vitamin-k-semiquinone-radical and Venous-Thrombosis

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

Venous thromboembolism (VTE) is the third most common cardiovascular disorder, affecting up to 5% of the population. VTE commonly manifests as lower-extremity deep venous thrombosis (DVT) or pulmonary embolism. Half of these events are associated with a transient risk factor and may be preventable with prophylaxis. Direct oral anticoagulants are effective and safe and carry a lower risk for bleeding than vitamin K antagonists. Many patients with VTE will have a chronic disease requiring long-term anticoagulation. Postthrombotic syndrome affects 25% to 40% of patients with DVT and significantly impacts function and quality of life.

Topics: Anticoagulants; Humans; Quality of Life; Venous Thromboembolism; Venous Thrombosis; Vitamin K

Direct oral anticoagulants recently became the first-line choice for anticoagulation in venous thromboembolic disease. Many studies have shown its non-inferiority regarding the risk of thromboembolic recurrence compared to anti-vitamin K without increasing the risk of bleeding in the general population. However, specific populations such as patients with cancer, patients with kidney failure, patients with constitutional thrombophilia, elderly patients, or patients with extreme weight are at risk of intolerance to the use of direct oral anticoagulants. Precautions in use may be necessary as discussed in recently published guidelines about antiphospholipid syndrome. This review aims to list the main clinical trials investigating direct oral anticoagulants in venous thromboembolic disease in the general population and populations at risk, as well as to provide an update on current international and French guidelines.

Topics: Administration, Oral; Aged; Anticoagulants; Humans; Venous Thromboembolism; Venous Thrombosis; Vitamin K

Portal vein thrombosis (PVT) is associated with a higher risk of liver-related complications. Recent guidelines recommend direct-acting anticoagulants (DOAC) in patients with cirrhosis and non-tumoral PVT. However, data on the efficacy and safety of DOAC in these patients remain limited. We aim to investigate the efficacy and safety of DOAC compared to vitamin K antagonists (VKA) to treat non-tumoral PVT in patients with cirrhosis.. We performed a systematic search of six electronic databases using MeSH term and free text. We selected all studies comparing the use of DOACs with vitamin K antagonist to treat PVT in cirrhosis. The primary outcome was PVT recanalization. Secondary outcomes were and PVT progression, major bleeding, variceal bleeding and death.. From 944 citations, we included 552 subjects from a total of 11 studies (10 observational and 1 randomized trial) that fulfilled the inclusion criteria. We found that DOAC were associated with a higher pooled rate of PVT recanalization (RR = 1.67, 95%CI: 1.02, 2.74, I. For the treatment of PVT in patients with cirrhosis, the bleeding risk was comparable between DOAC and VKA. However, DOAC were associated with a higher pooled rate of PVT recanalization. Dedicated randomized studies are needed to confirm these findings.

Topics: 4-Hydroxycoumarins; Administration, Oral; Anticoagulants; Humans; Indenes; Liver Cirrhosis; Observational Studies as Topic; Portal Vein; Randomized Controlled Trials as Topic; Treatment Outcome; Venous Thrombosis; Vitamin K

Cerebral venous thrombosis (CVT) causes significant disability and mortality. Current guidelines for CVT management support the initial use of unfractionated heparin or low molecular weight heparin followed by longer-term oral vitamin K antagonist (VKA). There has been increasing, albeit limited, evidence for the use of direct oral anticoagulants (DOAC) as an alternative to VKA. We performed a systematic review and meta-analysis of studies that compared the safety and efficacy of DOACs to VKA in treating CVT. A comprehensive literature search was carried out in Medline, Embase and Cochrane Stroke Group Trials Register using a suitable keyword/MeSH term search strategy. All studies published in English comparing outcomes of patients with CVT treated with DOAC or VKA were included. In total, 6 studies (5 observational studies and 1 randomized clinical trial) comprising 412 patients (age range 16-83 years) were analyzed. DOAC was used in 151 patients, while 261 received VKA. The follow-up period was 3-11 months. The efficacy of DOACs was comparable with VKA in terms of partial or full thrombus recanalization (RR 1.02, 95% CI 0.89-1.16) and excellent functional recovery with modified Rankin scale < 2 (RR 1.02, 95% CI 0.93-1.13). Patients treated with DOAC developed lower major bleeding events when compared to VKA, although this did not reach statistical significance (RR 0.44, 95% CI 0.12-1.59). We provide preliminary evidence to support DOAC as effective and safe alternatives to VKA in CVT treatment. We await the results of upcoming randomized trials to further support our results and validate the use of DOAC.

Topics: Anticoagulants; Cerebrovascular Disorders; Factor Xa Inhibitors; Humans; Treatment Outcome; Venous Thrombosis; Vitamin K

"Acute venous thromboembolism is a common disease seen by nearly all hospitalists. The advent of low molecular weight heparin (LMWH) several decades ago ushered in the era of early hospital discharge and home treatment. More recently, the direct oral anticoagulants (DOACs) have further simplified outpatient treatment and some offer treatment without parenteral therapy. Use of DOACs for cancer-associated venous thromboembolism is emerging and is a welcome evolution of care to spare oncologic patients the burden of daily LMWH injections."

Topics: Administration, Oral; Anticoagulants; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Pulmonary Embolism; Risk Assessment; Surgical Procedures, Operative; Venous Thromboembolism; Venous Thrombosis; Vitamin K

Direct oral anticoagulants (DOACs) may be good alternatives to low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) for treatment of cancer associated thrombosis (CAT). We conducted a meta-analysis of ten randomized clinical trials to evaluate the efficacy and safety of DOACs in patients with CAT. All had study populations composed in entirety or in part of patients with CAT. The primary outcome (efficacy) was recurrent VTE and the secondary outcomes (safety outcomes) included major bleeding, clinically relevant non-major bleeding (CRNMB), and all bleeding (major bleeding + CRNMB). Participants treated with DOACs had lower risk of recurrent VTE, overall (RR 0.63; 95% CI 0.51-0.79; p < 0.0001), compared to LMWH (RR 0.57; 95% CI 0.40-0.83; p = 0.003), but not compared to VKA (RR 0.69; 95% CI 0.44-1.06; p = 0.09). Compared to LMWH, DOACs showed no difference in major bleeding risk (RR 1.31; 95% CI 0.78-2.18; p = 0.31), though had higher risk of CRNMB (RR 1.60; 95% CI 1.13-2.26; p = 0.008) and all bleeding (RR 1.49; 95% CI 1.10-2.01; p = 0.010). These results indicate that DOACs are more effective than LMWH for prevention of recurrent VTE with CAT though carry an increased risk for non-major bleeding compared to standard of care, LMWH.

Topics: Administration, Oral; Anticoagulants; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Randomized Controlled Trials as Topic; Secondary Prevention; Thrombosis; Venous Thrombosis; Vitamin K

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

The aim was to review the relative efficacy and safety of anticoagulation for managing venous thromboembolism (VTE) in patients with cancer.. A systematic review and meta-analysis was carried out. On 17 May 2018 the MEDLINE and Scopus databases were searched for randomised controlled trials (RCTs). Eligible RCTs had to be performed in patients with cancer exclusively or to report results on a subset of patients with cancer. The main study outcomes (efficacy/recurrent VTE and safety/bleeding events) were expressed as risk ratios (RR) with a 95% confidence interval (CI). The quality of evidence was assessed following the GRADE method.. Twenty-three RCTs with 6980 patients were identified. Low molecular weight heparins (LMWHs) were more effective than vitamin K antagonists (VKAs) in preventing recurrent VTE (RR 0.58, 95% CI 0.45-0.75) and deep vein thrombosis (RR 0.44, 95% CI 0.29-0.69) but not pulmonary embolism (PE), bleeding, or overall mortality. Direct oral anticoagulants (DOACs) were more effective than VKAs in preventing recurrent VTE (RR 0.65, 95% CI 0.45-0.95) but not DVT, PE, overall mortality, or bleeding. However, anti-Xa DOACs were more effective (RR for VTE 0.64, 95% CI 0.42-0.97) and caused less bleeding than VKAs, although major bleeding was reduced only with DOACs not requiring initial parenteral anticoagulation (RR 0.45, 95% CI 0.21-0.97). In a direct comparison, DOACs were more effective than LMWHs in preventing VTE recurrence (RR 0.64, 95% CI 0.45-0.90) but caused more major bleeding (RR 1.75, 95% CI 1.10-2.77), with no difference in fatal bleeding and overall mortality. Quality of evidence, where sufficient, was mostly moderate or high.. Compared with VKAs, LMWHs and DOACs are more effective in treating VTE, but the former caused less bleeding. DOACs are more effective than LMWHs in preventing VTE recurrence but may carry a higher risk of major bleeding, pending additional information by ongoing trials.

Topics: Anticoagulants; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Oligosaccharides; Pulmonary Embolism; Secondary Prevention; Venous Thromboembolism; Venous Thrombosis; Vitamin K

Atrial fibrillation (AF) is the most frequently encountered sustained arrhythmia with a prevalence of 0.5-10%, depending predominantly on age. The arrhythmia is associated with significant morbidity and mortality, mainly due to thromboembolic events including stroke and systemic embolisms. These complications can be effectively prevented with anticoagulation therapy either with vitamin K antagonists (VKA) or with non-vitamin K antagonists (NOAC). VKA therapy is effective in preventing strokes but these medications are difficult to use, are associated with significant bleeding risk, and have pharmacokinetic/dynamic properties that make their use cumbersome. NOACs-either factor II or factor Xa inhibitors-have been developed over the past two decades and have been tested against VKA in large randomized controlled trials. This trial evidence was complemented more recently by increasing real-world data comprising several 100,000 patients. Finally, NOACs have been examined for their use in specific clinical situations, for example, in patients undergoing cardioversion, catheter ablation, or coronary interventions. In all of these clinical scenarios, NOACs have been similarly effective or-in many instances-even superior to treatment with VKA. Recent guidelines, therefore, recommend NOAC therapy for stroke prevention in AF as first-line therapy.

