weight heparins due to adverse effects.

Topics: Administration, Oral; Adult; Anticoagulants; Arm; Crohn Disease; Drug Resistance; Female; Heparin; Humans; Injections, Intravenous; International Normalized Ratio; Ultrasonography, Doppler; Venous Thrombosis; Warfarin

Paget-Schroetter syndrome, or 'effort' thrombosis of the axillary-subclavian vein, is an uncommon deep vein thrombosis usually caused by excessive upper limb activity. It may cause post-thrombotic syndrome, leading to significant disability if not treated appropriately. The optimal management for this syndrome is still controversial because the outcomes of different treatment strategies are based on case studies and series in small numbers. We report a case of Paget-Schroetter syndrome in a young male weight-lifter and discuss treatment strategies suggested by the current literature.

Topics: Adolescent; Anticoagulants; Heparin; Humans; Male; Subclavian Vein; Syndrome; Treatment Outcome; Ultrasonography; Urokinase-Type Plasminogen Activator; Venous Thrombosis; Warfarin; Weight Lifting

Hospitalized patients with medical illness are especially susceptible to the development of venous thromboembolism (VTE).. To improve our understanding of the demographics, comorbidities, risk factors, clinical presentation, prophylaxis, and treatment of hospitalized medical patients with deep vein thrombosis (DVT), we evaluated hospitalized medical patients in a prospective registry of 5,451 consecutive ultrasound-confirmed DVT patients at 183 institutions in the United States.. Of those patients who participated in the registry, 2,609 (48%) were hospitalized medical patients. Compared with 1,953 hospitalized nonmedical patients with DVT, medical patients with DVT experienced pulmonary embolism (PE) more often (22.2% vs 15.5%, respectively; p < 0.0001). However, medical patients in whom DVT developed had received VTE prophylaxis far less frequently than nonmedical patients (25.4% vs 53.8%, respectively; p < 0.0001). The underutilization of VTE prophylaxis among hospitalized medical patients extended to both pharmacologic and mechanical modalities. In a multivariable logistic regression analysis of all hospitalized VTE patients, status as a medical patient was negatively associated with receiving prophylaxis (adjusted odds ratio, 0.47; 95% confidence interval, 0.28 to 0.78).. Hospitalized medical patients face "double trouble." First, during hospitalization for a reason other than VTE, VTE prophylaxis is omitted in medical patients more often than in nonmedical patients. Second, when VTE develops as a complication of hospitalization, hospitalized medical patients experience PE more often. Further studies should focus on understanding why prophylaxis is often omitted in hospitalized medical patients and on improving its implementation in this vulnerable population.

Topics: Aged; Anticoagulants; Confidence Intervals; Female; Fibrinolytic Agents; Follow-Up Studies; Heparin, Low-Molecular-Weight; Humans; Incidence; Inpatients; Magnetic Resonance Angiography; Male; Massachusetts; Middle Aged; Odds Ratio; Prognosis; Prospective Studies; Pulmonary Embolism; Risk Factors; Tomography, X-Ray Computed; Vena Cava Filters; Venous Thrombosis; Warfarin

Topics: Biopsy; Blood Platelets; Child; Female; Hematopoiesis, Extramedullary; Hematopoietic Stem Cell Transplantation; Hepatocytes; Humans; Liver Diseases; Magnetic Resonance Imaging; Portal Vein; Primary Myelofibrosis; Transplantation, Homologous; Venous Thrombosis; Warfarin

A 40-year-old man complaining of epigastralgia for one week was admitted. Subacute chronic idiopathic portal thrombosis was diagnosed and he improved by anti-coagulation and fibrinolytic therapy. No predisposing factor was identified. As there are many idiopathic portal thrombosis cases in Japan, and there is a possibility that some inherent thrombus predisposing factors are hidden, further study of this condition is necessary.

Topics: Adult; Drug Administration Schedule; Fibrinolytic Agents; Genetic Predisposition to Disease; Heparin; Humans; Male; Portal Vein; Tomography, X-Ray Computed; Ultrasonography; Venous Thrombosis; Warfarin

Topics: Administration, Oral; Anticoagulants; Feeding Behavior; Humans; International Normalized Ratio; Medical Records; Phenindione; Pulmonary Embolism; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Drug Resistance; Humans; India; International Normalized Ratio; Vegetables; Venous Thrombosis; Warfarin; White People

Consecutive patients having elective total hip arthroplasty were prescribed 1 mg of warfarin for 7 days preceding surgery, variable doses while in hospital (target international normalized ratio, 1.5-2.0), and discharged to rehabilitation center or home taking 1 mg daily until 4-week to 6-week follow-up visit. Lower leg pneumatic compression was used postoperatively and elastic compression stockings after discharge. Hospital and clinic charts plus auxiliary sources were reviewed for evidence of thromboembolic diseases (TED). Of 1003 consecutive patients studied, 3 (0.3%, 95% CI 0.0-0.6%) had symptomatic TED, including 2 with deep venous thrombosis and 1 with nonfatal pulmonary embolus. Follow-up rate was 99.1%. Complications from warfarin were minimal. Very-low-dose warfarin coupled with lower leg compression is effective prophylaxis against TED after elective hip arthroplasty when prescribed as described.

Topics: Adult; Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Bandages; Female; Follow-Up Studies; Humans; Leg; Male; Middle Aged; Postoperative Complications; Pressure; Pulmonary Embolism; Retrospective Studies; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Contraindications; Dose-Response Relationship, Drug; Heparin; Heparin, Low-Molecular-Weight; Humans; Intermittent Pneumatic Compression Devices; Laparoscopy; Practice Guidelines as Topic; Risk Assessment; Stockings, Compression; Vena Cava Filters; Venous Thrombosis; Warfarin

Hip arthroplasty and extended travel are each recognized as risk factors for venous thromboembolism (VTE). The safety of travel after hip arthroplasty is currently unknown. Patients who had traveled more than 200 miles within 6 weeks of a hip arthroplasty or hip resurfacing were identified and contacted. All patients received VTE chemoprophylaxis with enoxaparin, dalteparin, fondaparinox, or warfarin. A total of 608 patients traveled an average of 1377 miles at an average of 6.5 days after surgery. Among these patients, 462 traveled by airplane, 143 by car, and 3 by train. There were no deaths, no symptomatic pulmonary embolisms, and only 5 (0.82%) symptomatic deep venous thromboses. Nine (1.5%) patients experienced bleeding complications. With chemical VTE prophylaxis, extended travel within 6 weeks of hip arthroplasty surgery is associated with a low rate of symptomatic deep venous thrombosis, with no known pulmonary embolisms and no deaths.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Dalteparin; Enoxaparin; Fondaparinux; Hip Joint; Humans; Polysaccharides; Postoperative Complications; Risk Factors; Safety; Time Factors; Transportation; Travel; Venous Thromboembolism; Venous Thrombosis; Warfarin

An 18-year-old healthy woman with no previous history of coagulation disorders underwent general anesthesia for tonsillectomy. The procedure was uneventful. After the surgery, she was ordered to rest on bed overnight. The next day, the patient experienced transient syncope followed by hypotension (< 60 mmHg) and severe dyspnea. Epinephrine 2 mg administration restored the blood pressure promptly, yet dyspnea persisted. The lung-perfusion scintigraphy showed upper-lobe perfusion defect in the left lung and she was diagnosed as having pulmonary embolism. She received low-molecular-weight heparin and warfarin therapy and recovered fully. The postoperative laboratory analysis did not show thrombophilic disorders or prothrombotic state. The pulmonary embolism was speculated to have occurred due to deep vein thrombosis which developed after postoperative immobilization. The prophylactic maneuvers such as elastic stockings were not applied to the patient preoperatively, who had been considered unlikely to develop deep vein thrombosis. Although deep vein thrombosis in children and adolescence are rare, postoperative children should be monitored carefully for thrombotic complications. Postoperative bed rest should be minimized in terms of prevention of thrombosis.

Topics: Adolescent; Anesthesia, General; Anticoagulants; Female; Heparin; Humans; Postoperative Complications; Pulmonary Embolism; Tonsillectomy; Treatment Outcome; Venous Thrombosis; Warfarin

Because the embryopathy associated with maternal warfarin use seems dose-dependent, some physicians advocate low-dose warfarin for pregnant women requiring anticoagulation. The current case, however, highlights that optic nerve dysfunction (as well as other signs of warfarin embryopathy) can occur after low-dose maternal warfarin exposure.

Topics: Abnormalities, Drug-Induced; Anticoagulants; Dose-Response Relationship, Drug; Face; Female; Humans; Infant; Nails, Malformed; Optic Nerve Diseases; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Trimester, First; Prenatal Exposure Delayed Effects; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Female; Heparin; Humans; Pregnancy; Pregnancy Complications, Hematologic; Thromboembolism; Venous Thrombosis; Warfarin

Topics: Aspirin; Atrial Fibrillation; Clopidogrel; Coronary Thrombosis; Drug Therapy, Combination; Fibrinolytic Agents; Humans; Risk Factors; Ticlopidine; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP2A6; Cytochrome P-450 CYP2C9; Drug Resistance; Humans; India; International Normalized Ratio; Mixed Function Oxygenases; Vegetables; Venous Thrombosis; Vitamin K Epoxide Reductases; Warfarin; White People

Warfarin sodium is commonly prescribed for the prophylaxis and treatment of venous thromboembolism. Dosing algorithms have not been widely adopted because they require a fixed initial warfarin dose (eg, 5 mg) and are not tailored to other factors that may affect the international normalized ratio (INR).. To develop an algorithm that could predict a therapeutic warfarin dose based on drug interactions, INR response after the initial warfarin doses, and other clinical factors.. We used stepwise regression to quantify the relationship between these factors in patients beginning prophylactic warfarin therapy immediately prior to joint replacement. In the derivation cohort (n = 271), we separately modeled the therapeutic dose after 2 and 3 initial doses. We prospectively validated these 2 models in an independent cohort (n = 105).. About half of the therapeutic dose variability was predictable after 3 days of therapy: R2 was 53% in the derivation cohort and 42% in the validation cohort. INR response after 3 warfarin doses (INR3) inversely correlated with therapeutic dose (p < 0.001). Intraoperative blood loss transiently, but significantly, elevated the postoperative INR values. Other significant (p < 0.03) predictors were the first and second warfarin doses (+7% and +6%, respectively, per 1 mg), and statin use (-15.0%). The model derived after 2 warfarin doses explained 32% of the variability in therapeutic dose.. We developed and validated algorithms that estimate therapeutic warfarin doses based on clinical factors and INR response available after 2-3 days of warfarin therapy. The algorithms are implemented online at www.WarfarinDosing.org.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Algorithms; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Blood Loss, Surgical; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; International Normalized Ratio; Male; Middle Aged; Prospective Studies; Pulmonary Embolism; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Drug Prescriptions; Enoxaparin; Female; Femoral Vein; Follow-Up Studies; Humans; Middle Aged; Patient Compliance; Popliteal Vein; Ultrasonography, Doppler; Venous Thrombosis; Warfarin

To determine the incidence of thromboembolism after one-stage bilateral total hip arthroplasty and the role of two different chemoprophylaxis agents, we retrospectively studied 644 consecutive patients who underwent one-stage bilateral total hip arthroplasties. All patients received a similar multimodal prophylaxis protocol, which differed only in the postoperative chemoprophylaxis: 292 patients received warfarin (Group 1) and 352 received aspirin (Group 2). All patients were followed for a minimum of 3 months. We observed no difference in the incidence of symptomatic venous thrombosis, pulmonary embolism, or mortality in the two groups. Twenty patients in each group had deep venous thrombosis (7% and 5.7%, respectively) develop. Seven patients (2.39%) in Group 1 and eight (2.27%) in Group 2 had proximal deep venous thrombosis. Four patients in each group had a nonfatal pulmonary embolism (1.36% and 1.13%, respectively). There were two deaths in each group, neither related to venous thromboembolism. One-stage bilateral total hip arthroplasties were associated with a low rate of venous thrombosis and embolism with our multimodal prophylaxis protocol, and we found no difference in the incidence of either in patients who received warfarin or aspirin for chemoprophylaxis.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Aspirin; Clinical Protocols; Female; Humans; Incidence; Male; Middle Aged; Platelet Aggregation Inhibitors; Postoperative Complications; Preoperative Care; Pulmonary Embolism; Retrospective Studies; Survival Rate; Thromboembolism; Venous Thrombosis; Warfarin

Recurrent deep venous thrombosis despite well conducted anticoagulant treatment is an uncommon, but possible, event. It has been hypothesized that overt hyperthyroidism may increase thromboembolic risk. We present the case of an elderly man with a recurrent episode of deep venous thrombosis during optimal oral vitamin K antagonist treatment, associated with a new diagnosis of overt hyperthyroidism, with no evidence of occult cancer and normal levels of antiphosholipid antibodies.

Topics: Aged; Anticoagulants; Antithyroid Agents; Humans; Hyperthyroidism; Male; Methimazole; Recurrence; Venous Thrombosis; Warfarin

Deep venous thrombosis (DVT) is common, but only 2%-4% of DVTs involve the upper extremities (Roos in Am J Surg 154:568-73, 1987). Upper extremity DVT has a primary or secondary cause, and primary thrombosis is much rarer than secondary thrombosis. Primary upper extremity DVT comprises effort venous thrombosis and idiopathic thrombosis. Effort subclavian venous thrombosis, also called Paget-Schroetter syndrome, is an uncommon entity, which usually develops after strenuous effort of the upper extremities. Effort thrombosis of the upper extremity has been described in athletes involved in a wide variety of sports, including ball games, combatant sport and heavy athletics, games with rackets or clubs, and aquatic sports (Zell et al. in Angiology 52:337-42, 2001). Push-up exercise is a strengthening exercise for building up strength and endurance in the muscles of the upper arm and shoulders. It is also considered to be a core exercise in shoulder rehabilitation programs to activate the serratus anterior muscle in people with shoulder dysfunction (Ludewig et al. in J Sports Med 32:484-93, 2004). We report what to our knowledge is the first case of effort DVT of an upper extremity caused by push-up exercise.

Topics: Adult; Anticoagulants; Chronic Disease; Exercise Therapy; Female; Follow-Up Studies; Headache; Humans; Phlebography; Subclavian Vein; Tomography, X-Ray Computed; Venous Thrombosis; Warfarin

Orthopaedic surgeons are increasingly challenged to find a prophylaxis regimen that protects patients from thromboembolism while minimizing adverse clinical outcomes such as bleeding. We used a multimodal approach in which the treatment regimen is selected according to patient risk factors.. We retrospectively reviewed the records on 1179 consecutive total joint arthroplasties in 970 patients who had undergone primary and revision total hip and total knee replacement. Preoperatively, patients were assigned to one of two deep venous thrombosis prophylactic regimens on the basis of an assessment of their risk factors. Eight hundred and fifty-six patients (1046 operations) were considered to be low risk and were managed with aspirin, dipyridamole, or clopidogrel bisulfate as well as intermittent pneumatic calf compression devices. One hundred and fourteen patients (133 operations) were considered to be high risk and were managed with low-molecular-weight heparin or warfarin and intermittent calf compression. All patients were mobilized from bed within twenty-four hours after surgery, and all underwent Doppler ultrasonography within the twenty-four hours before hospital discharge. All of the patients were followed for six months postoperatively. The prevalence of asymptomatic and symptomatic distal and proximal deep venous thrombosis, symptomatic and fatal pulmonary emboli, overall mortality, and bleeding complications was determined. Thrombotic events were expressed as a percentage of 1179 operations because some patients had two or more operations.. Overall, there were no fatal pulmonary emboli, three symptomatic pulmonary emboli (prevalence, 0.25%), and five clinically symptomatic deep venous thrombi (0.4%). Sixty-one asymptomatic deep venous thrombi (5.2%) were found with use of routine postoperative Doppler ultrasound scans. There were three deaths (prevalence, 0.25%) that were unrelated to thromboembolism, and there were two nonfatal gastrointestinal bleeding events (prevalence, 0.17%). Wound hematomas occurred in association with five (0.4%) of the 1179 operations. Three nonfatal pulmonary emboli (prevalence, 0.3%) were detected in association with the 1046 procedures in the low-risk group, and none were detected in association with the 133 operations in the high-risk group (p = 0.767). Clinically symptomatic deep venous thrombosis was detected in association with four (0.38%) of the 1046 operations in the low-risk group and one (0.75%) of the 133 operations in the high-risk group (p = 0.93). Asymptomatic distal deep venous thrombosis was detected in association with thirty-seven (3.5%) of the 1046 procedures in the low-risk group and four (3.0%) of the 133 operations in the high-risk group. Asymptomatic proximal thrombosis was detected in association with fourteen (1.3%) of the 1046 procedures in the low-risk group and six (4.5%) of the 133 procedures in the high-risk group (p = 0.03). Wound hematomas occurred only in patients being managed with warfarin or low-modular-weight heparin (p = 0.0001).. A multimodal thromboembolic prophylactic regimen is consistent with protecting patients while limiting adverse clinical outcomes secondary to thromboembolic, vascular, and bleeding complications.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Clopidogrel; Combined Modality Therapy; Dipyridamole; Early Ambulation; Enoxaparin; Female; Fibrinolytic Agents; Hematologic Agents; Humans; Intermittent Pneumatic Compression Devices; Male; Middle Aged; Platelet Aggregation Inhibitors; Pulmonary Embolism; Retrospective Studies; Risk Assessment; Thromboembolism; Ticlopidine; Venous Thrombosis; Warfarin

Transverse myelitis is a rare manifestation of antiphospholipid syndrome, usually secondary to systemic lupus erythematosus (Rheum Dis Clin North Am 20:129-158, 1994). Only about 110 reports of this complication have been reported (Lupus 10:851-856, 2001). A connection has been demonstrated between positive serology for antiphospholipid and transverse myelitis (Lupus 8:109-115, 1999). Herein, we report of a young patient admitted with deep vein thrombosis and neurological manifestations of transverse myelitis with negative serology for systemic lupus erythematosus and antiphospholipid, who developed positive anticardiolipin antibody during pulse therapy with cyclophosphamide and methylprednisolone.