Topics: Anticoagulants; Atrial Fibrillation; Coronary Disease; Drug Therapy, Combination; Factor Xa Inhibitors; Humans; Platelet Aggregation Inhibitors; Prothrombin; Pulmonary Embolism; Randomized Controlled Trials as Topic; Risk Factors; Stents; Thromboembolism; Venous Thrombosis; Vitamin K

Topics: Administration, Oral; Anticoagulants; Antithrombins; Drug Interactions; Factor Xa Inhibitors; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Neoplastic Cells, Circulating; Prospective Studies; Pulmonary Embolism; Treatment Outcome; Venous Thrombosis; Vitamin K

Central venous catheter (CVC) placement increases the risk of thrombosis in people with cancer. Thrombosis often necessitates the removal of the CVC, resulting in treatment delays and thrombosis-related morbidity and mortality. This is an update of the Cochrane Review published in 2014.. To evaluate the efficacy and safety of anticoagulation for thromboprophylaxis in people with cancer with a CVC.. We conducted a comprehensive literature search in May 2018 that included a major electronic search of Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), and Embase (Ovid); handsearching of conference proceedings; checking of references of included studies; searching for ongoing studies; and using the 'related citation' feature in PubMed. This update of the systematic review was based on the findings of a literature search conducted on 14 May 2018.. Randomized controlled trials (RCTs) assessing the benefits and harms of unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), vitamin K antagonists (VKA), or fondaparinux or comparing the effects of two of these anticoagulants in people with cancer and a CVC.. Using a standardized form, we extracted data and assessed risk of bias. Outcomes included all-cause mortality, symptomatic catheter-related venous thromboembolism (VTE), pulmonary embolism (PE), major bleeding, minor bleeding, catheter-related infection, thrombocytopenia, and health-related quality of life (HRQoL). We assessed the certainty of evidence for each outcome using the GRADE approach (Balshem 2011).. Thirteen RCTs (23 papers) fulfilled the inclusion criteria. These trials enrolled 3420 participants. Seven RCTs compared LMWH to no LMWH (six in adults and one in children), six RCTs compared VKA to no VKA (five in adults and one in children), and three RCTs compared LMWH to VKA in adults.LMWH versus no LMWHSix RCTs (1537 participants) compared LMWH to no LMWH in adults. The meta-analyses showed that LMWH probably decreased the incidence of symptomatic catheter-related VTE up to three months of follow-up compared to no LMWH (risk ratio (RR) 0.43, 95% confidence interval (CI) 0.22 to 0.81; risk difference (RD) 38 fewer per 1000, 95% CI 13 fewer to 52 fewer; moderate-certainty evidence). However, the analysis did not confirm or exclude a beneficial or detrimental effect of LMWH on mortality at three months of follow-up (RR 0.82, 95% CI 0.53 to 1.26; RD 14 fewer per 1000, 95% CI 36 fewer to 20 more; low-certainty evidence), major bleeding (RR 1.49, 95% CI 0.06 to 36.28; RD 0 more per 1000, 95% CI 1 fewer to 35 more; very low-certainty evidence), minor bleeding (RR 1.35, 95% CI 0.62 to 2.92; RD 14 more per 1000, 95% CI 16 fewer to 79 more; low-certainty evidence), and thrombocytopenia (RR 1.03, 95% CI 0.80 to 1.33; RD 5 more per 1000, 95% CI 35 fewer to 58 more; low-certainty evidence).VKA versus no VKAFive RCTs (1599 participants) compared low-dose VKA to no VKA in adults. The meta-analyses did not confirm or exclude a beneficial or detrimental effect of low-dose VKA compared to no VKA on mortality (RR 0.99, 95% CI 0.64 to 1.55; RD 1 fewer per 1000, 95% CI 34 fewer to 52 more; low-certainty evidence), symptomatic catheter-related VTE (RR 0.61, 95% CI 0.23 to 1.64; RD 31 fewer per 1000, 95% CI 62 fewer to 51 more; low-certainty evidence), major bleeding (RR 7.14, 95% CI 0.88 to 57.78; RD 12 more per 1000, 95% CI 0 fewer to 110 more; low-certainty evidence), minor bleeding (RR 0.69, 95% CI 0.38 to 1.26; RD 15 fewer per 1000, 95% CI 30 fewer to 13 more; low-certainty evidence), premature catheter removal (RR 0.82, 95% CI 0.30 to 2.24; RD 29 fewer per 1000, 95% CI 114 fewer to 202 more; low-certainty evidence), and catheter-related infection (RR 1.17, 95% CI 0.74 to 1.85; RD 71 more per 1000, 95% CI 109 fewer to 356; low-certainty evidence).LMWH versus VKAThree RCTs (641 participants) compared LMWH to VKA in adults. The available evidence did not confirm or exclude a beneficial or detrimental effect of LMWH relative to VKA on mortality (RR 0.94, 95% CI 0.56 to 1. The evidence was not conclusive for the effect of LMWH on mortality, the effect of VKA on mortality and catheter-related VTE, and the effect of LMWH compared to VKA on mortality and catheter-related VTE. We found moderate-certainty evidence that LMWH reduces catheter-related VTE compared to no LMWH. People with cancer with CVCs considering anticoagulation should balance the possible benefit of reduced thromboembolic complications with the possible harms and burden of anticoagulants.

Topics: Adult; Anticoagulants; Catheter-Related Infections; Catheterization, Central Venous; Child; Heparin; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Randomized Controlled Trials as Topic; Secondary Prevention; Thrombocytopenia; Venous Thrombosis; Vitamin K

Venous thrombosis (VTE) in children and neonates presents numerous management challenges. Although increasing in frequency, VTE in children and neonates is still uncommon compared with adults. The epidemiology of VTE is vastly different in neonates vs children vs adolescents vs adults. In reality, pediatric thrombosis should be viewed as a multitude of rare diseases (eg, renal vein thrombosis, spontaneous thrombosis, catheter-related thrombosis, cerebral sinovenous thrombosis), all requiring different approaches to diagnosis and with different short- and long-term consequences, but linked by the use of common therapeutic agents. Further, children have fundamentally different physiology in terms of blood flow, developmental hemostasis, and, likely, endothelial function.

Topics: Administration, Oral; Anticoagulants; Child; Child, Preschool; Evidence-Based Medicine; Female; Heparin, Low-Molecular-Weight; Humans; Infant; Infant, Newborn; Male; Practice Guidelines as Topic; Venous Thrombosis; Vitamin K

In daily practice, chemical substances called "direct oral anticoagulants" or DOACs are more convenient to administer when set beside vitamin K antagonists (VKA) due to improved pharmacologic properties, fewer drug interactions and rapid onset of action. The objective of this review was to assess whether DOACs are the alternative for VKA in subjects with mild-to-moderate chronic kidney disease (CKD). An analysis of current DOAC trials and studies was performed focusing on subjects with CKD. This review concludes that although DOACS are not recommended in the course of advanced chronic kidney disease (CrCl<30mL/min) or during dialysis, DOACS are a reasonable choice for individuals with mild to moderate CKD.

Topics: Anticoagulants; Hemorrhage; Humans; Renal Insufficiency, Chronic; Stroke; Venous Thrombosis; Vitamin K

People with venous thromboembolism (VTE) generally are treated for five days with intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin (LMWH), followed by three months of vitamin K antagonists (VKAs). Treatment with VKAs requires regular laboratory measurements and carries risk of bleeding; some patients have contraindications to such treatment. Treatment with LMWH has been proposed to minimise the risk of bleeding complications. This is the second update of a review first published in 2001.. The purpose of this review was to evaluate the efficacy and safety of long term treatment (three months) with LMWH versus long term treatment (three months) with VKAs for symptomatic VTE.. For this update, the Cochrane Vascular Information Specialist searched the Specialised Register (last searched November 2016) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 10), The Cochrane Vascular Information Specialistalso searched clinical trials registries for ongoing studies.. Randomised controlled trials comparing LMWH versus VKA for long treatment (three months) of symptomatic VTE. Two review authors independently evaluated trials for inclusion and methodological quality.. Review authors independently extracted data and assessed risk of bias. We resolved disagreements by discussion and performed meta-analysis using fixed-effect models with Peto odds ratios (Peto ORs) and 95% confidence intervals (CIs). Outcomes of interest were recurrent VTE, major bleeding, and mortality. We used GRADE to assess the overall quality of evidence supporting these outcomes.. Sixteen trials, with a combined total of 3299 participants fulfilled our inclusion criteria. According to GRADE, the quality of evidence was moderate for recurrent VTE, low for major bleeding, and moderate for mortality. We downgraded the quality of the evidence for imprecision (recurrent VTE, mortality) and for risk of bias and inconsistency (major bleeding).We found no clear differences in recurrent VTE between LMWH and VKA (Peto OR 0.83, 95% confidence interval (CI) 0.60 to 1.15; P = 0.27; 3299 participants; 16 studies; moderate-quality evidence). We found less bleeding with LMWH than with VKA (Peto OR 0.51, 95% CI 0.32 to 0.80; P = 0.004; 3299 participants; 16 studies; low-quality evidence). However, when comparing only high-quality studies for bleeding, we observed no clear differences between LMWH and VKA (Peto OR 0.62, 95% CI 0.36 to 1.07; P = 0.08; 1872 participants; seven studies). We found no clear differences between LMWH and VKA in terms of mortality (Peto OR 1.08, 95% CI 0.75 to 1.56; P = 0.68; 3299 participants; 16 studies; moderate-quality evidence).. Moderate-quality evidence shows no clear differences between LMWH and VKA in preventing symptomatic VTE and death after an episode of symptomatic DVT. Low-quality evidence suggests fewer cases of major bleeding with LMWH than with VKA. However, comparison of only high-quality studies for bleeding shows no clear differences between LMWH and VKA. LMWH may represent an alternative for some patients, for example, those residing in geographically inaccessible areas, those who are unable or reluctant to visit the thrombosis service regularly, and those with contraindications to VKA.