Topics: Adult; Antibodies, Anticardiolipin; Antiphospholipid Syndrome; Cyclophosphamide; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Male; Methylprednisolone; Myelitis, Transverse; Pulse Therapy, Drug; Serologic Tests; Treatment Outcome; Venous Thrombosis; Warfarin

Type II heparin-induced thrombocytopenia (HIT) is a rare but well-recognised and potentially life-threatening complication of unfractionated heparin therapy, and has been reported in association with heparin locks for central venous lines. We report a case of type II HIT complicated by iliofemoral deep venous thrombosis and pulmonary embolism in a 43-year-old woman in the course of plasma exchange for myasthenia gravis. A Gamcath central venous line had been inserted femorally due to poor peripheral venous access, and this was locked with heparin 5000 U/ml between procedures. Twelve days after initial heparin exposure, she presented with new-onset thrombocytopenia, a painfully swollen right leg, and pleuritic pain. Deep venous thrombosis and pulmonary embolism were confirmed radiologically, and serology for heparin/PF4 antibodies was unequivocally positive. The line was removed, and she was successfully managed with intravenous lepirudin, switching to warfarin on platelet recovery. This case demonstrates that Type II HIT can occur in association with heparin line locks in the course of plasmapheresis, despite previous reports of successful use of plasma exchange to treat Type II HIT.

Topics: Adult; Catheterization, Central Venous; Female; Heparin; Hirudins; Humans; Myasthenia Gravis; Plasma Exchange; Pulmonary Embolism; Recombinant Proteins; Thrombocytopenia; Venous Thrombosis; Warfarin

Patients with a central venous catheter (CVC) undergoing high-dose chemotherapy (HDC) followed by peripheral-blood stem-cell transplantation (PBSCT) for malignancies are at high risk of thrombosis, but the use of anti-coagulant prophylaxis remains debatable in this setting of patients. We analyzed the efficacy and the safety of minidose warfarin in 228 patients in whom CVCs had been placed and who had received 292 HDC courses of therapy. The catheters remained in place for a mean of 173 (range 40-298) days. All patients received prophylactic oral warfarin in the fixed dose of 1 mg/day starting on the day of CVC insertion. Prophylaxis was interrupted during aplasia when platelet counts fell below 50,000/dL. There were no toxic deaths related to the prophylaxis. Overall there were 4 thrombotic events. Three occurrences were directly related to the catheter, while the remaining event was a deep saphenous-vein thrombosis. A number of potential predictive factors were analyzed for their impact on thrombotic events without finding any significant correlation. Four episodes of bleeding occurred, with each of these individuals having a normal INR but a platelet count below 50,000/dL. Minidose warfarin is effective and safe to use for preventing thrombotic events in this setting of patients.

Topics: Administration, Oral; Anticoagulants; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Catheterization, Central Venous; Cytarabine; Female; Hemorrhage; Humans; Male; Melphalan; Neoplasms; Peripheral Blood Stem Cell Transplantation; Platelet Count; Podophyllotoxin; Retrospective Studies; Risk Factors; Transplantation, Homologous; Venous Thrombosis; Warfarin

Topics: Acute Disease; Anticoagulants; C-Reactive Protein; Child; Female; Humans; Leukocytosis; Neutrophils; Partial Thromboplastin Time; Portal Vein; Thrombosis; Time Factors; Tomography, X-Ray Computed; Venous Thrombosis; Warfarin

Patients with a supratherapeutic international normalised ratio (ST-INR) are at risk for bleeding. ST-INR is corrected by withholding warfarin therapy and often by supplementing vitamin K or providing vitamin K-dependent factors; the exact therapeutic decision is based on the extent of the prolonged INR. Currently, ST-INRs are frequently observed in clinical practice due to the use of sensitive recombinant tissue thromboplastin reagents and automation. However, there are scant data correlating an ST-INR with various vitamin K-dependent factors. This prospective cohort study, set in a large tertiary care teaching hospital for the University of Texas Southwestern Medical Center at Dallas, defined the relationship between ST-INR (>5.0) and measured vitamin K-dependent procoagulant factors. Prothrombin time, INR and vitamin K-dependent factors II, VII, IX and X were measured in 78 patients with an INR > 5.0 (ST-INR) who were on warfarin therapy for more than 2 months. There was no significant relationship between the ST-INR and levels of important vitamin K-dependent factors II and X. These data support the recent guidelines that the management of an INR > 5.0 should be driven by the clinical determinants rather than specific INR values per se.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation Disorders; Blood Coagulation Factors; Factor X; Female; Humans; International Normalized Ratio; Logistic Models; Male; Middle Aged; Prospective Studies; Prothrombin; Regression Analysis; Stroke; Venous Thrombosis; Vitamin K; Warfarin

Topics: Aged; Anticoagulants; Female; Humans; International Normalized Ratio; Self Care; Venous Thrombosis; Warfarin

We report a patient who had a history of deep vein thrombosis in a previous pregnancy. She was treated with heparins without any reactions in the index pregnancy. Subsequently, when the patient became pregnant again, she developed an acute cutaneous reaction to the low molecular heparin enoxaparin 3 weeks after initiation of therapy. She developed a similar reaction to delteparin as well. She was therefore treated with warfarin until 36 weeks of gestation. Then she was treated with fondaparinux (Arixtra, Sanofi-Synthelabo, Paris, France) 2.5 mg daily for the remainder of the pregnancy. Delivery was at term by induction of labour. Fondaparinux was stopped on the day of the induction of labour. It was re-started 6 h post-delivery and the patient was anticoagulated with warfarin in the post-partum period. There were no bleeding tendencies or recurrences of thrombosis during fondaparinux therapy. Both mother and baby were well after delivery.

Topics: Anticoagulants; Drug Hypersensitivity; Female; Fibrinolytic Agents; Fondaparinux; Heparin; Humans; Live Birth; Polysaccharides; Postpartum Period; Pregnancy; Pregnancy Complications, Hematologic; Venous Thrombosis; Warfarin

Topics: Adult; Anticoagulants; Blindness; Diagnosis, Differential; Factor VII Deficiency; Female; Humans; Retrobulbar Hemorrhage; Tomography, X-Ray Computed; Venous Thrombosis; Warfarin

The aim of this study was to compare the rate of recurrent venothromboembolic (VTE) events and factors contributing to VTE events in patients with inferior vena caval (IVC) filters on chronic anticoagulation to those in whom anticoagulation was discontinued.. Retrospective cohort study of 353 patients who received IVC filters between 1986 and 2002.. Anticoagulation status was available for 304 patients (132 on coumadin anticoagulation therapy and 172 who did not receive any anticoagulation therapy) whose IVC filters were placed within 30 days of their qualifying thromboembolic event. Two-year event-free survival for the anticoagulated group was 80.6% (95% confidence interval--CI--76.9, 84.3] and was 67.8% (95% CI 63.2, 72.3) for the non-anticoagulated group. Patients who had Greenfield filter had a higher, but not statistically significant different, rate of recurrence compared to those with other types of filters (hazard ratio 1.4; 95% CI 0.9, 2). The rate of recurrent VTE events was independent of age, gender, smoking status, or underlying medical condition.. Among those with IVC filters, long-term anticoagulation therapy prolonged event-free survival for up to 2 years but did not prevent recurrent VTE events.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Combined Modality Therapy; Disease-Free Survival; Female; Follow-Up Studies; Humans; Leg; Male; Middle Aged; Prosthesis Design; Recurrence; Retrospective Studies; Survival Analysis; Thromboembolism; Treatment Outcome; Vena Cava Filters; Venous Thrombosis; Warfarin

Topics: Abortion, Induced; Adult; Anticoagulants; Antithrombin III; Embryo Transfer; Female; Fertilization in Vitro; Fibrinogen; Heparin; Humans; Infusions, Intravenous; Jugular Veins; Ovarian Hyperstimulation Syndrome; Pleural Effusion; Pregnancy; Pregnancy Complications, Hematologic; Subclavian Vein; Venous Thrombosis; Warfarin

Upper-extremity deep venous thrombosis (UEDVT) is an increasingly important clinical problem in children. These events are classified as primary or secondary, with the latter being the most common and usually associated with the presence of a central venous line. Among primary UEDVT, the so-called Paget-Schroetter syndrome, effort-related or exercise-induced upper-extremity thrombotic event represents an extremely rare finding that has never been described in a pediatric series. The objective of the second part of this two-part article is to report the first pediatric series in a group of adolescents with this condition from a single center, describing their clinical features, management, and outcome. A retrospective chart review of 6 patients seen between December 2003 and April 2005 was conducted, with a median follow-up of 9 months (range 2-17). Four females and two males, all Caucasian, were enrolled with a median age of 16 years (range 14-17). In all cases, strenuous exercise was present in the month preceding diagnosis and mild trauma was present in only one case (weight lifting). At presentation, all patients had objective swelling of the affected limb for a median of 4 days (range 2-14), and 4 patients had UEDVT of the dominant arm. Thrombophilia investigation revealed that 50% had a combined prothrombotic state at presentation, and all patients were/are being treated with anticoagulation for 6 months (low-molecular-weight heparin followed by warfarin). Continuation of the initial symptoms was present in all cases but one at the 3-month clinic follow-up (last case has yet to reach 3 months of follow-up), and residual moderate to severe postthrombotic syndrome was present in all 3 cases followed for more than 12 months. Of those 3 patients followed for more than 1 year, 2 patients recurred despite having complete resolution of the thrombus after 6 months of anticoagulation, and the third patient underwent surgery with clinical improvement. Adolescents with UEDVT treated only with anticoagulation seem to have a poor outcome.

Topics: Adolescent; Anticoagulants; Axillary Vein; Exercise; Female; Follow-Up Studies; Heparin, Low-Molecular-Weight; Humans; Male; Subclavian Vein; Treatment Outcome; Upper Extremity; Venous Thrombosis; Warfarin

Topics: Adult; Anticoagulants; Cumulative Trauma Disorders; Edema; Exercise; Heparin, Low-Molecular-Weight; Humans; Male; Pain; Phlebography; Subclavian Vein; Upper Extremity; Venous Thrombosis; Warfarin

Unlike hyperthyroidism, few data exist regarding the impact of hypothyroidism on systemic anticoagulation with coumarin derivates. Therefore, we evaluated a potential impact of short-term hypothyroid conditions on systemic anticoagulation with coumarin derivates in patients after complete thyroidectomy for treatment of thyroid cancer. Fifteen patients with differentiated thyroid cancers and continued international normalized ratio (INR)-adjusted therapy with coumarin derivates were included in this retrospective analysis. A total of 88 laboratory tests was analyzed. INR values were compared between thyroid-stimulating hormone (TSH) values greater than 10 and 10 mU/L or less. An INR value of less than 2.0 was defined as being out of the therapeutic range. Analysis of significant differences between categorized TSH and INR values were performed by using X(2) analysis, correlation of continuous TSH and INR values by using the Pearson's analysis. When TSH was greater than 10 mU/L (n = 50) the INR value was less than 2.0 in 76.0% (n = 38) cases. In contrast, the INR value was less than 2.0 in only 21.1% (n = 8; p < 0.0001) of patients with TSH of 10 mU/L or less (n = 38). Correlation between continuous TSH and INR values was r = -0.589 (p < 0.0001). Based on the results of the present study, it seems to be necessary to monitor the anticoagulation parameters more often in patients with hypothyroidism and either to correct the hypothyroid state, or in cases of desired hypothyroid conditions, to adjust the therapy with coumarin derivates in order to ensure a sufficient anticoagulation.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Coumarins; Female; Humans; Hypothyroidism; Male; Middle Aged; Retrospective Studies; Thyroid Neoplasms; Thyroidectomy; Thyrotropin; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Arthroplasty, Replacement, Knee; Azetidines; Benzylamines; Humans; Pulmonary Embolism; Treatment Failure; Venous Thrombosis; Warfarin

Deep venous thrombosis (DVT) is a common complication of thalidomide treatment. There is little information to guide clinicians in selecting effective preventive treatments and physician practice varies. We sought to determine whether prophylactic anticoagulation with warfarin prevents DVT related to thalidomide treatment.. We reviewed the records of 131 patients receiving thalidomide for a variety of indications. Fifty-five patients were prescribed warfarin with the intent of preventing DVT. Thirty-seven patients received warfarin at a dose of 1-2 mg per day (low dose) and 18 received a dose intended to raise the INR to 2-3 (high dose).. Twenty-one of the 131 patients developed venous thrombosis during thalidomide treatment. Eighteen of the 76 patients (23.7%) who were not prescribed prophylactic anticoagulation developed DVT compared to 3 of the 55 patients (5.5%) who were prescribed any dose of prophylactic warfarin (P = 0.010). Only 1 of the 37 patients who received low-dose warfarin developed DVT (P = 0.011). Bleeding complications occurred in 4 patients, all of whom were receiving high-dose warfarin.. Prophylactic anticoagulation with warfarin reduces the risk of thrombosis during thalidomide treatment. Low-dose warfarin may be as effective as higher dose treatment and may result in fewer bleeding complications.

Topics: Adult; Aged; Aged, 80 and over; Angiogenesis Inhibitors; Anticoagulants; Cohort Studies; Female; Hemorrhage; Humans; Male; Middle Aged; Neoplasms; Retrospective Studies; Thalidomide; Venous Thrombosis; Warfarin

To evaluate the technical success and clinical outcome of the percutaneous treatment of acute renal vein thrombosis (RVT).. Retrospective review was conducted of all patients with acute RVT treated with percutaneous catheter-directed thrombectomy with or without thrombolysis at one institution between 2000 and 2004. Demographics, comorbid conditions, and clinical outcomes associated with therapy were assessed.. Seven thrombosed renal veins in six patients (mean age, 51.5 +/- 18.8 years) were treated with percutaneous catheter-directed thrombectomy/thrombolysis. Thrombosed renal veins included two allografts and five native veins, and diagnosis was confirmed in all cases by direct renal venography. Inferior vena cava thrombosis was the cause of RVT in one patient, and glomerulopathy was the cause in the remaining patients. Percutaneous mechanical thrombectomy was performed in all cases, and five renal veins were additionally treated with thrombolysis for a mean duration of 22.1 +/- 21.0 hours. Restoration of flow to renal veins was achieved in all thrombosed renal veins. Clinical improvement occurred in all patients: the mean serum creatinine level improved from a preoperative level of 3.3 +/- 1.92 mg/dL to a postoperative level of 1.92 +/- 1.32 mg/dL (P = .008). Mean glomerular filtration rate improved from a preoperative level of 30.8 +/- 23.0 mL/min per 1.73 m(2) to 64.2 +/- 52.4 mL/min per 1.73 m(2) (P = .04). There were no pulmonary emboli or hemorrhagic complications, and no RVT recurrence was documented during a median follow-up of 22.5 months.. Percutaneous catheter-directed thrombectomy with or without thrombolysis for acute RVT is associated with a rapid improvement in renal function and low incidence of morbidity. It is feasible for native and allograft renal veins and should be considered in patients with acute RVT, particularly in the setting of deteriorating renal function.