Topics: Anticoagulants; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Incidence; Odds Ratio; Randomized Controlled Trials as Topic; Recurrence; Venous Thromboembolism; Venous Thrombosis; Vitamin K

Venous thromboembolism (VTE) is a frequent complication in cancer patients and represents an important cause of morbidity and mortality. The treatment of VTE complications in cancer patients remains a difficult clinical task. Low-molecular-weight heparins (LMWH) are the cornerstone of VTE treatment in cancer patients, including the treatment of catheter-related thrombosis. LMWH dose adjustment is effective in treating recurrent thrombosis and in patients with bleeding or thrombocytopenia. The duration of treatment is dependent on several factors that need to be individually evaluated. The novel anticoagulants should be investigated more carefully before being routinely implemented in the treatment of cancer-associated VTE. Incidentally detected isolated sub-segmental pulmonary embolism is unlikely to require systematic full-dose anticoagulation. Whether the long-term use of LMWHs has the potential to prolong survival in subgroups of cancer patients requires further investigations.

Topics: Administration, Oral; Anticoagulants; Drug Administration Schedule; Drug Dosage Calculations; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Vascular Access Devices; Venous Thromboembolism; Venous Thrombosis; Vitamin K

Venous insufficiency following deep venous thrombosis is known as the post thrombotic syndrome. Whilst its presentation and symptoms can vary slightly between individuals, it can have a profound effect on quality of life. Symptoms range from mild limb swelling to severe intractable ulceration. A number of scoring systems have been developed to help monitor the disease progression, response to treatment as well as to classify patients for research purposes.Treatment involves a combination of therapies, including compression stockings, venous stenting for out flow obstruction and in some instances deep venous bypass. A considerable effort is made in preventing post thrombotic syndrome with a number of trials looking into the effect of prompt and stable anticoagulation, the effect of compression stockings, the effect of exercise and the outcomes following early thrombus removal strategies such as catheter directed and pharmacomechanical thrombolysis.

Topics: Anticoagulants; Disease Progression; Edema; Heparin, Low-Molecular-Weight; Humans; Leg Ulcer; Mechanical Thrombolysis; Postthrombotic Syndrome; Quality of Life; Severity of Illness Index; Stents; Stockings, Compression; Treatment Outcome; Venous Thrombosis; Vitamin K

Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used in patients with deep vein thrombosis (DVT), pulmonary embolism (PE) and atrial fibrillation (AF). However, there is insufficient data concerning the periinterventional, perioperative, and intensive care management of patients on NOACs. Therefore, the recommendations regarding this management rely on pharmacokinetics of the particular NOAC in combination with the individual patient's characteristics, bleeding risk of the planned intervention/surgery, and urgency of the procedure. This review summarizes evidence and recommendations regarding the optimal periinterventional/perioperative antithrombotic management of patients on NOACs.

Topics: Antibodies, Monoclonal, Humanized; Anticoagulants; Atrial Fibrillation; Critical Care; Drug Interactions; Half-Life; Hemorrhage; Humans; Kidney Failure, Chronic; Pulmonary Embolism; Risk Factors; Surgical Procedures, Operative; Thromboembolism; Venous Thrombosis; Vitamin K

Splanchnic vein thrombosis (SVT) encompasses Budd-Chiari syndrome (BCS), extrahepatic portal vein obstruction (EHPVO), and mesenteric vein thrombosis. Philadelphia-negative myeloproliferative neoplasms (MPNS) are the leading systemic cause of non-cirrhotic and non-malignant SVT and are diagnosed in 40% of BCS patients and one-third of EHPVO patients. In SVT patients the molecular marker JAK2 V617F is detectable up to 87% of those with overt MPN and up to 26% of those without. In the latter, other MPN molecular markers, such as mutations in JAK2 exon 12, CALR and MPL genes, are extremely rare. Immediate anticoagulation with heparin is used to treat acute patients. Upon clinical deterioration, catheter-directed thrombolysis or a transjugular intrahepatic portosystemic shunt is used in conjunction with anticoagulation. Orthotopic liver transplantation is the only reliable option in BCS patients with a lack of a response to other treatments, without contraindication due to MPN. Long-term oral anticoagulation with vitamin K-antagonists (VKA) is recommended in all SVT patients with the MPN-related permanent prothrombotic state; the benefits of adding aspirin to VKA are uncertain. Cytoreduction is warranted in all SVT patients with an overt MPN, but its appropriateness is doubtful in those with molecular MPN without hypercythaemia.

Topics: Administration, Oral; Anticoagulants; Biopsy; Bone Marrow Cells; Budd-Chiari Syndrome; Calreticulin; Exons; Genetic Markers; Haplotypes; Heparin; Humans; Janus Kinase 2; Liver Transplantation; Molecular Diagnostic Techniques; Mutation; Myeloproliferative Disorders; Portal Vein; Portasystemic Shunt, Surgical; Receptors, Thrombopoietin; Splanchnic Circulation; Thrombolytic Therapy; Treatment Outcome; Veins; Venous Thrombosis; Vitamin K

Cancer and venous thromboembolism (VTE) are closely related, with a high risk of VTE associated with cancer and a strong impact of VTE on cancer prognosis. The management and treatment of cancer-associated VTE are particularly challenging and, in many cases, are not guided by a high level of evidence.. In this review, we present the best therapeutic approach to acute deep vein thrombosis (DVT) and pulmonary embolism (PE) and to some controversial issues, such as home treatment, optimal duration of anticoagulation, management of VTE recurrence during anticoagulant treatment, and of unsuspected PE. Then, the available evidence on other cancer-related VTE manifestations is presented, such as catheter-related thrombosis and splanchnic vein thrombosis.. While solid evidence exists on the advantage of low molecular weight heparin (LMWH) over vitamin K antagonists (VKAs) during the first 3 to 6 months after acute DVT and/or PE, several issues have not been sufficiently investigated yet. These include the role of LMWH beyond the first 3 to 6 months, whether it is still more effective than VKA and if its intensity could be safely reduced, the strategies to identifying accurate predictors of VTE recurrence and the role of direct oral anticoagulants.

Topics: Acute Disease; Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Pulmonary Embolism; Recurrence; Venous Thromboembolism; Venous Thrombosis; Vitamin K

Topics: Aged; Anticoagulants; Atrial Fibrillation; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Orthopedic Procedures; Platelet Aggregation Inhibitors; Postoperative Complications; Randomized Controlled Trials as Topic; Risk Assessment; Venous Thrombosis; Vitamin K

The direct oral anticoagulants (DOACs) represent a major advance in oral anticoagulant therapy and have replaced the vitamin K antagonists as the preferred treatment for many indications. By simplifying long-term anticoagulant therapy and improving its safety, the DOACs have the potential to reduce the global burden of thrombosis. Postmarketing studies suggest that the favorable results achieved with DOACs in the randomized controlled trials can be readily translated into practice, but highlight the need for appropriate patient, drug and dose selection, and careful follow-up. Leveraging on their success to date, ongoing studies are assessing the utility of DOACs for the prevention of thrombosis in patients with embolic stroke of unknown source, heart failure, coronary artery disease, peripheral artery disease, antiphospholipid syndrome, and cancer. The purpose of this article is to (1) review the pharmacology of the DOACs, (2) describe the advantages of the DOACs over vitamin K antagonists, (3) summarize the experience with the DOACs in established indications, (4) highlight current challenges and limitations, (5) highlight potential new indications; and (6) identify future directions for anticoagulant therapy.

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Humans; Prothrombin; Randomized Controlled Trials as Topic; Venous Thrombosis; Vitamin K

Vitamin K-antagonists (VKA) are the most widely used anticoagulant drugs to treat patients at risk of arterial and venous thrombosis for the past 50 years. Due to unfavorable pharmacokinetics VKA have a small therapeutic window, require frequent monitoring, and are susceptible to drug and nutritional interactions. Additionally, the effect of VKA is not limited to coagulation, but affects all vitamin K-dependent proteins. As a consequence, VKA have detrimental side effects by enhancing medial and intimal calcification. These limitations stimulated the development of alternative anticoagulant drugs, resulting in direct oral anticoagulant (DOAC) drugs, which specifically target coagulation factor Xa and thrombin. DOACs also display non-hemostatic vascular effects via protease-activated receptors (PARs). As atherosclerosis is characterized by a hypercoagulable state indicating the involvement of activated coagulation factors in the genesis of atherosclerosis, anticoagulation could have beneficial effects on atherosclerosis. Additionally, accumulating evidence demonstrates vascular benefit from high vitamin K intake. This review gives an update on oral anticoagulant treatment on the vasculature with a special focus on calcification and vitamin K interaction.