Topics: Adult; Aged; Anticoagulants; Glomerulonephritis, Membranous; Heparin; Humans; Magnetic Resonance Angiography; Middle Aged; Radiography; Renal Veins; Retrospective Studies; Thrombectomy; Thrombolytic Therapy; Treatment Outcome; Vena Cava, Inferior; Venous Thrombosis; Warfarin

Inferior shoulder dislocation or luxatio erecta is an exceedingly rare form of shoulder dislocation and compromises less than 0.5% of all shoulder dislocations. Furthermore, bilateral luxatio erecta is reported only nine times in the English literature. This paper documents the tenth case of bilateral luxatio erecta. This tenth patient suffered an axial load injury to his outstretched arms and displaced both humeral heads inferiorly. After closed reduction, the patient was discharged home on hospital day two. However, he developed an axillary vein thrombosis 3 days later and required anticoagulation therapy. This report reviews the mechanisms of injury associated with inferior shoulder dislocations as well as the presentation and treatment of luxatio erecta. The complication of axillary vein thrombosis and its treatment in this patient are discussed also.

Topics: Accidents, Traffic; Adult; Anticoagulants; Arm Injuries; Axillary Vein; Drug Therapy, Combination; Emergencies; Follow-Up Studies; Heparin, Low-Molecular-Weight; Humans; Male; Manipulation, Orthopedic; Postoperative Complications; Radiography; Shoulder Dislocation; Ultrasonography, Doppler; Venous Thrombosis; Warfarin; Weight-Bearing; Wounds, Nonpenetrating

Topics: Anticoagulants; Biomarkers; Factor VIII; Fibrin Fibrinogen Degradation Products; Hemorrhage; Humans; Risk Factors; Secondary Prevention; Thromboembolism; Venous Thrombosis; Warfarin

Topics: Adult; Anticoagulants; Humans; Illicit Drugs; International Normalized Ratio; Male; Self Medication; Substance Abuse, Intravenous; Venous Thrombosis; Warfarin

53-year-old woman with a history of deep vein thrombosis and pulmonary embolism was receiving warfarin to prevent thromboembolic complications; her international normalized ratio (INR) had been stable for 1 month. Extended-release tolterodine 4 mg/day was then prescribed to manage overactive bladder. On her next anticoagulation clinic visit, the patient's INR had increased, although the dosage of warfarin had been reduced when the tolterodine had been prescribed. Due to the absence of other contributing factors and the temporal relationship between tolterodine and prolonged INR, the event was determined to be a probable drug interaction. When patients are prescribed tolterodine and warfarin concurrently, clinicians should monitor INR carefully, and a reduction in warfarin dosage may be required.

Topics: Anticoagulants; Benzhydryl Compounds; Cresols; Drug Interactions; Female; Humans; International Normalized Ratio; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Pulmonary Embolism; Thromboembolism; Tolterodine Tartrate; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Carcinoma, Signet Ring Cell; Female; Gangrene; Heparin, Low-Molecular-Weight; Humans; Lower Extremity; Lymphatic Metastasis; Middle Aged; Necrosis; Neoplasms, Unknown Primary; Purpura, Thrombotic Thrombocytopenic; Skin; Venous Thrombosis; Warfarin

As the problem of morbid obesity has increased over the past several years in the United States, gastric bypass has become a viable option for many people seeking treatment. The risk of a venous thromboembolic event after gastric bypass is significant and linked to several factors. As the gastric bypass program at this southeastern hospital progressed, the number of thromboembolic complications increased. Because of the increase in postoperative thromboembolic events, a program was developed to improve outcomes and reduce the number of these events. The program currently uses a protocol that includes research-based preventive measures in conjunction with warfarin (Coumadin, Bristol Myers Squibb, Princeton, NJ) 1 mg daily for 30 days postoperatively with a target international normalized ratio of 1.8 or less. Before the initiation of the program, the event rate was 6.9%. The event rate for the evaluation period after initiation of the protocol was 1.3%. Further studies are needed to determine the full benefit of this type of program and whether the improvements gained were related to the use of warfarin (Coumadin).

Topics: Adult; Aged; Anticoagulants; Aspirin; Bandages; Clinical Protocols; Drug Monitoring; Early Ambulation; Evidence-Based Medicine; Female; Gastric Bypass; Heparin; Humans; International Normalized Ratio; Male; Middle Aged; Obesity, Morbid; Postoperative Care; Program Evaluation; Risk Factors; South Carolina; Thromboembolism; Vena Cava Filters; Venous Thrombosis; Warfarin

This study reviewed the effectiveness of a trimodality deep venous thrombosis (DVT) prophylactic regimen after primary and revision total hip arthroplasty. Seven hundred five patients were treated with pneumatic compression, adjusted dose warfarin (7 days), and early mobilization. Bilateral lower extremity venous ultrasonography was obtained on postoperative day 3 or 4. The incidence of asymptomatic DVT, symptomatic DVT/pulmonary embolus events within 90 days of surgery, and potential influence of risk factors was retrospectively assessed. Deep venous thrombosis incidence was 4.4% with one (0.1%) nonfatal pulmonary embolus. Increased age, male sex, and DVT history were significant risk factors for thromboembolic events within 90 days of hip arthroplasty. The combination of short-duration warfarin and mechanical prophylaxis with predischarge ultrasound screening was safe and effective in limiting the occurrence of venous thromboembolism.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Bandages; Combined Modality Therapy; Female; Humans; Male; Middle Aged; Motor Activity; Postoperative Complications; Regression Analysis; Retrospective Studies; Thromboembolism; Treatment Outcome; Venous Thrombosis; Walking; Warfarin

A 26-year-old man was admitted with fever and abdominal pain. Abdominal ultrasonography and Doppler ultrasound eventually revealed portal vein thrombosis and a pyogenic liver abscess (17x11x11 cm). Lactococcus lactis was isolated from a culture of the abscess material. This organism is not a common pathogen in humans. This is the first published description of portal vein thrombosis and pyogenic liver abscess due to L. lactis.

Topics: Adult; Anti-Bacterial Agents; Anticoagulants; Catheterization; Drainage; Gram-Positive Bacterial Infections; Heparin; Humans; Lactococcus lactis; Liver Abscess; Male; Meropenem; Microbial Sensitivity Tests; Portal Vein; Thienamycins; Ultrasonography, Doppler; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Drug Administration Schedule; Humans; Practice Guidelines as Topic; Pulmonary Embolism; Secondary Prevention; Venous Thrombosis; Warfarin

Topics: Adult; Anticoagulants; Diagnosis, Differential; Football; Heparin; Humans; Leg Injuries; Male; Popliteal Vein; Risk Assessment; Risk Factors; Spasm; Venous Thrombosis; Warfarin

We determined if negative ultrasound screening at the time of acute care hospital discharge or 2 weeks post operatively would reliably identify patients without deep venous thrombosis, thus allowing discontinuation of warfarin chemoprophylaxis. Patients undergoing primary TKA (1344) were treated with adjusted-dose warfarin (target prothrombin time, 15-18 seconds; internationalized normalization ratio, 1.4-1.7) until screening and then aspirin (325 mg po bid) until 6 weeks postoperatively. Deep venous thrombosis as determined by ultrasound was the measured outcome. From 1994 to 1997, 525 patients underwent screening ultrasound before discharge (usually postoperative Day 3): 12 (2.3%) patients with proximal deep venous thrombosis and three (0.6%) patients with distal deep venous thrombosis were identified. From 1997 to 2001, 819 patients underwent ultrasound screening at Day 14 postoperatively: 10 (1.2%) patients with proximal deep venous thrombosis and 29 (3.6%) patients with distal deep venous thromboses were identified. There was no difference in proximal deep venous thrombosis detection, but there was a difference in distal deep venous thrombosis detection. We no longer screen asymptomatic patients with ultrasound for deep venous thrombosis after TKA.

Topics: Anticoagulants; Arthroplasty, Replacement, Knee; Humans; Prospective Studies; Ultrasonography, Doppler, Duplex; Venous Thrombosis; Warfarin

Topics: Acute Disease; Anticoagulants; Humans; Male; Middle Aged; Radiography, Interventional; Recurrence; Thrombectomy; Treatment Outcome; Vena Cava, Inferior; Venous Thrombosis; Warfarin

Approximately one third of children with malignancy and central venous lines develop catheter-related thrombosis, with the reported sequelae including death, pulmonary embolism, chylothoraces, superior vena cava syndrome and post-thrombotic syndrome. These complications prompt the design and completion of randomized, controlled trials to determine a safe and efficacious therapy to prevent these thromboses. The authors Ruud et al. have presented a well-designed, randomized, controlled trial which demonstrates the lack of utility of using low-dose warfarin to prevent catheter-related thrombosis in children with central lines and acute lymphoblastic leukaemia. The difficulties with warfarin in children are again demonstrated in this study.. Further studies are warranted using other thromboprophylactic agents with less or no monitoring and fewer drug interactions, including the newer anticoagulant agents such as direct thrombin inhibitors.

Topics: Anticoagulants; Catheterization, Central Venous; Catheters, Indwelling; Child; Humans; Neoplasms; Venous Thrombosis; Warfarin

A significant need exists for new chronic oral anticoagulation therapies to replace warfarin. Previous studies have shown that beta-D-xylosides, which prime glycosaminoglycan (GAG) synthesis, have antithrombin and antithrombotic activity. In the following report, a new orally active beta-D-xyloside (odiparcil) has been characterized in a rat model of venous thrombosis and its efficacy and bleeding liability compared to warfarin. Additionally, studies were conducted to investigate odiparcil's ex vivo antithrombin and antiplatelet activity, and also to explore the potential utility of protamine sulfate as a neutralizing agent.. In vivo thrombosis studies were conducted in a rat inferior vena cava model, and bleeding studies in a rat tail transection model. Following oral dosing, warfarin and odiparcil produced dose-related suppression of thrombus formation. A therapeutically relevant dose of warfarin in this model (international normalized ratio; INR 3.0) achieved approximately 65% inhibition of thrombus formation. Warfarin caused dose-related significant increases in bleeding indices. Odiparcil antithrombotic activity was limited by its mechanism to a maximum suppression of thrombus formation of 65-70%, and did not prolong bleeding indices. Additionally, odiparcil-induced heparin cofactor II (HCII)-dependent antithrombin activity was shown to be a function of dermatan sulfate-like GAG production. Other than thrombin-related effects, no odiparcil effects on platelet function were observed. In antidote studies, it was demonstrated that odiparcil-induced antithrombotic activity could be partially neutralized by protamine sulfate.. These experiments suggest that an antithrombotic approach based upon xyloside induction of circulating GAGs may have the potential to approximate the efficacy of warfarin and yet with a reduced risk to hemostasis.

Topics: Animals; Anticoagulants; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Glycosaminoglycans; Glycosides; Hemorrhage; Heparin Cofactor II; Protamines; Rats; Vena Cava, Inferior; Venous Thrombosis; Warfarin

To determine whether treatments guidelines for lower extremity venous thrombosis (DVT) could be applied to patients with cerebral venous sinus thrombosis (CVST), the rates of recurrent venous thrombosis and survival for these two diseases were compared.. The authors studied all patients diagnosed with CVST at the Mayo Clinic between 1978 and 2001. Survival and recurrent venous thrombosis rates (cerebral or noncerebral) were compared with those from patients with DVT. Survival rates were also compared with white US residents.. One hundred fifty-four patients (age 40 +/- 19 years) were included (58% women). Warfarin, prescribed in 50% of patients, was continued for an average of 9 months. During a mean of follow up of 36 +/- 47 months (464 patient-years), 20 patients experienced 23 recurrent venous thrombi for an event rate of 5.0/100 patient-years. This recurrence rate was similar to patients with lower extremity DVT (3.8/100 patient-years). Mortality rates were lower for CVST (2.8/100 patient-years) compared with DVT (6.2/100 patient-years; p = 0.001) patients but higher than expected for white US residents (p = 0.001). Increasing age and active malignancy were the only predictors of poor survival. Neither recurrent thrombosis nor survival was influenced by warfarin therapy.. The likelihood of recurrent venous thrombosis is similar after cerebral venous sinus thrombosis (CVST) and lower extremity deep venous thrombosis (DVT). Compared with DVT, survival rates are higher following CVST but are adversely influenced by malignancy and older age.

Topics: Adolescent; Adult; Age Distribution; Aged; Anticoagulants; Cerebral Veins; Demography; Female; Follow-Up Studies; Heparin; Humans; Incidence; Lower Extremity; Male; Middle Aged; Recurrence; Reference Values; Retrospective Studies; Thrombophilia; Venous Thrombosis; Warfarin

Topics: Anesthesia, Spinal; Anticoagulants; Colorectal Surgery; Drug Interactions; Humans; Intermittent Pneumatic Compression Devices; Postoperative Complications; Risk Factors; Stockings, Compression; Venous Thrombosis; Warfarin

Tramadol is a commonly used synthetic opioid with the advantage of lowering the potential for dependence. Two reports of a tramadol-warfarin drug interaction have been published, and the current product insert states that increased international normalized ratios (INRs) with concomitant tramadol-warfarin use have been reported. We report a tramadol-warfarin drug interaction that caused a supratherapeutic INR in a 65-year-old man in previously stable condition who was being treated at our anticoagulation clinic. Within 6 days of starting tramadol 50 mg twice/day, the patient's INR rose from 2.5 to 6.14. He elected to continue therapy with the tramadol. A 30% dosage reduction from warfarin 60 to 42 mg/week was eventually needed. To our knowledge, this is the first case report of the successful continuation of tramadol after a tramadol-warfarin drug interaction. Based on our experience, we suggest an empiric dosage reduction of 25-30% in warfarin followed by repeat measurement of the INR within 1 week in patients who are starting tramadol therapy. As an alternative, maintaining the current dose of warfarin, followed by a repeat INR determination in 3 days, may be appropriate.

Topics: Aged; Analgesics, Opioid; Anticoagulants; Back Pain; Drug Interactions; Humans; International Normalized Ratio; Male; Pulmonary Embolism; Tramadol; Venous Thrombosis; Warfarin

Thromboembolic disease in the form of deep venous thrombosis and pulmonary embolism is a risk following hip and knee joint replacement. Prophylactic and screening protocols have been employed to prevent thromboembolic disease following lower extremity joint reconstruction. The purpose of the present study was to evaluate two noninvasive venous screening protocols, specifically, compression ultrasonography performed either at the time of hospital discharge or two weeks after the operation.. From 1994 through 2001, 2364 patients undergoing primary unilateral total hip or total knee arthroplasty were managed with an anticoagulation chemoprophylaxis protocol (adjusted-dose warfarin) until the time of noninvasive venous screening with use of one of two protocols. Nine hundred thirty-one patients (406 hips and 525 knees) underwent compression ultrasonography prior to hospital discharge, and the other 1433 patients (614 hips and 819 knees) underwent ultrasonographic screening two weeks after the operation.. Twenty-three proximal deep venous thromboses (prevalence, 2.5%) were identified in the group that underwent ultrasound screening at the time of hospital discharge, and thirty-one proximal thromboses (prevalence, 2.2%) were identified in the group that underwent ultrasound screening two weeks after the operation. There was no significant difference between the two protocols with regard to the detection of deep venous thrombosis.. There was no significant difference between the group that received two weeks of warfarin chemoprophylactic prophylaxis and the group that was screened at the time of hospital discharge with regard to the detection of deep venous thrombosis with use of compression ultrasound. On the basis of these findings, we no longer screen asymptomatic patients for deep venous thrombosis following hip and knee replacement, and all patients receive warfarin anticoagulation for two weeks.

Topics: Anticoagulants; Arthroplasty, Replacement; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Humans; Patient Discharge; Postoperative Complications; Ultrasonography, Doppler, Duplex; Venous Thrombosis; Warfarin

Concurrent development of retinal venous drainage and cerebral venous thrombosis has not been reported. Case Description We describe a 23-year-old man with bilateral central retinal vein occlusions and cerebral venous thrombosis. Initially observed bilateral hemorrhagic retinopathy and thrombus in the right transverse sinus of the patient began to resolve after 2 weeks of low-molecular-weight heparin. Hemorrhagic retinopathy progressively improved to previous visual acuity and the right lateral sinus remained patent by maintenance of anticoagulation with warfarin.. The present case shows effectiveness of low-molecular-weight heparin for the initial management of hemorrhagic retinopathy of central retinal vein occlusion combined with cerebral venous thrombosis.