Topics: Administration, Oral; Animals; Anticoagulants; Atherosclerosis; Carotid Artery Thrombosis; Disease Models, Animal; Humans; Osteocalcin; Randomized Controlled Trials as Topic; Venous Thrombosis; Vitamin K

The major practical advantage of the direct oral anticoagulants (DOACs), comprising the thrombin inhibitor dabigatran and the factor Xa inhibitors apixaban, edoxaban, and rivaroxaban, over vitamin K antagonists is their fixed dosing without the need for laboratory monitoring. With the recent, rapid introduction of the DOACs for the treatment of acute venous thromboembolism (VTE), clinicians are now faced with various questions regarding the efficacy and safety of these compounds overall and in specific high-risk populations. The collective evidence from 6 large clinical trials involving 27,000 patients has demonstrated that DOACs are as effective as vitamin K antagonists (VKA) in preventing recurrent VTE while being associated with a significantly lower risk of major bleeding. These findings are consistent in subgroups of patients with pulmonary embolism, the elderly, and those patients with a high body weight or moderate renal insufficiency, making these agents suitable for a broad spectrum of patients with VTE. DOACs are also an attractive treatment option in patients with VTE and concomitant cancer, thrombotic antiphospholipid syndrome, or heparin-induced thrombocytopenia, but the currently available clinical data is insufficient to make evidence-based recommendations on the use of DOACs in these settings. Several studies evaluating the efficacy and safety of DOACs in these high-risk populations are underway.

Topics: Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Clinical Trials as Topic; Factor Xa Inhibitors; Hemorrhage; Humans; Neoplasms; Pulmonary Embolism; Recurrence; Renal Insufficiency; Risk; Thrombin; Thrombocytopenia; Thrombosis; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis; Vitamin K

Currently, the most frequently used secondary treatment for patients with venous thromboembolism (VTE) consists of vitamin K antagonists (VKA) targeted at an international normalized ratio (INR) of 2.5 (range 2.0 to 3.0). However, based on the continuing risk of bleeding and uncertainty regarding the risk of recurrent VTE, discussion on the proper duration of treatment with VKA for these patients is ongoing. Several studies have compared the risks and benefits of different durations of VKA in patients with VTE. This is the third update of a review first published in 2000.. To evaluate the efficacy and safety of different durations of treatment with vitamin K antagonists in patients with symptomatic venous thromboembolism.. For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched October 2013) and the Cochrane Central Register of Controlled Trials (CENTRAL) 2013, Issue 9.. Randomized controlled clinical trials comparing different durations of treatment with vitamin K antagonists in patients with symptomatic venous thromboembolism.. Three review authors (SM, MP, and BH) extracted the data and assessed the quality of the trials independently.. Eleven studies with a total of 3716 participants were included. A consistent and strong reduction in the risk of recurrent venous thromboembolic events was observed during prolonged treatment with VKA (risk ratio (RR) 0.20, 95% confidence interval (CI) 0.11 to 0.38) independent of the period elapsed since the index thrombotic event. A statistically significant "rebound" phenomenon (ie, an excess of recurrences shortly after cessation of prolonged treatment) was not found (RR 1.28, 95% CI 0.97 to 1.70). In addition, a substantial increase in bleeding complications was observed for patients receiving prolonged treatment during the entire period after randomization (RR 2.60, 95% CI 1.51 to 4.49). No reduction in mortality was noted during the entire study period (RR 0.89, 95% CI 0.66 to 1.21, P = 0.46).. In conclusion, this review shows that treatment with VKA strongly reduces the risk of recurrent VTE for as long as they are used. However, the absolute risk of recurrent VTE declines over time, although the risk for major bleeding remains. Thus, the efficacy of VKA administration decreases over time since the index event.

Topics: Anticoagulants; Drug Administration Schedule; Hemorrhage; Humans; International Normalized Ratio; Randomized Controlled Trials as Topic; Secondary Prevention; Thromboembolism; Time Factors; Venous Thrombosis; Vitamin K

Central venous catheter (CVC) placement increases the risk of thrombosis in people with cancer. Thrombosis often necessitates the removal of the CVC, resulting in treatment delays and thrombosis-related morbidity and mortality.. To evaluate the relative efficacy and safety of anticoagulation for thromboprophylaxis in people with cancer with a CVC.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 12, 2012), MEDLINE Ovid (January 1966 to February 2013), and EMBASE Ovid (1980 to February 2013). We handsearched conference proceedings, checked references of included studies, used the 'related citations' feature within PubMed, and searched clinicaltrials.gov for ongoing studies.. Randomized controlled trials (RCTs) comparing the effects of any dose of unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), vitamin K antagonists (VKA), or fondaparinux with no intervention or placebo or comparing the effects of two different anticoagulants in people with cancer and a CVC.. Teams of two review authors independently used a standardized form to extract data in duplicate. They resolved any disagreements by discussion. They extracted data on risk of bias, participants, interventions, and outcomes. Outcomes of interest included mortality, symptomatic deep venous thrombosis (DVT), asymptomatic DVT, major bleeding, minor bleeding, infection, and thrombocytopenia. Where possible, we conducted meta-analyses using the random-effects model.. Of 9559 identified citations, we included 12 RCTs (17 publications) reporting follow-up data on 2823 participants. Two of the RCTs included children. Of the 10 RCTs including 2564 adults, one compared prophylactic dose heparin with low-dose VKA. Three RCTs compared VKA with no VKA and four RCTs compared heparin with no heparin. Two additional trials had three separate arms comparing heparin, VKA, and no intervention. Prophylactic-dose heparin, compared with no heparin, was associated with a statistically significant reduction in symptomatic DVT (risk ratio (RR) 0.48; 95% confidence interval (CI) 0.27 to 0.86; moderate-quality evidence). However, results did not confirm or exclude a beneficial or detrimental effect of heparin on mortality (RR 0.82; 95% CI 0.53 to 1.26; moderate-quality evidence), major bleeding (RR 0.49; 95% CI 0.03 to 7.84; low-quality evidence), infection (RR 1.00; 95% CI 0.54 to 1.85; moderate-quality evidence); thrombocytopenia (RR 1.03; 95% CI 0.80 to 1.33; moderate-quality evidence), or minor bleeding (RR 1.35; 95% CI: 0.62 to 2.92). Low-dose VKAs, compared with no VKAs, were associated with a statistically significant reduction in asymptomatic DVT (RR 0.43; 95% CI 0.30 to 0.62). Results did not confirm or exclude a beneficial or detrimental effect of VKAs on mortality (RR 1.04; 95% CI 0.89 to 1.22; low-quality evidence), symptomatic DVT (RR 0.51; 95% CI 0.21 to 1.22; low-quality evidence), major bleeding (RR 7.60; 95% CI 0.94 to 61.49; very-low-quality evidence), or minor bleeding (RR 3.14; 95% CI 0.14 to 71.51). The use of heparin, compared with VKA was associated with a statistically significant increase in thrombocytopenia (RR 3.73; 95% CI 2.26 to 6.16; low-quality evidence) and asymptomatic DVT (RR 1.74; 95% CI 1.20 to 2.52). However, results did not show or exclude a beneficial or detrimental effect on any of the other outcomes of interest (very-low-quality evidence).. Compared with no anticoagulation, we found a statistically significant reduction of symptomatic DVT with heparin and asymptomatic DVT with VKA. Heparin was associated with a higher risk of thrombocytopenia and asymptomatic DVT when compared with VKA. However, the findings did not rule out other clinically important benefits and harms. People with cancer with CVCs considering anticoagulation should balance the possible benefit of reduced thromboembolic complications with the possible harms and burden of anticoagulants.

Topics: Adult; Anticoagulants; Catheterization, Central Venous; Child; Heparin; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Randomized Controlled Trials as Topic; Secondary Prevention; Venous Thrombosis; Vitamin K

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

Topics: Antibodies; Anticoagulants; Antithrombins; Arthroplasty, Replacement, Knee; Chondroitin Sulfates; Dermatan Sulfate; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Humans; Immunoglobulin G; Male; Middle Aged; Platelet Activation; Platelet Count; Platelet Factor 4; Polysaccharides; Practice Guidelines as Topic; Thrombocytopenia; Venous Thrombosis; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Humans; Pulmonary Embolism; Stroke; Venous Thromboembolism; Venous Thrombosis; Vitamin K

Anticoagulant drugs belong to the group of antithrombotic agents and are successfully used in the prophylaxis and treatment of thromboembolic disorders. The use of anticoagulants in the prevention of deep venous thrombosis has significantly lowered the risk of venous thrombosis and fatal pulmonary embolisms even in high-risk situations such as orthopedic surgery. Anticoagulants play a central role in the treatment of acute venous thrombosis and in the prevention of recurrent events. Long-term anticoagulation therapy with orally active anticoagulants significantly reduces the risk of thromboembolic complications in patients showing cardiac arrhythmias. Whereas a few years ago heparins and vitamin K antagonists were the dominant anticoagulants, today a wide range of anticoagulants with improved pharmacological profiles are available. It remains an open question whether these new anticoagulants will improve the efficacy, safety, and acceptance of anticoagulant treatment approaches.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Arginine; Arrhythmias, Cardiac; Blood Coagulation Tests; Factor Xa Inhibitors; Hemorrhage; Heparin; Heparinoids; Hirudins; Humans; Infusions, Intravenous; Orthopedic Procedures; Peptide Fragments; Pipecolic Acids; Postoperative Complications; Pulmonary Embolism; Recombinant Proteins; Risk Factors; Secondary Prevention; Sulfonamides; Thromboembolism; Treatment Outcome; Venous Thrombosis; Vitamin K

Thromboembolic complications are among the most important extrarenal consequences of nephrotic syndrome (NS). In addition to deep vein thrombosis in the legs and pulmonary embolism, NS is very frequently accompanied by renal vein thrombosis. Due to enhanced procoagulatory and antifibrinolytic potential and reduced anticoagulatory potential, multifactor disruption of hemostatic equilibrium leads to hypercoagulability in NS patients, which is aggravated by an increase in blood viscosity and endothelial dysfunction. Circulating antibodies against α-enolase, a plasmin(ogen)-binding protein, and the possibility of certain molecules being renally eliminated in specific manner are discussed as reasons for the particular frequency of thromboembolic complications in patients with idiopathic membranous nephropathy. Serum albumin concentration is an indicator for the risk of thrombosis in NS patients. When applying the current KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guideline for glomerulonephritis to NS patients with a serum albumin concentration of less than 25 g/l and at least one additional thrombogenic risk factor, primary prophylactic anticoagulation ("conditioned prophylaxis") with an orally administered vitamin K antagonist (target INR 2-3) is recommended as long as the serum albumin concentration is less than 30 g/l.