Topics: Adult; Anticoagulants; Cerebral Veins; Heparin; Humans; Male; Retinal Vein Occlusion; Time Factors; Venous Thrombosis; Warfarin

The effects of prednisone on the International Normalized Ratio (INR) values of a patient were examined.. A 66-year-old white man with a history of multiple myeloma was treated in an ambulatory care anticoagulation clinic for deep vein thrombosis. His INR values were normal during therapy with warfarin 14 mg weekly and thalidomide 300 mg daily. His INR values began to increase after three months of starting prednisone 10 mg daily. His weekly dose of warfarin was changed over the next two years, and his dietary intake of vitamin K was increased. For every INR value that was below the therapeutic goal, the patient was not taking prednisone; every time the INR value was above the therapeutic goal, he was taking prednisone. In November 2004, the prednisone and thalidomide were stopped and only the warfarin was continued. After a few dosage increases, ending with a weekly warfarin dose of 21 mg, the patient's INR values remained in the therapeutic range. Multiple variables must be examined when assessing INR values, as many things interact with warfarin. For example, tobacco use, alcohol consumption, and changes in vitamin K intake can affect the INR. Since this patient did not use tobacco or consume alcohol and had a fairly consistent dietary intake of vitamin K, these variables were ruled out as influencing the INR. In this case, the changes in his INR values corresponded to the addition or deletion of prednisone.. A patient's INR values increased after the addition of prednisone to his warfarin regimen.

Topics: Aged; Anti-Inflammatory Agents; Anticoagulants; Antineoplastic Agents, Hormonal; Glucocorticoids; Humans; International Normalized Ratio; Male; Multiple Myeloma; Prednisone; Venous Thrombosis; Warfarin

Pulmonary embolism is a leading cause of death for bariatric patients. Numerous regimens have been proposed, but a comprehensive, simple approach is lacking. This study provides a simple, easily implemented prophylaxis regimen.. One hundred fifty bariatric surgery patients were evaluated. Patients considered at high risk for venous thromboembolism had heart failure, a BMI of >/=50 kg/m(2), or a history of venous thromboembolism or pelvic surgery. Preoperatively and postoperatively, all patients received subcutaneous enoxaparin or unfractionated heparin. High-risk patients received either preoperatively inserted inferior vena cava filters or continuous heparin infusions intraoperatively. All high-risk patients were anticoagulated with warfarin (Coumadin; Bristol Myers-Squibb, Princeton, NJ) for at least 3 months postoperatively. Initially, some patients experienced significant hemorrhage; to prevent this, sutures were oversewn into staple lines.. No patient experienced venous thromboembolism; a binomial test showed that the regimen reduced the risk of this complication to less than 2% (p < 0.05). Hemorrhage sufficient to require transfusion occurred in 4 of the first 20 patients; of the remaining 130 patients, into whose staple lines sutures were oversewn, none required transfusion (p < 0.05).. Patients should be divided into those who are at high risk and those who are at low risk for venous thromboembolism. All patients should receive pre- and postoperative anticoagulation. High-risk patients should also receive either an inferior vena cava filter or intraoperative heparin infusions, as well as at least 3 months of Coumadin therapy. Oversewing of staple lines may reduce the risk of hemorrhage.

Topics: Anticoagulants; Bariatric Surgery; Body Mass Index; Enoxaparin; Hemorrhage; Heparin; Humans; Obesity, Morbid; Postoperative Complications; Retrospective Studies; Risk Factors; Thrombolytic Therapy; Treatment Outcome; Vena Cava Filters; Venous Thrombosis; Warfarin

Topics: Aged; Aged, 80 and over; Angina Pectoris; Anticoagulants; Diagnosis, Differential; Dyspnea; Echocardiography; Edema; Female; Humans; Pulmonary Embolism; Venous Thrombosis; Warfarin

The article contains data on venous thrombosis (VT) recurrence rate in patients with the first episode of thrombus formation after the completion of one-year therapy with warfarin. The investigation included study of the prognostic value of intravascular coagulation marker (thrombus precursor protein --TPP) for the risk of venous retrombosis. The study showed that a high TPP level at the end of standard therapy course with warfarin in patients who had the first episode of spontaneous venous thrombosis is a significant indicator of a possible thrombosis recurrence during the nearest two tears after treatment with anticoagulants.

Topics: Adult; Anticoagulants; Biomarkers; Enzyme-Linked Immunosorbent Assay; Female; Fibrin; Follow-Up Studies; Humans; Male; Prognosis; Prospective Studies; Risk Factors; Secondary Prevention; Venous Thrombosis; Warfarin

Popliteal vascular entrapment syndrome can result in calf claudication, aneurysm formation, distal arterial emboli, or popliteal vessel thrombosis. The most commonly reported causes of this syndrome have been anomalies of the medial head of the gastrocnemius muscle as it relates to the course of the popliteal artery. We report two cases of rare anomalous slips of the lateral head of the gastrocnemius muscle causing popliteal vascular entrapment syndrome.

Topics: Angiography, Digital Subtraction; Anticoagulants; Arterial Occlusive Diseases; Constriction, Pathologic; Female; Fibrinolytic Agents; Humans; Leg; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Male; Middle Aged; Muscle, Skeletal; Popliteal Artery; Popliteal Vein; Rare Diseases; Syndrome; Tissue Plasminogen Activator; Tomography, X-Ray Computed; Ultrasonography, Doppler, Color; Venous Thrombosis; Warfarin

Topics: Adult; Androstenes; Angiography; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Contraceptives, Oral, Synthetic; Cytarabine; Etoposide; Female; Hodgkin Disease; Humans; Immunotherapy; International Normalized Ratio; Lynestrenol; Melphalan; Mineralocorticoid Receptor Antagonists; Risk; Risk Factors; Time Factors; Venous Thrombosis; Warfarin

Data evaluating the safety of using weight-based low-molecular-weight heparin in the treatment of obese patients with acute venous thromboembolism are limited. The product monograph of dalteparin suggests the maximum dose should be limited to 18,000 U subcutaneously once daily. There are no specific data regarding the risk of recurrence or bleeding in patients given dalteparin in a weight-based dose of 200 IU kg(-1). We report a retrospective chart review of 193 obese patients who weighed more than 90 kg and who received dalteparin at or near to 200 IU kg(-1) actual body weight for 5-7 days for acute venous thromboembolism with 90 day follow-up information. Of the patients, 77% had idiopathic venous thromboembolism, 16% had an underlying malignancy, and 7% had a transient risk factor. Warfarin was initiated within 2 days with a target International Normalized Ratio range of 2.0-3.0. All patients were followed for 12 weeks post diagnosis. Only two patients had a major hemorrhage, 4 and 8 weeks from diagnosis. This study supports the safety of dosing dalteparin based on actual body weight in obese patients.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Body Weight; Dalteparin; Female; Humans; International Normalized Ratio; Male; Medical Records; Middle Aged; Obesity; Recurrence; Retrospective Studies; Risk Factors; Thromboembolism; Time Factors; Venous Thrombosis; Warfarin

Topics: Adult; Anticoagulants; Colitis, Ulcerative; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Male; Portal Vein; Ultrasonography; Venous Thrombosis; Warfarin

To assess the potential roles of protein Z (PZ) and protein Z-dependent protease inhibitor (ZPI) in venous thrombosis, their plasma levels were measured in 426 individuals with venous thrombosis and 471 control individuals participating in the Leiden Thrombophilia Study. A relationship between the level of PZ or ZPI and venous thrombosis was not detected in the overall case-control study. PZ and ZPI circulate as a complex and their plasma levels are interdependent. Both PZ and ZPI are increased with oral contraceptive use and reduced with oral anticoagulant therapy.

Topics: Adolescent; Adult; Aged; Blood Proteins; Case-Control Studies; Contraceptives, Oral; Female; Humans; Male; Middle Aged; Risk Factors; Serpins; Venous Thrombosis; Warfarin

Although extended secondary prophylaxis with low-molecular-weight heparin was recently shown to be more effective than warfarin for cancer-related venous thromboembolism, its cost-effectiveness compared to traditional prophylaxis with warfarin is uncertain. We built a decision analytic model to evaluate the clinical and economic outcomes of a 6-month course of low-molecular-weight heparin or warfarin therapy in 65-year-old patients with cancer-related venous thromboembolism. We used probability estimates and utilities reported in the literature and published cost data. Using a US societal perspective, we compared strategies based on quality-adjusted life-years (QALYs) and lifetime costs. The incremental cost-effectiveness ratio of low-molecular-weight heparin compared with warfarin was 149,865 dollars/QALY. Low-molecular-weight heparin yielded a quality-adjusted life expectancy of 1.097 QALYs at the cost of 15,329 dollars. Overall, 46% (7108 dollars) of the total costs associated with low-molecular-weight heparin were attributable to pharmacy costs. Although the low-molecular-weigh heparin strategy achieved a higher incremental quality-adjusted life expectancy than the warfarin strategy (difference of 0.051 QALYs), this clinical benefit was offset by a substantial cost increment of 7,609 dollars. Cost-effectiveness results were sensitive to variation of the early mortality risks associated with low-molecular-weight heparin and warfarin and the pharmacy costs for low-molecular-weight heparin. Based on the best available evidence, secondary prophylaxis with low-molecular-weight heparin is more effective than warfarin for cancer-related venous thromboembolism. However, because of the substantial pharmacy costs of extended low-molecular-weight heparin prophylaxis in the US, this treatment is relatively expensive compared with warfarin.

Topics: Cost-Benefit Analysis; Decision Making, Computer-Assisted; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Premedication; Quality-Adjusted Life Years; Thromboembolism; United States; Venous Thrombosis; Warfarin

Topics: Administration, Oral; Anticoagulants; Evidence-Based Medicine; Humans; International Normalized Ratio; Thromboembolism; Venous Thrombosis; Warfarin

Cerebral venous thrombosis (CVT) is an uncommon but serious type of stroke. Thrombosis may involve the cortical or deep veins or the venous sinuses. The presenting clinical features are non-specific. We report a 48-year-old man with CVT who presented with fever, bitemporal throbbing headache, and generalised convulsion. Computed tomography (CT) of the brain revealed acute haemorrhages over right anterior frontal and posterior temporal regions with surrounding oedema and right anterior temporal subcortical oedema. The initial diagnosis was herpes simplex encephalitis. Absence of venous flow over the right transverse and sigmoid sinuses during the venous phase of digital subtraction angiography (DSA) revealed CVT. He was anti-coagulated for 6 months. An underlying cause of CVT was not detected. A high index of suspicion is required when risk factors of CVT are present. CT brain may be normal or showing non-specific findings. Magnetic resonance imaging plus venography, CT venography, or DSA is diagnostic.

Topics: Angiography, Digital Subtraction; Anticoagulants; Brain; Diagnosis, Differential; Encephalitis, Herpes Simplex; Fever; Frontal Lobe; Heparin, Low-Molecular-Weight; Humans; Intracranial Hemorrhages; Intracranial Thrombosis; Male; Middle Aged; Seizures; Temporal Lobe; Tomography, X-Ray Computed; Venous Thrombosis; Warfarin

We describe a case of impending paradoxical embolism in a 43-year-old male patient with pulmonary embolism. Transesophageal echocardiography revealed a thromboembolus straddling a patent foramen ovale. The patient underwent emergency removal of the intracardiac clot with closure of the patent foramen ovale. A postoperative work-up for a hypercoagulable state revealed a protein-S deficiency and bilateral lower extremity deep vein thromboses. A Greenfield inferior vena cava filter was inserted, anticoagulation was performed, and warfarin treatment was continued after the patient was discharged home.

Topics: Adult; Anticoagulants; Echocardiography, Transesophageal; Embolism, Paradoxical; Heart Septal Defects, Atrial; Humans; Leg; Male; Protein S Deficiency; Pulmonary Embolism; Vena Cava Filters; Venous Thrombosis; Warfarin

Although there are many reports describing spontaneous rupture of either the spleen or the liver, the simultaneous rupture of both organs is a rare event, especially during anticoagulant therapy. We report a case of spontaneous rupture of the spleen and liver in a patient on warfarin therapy for deep venous thrombosis.

Topics: Adult; Chemical and Drug Induced Liver Injury; Follow-Up Studies; Hepatectomy; Humans; Liver Diseases; Male; Risk Assessment; Rupture, Spontaneous; Splenectomy; Splenic Rupture; Tomography, X-Ray Computed; Treatment Outcome; Ultrasonography, Doppler; Venous Thrombosis; Warfarin

Temporary interruption of oral anticoagulation to perform invasive procedures is a frequently occurring medical problem. There are only a few studies available on the optimal clinical approach in this situation. The published clinical studies and guidelines are summarized.

Topics: Acenocoumarol; Anticoagulants; Dose-Response Relationship, Drug; Endoscopy; Heparin, Low-Molecular-Weight; Humans; Infant, Newborn; Minor Surgical Procedures; Practice Guidelines as Topic; Pulmonary Embolism; Risk Factors; Secondary Prevention; Venous Thrombosis; Vitamin K; Warfarin

To assess if pneumatic compression in conjunction with chemoprophylaxis is an effective way to reduce the incidence of deep vein thrombosis in orthopedic trauma patients sustaining fragility hip fractures.. Two hundred patients admitted to the authors' institution between May 1998 and June 2002 for fractures of the hip were prospectively studied. All patients were treated operatively and received the VenaFlow calf compression device on both lower extremities immediately following surgery. Chemical prophylaxis of either aspirin (n = 67) or warfarin (n = 133) was administered in addition to mechanical compression. A noninvasive serial color flow duplex scan was performed 1 to 11 days postoperatively (mean 4.5 days) to determine the presence or absence of deep vein thrombosis. All patients were followed clinically 3 months postoperatively for a clinical evaluation of symptomatic deep vein thrombosis or pulmonary embolism.. Overall, the incidence of deep vein thrombosis was 3.5% (7 of 200) and included only 1 proximal thrombosis (1 out of 200, or 0.5%) and no pulmonary embolism. Five of the 7 patients positive for deep vein thrombosis were in the mechanical compression and warfarin prophylaxis group and 2 were in the aspirin arm of the study. For patients with deep vein thrombosis, the average number of risk factors was 3.71, whereas patients without clots averaged 1.75 clinical risk factors (P < or = 0.05). Three patients in the warfarin group developed bleeding complications (1 with a gastrointestinal bleed and 2 with minor bleeding not at the operative site). No evidence of a symptomatic deep vein thrombosis or pulmonary embolism was reported within a 3-month period following hospitalization.. Our findings suggest mechanical compression with the VenaFlow calf compression device in conjunction with chemoprophylaxis is an effective means of reducing thromboembolic disease in this high-risk population.

Topics: Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Female; Femoral Neck Fractures; Heparin; Hip Fractures; Humans; Male; Prospective Studies; Pulmonary Embolism; Risk Factors; Ultrasonography, Doppler, Duplex; Venous Thrombosis; Warfarin

A 54-year-old man who had been administered chlormadinone acetate 3 months after prostatectomy for prostate cancer, acutely developed disorientation and memory disturbance. Six days later, he experienced high grade fever and epigastralgia. He was suspected to have hepatic encephalopathy, because the Fischer ratio was low although serum ammonia level remained normal. Further examinations including abdominal echography and CT scan disclosed a thrombus extending from the portal vein to the superior mesenteric vein together with abnormal collateral vessels originating from the portal vein. He was successfully treated with warfarin potassium, urokinase and heparin sodium. It was suggested that the patient developed hepatic encephalopathy due to portal-systemic circulation shunting secondary to portal vein thrombosis.