Topics: Anticoagulants; Autoantibodies; Blood Viscosity; Endothelium, Vascular; Hemostasis; Humans; Nephrotic Syndrome; Pulmonary Embolism; Renal Veins; Risk Factors; Serum Albumin; Thromboembolism; Thrombosis; Venous Thrombosis; Vitamin K

Randomized controlled trials have shown that patients with venous thromboembolism benefit from a minimum of three months of anticoagulant therapy. After this period, it was suggested that patients with an expected annual recurrence rate of < 5% could safely discontinue treatment. Using a population-based approach for stratification, these patients are those with major transient risk factors, and represent the minority. For all other patients, including those with previous episodes of venous thromboembolism, cancer, or unprovoked events, this treatment duration may not be sufficiently protective. Because extending anticoagulation for additional three to nine months does not result in further, long-term reduction of recurrences, indefinite treatment duration should be considered. However, case-fatality rate for major bleeding in patients taking warfarin for more than three months is higher than case-fatality rate of recurrent venous thromboembolism. Thus, an individual patient approach to improve and increase the identification of those who can safely discontinue treatment at three months becomes necessary. Clinical prediction rules or management strategies based on D-dimer levels or residual vein thrombosis have been proposed and need further refinement and validation. Specific bleeding scores are lacking. Meanwhile, the oral direct inhibitors have been proposed as potential alternatives to the vitamin K antagonists, and aspirin may provide some benefit in selected patients who discontinue anticoagulation. Deep vein thrombosis in unusual sites is associated with less, but potentially more severe recurrences, in particular in patients with splanchnic vein thrombosis who also face an increased risk of bleeding complications while on treatment.

Topics: Anticoagulants; Humans; Recurrence; Venous Thrombosis; Vitamin K

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

The currently recommended method of venous thromboembolism (VTE) treatment is the application of vitamin K antagonists (VKA) in most patients, and low-molecular-weight heparins (LMWH) in selected groups. The VKA dose adjustment is difficult which might well render the treatment ineffective. The study aimed to compare LMWH with VKA in treating VTE in terms of efficacy and safety. A systematic review of literature and the meta-analysis of the treatment results were performed. The main differences between LMWH and VKA in terms of their respective effectiveness in treating VTE consist in appreciably more advantageous effects of LMWH in preventing deep venous thrombosis (DVT). The key difference in terms of respective safety is the greater effectiveness of LMWH inpreventing minor bleedings. The advantage of LMWH in cancer patients consists predominantly in a significantly better protection against DVT episodes, whereas the advantage of LMWH in non-cancer patients is mainly owed to better protection against minor bleedings. In none of the analysed outcomes of VTE treatment, the application of VKA proved to hold any advantage over LMWH. Although, arguably, there might well be sufficient medical grounds to propose more widespread use of LMWH, it still remains a debatable issue whether the currently used therapeutic standard should also be modified accordingly. Apart from the actual findings of the present meta-analysis, pertinent economic considerations must also be addressed.

Topics: Anticoagulants; Dose-Response Relationship, Drug; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Models, Statistical; Odds Ratio; Treatment Outcome; Venous Thrombosis; Vitamin K

Venous thromboembolism (VTE) is a common complication of cancer. Prolonged use of low-molecular-weight heparin in cancer patients provides better VTE prophylaxis compared with vitamin K antagonists. Both therapeutic options have a similar safety profile. If patients on long-term oral anticoagulation are diagnosed with cancer, they should continue treatment with vitamin K antagonists.

Topics: Administration, Oral; Anticoagulants; Blood Coagulation; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Thromboembolism; Venous Thrombosis; Vitamin K

The Authors describe diagnosis, treatment and therapy of deep venous thrombosis in Emergency Department following the last guidelines indications.. Deep venous thrombosis of the legs, ranges from asymptomatic, incidentally discovered emboli to massive embolism causing immediate death. Chronic sequelae of venous thromboembolism (deep venous thrombosis and pulmonary embolism) include the post-thrombotic syndrome and chronic thromboembolic pulmonary hypertension. Acute pulmonary embolism may occur rapidly and unpredictably and may be difficult to diagnose. Diagnosis and treatment can reduce the risk of death, and appropriate primary prophylaxis is usually effective. Patients treated for acute pulmonary embolism appear to be more times as likely to die of recurrent thromboembolism in the next year.

Topics: Anticoagulants; Antifibrinolytic Agents; Emergency Medical Services; Emergency Service, Hospital; Fibrin Fibrinogen Degradation Products; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Risk Factors; Stockings, Compression; Thrombectomy; Thromboembolism; Thrombolytic Therapy; Tomography, Spiral Computed; Ultrasonography; Vena Cava Filters; Venous Thrombosis; Vitamin K

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

Cirrhotic patients can develop thrombotic complications, which in this group of patients occur with a greater frequency than in the general population. Portal vein thrombosis (PVT) is the most common thrombotic phenomenon, although deep venous thrombosis and pulmonary embolism can also occur. Risk factors for thrombosis include inherited and acquired deficiency of factors involved in anticoagulation mechanisms, venous stasis of the portal vein owing to architectural derangement of the liver and possibly local factors related to the endothelium. Clinical manifestations of PVT range from asymptomatic disease to a life-threatening complication, and although it is no longer considered an absolute contraindication for liver transplant, its presence may require challenging surgical techniques, which entail greater morbidity. Anticoagulation therapy is henceforth an important strategy to treat cirrhotic patients with PVT, although experience in this group of patients is limited. Vitamin K antagonists and low-molecular-weight heparin have been used successfully, achieving recanalization of the thrombosed vessel in patients with cirrhosis; however, the precise drug regimen management and monitoring has not be fully explored in this group of patients.

Topics: Anticoagulants; Contraindications; Heparin; Humans; Incidence; Liver Cirrhosis; Liver Transplantation; Prevalence; Risk Factors; Venous Thrombosis; Vitamin K

Thromboses of abdominal veins outside the iliac-caval axis are rare but clinically relevant. Early deaths after splanchnic vein thrombosis occur in 5-30% of cases. Sequelae can be liver failure or bowel infarction after splanchnic vein thrombosis, renal insufficiency after renal vein thrombosis, ovarian infarction after ovarian vein thrombosis. Local cancer or infections are rare in Budd-Chiari syndrome, and common for other sites. Inherited thrombophilia is detected in 30-50% of patients. Myeloproliferative neoplasms are the main cause of splanchnic vein thrombosis: 20-50% of patients have an overt myeloproliferative neoplasm and/or carry the molecular marker JAK2 V617F. Renal vein thrombosis is closely related to nephrotic syndrome; finally, ovarian vein thrombosis can complicate puerperium. Heparin is used for acute treatment, sometimes in conjunction with systemic or local thrombolysis. Vitamin K-antagonists are recommended for 3-6 months, and long-term in patients with Budd-Chiari syndrome, unprovoked splanchnic vein thrombosis, or renal vein thrombosis with a permanent prothrombotic state such as nephrotic syndrome.

Topics: Anticoagulants; Biomarkers, Tumor; Budd-Chiari Syndrome; Female; Heparin; Humans; Janus Kinase 2; Leukemia; Nephrotic Syndrome; Ovary; Portal Vein; Splanchnic Circulation; Vena Cava, Inferior; Venous Thrombosis; Vitamin K

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

People with venous thromboembolism (VTE) are generally treated for five days with intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin (LMWH) followed by three months of vitamin K antagonist treatment. Treatment with vitamin K antagonists requires regular laboratory measurements and some patients have contraindications to treatment. This is an update of a review first published in 2000 and updated in 2002.. To evaluate the efficacy and safety of long term treatment of VTE with LMWH compared to vitamin K antagonists.. For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched their Specialised Register (last searched February 2012) and CENTRAL (2012, Issue 1).. Two authors evaluated trials independently for methodological quality.. The review authors extracted data independently. Primary analysis included all trial participants randomised to the allocated treatment groups. Separate analyses were performed according to the quality of the trials and for subgroups such as trials initially using similar treatments in both trial arms and those that did not, trials concerning deep vein thrombosis (DVT) and pulmonary embolism (PE) and the different periods of follow-up.. All 15 trials, with a combined total of 3197 patients, fulfilling our criteria were combined in a meta-analysis. We found a non-statistically significant reduction in the risk of recurrent VTE between the two treatments (odds ratio (OR) 0.82, 95% CI 0.59 to 1.13). Analysis of pooled data for category I trials (those with a high methodological quality) showed a non-significant reduction in the odds of recurrent VTE favouring LMWH treatment (OR 0.80, 95% CI 0.54 to 1.18).For all trials combined, the difference in bleeding significantly favoured treatment with LMWH (OR 0.50, 95% CI 0.31 to 0.79). Considering only category I trials, a non-significant trend favouring LMWH remained (OR 0.62, 95% CI 0.36 to 1.07). No difference was observed in mortality (OR 1.06, 95% CI 0.74 to 1.54).. LMWHs are possibly as effective as vitamin K antagonists in preventing symptomatic VTE after an episode of symptomatic deep venous thrombosis, but are much more expensive. Treatment with LMWH is significantly safer than treatment with vitamin K antagonists. LMWH may result in fewer episodes of bleeding and is possibly a safe alternative in some patients, especially those in geographically inaccessible areas, are reluctant to visit the thrombosis service regularly, or with contraindications to vitamin K antagonists. However, treatment with vitamin K antagonists remains the treatment of choice for the majority of patients.