Topics: Drug Therapy, Combination; Fibrinolytic Agents; Heparin; Hepatic Encephalopathy; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Portal Vein; Urokinase-Type Plasminogen Activator; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Celecoxib; Cyclooxygenase Inhibitors; Enoxaparin; Gout; Humans; International Normalized Ratio; Male; Middle Aged; Prothrombin Time; Pyrazoles; Risk Factors; Sulfonamides; Venous Thrombosis; Warfarin

The optimal dose of warfarin varies among individuals, and the prediction of a maintenance dose is difficult. Ethnicity has been reported to influence warfarin dosing.. To quantitate the influence of ethnicity on warfarin dose requirement.. We conducted a retrospective cohort study at a university anticoagulation clinic to evaluate the influence of ethnicity on warfarin dose. Inclusion criteria included age > or = 18 years, target international normalized ratio (INR) 2-3, and warfarin management within the clinic for > or = 3 months with a minimum of 5 clinic visits. We collected clinical and demographic data including age, gender, weight, ethnicity, disease states, concomitant medications, indication, weekly warfarin dosage, and INR. To assess potential confounders, multivariate, repeated-measures regression analysis was used to identify and adjust for variables that may influence the maintenance dose of warfarin.. Of the 345 patients who met the inclusion criteria, 27% were Asian American, 6% Hispanic, 54% white, and 14% African American. The adjusted mean (95% CI) weekly warfarin doses for patients with an INR goal of 2 to 3 were Asian Americans 24 mg (21 to 27), Hispanics 31 mg (25 to 37), whites 36 mg (34 to 39), and African Americans 43 mg (39 to 47) (p < 0.001). Additional factors found to influence warfarin dose requirement included age, weight, concomitant use of amiodarone, and diagnosis of venous thromboembolism.. Warfarin dose requirements vary across ethnic groups even when adjusted for confounding factors, suggesting that genetic variation contributes to interpatient variability.

Topics: Aged; Asian People; Atrial Fibrillation; Black or African American; Cohort Studies; Diabetes Mellitus; Dose-Response Relationship, Drug; Female; Hispanic or Latino; Humans; Hypothyroidism; International Normalized Ratio; Ischemic Attack, Transient; Male; Middle Aged; Retrospective Studies; Stroke Volume; Venous Thrombosis; Ventricular Function, Left; Warfarin; White People

Topics: Administration, Oral; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Aspirin; Clinical Trials as Topic; Female; Humans; International Normalized Ratio; Lupus Coagulation Inhibitor; Male; Retrospective Studies; Risk; Thromboembolism; Venous Thrombosis; Warfarin

Several factors are associated with an increased risk of recurrent venous thromboembolism (VTE). The aim of the study was to investigate whether the quality of oral anticoagulation therapy (OAT) is a long-term risk factor for recurrence of VTE after OAT interruption.. A total of 297 patients (170 males) with a recent acute unprovoked VTE episode were prospectively monitored during OAT in our anticoagulation clinic and followed up for 21 months after OAT interruption. Recurrent events were recorded in 42 subjects for 493 years of follow-up [14.1% of patients; 8.5% patient-years (pt-y)] after OAT withdrawal. The rate of recurrence was not correlated to OAT duration. Subjects experiencing recurrence after OAT interruption had spent significantly more time at markedly subtherapeutic international normalized ratio (INR) levels (<1.5) and less time within the therapeutic range (2.0-3.0 INR) during OAT. Relative risk (RR) of recurrence was significantly higher [2.77 (95% confidence interval (CI) 1.49-5.18; P = 0.001) and 2.70 (95% CI 1.39-5.25; P = 0.003) at univariate and multivariate analysis, respectively] in those who spent more time (upper quintile) at INR values <1.5, being especially evident in the first 90 days of OAT. RR was significantly higher at univariate [2.05 (95% CI 1.07-3.96; P = 0.031)] but not at multivariate [1.98 (95% CI 0.98-4.0; P = 0.056)] analysis when the entire OAT period was considered. Subjects in the upper quintile of time spent at INR values <1.5 had significantly higher D-dimer values when OAT was stopped and after 3 months.. The amount of time that subjects with an acute unprovoked VTE event spend at near-normal INR values (<1.5) during the first 3 months of treatment is associated with higher D-dimer values measured during OAT and after its interruption and is a significant risk factor for late VTE recurrence.

Topics: Acenocoumarol; Administration, Oral; Adult; Aged; Aged, 80 and over; Algorithms; Anticoagulants; Female; Fibrin Fibrinogen Degradation Products; Heparin; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Male; Middle Aged; Partial Thromboplastin Time; Prospective Studies; Pulmonary Embolism; Recurrence; Regression Analysis; Risk; Risk Factors; Thromboembolism; Time Factors; Treatment Outcome; Venous Thrombosis; Warfarin

The antithrombotic and bleeding properties of the oral direct thrombin inhibitor ximelagatran and of warfarin were investigated in an experimental venous thrombosis and bleeding model in anaesthetized rats. Rats were randomized to receive ximelagatran (1-20 micromol/kg), warfarin (0.20-0.82 micromol/kg), or vehicle (tap water) once daily orally for 4 days before surgery. Thrombosis was induced by partial stenosis and application of ferric chloride to the wall of the abdominal vena cava under anaesthesia. Sixty minutes after thrombus induction, rats were sacrificed, thrombi harvested, and their fresh weight determined. Bleeding was determined as haemoglobin in fluid collected from the abdominal cavity. Blood samples were taken before thrombus induction and sacrifice for determination of coagulation parameters and plasma concentrations of melagatran, the active form of ximelagatran. Ximelagatran and warfarin dose-dependently reduced thrombus formation. The highest doses of ximelagatran and warfarin almost completely prevented thrombus formation; however, the increase in bleeding (versus vehicle) was significantly lower with the highest dose of ximelagatran than with the highest dose of warfarin. The oral direct thrombin inhibitor ximelagatran is thus as at least as effective as warfarin in the prevention of thrombus formation in this animal model, but with a wider separation between antithrombotic effects and bleeding.

Topics: Animals; Azetidines; Benzylamines; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Glycine; Hemorrhage; Male; Rats; Rats, Sprague-Dawley; Venae Cavae; Venous Thrombosis; Warfarin

Evidence suggests that alterations in the dietary intake of vitamin K can affect anticoagulation response to warfarin. It is possible that a low and erratic intake of dietary vitamin K is at least partly responsible for the variable response to warfarin in patients with unstable control of anticoagulation. Twenty-six patients with unstable and twenty-six with stable control of anticoagulation completed dietary records of all foods and drinks consumed on a daily basis for two consecutive weeks. The mean daily intake of vitamin K in unstable patients was considerably lower than that for stable patients during the study period (29+/-17 microg v . 76+/-40 microg). The logarithm of vitamin K intake was consistently and significantly lower in the unstable patients than the stable patients over the two week period (5.9+/-0.4 microg v. 6.9+/-0.5 microg; p<0.001; 95% CI: 0.7-1.2). Changes in vitamin K intake between weeks 1 and 2 of the study were negatively correlated with changes in International Normalised Ratio (INR) amongst the unstable patients, however this failed to reach significance (r=-0.25; p=0.22). Daily supplementation with oral vitamin K in unstable patients could lead to a more stable anticoagulation response to warfarin.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Diet; Drug Interactions; Female; Humans; International Normalized Ratio; Male; Middle Aged; Nutritional Status; Time Factors; Treatment Outcome; Venous Thrombosis; Vitamin K; Warfarin

A 68-year-old woman was admitted to our hospital due to brain embolism in the right middle cerebral artery. Patent foramen ovale was detected by transesophageal echocardiogram. The sonogram of the legs revealed a floating thrombus originating from the left posterior tibial vein and extended to the superficial femoral vein. Both right middle lobe and left upper lobe were defected in perfusion scans of lung. She was treated with administration of warfarin potassium and caval filters placed in the inferior vena cava and the azygos vein. Thereafter, she had never experienced brain embolism or pulmonary embolism. A floating deep venous thrombus, which is a high risk of pulmonary embolism, could be observed in patients with paradoxical brain embolism. It was suggested that sonography of veins in the legs is essential for detecting embolic sources of brain infarction, as well as evaluating the risk of pulmonary embolism.

Topics: Aged; Anticoagulants; Echocardiography, Transesophageal; Embolism, Paradoxical; Female; Heart Septal Defects, Atrial; Humans; Intracranial Embolism; Lower Extremity; Vena Cava Filters; Venous Thrombosis; Warfarin

Topics: Adult; Anticoagulants; Female; Heparin; Humans; Renal Veins; Venous Thrombosis; Warfarin

The optimal duration and intensity of warfarin therapy after a first idiopathic venous thromboembolic event are uncertain. We used decision analysis to evaluate clinical and economic outcomes of different anticoagulation strategies with warfarin.. We built a Markov model to assess 6 strategies to treat 40- to 80-year-old men and women after their first idiopathic venous thromboembolic event: 3-month, 6-month, 12-month, 24-month, and unlimited-duration conventional-intensity anticoagulation (International Normalized Ratio, 2-3) and unlimited-duration low-intensity anticoagulation (International Normalized Ratio, 1.5-2). The model incorporated age- and sex-specific clinical parameters, utilities, and costs. Using a societal perspective, we compared strategies based on quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratios.. In our baseline analysis, incremental cost-effectiveness ratios were lower in younger patients and in men, reflecting the higher bleeding risk at older ages, and the lower risk of recurrence among women. Based on a willingness-to-pay of <$50000/QALY, the 24-month strategy was most cost-effective in 40-year-old men ($48805/QALY), while the 6-month strategy was preferred in 40-year-old women ($35977/QALY) and 60-year-old men ($29878/QALY). In patients aged >/=80 years, 3-month anticoagulation was less costly and more effective than other strategies. Cost-effectiveness results were influenced by the risks associated with recurrent venous thromboembolism, the major bleeding risk of conventional-intensity anticoagulation and the disutility of taking warfarin.. Longer initial conventional-intensity anticoagulation is cost-effective in younger patients while 3 months of anticoagulation is preferred in elderly patients. Patient age, sex, clinical factors, and patient preferences should be incorporated into medical decision making when selecting an appropriate anticoagulation strategy.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Cost-Benefit Analysis; Decision Support Techniques; Female; Humans; Male; Markov Chains; Middle Aged; Pulmonary Embolism; Quality of Life; Secondary Prevention; Venous Thrombosis; Warfarin

Warfarin is an anticoagulant which acts through interference with the recycling of vitamin K in the liver, leading to reduced activation of several clotting factors. Apolipoprotein E plays a central role in the uptake of the lipid-soluble vitamin K. The apolipoprotein E (APOE) alleles E2, E3 and E4 encode the three major isoforms of apolipoprotein E. The aim of this project was to evaluate whether variation in the APOE gene influences warfarin dose.. We genotyped APOE in 183 warfarin-treated patients. Information about warfarin dose, prothrombin time, age, gender, body weight, treatment indication and duration, other diseases and concurrent medication was taken from the patients' medical records. Cytochrome P450 2C9 genotyping had been performed previously, and patients were stratified according to CYP2C9 genotype.. Patients homozygous for APOE*E4 tended to receive higher warfarin doses than others. Among CYP2C9 extensive metabolisers, APOE*E4 homozygous patients received significantly higher warfarin doses than patients with one or no E4 alleles; 56.9 compared with 34.3 and 34.6 mg/week, (Bonferroni corrected P=0.008 and 0.007, respectively). APOE genotype explains 6% of warfarin dose variance among CYP2C9 extensive metabolisers (analysis of variance, P=0.009).. Previous studies have shown that individuals carrying the APOE*E4 allele have a faster uptake of lipoproteins into the liver and lower levels of circulating vitamin K than others. It is therefore plausible that patients carrying E4 alleles have an enhanced uptake of vitamin K into the liver and require higher doses of warfarin to compensate for this.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Apolipoproteins E; Aryl Hydrocarbon Hydroxylases; Atrial Fibrillation; Cytochrome P-450 CYP2C9; Female; Gene Frequency; Genotype; Humans; Male; Middle Aged; Polymorphism, Genetic; Pulmonary Embolism; Venous Thrombosis; Warfarin

Congenital anomalies of the inferior vena cava (IVC), such as absence or atresia, although well documented, are uncommon and result from aberrant development during embryogenesis. Absence or atresia of the IVC is usually discovered accidentally. Patients are typically asymptomatic of the condition itself. Many concurrent cardiovascular-associated abnormalities have been described. We report a 10-y-old boy admitted to the emergency room with painful swelling of his right lower limb without previous trauma or surgery. After 3 d, swelling also involved the left lower limb. A Doppler ultrasound of the lower limbs revealed bilateral thrombosis of the vena iliaca communis, vena iliaca externa, femoral vein communis and superficial extending to the IVC. Magnetic resonance imaging (MRI) of the abdomen was performed. On MRI, we demonstrated a hypoplastic IVC. The results of blood coagulation studies, including levels of antiphospholipid antibodies, proteins C and S, and antithrombin III, were normal. The patient was treated with intravenous heparin for 8 d and discharged with oral warfarin therapy, which has been recommended for life. Therapy against deep venous thrombosis must be focused on its prevention in the future. An abnormal inferior vena cava should be considered in young patients with deep venous thrombosis without apparent cause.

Topics: Anticoagulants; Child; Humans; Magnetic Resonance Imaging; Male; Ultrasonography, Doppler, Color; Vena Cava, Inferior; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Humans; Venous Thrombosis; Warfarin

Major bleeding complications were investigated in 2,460 patients with 3,684 patient-years of warfarin exposure from 2000 to 2003. The most common indications for anticoagulation were atrial fibrillation (30%), venous thromboembolic disease (28%), and mechanical heart valve prosthesis (15%). Eleven patients had 12 nonfatal major bleeding complications, with no fatal bleeds during the study. The incidence of major bleeding complications was 0.12%/year; there were 0.32 bleeds/100 patient-years of coverage. Of the 12 bleeding events, 5 (42%) were intracranial hemorrhages. The average hospitalization cost per patient was dollar 15,988, and the average length of hospitalization was 6.0 days.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Hemorrhage; Hospital Costs; Hospital Departments; Humans; Incidence; Length of Stay; Male; Middle Aged; Retrospective Studies; Risk Factors; Survival Rate; Venous Thrombosis; Warfarin

Therapy for venous thromboembolism (VTE) currently involves a minimum of 3 months of anticoagulation. After cessation of therapy, however, recurrent venous thrombosis occurs at rates of 6 to 9% per year. Clinical trials have demonstrated the benefits of extending anticoagulation beyond 3 months for the prevention of recurrent VTE events. Despite this, many eligible patients do not receive the required thromboprophylaxis and the incidence of recurrent VTE remains too high for a preventable condition. A reason for failure to use prophylaxis is the fear of bleeding complications with current oral anticoagulants such as warfarin. Warfarin has an unpredictable pharmacokinetic profile and a variable dose-response relationship that requires frequent coagulation monitoring and dose adjustments to maintain a target intensity that is both safe and effective. Alternative strategies for long-term prophylaxis, which may potentially provide more consistent anticoagulant responses and reduce coagulation monitoring requirements, include the use of low-molecular-weight heparin (LMWH), treatment with warfarin at a lower intensity, and the introduction of novel anticoagulants. The long-term use of LMWH has been found to be a particularly favorable treatment option for cancer patients in whom it is difficult to control the intensity of anticoagulation. In clinical trials, LMWH significantly reduced the risk of recurrent VTE without increasing bleeding risk. The parenteral administration of the LMWHs, however, is a drawback for long-term use in the outpatient setting. A clinical trial assessing the efficacy and safety of long-term low-intensity warfarin treatment found this therapy to be better than placebo, but another study showed that conventional intensity warfarin was significantly more efficacious than low-intensity warfarin. New therapies in development that may offer improved safety-efficacy profiles are the synthetic pentasaccharides fondaparinux and idraparinux and the oral direct thrombin inhibitor ximelagatran. Parenterally administered fondaparinux has been shown to be as effective as LMWH for the acute treatment (5 to 7 days) of symptomatic deep vein thrombosis. Idraparinux, with once-weekly parenteral dosing, is currently being assessed in phase III clinical trials for the long-term secondary prevention of VTE. Ximelagatran is the first oral agent in the new class direct thrombin inhibitors. With a fast onset of action and oral administration, ximelagatran is a

Topics: Anticoagulants; Azetidines; Benzylamines; Chemical and Drug Induced Liver Injury; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Myocardial Ischemia; Oligosaccharides; Polysaccharides; Recurrence; Thrombin; Time Factors; Venous Thrombosis; Warfarin

Henoch-Schönlein purpura (HSP) belongs to the category of systemic small-vessel vasculitis. Although long-term outcome is generally good, serious complications may occur. Thrombosis and priapism have been reported only as extremely rare complications of HSP. We describe a 37-year-old man who developed recurrent thrombotic events shortly after he had been diagnosed as having HSP. Although he had additional risk factors for thrombosis, such as prothrombin G20210A mutation and use of celecoxib before the last episode, temporal relation of the thrombotic attacks to the onset of HSP suggest that the disease itself may lead to a prothrombotic state. This case is the first adult HSP patient with priapism, which probably developed secondary to thrombosis of the dorsal penile vein.