Topics: Anticoagulants; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Odds Ratio; Randomized Controlled Trials as Topic; Venous Thromboembolism; Venous Thrombosis; Vitamin K

The therapeutic management of catheter-related thromboembolic events in children is still a challenge due to the large number of potentially effective pharmacological alternatives and the insufficient scientific evidence available. A bibliographic review was performed in order to identify the available pharmacological alternatives for the prophylaxis and therapeutic management of catheter-related thrombosis in children.. A literature search was carried out on MEDLINE using the medical subject heading (MeSH) central venous catheter thrombosis and on Google Scholar. The search was limited to review papers, meta-analyses, clinical practice guidelines, and randomized controlled trials performed on pediatric populations until November 2011.. The different options for anticoagulation include unfractionated heparin, low molecular weight heparin and vitamin K antagonists. Thrombus resolution is stimulated more rapidly with thrombolytic agents than with anticoagulants, but the risk-benefit ratio must be considered. Streptokinase is not considered an optimal alternative due to the risk of anaphylactic reactions and has been replaced by urokinase, alteplase or the newer reteplase. Preventive strategies have been considered and most centers have protocols for routine flushing of the catheter with heparin or normal saline. Intraluminal application of urokinase and alteplase has also been studied.. The wide range of options available for the pharmacotherapeutic management of catheter-related thromboembolism in children and the lack of strong evidence on the comparative efficacy and safety of the different therapeutic options, make its positioning rather difficult. Randomized controlled trials and national plans should be set up urgently.

Topics: Anticoagulants; Catheterization, Central Venous; Child; Fibrinolytic Agents; Humans; Venous Thromboembolism; Venous Thrombosis; Vitamin K

Central venous catheter (CVC) placement increases the risk of thrombosis in cancer patients. Thrombosis often necessitates the removal of the CVC, resulting in treatment delays and thrombosis related morbidity and mortality.. To evaluate the efficacy and safety of anticoagulation in cancer patients with a CVC.. We searched The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1 2010), MEDLINE (January 1966 to February 2010; accessed via OVID), EMBASE (January 1980 to February 2010; accessed via OVID) and ISI the Web of Science (1975 to February 2010). We handsearched conference proceedings, checked references of included studies and used the "related article" feature within PubMed.. Randomized controlled trials (RCTs) comparing any dose of unfractionated heparin (UFH), low molecular weight heparin (LMWH), vitamin K antagonists (VKA), or fondaparinux to no intervention or placebo or comparing two different anticoagulants in cancer patients with a CVC.. Two authors independently extracted data from each included study and resolved their disagreements by discussion.. Of 8187 identified citations, we included 12 RCTs enrolling 3611 patients and assessing either prophylactic dose heparin or low dose VKAs. Prophylactic dose heparin was not associated with a statistically significant effect on death (relative risk (RR) = 0.85; 95% confidence interval (CI): 0.53 to 1.37), symptomatic deep venous thrombosis (DVT) (RR = 0.54; 95% CI: 0.28 to 1.05) asymptomatic DVT (RR = 0.81; 95% CI: 0.64 to 1.02), major bleeding (RR = 0.68; 95% CI: 0.10 to 4.78), thrombocytopenia (RR = 0.85; 95% CI: 0.49 to 1.46), or infection (RR = 0.91; 95% CI: 0.49 to 1.68). Similarly, low dose VKAs were not associated with a statistically significant effect on death (RR = 0.97; 95% CI: 0.82 to 1.15), symptomatic DVT (RR = 0.63; 95% CI: 0.35 to 1.11) or major bleeding (RR = 6.93; 95% CI: 0.86 to 56.08). However, they were associated with a statistically significant reduction in asymptomatic DVT (RR = 0.42; 95% CI: 0.28 to 0.61). Studies comparing heparin to VKA found no effects on any of the outcomes of interest.. We found no statistically significant effect of heparin or VKA on the outcomes of interest. However, the findings did not rule out clinically important benefits and harms. Patients with cancer with CVCs considering anticoagulation should balance the possible benefit of reduced thromboembolic complications with the possible harms and burden of anticoagulants.

Topics: Anticoagulants; Catheterization, Central Venous; Heparin; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Randomized Controlled Trials as Topic; Venous Thrombosis; Vitamin K

About half of patients with a first unprovoked proximal deep vein thrombosis (DVT) or pulmonary embolism (PE) will have a recurrent venous thromboembolism (VTE) within 10 years if they stop treatment, and randomized trials have shown clear benefit from extended anticoagulant therapy in these patients. Although the risk of recurrence varies among patients with a first unprovoked proximal DVT or PE, and a number of factors can identify patients with a lower risk of recurrence, the safety of routinely stopping anticoagulant therapy based on the presence of these factors needs to be established in prospective studies before this is done in clinical practice. As isolated distal DVT is associated with about half the risk of recurrence of proximal DVT or PE, a first episode of unprovoked distal DVT does not justify extended anticoagulation. High risk for bleeding, and patient preference, are good reasons not to treat unprovoked proximal DVT or PE indefinitely. New anticoagulants, because they are easier to use and may be associated with less bleeding that vitamin K antagonists, have the potential to increase the proportion of patients with unprovoked VTE who are candidates for extended anticoagulant therapy.

Topics: Anticoagulants; Hemorrhage; Humans; Pulmonary Embolism; Recurrence; Time Factors; Venous Thromboembolism; Venous Thrombosis; Vitamin K

Central venous catheter (CVC) placement increases the risk of thrombosis in cancer patients. Thrombosis often necessitates the removal of the CVC, resulting in treatment delays and thrombosis related morbidity and mortality.. To evaluate the efficacy and safety of anticoagulation in cancer patients with a CVC.. We searched The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1 2010), MEDLINE (January 1966 to February 2010; accessed via OVID), EMBASE (January 1980 to February 2010; accessed via OVID) and ISI the Web of Science (1975 to February 2010). We handsearched conference proceedings, checked references of included studies and used the "related article" feature within PubMed.. Randomized controlled trials (RCTs) comparing any dose of unfractionated heparin (UFH), low molecular weight heparin (LMWH), vitamin K antagonists (VKA), or fondaparinux to no intervention or placebo or comparing two different anticoagulants in cancer patients with a CVC.. Two authors independently extracted data from each included study and resolved their disagreements by discussion.. Of 8187 identified citations, we included 12 RCTs enrolling 3611 patients and assessing either prophylactic dose heparin or low dose VKAs. Prophylactic dose heparin was not associated with a statistically significant effect on death (relative risk (RR) = 0.85; 95% confidence interval (CI): 0.53 to 1.37), symptomatic deep venous thrombosis (DVT) (RR = 0.54; 95% CI: 0.28 to 1.05) asymptomatic DVT (RR = 0.81; 95% CI: 0.64 to 1.02), major bleeding (RR = 0.68; 95% CI: 0.10 to 4.78), thrombocytopenia (RR = 0.85; 95% CI: 0.49 to 1.46), or infection (RR = 0.91; 95% CI: 0.49 to 1.68). Similarly, low dose VKAs were not associated with a statistically significant effect on death (RR = 0.97; 95% CI: 0.82 to 1.15), symptomatic DVT (RR = 0.63; 95% CI: 0.35 to 1.11) or major bleeding (RR = 6.93; 95% CI: 0.86 to 56.08). However, they were associated with a statistically significant reduction in asymptomatic DVT (RR = 0.42; 95% CI: 0.28 to 0.61). Studies comparing heparin to VKA found no effects on any of the outcomes of interest.. We found no statistically significant effect of heparin or VKA on the outcomes of interest. However, the findings did not rule out clinically important benefits and harms. Patients with cancer with CVCs considering anticoagulation should balance the possible benefit of reduced thromboembolic complications with the possible harms and burden of anticoagulants.

Topics: Anticoagulants; Catheterization, Central Venous; Heparin; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Randomized Controlled Trials as Topic; Venous Thrombosis; Vitamin K

Pulmonary embolism (PE) is common and the majority of patients survive the acute event. Survivors are at increased risk for adverse outcomes, including persistent thrombi, recurrent embolism, chronic thromboembolic pulmonary hypertension (CTEPH), and death. Anticoagulation protects against recurrence, which has a high mortality rate. The recommended duration of anticoagulation for patients with reversible PE risk factors is 3 months. For patients with idiopathic PE or persistent risk factors, extended duration of anticoagulation is preferred, balanced with an individual patient's risk of hemorrhage, which in itself is a major cause of morbidity and mortality. Among patients with malignancy who develop venous thromboembolism (VTE), low-molecular-weight heparin is preferred over oral vitamin K antagonists in the first 6 months. Thereafter, anticoagulation should be continued indefinitely with either low-molecular-weight heparin or oral vitamin K antagonists. Inferior vena cava filters are not routinely recommended and should only be used in patients who have a contraindication to anticoagulation. Patients who have had VTE and with persistent or recurrent dyspnea should be evaluated for recurrence of VTE or development of CTEPH. Patients with recurrent VTE should be anticoagulated indefinitely. Routine screening for CTEPH in asymptomatic patients is not recommended. Echocardiography often provides the first indication of the presence of pulmonary hypertension. Once presence of CTEPH is established by right-sided heart catheterization and perfusion imaging (ie, ventilation/perfusion scintigraphy, computed tomography angiography, or pulmonary angiography), patients should be referred early to a center with expertise, as it is potentially surgically curable by pulmonary endarterectomy. Those who are deemed inoperable after being evaluated may gain symptomatic benefit from drugs approved for idiopathic pulmonary arterial hypertension. Lung transplantation may also be an option for patients who are not candidates for pulmonary endarterectomy.

Topics: Anticoagulants; Blood Coagulation Tests; Chronic Disease; Drug Administration Schedule; Dyspnea; Heparin, Low-Molecular-Weight; Humans; Hypertension, Pulmonary; Neoplasms; Pulmonary Embolism; Risk Factors; Vena Cava Filters; Venous Thrombosis; Vitamin K

The risk of venous thromboembolic events (VTE) in cancer patients is higher than in the general population. Treatment may also increase this risk in these patients. Based on the appropriate criteria (of which the most important are the current ministerial guidelines) thrombosis prophylaxis should be started (given that there is no contraindication) on these patients and be continued while they are at risk. In the event of permanent risk thrombosis prophylaxis should be given lifelong. The drug of choice is low-molecular-weight heparin (LMWH) which is safer and more effective than the oral vitamin K antagonists. Platelet aggregation inhibitors have proved unsuccessful in this patient group. The evidence so far suggests that LMWH (during VTE prophylaxis) can have a positive impact on the course of cancer and perhaps it will be registered under the indication section for cancer patients in the future.

Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Risk Assessment; Risk Factors; Thromboembolism; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis; Vitamin K

The optimal course of oral anticoagulant therapy is determined according to the risk of recurrent venous thromboembolism after stopping therapy and the risk of anticoagulant-related bleeding. Clinical risk factors appear to be important in predicting the risk of recurrence whereas the influence of biochemical and morphological tests is uncertain. The risk of recurrent venous thromboembolism is low when the initial episode was provoked by a reversible major risk factor (surgery): 3 months of anticoagulation is sufficient. Conversely, the risk is high when venous thromboembolism was unprovoked or associated with persistent risk factor (cancer): 6 months or more prolonged anticoagulation is necessary. After this first estimation, the duration of anticoagulation may be modulated according to the presence or absence of certain additional risk factors (major thrombophilia, chronic pulmonary hypertension, massive pulmonary embolism): 6 months if pulmonary embolism was provoked and 12 to 24 months if pulmonary embolism was unprovoked. If the risk of anticoagulant-related bleeding is high, the duration of anticoagulation should be shortened (3 months if pulmonary embolism was provoked and 3 to 6 months if it was unprovoked). Lastly, if pulmonary embolism occurred in association with cancer, anticoagulation should be conducted for 6 months or more if the cancer is active or treatment is on going. Despite an increasing knowledge of the risk factors for recurrent venous thromboembolism, a number of issues remain unresolved. Randomised trials comparing different durations of anticoagulation are needed.

Topics: Age Factors; Anticoagulants; Antiphospholipid Syndrome; Cohort Studies; Drug Administration Schedule; Female; Fibrin Fibrinogen Degradation Products; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Hypertension, Pulmonary; Male; Neoplasms; Prospective Studies; Pulmonary Embolism; Randomized Controlled Trials as Topic; Recurrence; Risk Factors; Sex Factors; Thrombophilia; Time Factors; Vena Cava Filters; Venous Thrombosis; Vitamin K

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

Venous thromboembolism, comprising deep vein thrombosis and pulmonary embolism, is a common disorder with at least 250 000 new events occurring each year in the United States alone. Treatment of venous thromboembolism includes anticoagulation, which is achieved initially with the use of a parenterally administered agent followed by a more prolonged course of treatment with an oral vitamin K antagonist. The duration of treatment depends on the clinical assessment of the benefit-to-risk ratio of prolonged anticoagulation versus the risk of recurrent events. In this review, we discuss some of the issues that we believe are among the most critical unanswered questions in the management of venous thromboembolism in the present era.

Topics: Anticoagulants; Humans; Postthrombotic Syndrome; Secondary Prevention; Venous Thrombosis; Vitamin K

Many years of practical use and intensive scientific research have allowed vitamin K antagonists to become a cornerstone of treatment of internal diseases. Nevertheless, limitations in pharmacokinetics and -dynamics of vitamin K antagonists and the availability of new drugs in regard to a targeted anticoagulation therapy ask for a new review of the situation. Proof of effectiveness for the perioperative prophylaxis of venous thrombosis after hip and knee replacement has already been achieved for the direct thrombin inhibitor dabigatran etexilate as well as for the factor Xa inhibitors rivaroxaban und apixaban compared to low molecular weight heparins. These new drugs are now also investigated in patients with internal diseases. For the long-term application (6 or 12 months) concerning the treatment of venous thrombosis and/or stroke prophylaxis in patients with atrial fibrillation data is already available for the direct thrombin inhibitor dabigatran etexilate. Depending on its dosage its effectiveness in comparison with vitamin K antagonists is equal or even better without disadvantages in safety. However, vitamin K antagonists will remain the standard oral anticoagulation until open questions regarding e.g. insufficient therapy adherence (with termination rates up to 20%) or problems with drug interactions of the new competitive products have been completely answered.

Topics: Anticoagulants; Antithrombin Proteins; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Atrial Fibrillation; Benzimidazoles; Dabigatran; Humans; Morpholines; Postoperative Complications; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiophenes; Venous Thrombosis; Vitamin K

Long-term anticoagulant treatment is highly effective in preventing recurrent Venous Thrombo-Embolism (VTE) in patients with idiopathic Deep Vein Thrombosis (DVT) of the lower limbs, though associated with an increased risk for major bleeding that may offset the benefits of anticoagulation. Accordingly to recent guidelines, patients with idiopathic DVT should be treated for at least 3 months and then should be evaluated for the risk-benefit ratio of long-term therapy. However, such 'time for decision' is often unclear and the optimal duration of VKA remains debatable. In recent studies, markers for the assessment of the individual risk for recurrent thrombosis have been proposed, which can be of help to establish the optimal duration of VKA treatment; among them, the D-dimer (D-d) assay and the Residual Vein Thrombosis (RVT) assessment by Compression Ultra-Sonography (CUS) were shown to be the most suitable. Studies' results showed that negative results of these parameters after 3 to 6 months of therapy, identify a group of patients at low-risk for recurrent thrombosis in whom VKA treatment can be withheld. In the present review we will discuss advantages and potential limits of using these individual markers for the management of patients with a first episode of DVT of the lower limbs.

Topics: Anticoagulants; Drug Administration Schedule; Fibrin Fibrinogen Degradation Products; Humans; Neoplasms; Risk Factors; Secondary Prevention; Ultrasonography; Venous Thrombosis; Vitamin K

Topics: Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Education, Medical, Continuing; Female; Humans; Male; Prognosis; Risk Assessment; Severity of Illness Index; Treatment Outcome; Venous Thrombosis; Vitamin K

Inferior vena cava agenesis (IVCA) is a rare condition, found in almost 5% of patients under 30 years old with unprovoked deep venous thrombosis (DVT). We describe 10 consecutive patients with IVCA-associated DVT and conducted an extensive literature review to investigate the typical spectrum of IVCA-associated DVT. Among our patients (eight men and two women; mean age, 25 ± 4.5 years), DVT followed intense and unusual (major) physical activity for eight of them. DVT was bilateral in six patients and unilateral in four. Ultrasonography was unable to detect IVCA, which was visualized by computed-tomography scans for seven patients, and magnetic resonance imaging and angiography for 10. Hereditary thrombophilia screening, to detect factor V Leiden or prothrombin gene heterozygosity (G20210A mutation), was positive for only two patients. Wearing elastic stockings and taking an indefinite or long-term vitamin K antagonist were prescribed for all 10 patients and nine complied with the latter. To date, 62 patients with IVCA-associated DVT have been reported in the English literature. Analysis of them and our patients yielded a typical spectrum of IVCA-associated DVT characteristics: IVCA occurs in young adults, particularly males, and is revealed by proximal DVT following major physical exertion. All were treated with a prolonged vitamin K antagonist and advised to wear elastic stockings. No precise duration of anticoagulation has been established.

Topics: Adolescent; Adult; Anticoagulants; Female; France; Genetic Predisposition to Disease; Humans; Magnetic Resonance Angiography; Male; Risk Assessment; Risk Factors; Stockings, Compression; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Ultrasonography, Doppler, Color; Vascular Malformations; Vena Cava, Inferior; Venous Thrombosis; Vitamin K; Young Adult

The treatment of choice for acute venous thromboembolism is anticoagulant therapy with fast-acting drugs (unfractionated or low-molecular-weight heparin or fondaparinux) aimed at preventing thrombus extension, followed by extended prophylaxis with vitamin K antagonists aimed at preventing recurrence. Experience accumulated over the years has demonstrated that strict laboratory monitoring is required for unfractionated heparin and vitamin K antagonists, making use of these drugs problematic for patients and physicians and prompting researchers to develop new anticoagulants equally effective but without the requirement for laboratory monitoring. The results of clinical trials to date, albeit limited, suggest that these new drugs will probably keep their promise. However, the definitive answer will come subsequent to these clinical trials, when clinicians will start to use these drugs to treat patients in the real world. It is likely that some sort of laboratory monitoring will be required at least for selected categories of patients. Accordingly, clinical laboratories should still be prepared to monitor patients, although the numbers may hopefully decrease sharply in the next decade or so.