Topics: Adult; Anticoagulants; Humans; IgA Vasculitis; Male; Penis; Priapism; Venous Thrombosis; Warfarin

To measure the per-event health plan costs for acute and follow-up treatment not directed by a clinical study protocol in a group of commercially insured patients in 2 managed care organizations following an incident hospitalization that included a diagnosis for a venous thromboembolism (VTE) event.. A cohort of patients with an incident in-hospital VTE event, consisting of deep vein thrombosis (DVT), or pulmonary embolism (PE), or both DVT + PE, was retrospectively identified from the administrative claims databases of 2 large U.S. health care plans. Inclusion criteria were (a) an inpatient VTE event between January 1, 1998, and December 31, 2000, (b) no VTE diagnosis or anticoagulation therapy 3 months prior to the incident VTE in-hospital event, (c) at least 1 anticoagulation pharmacy fill following the incident hospital VTE, and (d) continuous health plan enrollment 3 months prior to and 6 months following the incident hospital VTE event. Total costs were reported on a per-event basis and consisted of the aggregated amount paid by the health plan to the provider after subtraction of member cost-share. Costs were collected separately, first for the incident VTE event for all patients identified and second for patients who had at least 1 of the following events in the follow-up period: bleed requiring or not requiring hospitalization, a recurrent VTE event requiring hospitalization, or a recurrent VTE and bleed (VTE + bleed) event requiring hospitalization. Costs were compared between incident diagnosis groups using multivariate generalized linear model techniques.. A total of 2,147 patients (DVT=1,499 [69.8%], PE=373 [17.4%], DVT+PE= 275 [12.8%]) were identified (mean age=61.6standard deviation [SD] 16 years; 46.3% male) and were followed for an average of 21.3 (median, 19.2) months. Disease severity was high in these patients, including 59.2% with a history of or active malignancy. The prevalence of VTE was 2.04 per 100,000 study-eligible health plan members. For the incident VTE events, average costs were 7,712+/-18,339 US dollars (median, 3,131 US dollars) per incident DVT event; 9,566+/-13,512 US dollars (median, 6,424 US dollars) per PE incident event; and 12,200+/-24,038 US dollars (median, 6,678 US dollars) per incident DVT+PE event. Warfarin treatment following the incident VTE event was administered to 97.3% of patients for an average of 6.7 (median, 5.0) months at an average cost of 19.40 US dollars per patient per month. During the average period of 21.3 months, 534 patients (24.9%) experienced an average of 1.24 bleed or recurrent VTE events per patient that required hospitalization at a mean cost of 14,975 US dollars per event or 2,101 US dollars per patient per year. For patients with a bleed in the follow-up period that required hospitalization, average costs were 12,326+/-24,448 US dollars (median, 5,736 US dollars) per recurrent VTE; 15,339+/-52,029 US dollars (median, 4,999 US dollars) per bleed; or 24,085+/-65,411 US dollars (median, 10,185 US dollars) per recurrent VTE + bleed event. During the follow-up period, a total of 612 patients (28.5%) experienced 1,489 recurrent bleed events that did not require hospitalization, at an average cost of 239+/-386 US dollars (median, 95 US dollars) per event. There were no significant differences in mean total costs for all pair-wise comparisons between the 3 incident diagnosis groups.. Of patients who experienced a VTE event during the incident hospital stay for any diagnosis, 1 in 4 experienced an average of 1.24 bleed or recurrent VTE events that required hospitalization in the 21 months of follow-up and incurred an average health plan cost of 14,957 US dollars per event. These data may be of interest to managed care decision makers when evaluating the cost impact of new therapies or providing more comprehensive anticoagulation management services for existing therapies.

Topics: Age Distribution; Anticoagulants; Drug Utilization; Female; Follow-Up Studies; Health Care Costs; Hemorrhage; Heparin, Low-Molecular-Weight; Hospitalization; Humans; Longitudinal Studies; Male; Managed Care Programs; Middle Aged; Patients; Pulmonary Embolism; Sex Distribution; Time Factors; Venous Thrombosis; Warfarin

Topics: Aged; Anticoagulants; Arginine; Humans; International Normalized Ratio; Kidney; Kidney Function Tests; Liver; Lung Neoplasms; Partial Thromboplastin Time; Pipecolic Acids; Sulfonamides; Venous Thrombosis; Warfarin

The coexistence of human immunodeficiency virus (HIV) infection and systemic lupus erythematosus (SLE) is being increasingly reported and, because of the immunological disturbances demonstrated in HIV-infected patients, diagnostic and therapeutic difficulties may arise when the 2 conditions coexist. Antiphospholipid antibodies are demonstrable in patients with both conditions, but clinical manifestations of the antiphospholipid syndrome (APS) in HIV-infected patients, although reported, are uncommon.. We describe a patient with HIV infection and SLE who manifested 4 episodes of deep vein thrombosis (DVT) complicated by pulmonary embolism. Enzyme-linked immunosorbant assay was used to test for the presence of antiphospholipid antibodies, including anticardiolipin antibodies, anti- beta 2-glycoprotein 1 antibodies, and antiprothrombin antibodies (anti-PT). Additionally, we performed a computer-assisted search of the literature (via the Medline database) to identify all reported cases of HIV infection plus SLE.. We document the case of 35-year-old African woman with HIV infection and SLE who developed recurrent episodes of DVT and pulmonary embolism in the presence of anti-PT and discuss in depth the pathogenic role of these antibodies and the clinical challenges posed to clinicians by the coexistence of HIV and SLE in the same patient.. Immunological reconstitution in HIV-infected patients contributes to the appearance of multiple autoimmune conditions, including SLE and APS. The recognition of the coexistence of these autoimmune disorders in HIV-infected patients has important implications in the treatment of and prognosis for these individuals.

Topics: Adrenal Cortex Hormones; Adult; Anti-HIV Agents; Antibodies; Anticoagulants; Female; HIV Infections; Humans; Lupus Erythematosus, Systemic; Prothrombin; Pulmonary Embolism; Venous Thrombosis; Warfarin

To assess the treatment of venous thromboembolism (VTE) in hospitalized patients enrolled in a national, multicenter database.. This was a retrospective, cohort study that randomly selected VTE patients from 38 academic/teaching, community, and Veterans Administration (VA) hospitals. The study included a physician survey component. The patients selected were those treated between January 2002 and June 2003 who had an ICD-9-CM code for pulmonary embolus (PE), deep vein thrombosis (DVT), or pregnancy-related PE or DVT.. The study included 939 patients: 52.7% with DVT, 28.4% with PE, and 18.8% with PE and DVT. Mean age was 59.5 years. Risk factors included obesity (body mass index > 30) in 30.1%, history of VTE in 28.0%, malignancy in 27.4%, surgery in 21.1%, and immobility in 18.5%. Only 56.1% of patients were treated with low-molecular-weight heparin (LMWH). Bridging from LMWH or unfractionated heparin (UFH) to warfarin was completed during hospitalization in 486 (68.6%), but only 246 (50.6%) had an international normalized ratio (INR) > or = 2 for 48 hours before discontinuation of the injectable anticoagulant. Length of stay in patients discharged on bridge therapy was 4.0 +/- 3.7 days vs 8.1 +/- 5.8 days for patients discharged on warfarin therapy (P < .001). Ninety-two (10.1%) patients were discharged with neither oral nor injectable anticoagulation and had a mean duration of treatment of only 10.6 +/- 16.2 days. Of 245 physicians surveyed from participating hospitals, 84% and 53%, respectively, indicated that LMWH was their preferred agent for treatment of DVT and treatment of PE. With regard to warfarin, 30% did not believe it was necessary to have a therapeutic INR for > or = 2 days before discontinuing LMWH or UFH, and 27% responded that it was necessary to keep DVT patients in the hospital until they were therapeutic.. In this cross-section of United States hospitals, lower than anticipated use of LMWH, insufficient bridging from UFH or LMWH to warfarin, and continuation of anticoagulation after hospitalization were all problems discovered with the treatment of VTE. Physician knowledge, attitudes, and beliefs are partially responsible for the gap between actual practice and international guidelines. These results suggest that hospitals should evaluate their adherence to international VTE treatment guidelines and develop strategies to optimize antithrombotic therapy.

Topics: Anticoagulants; Attitude of Health Personnel; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Guideline Adherence; Health Knowledge, Attitudes, Practice; Health Services Research; Heparin, Low-Molecular-Weight; Humans; Injections, Subcutaneous; Male; Practice Guidelines as Topic; Practice Patterns, Physicians'; Probability; Pulmonary Embolism; Retrospective Studies; Risk Assessment; Severity of Illness Index; Statistics, Nonparametric; Survival Rate; Treatment Outcome; Venous Thrombosis; Warfarin

We report a patient with protein C and protein S deficiency and factor V Leiden mutation presenting with splenic vein thrombosis and with a web between the hepatic venous confluence and vena cava inferior. These two findings were thought to be due to the hypercoagulable state of the patient. Interestingly, there was no need for invasive procedures as the inferior accessory hepatic vein was patent. Hepatic venous flow was being maintained by the inferior accessory hepatic vein or a dominant collateral vein.

Topics: Anticoagulants; Female; Humans; Liver Circulation; Middle Aged; Splenic Vein; Thrombophilia; Vena Cava, Inferior; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Heparin; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Venous Thrombosis; Warfarin

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Dexamethasone; Enoxaparin; Humans; Male; Middle Aged; Multiple Myeloma; Prognosis; Thalidomide; Venous Thrombosis; Warfarin

The thrombogenicity of newer anticancer agents and the challenges associated with managing cancer patients on warfarin have led to the evaluation of the low-molecular-weight heparins (LMWHs) for primary and secondary prophylaxis in this high-risk patient population.. The first published trial of LMWH in cancer compared three months of warfarin therapy with enoxaparin in cancer patients with proximal deep venous thrombosis (DVT), pulmonary embolism (PE), or both. All patients received four days of enoxaparin 1.5 mg/kg and were then randomized to continue receiving enoxaparin or begin warfarin therapy. Due to inadequate patient enrollment, no statistically significant differences were detected between the two treatment groups. In a similar patient population, the Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) trial evaluated the use of long-term dalteparin for the prevention of recurrent venous thromboembolism (VTE) in patients with cancer. Cancer patients with proximal DVT, PE, or both were randomized to initial treatment with dalteparin followed by either six months of oral anticoagulant therapy or dalteparin monotherapy. The primary outcome was symptomatic, recurrent VTE, and secondary outcomes were bleeding events and survival time. The cumulative risk of recurrent VTE at six months was reduced from 17% in the oral anticoagulant group to 9% in the dalteparin group, a risk reduction of 52% (p=0.002). No significant differences in bleeding events or overall mortality occurred between the groups. Recent recommendations from the American College of Chest Physicians on the treatment of cancer-associated thrombosis are based in part on data from the CLOT trial and support the use of dalteparin and tinzaparin in the long-term treatment of patients with DVT and cancer. Finally, results of recent trials support the concept that antithrombotic therapy with dalteparin or nadroparin may have an antineoplastic effect, resulting in improved survival time. However, these results require further validation.. Despite the absence of oncology-specific guidelines for cancer-associated thrombosis, pharmacists now have a number of new tools available for selecting an anticoagulant, including results from several clinical trials with LMWHs and recent reports from national meetings.

Topics: Anticoagulants; Clinical Trials as Topic; Dalteparin; Enoxaparin; Heparin, Low-Molecular-Weight; Humans; Prognosis; Survival Analysis; Thromboembolism; Tinzaparin; Venous Thrombosis; Warfarin

Conventionally warfarin therapy is initiated using a loading dose given over several days. Daily international normalised ratio (INR) monitoring is recommended to prevent overdose; however, with a large proportion of patients with deep vein thrombosis now receiving treatment out of hospital daily blood tests are inconvenient. We introduced a low-dose protocol for starting anticoagulant therapy that only required INR testing on days 4 and 6 and audited the results to assess safety and efficacy.. Two-hundred and forty-eight patients with confirmed deep vein thrombosis were started on warfarin therapy at 5 mg daily for 3 days. INR measurements were taken at day 4 and day 6.. Of these patients, 21% had an INR within the therapeutic range on day 4 and 52% had a therapeutic INR on day 6. The risk of overdose was small with only one case with an INR above 4.0 on day 4 and nine cases on day 6. There were no reported cases of bleeding.. The low-dose protocol with infrequent testing is safe and convenient for outpatient management. However, our results suggest that patients on this protocol take between 6-10 days to achieve a stable INR.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Child; Drug Overdose; Female; Humans; International Normalized Ratio; Male; Middle Aged; Retrospective Studies; Venous Thrombosis; Warfarin

Factors that predispose to thrombus propagation from the femoropopliteal veins to the pelvic veins are poorly understood. Our goal was to determine whether there are characteristics that identify patients with massive deep vein thrombosis (DVT). We compared the 122 (2.5%) patients presenting with massive DVT (pelvic plus lower-extremity DVT) to the 4,674 (97.5%) patients with isolated lower-extremity DVT from a prospective United States multicenter DVT registry. Patients with massive DVT were younger (59.4+/-18.9 years vs. 64.3+/-16.8 years; p<0.01), less likely to have hypertension (40% vs. 51%; p=0.02), and more likely to smoke (21% vs. 13%; p=0.02) and have ongoing radiation therapy (7% vs. 3%; p=0.02). The massive DVT group more commonly presented with extremity edema (80% vs. 69%; p<0.01) and erythema (21% vs. 12%; p<0.01) than the isolated lower-extremity DVT group. However, after multivariable logistic regression analysis, extremity erythema (adjusted odds ratio 1.86; 95% CI 1.13-3.04) was the only independent sequela of massive DVT and younger age (adjusted odds ratio 1.17 per decreasing decade of age; 95% confidence interval: 1.02-1.34) was the only independent predictor of massive DVT. Thrombus propagation from the femoropopliteal system cannot be reliably predicted using demographic or clinical characteristics.

Topics: Adult; Aged; Anticoagulants; Comorbidity; Female; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Registries; Risk Factors; Ultrasonography; Venous Thrombosis; Warfarin

Topics: Adolescent; Adult; Anticoagulants; Blood Coagulation Disorders; Family; Female; Fibrinogens, Abnormal; Humans; Male; Point Mutation; Prothrombin; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Drug Administration Schedule; Humans; Male; Pulmonary Embolism; Venous Thrombosis; Warfarin

Topics: Age Factors; Anticoagulants; Humans; Leg; Radiography; Recurrence; Thromboembolism; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Arthroplasty, Replacement, Knee; Humans; Postoperative Complications; Research Design; Retrospective Studies; Venous Thrombosis; Warfarin

The use of warfarin is rarely complicated by skin necrosis. We describe a 50-year-old woman who presented with a left leg deep venous thrombosis and subsequent pulmonary embolism. She was initially anticoagulated with low-molecular weight heparin and subsequently warfarin. Within 4 days abdominal skin necrosis developed. Investigations revealed the presence of protein S deficiency and in addition, a mutation in the methylenetetrahydrofolate reductase gene (MTHFR). We present, to our best knowledge, the first case of warfarin skin necrosis associated with a methylenetetrahydrofolate reductase mutation.

Topics: Anticoagulants; Drug Eruptions; Female; Humans; Leg; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Mutation; Necrosis; Protein S Deficiency; Venous Thrombosis; Warfarin

Topics: Ambulatory Care; Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Injections, Intravenous; Length of Stay; Venous Thrombosis; Warfarin

Although a success rate of 80% has been reported in patients with iliofemoral venous thrombosis treated with catheter-based thrombolysis, the possible long-term benefit of this treatment is not known.. 28 consecutive patients referred for catheter-based thrombolysis of iliofemoral venous thrombosis were treated with infusion of alteplase into the thrombus for two to five days. Following thrombolysis, warfarin was given for at least one year. All patients were examined every six months with colour duplex scanning and air pletysmography.. 100% thrombolysis was achieved in eight patients, 75-99% in ten, 50-74% in nine and < 50% in one patient. Angioplasty (four) or stent implantation (four) was successful in eight out of twelve patients with stenosis of the left common iliac vein. Early recurrence of thrombosis (< 7 days) occurred in three patients, pulmonary embolism in one, and bleeding at the insertion site in six. After a mean follow-up of 2.5 years, 17 patients were free of symptoms, seven had a mild degree and four a moderate degree of postthrombotic syndrome. Eighteen patients had normal venous physiology, nine deep venous reflux, and three functional obstruction of deep veins. Postthrombotic syndrome was associated with deep venous reflux and/or functional obstruction of the iliofemoral segment.. Catheter-based thrombolysis is a safe and effective treatment of proximal deep venous thrombosis and might reduce the occurrence of postthrombotic syndrome compared to treatment with anticoagulation alone.

Topics: Adolescent; Adult; Female; Femoral Vein; Fibrinolytic Agents; Humans; Iliac Vein; Male; Middle Aged; Thrombolytic Therapy; Tissue Plasminogen Activator; Venous Thrombosis; Warfarin

Topics: Age Factors; Anticoagulants; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Pulmonary Embolism; Venous Thrombosis; Warfarin

Topics: Age Factors; Anticoagulants; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Pulmonary Embolism; Venous Thrombosis; Warfarin

Topics: Age Factors; Anticoagulants; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Pulmonary Embolism; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Pulmonary Embolism; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Pulmonary Embolism; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Drug Labeling; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Pulmonary Embolism; Venous Thrombosis; Warfarin

Topics: Age Factors; Anticoagulants; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Pulmonary Embolism; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Pulmonary Embolism; Venous Thrombosis; Warfarin

Topics: Aged; Anticoagulants; Antineoplastic Agents; Aromatase Inhibitors; Breast Neoplasms; Contraindications; Enzyme Inhibitors; Female; Humans; Letrozole; Nitriles; Pulmonary Embolism; Risk; Tamoxifen; Triazoles; Venous Thrombosis; Warfarin

A 43-year-old man presented 10 days after a Roux-en-Y gastric bypass with abdominal pain radiating to the back. Investigation revealed a thrombus in the superior mesenteric vein. The patient was found to have a hypercoagulable state. He responded successfully to anticoagulant therapy.

Topics: Adult; Anastomosis, Roux-en-Y; Anticoagulants; Gastric Bypass; Humans; Male; Mesenteric Vascular Occlusion; Mesenteric Veins; Obesity, Morbid; Radiography; Thrombophilia; Treatment Outcome; Venous Thrombosis; Warfarin

A 78-year-old woman with unstable angina underwent coronary bypass surgery with complete cardiac revascularization and no immediate postoperative complications. Six days after surgery, during hospitalization for cardiac rehabilitation, the patient developed severe respiratory distress and pulmonary embolism was diagnosed. Color duplex ultrasound revealed the presence of concomitant upper extremity deep vein thrombosis (UEDVT), ipsilateral to the site of placement of a central venous line, in the absence of lower extremity deep vein thrombosis. We describe this case and provide preliminary data from a prospective observational study evaluating the prevalence of catheter-related UEDVT and symptomatic pulmonary embolism (55 and 1.4% respectively) in a series of 71 consecutive coronary bypass surgery patients admitted to a cardiac rehabilitation facility. Catheter-related UEDVT and pulmonary embolism may complicate coronary bypass surgery and should be taken into consideration when managing patients after surgery.

Topics: Aged; Angina, Unstable; Anticoagulants; Coronary Artery Bypass; Echocardiography; Female; Humans; Jugular Veins; Male; Middle Aged; Postoperative Complications; Prospective Studies; Pulmonary Embolism; Ultrasonography, Doppler, Color; Upper Extremity; Venous Thrombosis; Warfarin

Evidence-based international guidelines recommend that all patients undergoing elective hip or knee arthroplasty receive thromboprophylaxis with low-molecular-weight heparin or adjusted-dose warfarin. Our objective was to determine what proportion of patients undergoing elective hip or knee arthroplasty actually receive recommended thromboprophylaxis according to international guidelines.. We performed a prospective cohort study of 396 consecutive patients undergoing elective hip or knee arthroplasty between 1 May and 30 October, 2002. We collected baseline data, surgical and anesthetic details and recorded use of thromboprophylaxis and episodes of venous thromboembolism that occurred within 3 months of surgery.. The mean age of the patients was 69.4 years (SD 11.5 years), and 62.2% (95% CI: 57.3 to 66.9%) were female. Hip arthroplasty was performed in 39.4% (34.6 to 44.2%) and knee arthroplasty in 57.1% (52.2 to 61.9%). Recommended thromboprophylaxis with low-molecular-weight heparin or warfarin was administered to 51.5% (46.6 to 56.4%). Objectively diagnosed venous thromboembolism occurred in 5.3% (3.3 to 8.0%) of patients; 3.5% (1.9 to 5.9%) of events occurred during hospitalization and 1.8% (0.7 to 3.6%) occurred following discharge from hospital. There was no significant reduction in the incidence of venous thromboembolism among patients treated with recommended thromboprophylaxis compared with those who did not but this is not a randomized comparison and is potentially confounded by the indication for treatment.. Current thromboprophylaxis practice at our institutions falls substantially short of national and international guidelines. The reasons for low thromboprophylaxis use should be further explored and strategies for change implemented in order to optimize clinical practice.

Topics: Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Female; Guideline Adherence; Heparin, Low-Molecular-Weight; Hospitals, Teaching; Humans; Male; Middle Aged; Practice Guidelines as Topic; Practice Patterns, Physicians'; Prospective Studies; Thromboembolism; Venous Thrombosis; Warfarin; Western Australia

Graft thrombosis in long-term postoperative period after lower extremity arterial reconstructions often results in limb loss. In some studies prolonged antithrombotic therapy was demonstrated to improve long-term patency of vascular grafts. Nevertheless little consensus exists on the optimal antithrombotic agents. The paper reviews publications on the problem. Oral anticoagulants seem to be feasible for reconstructions with poor outflow. In such cases strict laboratory monitoring of blood coagulation system is mandatory to prevent hemorrhagic complications.

Topics: Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Drug Administration Schedule; Humans; Lower Extremity; Plastic Surgery Procedures; Postoperative Care; Venous Thrombosis; Warfarin

Antiphospholipid syndrome is a disorder characterized by arterial and venous thromboses, thrombocytopaenia and stroke. Acute myocardial infarction is rarely associated with this syndrome. The treatment of these patients is a clinical challenge. This report is about a patient with antiphospholipid syndrome presenting with an acute myocardial infarction after an exercise test. The infarct-related coronary artery was successfully revascularized by primary angioplasty and stenting without any major bleeding complications. We think that the physical exertion could have favoured acute coronary thrombosis in this particular setting.

Topics: Angioplasty, Balloon, Coronary; Antiphospholipid Syndrome; Exercise Test; Humans; Male; Middle Aged; Myocardial Infarction; Pulmonary Embolism; Stents; Treatment Outcome; Venous Thrombosis; Warfarin

Paradoxical embolism through a patent foramen ovale (PFO) is a recognized cause of stroke, but its prognosis is not well known. The aim of our study is to evaluate differences in risk factors, recurrent stroke subtypes and effects of various preventive therapies between PFO associated stroke patients with and without deep vein thrombosis (DVT). A total of 63 patients who had an embolic stroke with a PFO within 3 months from stroke onset were enrolled. Venous ultrasonography, which was performed in all the patients, revealed DVT in 26 patients (41%). Venous thrombosis was confined to the isolated calf veins in 24 of 26 cases (92%). For prevention of stroke recurrence, warfarin was administrated in 32 patients, antiplatelet therapy was given in 21 patients, and combination of warfarin and antiplatelet therapy was chosen in 10 patients. Three patients with DVT and three other patients without DVT had recurrent ischemic events during a mean follow-up period of 14.6 months. In all the 3 patients without DVT, complicated aortic arch lesions were also observed, and 2 of them had lacunar infarcts. In all the three patients with DVT recurrent embolic stroke or TIA occurred in spite of anticoagulant therapy. Their INR values at the time of recurrence were all below 1.7, and 2 of them were associated with atrial septal aneurysm (ASA). Association with PFO, ASA, and DVT may be a substantial risk factor for recurrent stroke. Higher INR value in anticoagulation may be recommended for such patients to prevent stroke recurrence.

Topics: Aged; Anticoagulants; Echocardiography, Transesophageal; Female; Heart Septal Defects, Atrial; Humans; Intracranial Embolism; Magnetic Resonance Imaging; Male; Middle Aged; Prognosis; Recurrence; Stroke; Venous Thrombosis; Warfarin

Ximelagatran (Exanta (TM)) is the first oral agent in a new class of anticoagulants called direct thrombin inhibitors. Most of the available evidence regarding venous thromboembolism is from studies focusing on its prevention after major orthopedic surgery. Ximelagatran's efficacy is comparable to that of warfarin and low-molecular-weight heparin in this setting. The rates of bleeding complications for ximelagatran and its comparators were not statistically different. The elevation of liver enzymes was observed in longer term trials.

Topics: Administration, Oral; Anticoagulants; Azetidines; Canada; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Approval; Europe; Evidence-Based Medicine; Heparin, Low-Molecular-Weight; Humans; Orthopedic Procedures; Randomized Controlled Trials as Topic; Risk Factors; Venous Thrombosis; Warfarin

Few studies have evaluated patient-reported outcomes in connection with a primary event of deep venous thrombosis, partly due to a lack of disease-specific measures. The aim here was to develop a disease-specific health-related quality of life (HRQL) measure, the deep venous thrombosis quality of life questionnaire (DVTQOL), for patients with recent exposition and treatment of proximal deep venous thrombosis.. A total of 121 consecutive outpatients (50 % males; mean age 61.2 +/- 14 years) treated with warfarin (Waran) for symptomatic proximal deep venous thrombosis were included in the study. Patients completed the SF-36, EQ-5D and the pilot version of the DVTQOL.. Items having: high ceiling and floor effect, items with lower factor loadings than 0.50 and items loading in several factors were removed from the pilot version of DVTQOL. In addition, overlapping and redundant items identified by the Rasch analysis were excluded. The final DVTQOL questionnaire consists of 29 items composing six dimensions depicting problems with: emotional distress; symptoms (e.g. pain, swollen ankles, cramp, bruising); limitation in physical activity; hassle with coagulation monitoring; sleep disturbance; and dietary problems. The internal consistency reliability was high (alpha value ranged from 0.79 to 0.93). The relevant domains of the SF-36 and EQ-5D significantly correlated with DVTQOL, thereby confirming its construct validity.. The DVTQOL is a short and user-friendly instrument with good reliability and validity. Its test-retest reliability and responsiveness to change in clinical trials, however, must be explored.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Female; Humans; Male; Middle Aged; Pilot Projects; Psychometrics; Quality of Life; Sex Factors; Sickness Impact Profile; Surveys and Questionnaires; Sweden; Treatment Outcome; Venous Thrombosis; Warfarin

Topics: Clinical Trials as Topic; Hemorrhage; Humans; Risk Assessment; Secondary Prevention; Thromboembolism; Time; Venous Thrombosis; Warfarin

Topics: Clinical Trials as Topic; Hemorrhage; Humans; Risk Assessment; Secondary Prevention; Thromboembolism; Time; Venous Thrombosis; Warfarin

Topics: Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Monitoring; Hemorrhage; Humans; Risk Assessment; Secondary Prevention; Thromboembolism; Venous Thrombosis; Warfarin

Transradial cardiac catheterization is an increasingly popular technique mainly because of the low vascular complication rate. We report a case of arm deep vein thrombosis that may be related to a common puncture site hemostasis technique. This complication supports the use of specific unilateral compression hemostatic systems following transradial procedures.

Topics: Aged; Anticoagulants; Arm; Bandages; Cardiac Catheterization; Female; Humans; Punctures; Radial Artery; Venous Thrombosis; Warfarin

Warfarin-induced skin necrosis is a rare complication associated with the use of oral anticoagulants. Most patients develop this at the initiation of therapy, often while still receiving intravenous unfractionated heparin (UFH). Recently, low-molecular-weight heparins (LMWHs) have gained wider use, providing an option for outpatient treatment of deep-vein thrombosis. The treatment protocols are similar to UFH, including the early initiation of oral anticoagulation with warfarin. A Medline search failed to reveal any cases of warfarin-induced skin necrosis while using a LMWH. We present a patient with protein S deficiency who developed warfarin skin necrosis despite appropriate anticoagulation with enoxaparin, and review the chemical and clinical difference between UFH and LMWH.

Topics: Anticoagulants; Arterial Occlusive Diseases; Enoxaparin; Female; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Middle Aged; Necrosis; Popliteal Artery; Postoperative Complications; Protein S Deficiency; Skin Diseases; Subclavian Vein; Tibial Arteries; Treatment Failure; Vascular Surgical Procedures; Venous Thrombosis; Warfarin

Topics: Adult; Anticoagulants; Arm; Cohort Studies; Female; Follow-Up Studies; Heparin; Humans; Male; Prospective Studies; Recurrence; Venous Thrombosis; Warfarin

This report describes a patient who suffered multiple-vein thrombosis following permanent pacemaker implantation and developed a pulmonary embolism while on anticoagulation treatment, which was successfully treated by thrombolytic therapy.

Topics: Aged; Anticoagulants; Fibrinolytic Agents; Humans; Male; Pacemaker, Artificial; Postoperative Complications; Pulmonary Embolism; Streptokinase; Thrombolytic Therapy; Venous Thrombosis; Warfarin

D-003 is a mixture of higher aliphatic primary acids isolated and purified from sugarcane wax, the main component of which is octacosanoic acid. D-003 exhibits a cholesterol-lowering effect as well as antiplatelet and antithrombotic effects in experimental models. Warfarin is a coumarin derivative with anticoagulant activity that acts as a vitamin K antagonist. Since in clinical practice warfarin and D-003 could be administered together, the objective of this study was to evaluate the effects of the simultaneous administration of both drugs on the bleeding time and the venous thrombosis experimentally induced in rats. The combined therapy of minimally effective doses of D-003 and warfarin produced an antithrombotic effect significantly higher than those produced by each monotherapy. Likewise, the prolongation of bleeding time induced by warfarin was increased by the simultaneous administration with D-003, showing a synergistic effect between both drugs.

Topics: Animals; Bleeding Time; Drug Synergism; Drug Therapy, Combination; Fatty Acids; Fibrinolytic Agents; Rats; Rats, Sprague-Dawley; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Contraindications; Education, Medical, Continuing; Heart Valve Prosthesis; Heparin, Low-Molecular-Weight; Humans; Perioperative Care; Postoperative Hemorrhage; Practice Guidelines as Topic; Pulmonary Embolism; Risk Assessment; Surgical Procedures, Operative; Thrombolytic Therapy; Venous Thrombosis; Warfarin

The objectives of this study were to observe a commercially insured sample diagnosed with a venous thromboembolism (VTE) event and treated postevent with warfarin and to detail the thromboembolic and bleeding outcomes in the time periods during warfarin therapy and after discontinuation of such therapy.. This retrospective, observational cohort study used medical, pharmacy, and eligibility data from 2 US health plans. Study inclusion required an inpatient diagnosis of deep venous thrombosis (DVT) or pulmonary embolism (PE) between January 1, 1998, and December 31, 2000; warfarin, heparin, or low-molecular-weight heparin within 30 days after diagnosis; no VTE diagnosis; and no anticoagulant use for 3 months preceding diagnosis. A random sample of medical charts was abstracted to validate VTE events and collect prothrombin time/international normalized ratio (INR) result data. Recurrent VTE events, bleeding events, and proportion of time within INR range were captured in the postindex VTE event time period. Univariate and multivariate statistical techniques were used to assess outcomes.. A total of 2,090 patients were identified with a newly diagnosed VTE event (DVT only, 1450; PE with or without DVT, 640). Mean (SD) age was 61.7 (16) years; mean (SD) follow-up time after the index diagnosis was 21.3 (10) months. Overall mean (SD) length of warfarin therapy was 6.6 (6) months. During the follow-up period, 224 patients (10.7%) experienced a recurrent VTE event and 122 patients (5.8%) experienced a bleeding event requiring hospitalization. The cumulative incidence of recurrent VTE events over 3 and 6 months was 9.0% and 10.9%, respectively. Using the chart abstraction subset, patients were within the appropriate INR range 37.7% of the time while receiving warfarin.. Negative outcomes associated with warfarin therapy-recurrent VTE events and bleeding requiring hospitalization-were experienced by 10.7% and 5.8% of patients, respectively. These data suggest that negative outcomes may be more prevalent in usual community medical practice compared with rates observed in the controlled environment of the clinical trial or specialized anticoagulation clinic.

Topics: Aged; Aged, 80 and over; Anticoagulants; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Incidence; International Normalized Ratio; Male; Medical Records; Middle Aged; Pulmonary Embolism; Recurrence; Retrospective Studies; Risk Factors; Treatment Outcome; United States; Venous Thrombosis; Warfarin

The aim of the study was to assess venous reflux and the obstruction pattern after catheter-directed and systemic thrombolysis of deep iliofemoral venous thrombosis.. Thirty-two patients treated either with systemic (16) or catheter-directed local thrombolysis (16) for massive iliofemoral thrombosis were identified from the hospital registry.. Clinical evaluation at follow up was based on the CEAP classification and disability score. Reflux was assessed by colour duplex ultrasonography and standardised reflux testing. A vascular surgeon blinded to treatment established the clinical status of the lower limb following the previous DVT.. Valvular competence was preserved in 44% of patients treated with catheter-directed thrombolysis compared with 13% of those treated with systemic thrombolysis (p=0.049, Chi squared). Reflux in any deep vein was present in 44% of patients treated by catheter-directed lysis compared with 81% of patients receiving systemic thrombolysis (p=0.03, Chi squared). Reflux in any superficial vein was observed in 25% vs. 63% of the patients, respectively (p=0.03, Chi squared). There were significantly more patients with venous insufficiency of classes C0-1 in the group treated with catheter-directed thrombolysis.. In this clinical series venous valvular function was better preserved after iliofemoral DVT when treated with catheter-directed thrombolysis.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Bandages; Catheterization, Peripheral; Female; Femoral Vein; Finland; Follow-Up Studies; Humans; Iliac Vein; Male; Middle Aged; Retrospective Studies; Thrombolytic Therapy; Treatment Outcome; Ultrasonography, Doppler, Duplex; Vascular Patency; Venous Thrombosis; Warfarin

Among 199 patients treated with thalidomide for multiple myeloma, four thromboses occurred in 49 cases during erythropoietin therapy (prevalence 8.1%; annual rate 7.25%), and another 14 events occurred in patients not on erythropoietin (9.3%; 7.56%). Thus, erythropoietin would seem not to increase the risk of thrombosis of myeloma patients receiving thalidomide.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Antineoplastic Agents; Drug Synergism; Erythropoietin; Female; Humans; Male; Middle Aged; Multiple Myeloma; Recombinant Proteins; Risk; Thalidomide; Thrombosis; Venous Thrombosis; Warfarin

The quality control of oral anticoagulant therapy (OAT) during the initiation and maintenance treatment is generally poor. Physicians' ordering of OAT (especially fluindione and warfarin) can be improved by dose adjustment algorithms, taking into account the results of International Normalized Ratio (INR). Reminders at the point of care, computerized or not, have been demonstrated to be effective in changing physicians prescription behavior.However, few studies have addressed the benefit of personalized reminders versus non personalized reminders, whereas the personalized reminders require more development to access patient record data and integrate with the computerized physician order entry system. The Hospital Information System of George Pompidou European Hospital integrates an electronic medical record, lab test and drugs order entry system. This system allows to evaluate such reminders and to consider their implementation for routine use as well as the continuous evaluation of their impact on medical practice quality indicators. The objective of this study is to evaluate the impact of two types of reminders on overtreatment by oral anticoagulant: a simple reminder of text formatted dose adjustment table and a personalized recommendation for oral anticoagulant dose and next date of INR control, adapted to patient data. Both types of reminders appear to the physician at the moment of drug ordering.

Topics: Administration, Oral; Anticoagulants; Cerebral Hemorrhage; Chemoprevention; Clinical Pharmacy Information Systems; Decision Support Systems, Clinical; Drug Utilization Review; France; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Medical Staff, Hospital; Medication Errors; Nomograms; Phenindione; Quality Control; Reminder Systems; Systems Integration; Time; Treatment Outcome; Venous Thrombosis; Warfarin

Topics: Abdominal Pain; Administration, Oral; Adult; Age Factors; Back Pain; Drug Therapy, Combination; Heparin; Humans; Infusions, Intravenous; Male; Mesenteric Veins; Venous Thrombosis; Warfarin

The authors describe a case of DVT during pregnancy in a 41-year-old woman who had a normal haemocoagulative picture during pregnancy and in puerperium (PT, PTT, S protein, C protein, ATIII, xdp and fibrinogenous). All the haemocoagulative dosages were within the norm and compatible with the gestation period. Both homocysteine and antiphospholipid antibodies (mostly in puerperium) were always within normal limits. The authors believe that DVT occurs infrequently but it is also unforeseeable. Systematic heparin prophylaxis for seven to ten days, ante- and postpartum, can prevent this problem.

Topics: Adult; Anticoagulants; Betamethasone; Female; Femoral Vein; Glucocorticoids; Heparin, Low-Molecular-Weight; Humans; Iliac Vein; Platelet Aggregation Inhibitors; Pregnancy; Pregnancy Complications, Hematologic; Puerperal Disorders; Sulfonamides; Vena Cava, Inferior; Venous Thrombosis; Warfarin

Many orthopaedic surgeons use warfarin to prevent venous thromboembolism (VTE) following hip or knee arthroplasty. Since warfarin's antithrombotic effects are delayed, we hypothesized that early VTE (occurring within 5 days post-operatively) would be more common in arthroplasty patients receiving warfarin monotherapy compared to those receiving enoxaparin. We performed a secondary analysis of a case-control study examining risk factors for post-operative thrombosis in postmenopausal women. We defined cases as patients who were diagnosed with thrombosis within 5 days of surgery. Controls without thrombosis were matched with cases by age, surgeon, year of surgery and surgical joint. 84 women with early post-operative thrombosis (cases) were matched with 206 controls. 18 cases (21.4%) had been prescribed warfarin mono-therapy, compared with 7 controls (3.4%). 58 (69.1%) cases and 195 (94.7%) controls had been prescribed subcutaneous enoxaparin 30 mg twice daily, starting 12-24 hours after surgery. The odds ratio for any early thrombosis in patients receiving warfarin as opposed to enoxaparin 30 mg twice daily was 8.6 (p<0.0001). For proximal thrombosis, the odds ratio was 11.3 (p<0.0001). Multivariate analysis did not alter these findings. Warfarin's delayed antithrombotic effects may not provide adequate VTE prophylaxis in the immediate post-operative setting. We suggest caution in employing warfarin monotherapy following joint arthroplasty.

Topics: Aged; Aged, 80 and over; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Case-Control Studies; Drug Evaluation; Enoxaparin; Female; Humans; Odds Ratio; Postoperative Complications; Premedication; Retrospective Studies; Thromboembolism; Time; Venous Thrombosis; Warfarin

Topics: Female; Fibrinolytic Agents; Heparin; Humans; Male; Thrombolytic Therapy; Venous Thrombosis; Warfarin

Topics: Adult; Anticoagulants; Humans; Long-Term Care; Randomized Controlled Trials as Topic; Risk Factors; Secondary Prevention; Thromboembolism; Treatment Outcome; Venous Thrombosis; Warfarin

Warfarin is a widely used anticoagulant with efficacy in treatment and prevention of thrombosis. Patient management, however, is difficult because of interindividual variation in response to standard doses due to significant differences in metabolic rates. Warfarin metabolism is under genetic control, involving primarily the CYP2C9 gene encoding the enzyme that catalyzes the conversion of warfarin to inactive metabolites.. Several polymorphisms of CYP2C9 have been reported; the variant alleles *2 and *3 have decreased enzymatic activity. The objective of this case study is to investigate the relationship between CYP2C9 genotype and warfarin anticoagulation.. A case of deep vein thrombosis treated with the standard warfarin dose is investigated for intensity of anticoagulation and CYP2C9 genotype; the case illustrates the relationship between CYP2C9 variant and overanticoagulation with subsequent bleeding complication.. The patient's genotype, CYP2C9*1*3, correlated with an exaggerated anticoagulant response during the initiation of warfarin therapy at standard dose, and a bleeding episode ensued. Based on heterozygosity for the *3 variant allele, it was recommended that the patient be maintained on a low-dose warfarin regimen.. The practical implications of identifying genetic risk factors that lead to overanticoagulation are multiple. Genotype knowledge of the CYP2C9 variant alleles may help the clinician to individualize warfarin therapy with the ultimate goals of shortening the initial period of induction therapy, reaching a stable maintenance dose earlier, and minimizing bleeding complications in patients who are high responders and need lower warfarin doses.

Topics: Administration, Oral; Aged; Aryl Hydrocarbon Hydroxylases; Blood Coagulation; Cytochrome P-450 CYP2C9; Genetic Predisposition to Disease; Genetic Variation; Hemorrhage; Humans; Male; Pharmacogenetics; Polymorphism, Genetic; Venous Thrombosis; Warfarin

Isolated reports of a possible positive effect of anti-coagulant drugs, among them heparin, warfarin and acenocumarol, in migraine prophylaxis are found in the literature. We report the case of a 37 years old man suffering from refractory chronic cluster headache that presented remission with the administration of warfarin for the treatment of deep venous thrombosis associated to arterial thrombosis. We did not found any case like that in the literature.

Topics: Adult; Anti-Inflammatory Agents; Anticoagulants; Cluster Headache; Heparin; Humans; Male; Prednisone; Remission Induction; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Catheterization, Peripheral; Chronic Disease; Clinical Trials as Topic; Fibrinolytic Agents; Heparin; Humans; Infusions, Intravenous; Recurrence; Stents; Streptokinase; Thrombolytic Therapy; Thrombophlebitis; Ultrasonography; Venous Insufficiency; Venous Thrombosis; Warfarin

Topics: Adenocarcinoma; Adult; Anticoagulants; Arterial Occlusive Diseases; Autoimmune Diseases; Drug Resistance; Female; Heparin; Heparin, Low-Molecular-Weight; Hepatitis C, Chronic; Hirudins; Humans; Inflammatory Bowel Diseases; Male; Middle Aged; Neoplasms, Unknown Primary; Platelet Aggregation Inhibitors; Portal Vein; Pulmonary Embolism; Recombinant Proteins; Recurrence; Thrombocytopenia; Vena Cava, Inferior; Venous Thrombosis; Warfarin

Patients with deep venous thrombosis (DVT) treated out of hospital usually start warfarin with the recommended 5 mg loading dose and have their International Normalized Ratio (INR) test performed every 2-3 days. Thus, achievement of the therapeutic range may be more difficult than for inpatients, possibly resulting in extended duration of low molecular weight heparin (LMWH) treatment. We retrospectively examined the charts of 55 DVT outpatients (mean age, 61.4 years; 30 males) to assess the actual duration of LMWH treatment and to identify predictors of a slow achievement of the INR range. Thirty patients (54.4%) reached the therapeutic INR range and stopped LMWH within 7 days, and 25 patients (45.6%) had to continue for an average of 10.5 days. The latter group was significantly younger than the former (57 and 65 years, respectively; P = 0.039). Patients younger than 60 years old had an odds ratio for an extended treatment of 4.92 (P = 0.0057). Algorithms with different loading doses of warfarin according to age should be proposed for outpatient treatment of DVT.

Topics: Administration, Oral; Age Factors; Aged; Anticoagulants; Drug Administration Schedule; Female; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Male; Middle Aged; Outpatients; Retrospective Studies; Time Factors; Venous Thrombosis; Warfarin

A potential influence of idraparinux--a synthetic analogue of the pentasaccharide sequence in heparins--on plasma liver enzyme levels was analysed in 37 patients suffering from deep vein thrombosis and participating in the PERSIST trial. Plasma gamma-glutamyl-transferase, aspartate aminotransferase and alanine aminotransferase were determined prior to enoxaparin treatment (screening), prior to randomization (baseline) and once weekly during the 12-week treatment period. Patients were initially treated with weight-adjusted enoxaparin for 4-7 days and then randomized to either idraparinux (2.5, 5, 7.5 or 10 mg) or warfarin. Gamma-glutamyl-transferase was significantly increased after administration of enoxaparin at the baseline visit (P = 0.004) and in week 2 (P = 0.009) to return to screening levels in week 3 for the remaining study period (all P > 0.05). Aspartate aminotransferase (P = 0.001) and alanine aminotransferase (P < 0.001) were significantly increased at the baseline visit and returned to screening values at week 2 for the remaining study period (all P > 0.05). There was no significant difference between the mean values of plasma liver enzymes of the four idraparinux groups and the warfarin group in all 13 measurements. We concluded that idraparinux in contrast to enoxaparin does not increase plasma liver enzymes significantly.

Topics: Adult; Aged; Alanine Transaminase; Anticoagulants; Aspartate Aminotransferases; Enoxaparin; Female; gamma-Glutamyltransferase; Heparin; Humans; Liver; Male; Middle Aged; Oligosaccharides; Randomized Controlled Trials as Topic; Transferases; Venous Thrombosis; Warfarin

With rising health care costs, methods to decrease length of hospital stay without compromising care are necessary. One area that extends length of stay in trauma patients is inpatient anticoagulation to a therapeutic international normalized ratio. The 1998 American College of Chest Physicians guidelines recommend thromboprophylaxis with low-molecular-weight heparin (LMWH) and oral warfarin in this population. The LMWH Expedited Anticoagulation Program (LEAP) was created with the following goals: to decrease the number of inpatient warfarin days and to reduce overall number of hospital days.. Inpatient anticoagulation was initiated with warfarin and LMWH. LEAP included early multidisciplinary collaboration to ensure third-party approval, outpatient primary care physician follow-up, and LMWH self-injection before discharge. Patients were discharged on LMWH (discontinued by primary care provider when a therapeutic international normalized ratio was attained) and warfarin (continued until resolution of orthopedic injuries). From August 2000 to August 2001, adult patients were included in the prospective study. Primary inclusion criteria were blunt acetabular fracture, bilateral lower extremity fracture, and contralateral upper and lower extremity fractures. Patients with similar injuries receiving warfarin for deep venous thrombosis prophylaxis between June 1999 and June 2000 were the control population. Anticoagulation care was similar for the study and control subjects.. There were 182 patients evaluated for LEAP inclusion. After initial evaluation, 108 patients were enrolled in LEAP (Injury Severity Score of 13). There were 69 control subjects (Injury Severity Score of 13). The average number of inpatient warfarin days was decreased from 8.8 days to 5.0 days in the control and study populations, respectively (p < 0.0001). The average length of hospitalization was shortened from 17.3 days in the control group to 12.9 days in the study (LEAP) population (p < 0.002).. LEAP has successfully decreased the number of inpatient days on warfarin and total hospital days for trauma patients requiring deep venous thrombosis prophylaxis. These results have substantially decreased health care costs and increased available hospital beds in this era of high hospital occupancy.

Topics: Adult; Aged; Anticoagulants; Case-Control Studies; Female; Heparin, Low-Molecular-Weight; Humans; Injury Severity Score; Length of Stay; Male; Middle Aged; Venous Thrombosis; Warfarin; Wounds and Injuries

Topics: Aged; Anticoagulants; Antineoplastic Agents, Phytogenic; Binding Sites; Blood Coagulation; Drug Interactions; Female; Humans; International Normalized Ratio; Ovarian Neoplasms; Paclitaxel; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Humans; Pulmonary Embolism; Secondary Prevention; Thromboembolism; Venous Thrombosis; Warfarin

Topics: Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Blood Proteins; Female; Humans; Middle Aged; Thromboembolism; Venous Thrombosis; Warfarin

Venous compression is a rare but accepted cause of Deep Venous Thrombosis. We report a case of DVT caused by extrinsic compression of the popliteal vein by constricting elasticated knee pads. The knee pads were worn at work by a Tiler who did not have any hypercoagulability disorder.

Topics: Adult; Anticoagulants; Clothing; Elasticity; Humans; Knee; Male; Occupations; Popliteal Vein; Ultrasonography; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Humans; Venous Thrombosis; Warfarin

We describe a family in which four generations (eight members) had deep vein thrombosis of the lower limb and three of the alive members had documented hyperhomocysteinemia. In addition, one of the family members had evidence of arterial thrombosis in the form of cerebral infarcts. Interestingly, all affected members in the family were males.

Topics: Adult; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Nitroprusside; Pedigree; Venous Thrombosis; Vitamin B 12; Warfarin

Topics: Anticoagulants; Dose-Response Relationship, Drug; Humans; United States; Venous Thrombosis; Warfarin