Topics: Anticoagulants; Blood Coagulation; Clinical Trials as Topic; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Incidence; International Normalized Ratio; Monitoring, Physiologic; Morpholines; Polysaccharides; Prothrombin Time; Pulmonary Embolism; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism; Venous Thrombosis; Vitamin K

Critical care physicians are increasingly facing patients receiving oral anticoagulation for either cessation of major haemorrhage or to reverse the effects of vitamin K antagonists ahead of emergency surgery. Rapid reversal of anticoagulation is particularly essential in cases of life-threatening bleeding. In these situations, guidelines recommend the concomitant administration of prothrombin complex concentrates (PCCs) and oral or intravenous vitamin K for the fastest normalisation of the international normalised ratio (INR). Despite their universal recommendation, PCCs remain underused by many physicians who prefer to opt for fresh frozen plasma despite its limitations in anticoagulant reversal, including time to reverse INR and high risk of transfusion-related acute lung injury. In contrast, the lower volume required to normalise INR with PCCs and the room temperature storage facilitate faster preparation and administration time, thus increasing the speed at which haemorrhages can be treated. PCCs therefore allow faster, more reliable and complete reversal of vitamin K anticoagulation, especially when administered immediately following confirmation of haemorrhage. In the emergency setting, probabilistic dosing may be considered.

Topics: Antifibrinolytic Agents; Blood Coagulation Factors; Critical Care; Factor VIIa; Hemorrhage; Humans; International Normalized Ratio; Severity of Illness Index; Venous Thrombosis; Vitamin K

Vitamin K-antagonists and heparin belong to the established indirect acting anticoagulants. For many years these drugs were the only possibility for prophylaxis and treatment of venous and arterial thrombosis. The challenges for the routine laboratory related to the treatment with vitamin K-antagonists and heparin can be regarded as solved. However, in recent years a rapid development of new anticoagulants began. Although they are developed with guidelines for use without monitoring, the control of effective levels may be necessary in selected cases. As a consequence new challenges for the routine laboratory have to be solved. This paper presents an overview concerning monitoring methods.

Topics: Anticoagulants; Arterial Occlusive Diseases; Drug Monitoring; Hemostasis; Humans; Venous Thrombosis; Vitamin K

In the diagnosis of deep vein thrombosis in ambulatory patients, the recommended initial steps are assessment of clinical probability (CP) and a sensitive D-dimer test. With a low CP and negative D-dimer, thrombosis can be ruled out. All other constellations require further investigation with imaging techniques. Compression ultrasonography is the first-line investigation. Low-molecular weight heparin or fondaparinux is the treatment of choice for uncomplicated venous thrombosis. Secondary prophylaxis with a vitamin K antagonist is introduced in parallel as quickly as possible. The duration of treatment depends on the exposure and predisposing factors, weighing carefully the risk of recurrence on the one hand against the risk of bleeding on the other. The danger of a post thrombotic syndrome is reduced by the immediate begin of a long lasting compression therapy.

Topics: Anticoagulants; Diagnosis, Differential; Fibrin Fibrinogen Degradation Products; Heparin, Low-Molecular-Weight; Humans; Phlebography; Stockings, Compression; Thrombolytic Therapy; Ultrasonography, Doppler, Duplex; Venous Thrombosis; Vitamin K

Topics: Algorithms; Anticoagulants; Exercise Therapy; Female; Humans; Platelet Aggregation Inhibitors; Pregnancy; Pregnancy Complications, Cardiovascular; Risk Factors; Stockings, Compression; Thrombectomy; Thrombolytic Therapy; Venous Thrombosis; Vitamin K

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

The surgical and hereditary risk factors for post-operative venous thromboembolism (VTE) are discussed and the heightened risk associated with particular risk factors quantified. Mechanical and pharmacological methods of prophylaxis are described, together with the different recommendations for use with general and regional anaesthesia. Prophylaxis may be started post-operatively and the duration of prophylaxis is discussed. The use of prophylaxis in vascular surgery is illustrated with case examples.

Topics: Anesthesia, Conduction; Anticoagulants; Embolism; Heparin, Low-Molecular-Weight; Hospitalization; Humans; Risk Assessment; Risk Factors; Stockings, Compression; Thrombin; Venous Thrombosis; Vitamin K

New treatments are available for treatment of venous thromboembolism.. To review the evidence on the efficacy of interventions for treatment of deep venous thrombosis (DVT) and pulmonary embolism.. MEDLINE, MICROMEDEX, the Cochrane Controlled Trials Register, and Cochrane Database of Systematic Reviews from the 1950s through June 2006.. Randomized, controlled trials; systematic reviews of trials; and observational studies; all restricted to English-language articles.. Paired reviewers assessed study quality and abstracted data. The authors pooled results about optimal duration of anticoagulation.. This review includes 101 articles. Low-molecular-weight heparin (LMWH) is modestly superior to unfractionated heparin at preventing recurrent DVT and is at least as effective as unfractionated heparin for treatment of pulmonary embolism. Outpatient treatment of venous thromboembolism is likely to be effective and safe in carefully chosen patients, with appropriate services available. Inpatient or outpatient use of LMWH is cost-saving or cost-effective compared with unfractionated heparin. In observational studies, catheter-directed thrombolysis safely restored vein patency in select patients. Moderately strong evidence supports early use of compression stockings to reduce postthrombotic syndrome. Limited evidence suggests that vena cava filters are only modestly efficacious for prevention of pulmonary embolism. Conventional-intensity oral anticoagulation beyond 12 months may be optimal for patients with unprovoked venous thromboembolism, although patients with transient risk factors benefit little from more than 3 months of therapy. High-quality trials support use of LMWH in place of oral anticoagulation, particularly in patients with cancer. Little evidence is available to guide treatment of venous thromboembolism during pregnancy.. The authors could not address all management questions, and excluded non-English-language literature.. The strength of evidence varies across the study questions but generally is strong.

Topics: Ambulatory Care; Anticoagulants; Cost-Benefit Analysis; Female; Heparin; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Pregnancy; Pregnancy Complications, Hematologic; Pulmonary Embolism; Secondary Prevention; Stockings, Compression; Thromboembolism; Thrombolytic Therapy; Vena Cava Filters; Venous Thrombosis; Vitamin K

Central venous catheter (CVC) placement increases the risk of thrombosis in cancer patients. Thrombosis often necessitates the removal of the CVC, resulting in treatment delays and thrombosis related morbidity and mortality.. To evaluate the efficacy and safety of anticoagulation in reducing venous thromboembolic (VTE) events in cancer patients with CVC.. A comprehensive search for studies of anticoagulation in cancer patients up to January 2006 was conducted in the following databases: The Cochrane Central Register of Controlled Trials ( CENTRAL), MEDLINE, EMBASE and ISI the Web of Science.. Randomized controlled trials (RCTs) comparing unfractionated heparin (UFH), low molecular weight heparin (LMWH), vitamin K antagonists (VKA), fondaparinux or ximelagatran to no intervention or placebo in cancer patients with a CVC or comparing two different anticoagulants.. Data was extracted on methodological quality, patients, interventions and outcomes including all cause mortality (primary outcome), premature CVC removal, catheter-related infections, CVC site and non CVC site deep venous thrombosis (DVT), pulmonary embolism (PE), major and minor bleeding and thrombocytopenia.. Of 3986 identified citations nine RCTs were included in the meta-analysis including one published as an abstract and one focusing on paediatric patients not included in the meta-analysis. None of these RCTs tested fondaparinux or ximelagatran. The use of heparin in cancer patients with CVC was associated with a trend towards a reduction in symptomatic DVT (Relative Risk (RR) = 0.43; 95% Confidence Interval (CI): 0.18 to 1.06), but the data did not show any statistically significant effect on mortality (RR = 0.74; 95% CI: 0.40 to 1.36), infection (RR = 0.91; 95% CI: 0.36 to 2.28), major bleeding (RR = 0.68; 95% CI: 0.10 to 4.78) or thrombocytopenia (RR = 0.85; 95% CI: 0.49 to 1.46). The effect warfarin on symptomatic DVT was not statistically significant (RR = 0.62; 95% CI: 0.30 to 1.27). When studies assessing different types of anticoagulants were pooled, symptomatic DVT rates were significantly reduced (RR = 0.56; 95% CI: 0.34 to 0.92).. Cancer patients with CVC considering anticoagulation, should consider the possible benefit of reduced incidence of thromboembolic complications with the burden and harms of anticoagulation. Future studies should be adequately powered and evaluate the effects of newer anticoagulants such as fondaparinux and ximelagatran in cancer patients with CVC.

Topics: Anticoagulants; Catheterization, Central Venous; Heparin; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Randomized Controlled Trials as Topic; Venous Thrombosis; Vitamin K

Currently, the most frequently used secondary treatment for patients with venous thromboembolism is vitamin K antagonists targeted at an INR of 2.5 (range 2.0 to 3.0). However, based on the continuing risk of bleeding and uncertainty regarding the risk of recurrent venous thromboembolism, there is discussion on the proper duration of treatment with vitamin K antagonists for these patients. Recently, several studies were published in which the risk and benefits of different durations of oral anticoagulants were compared in patients with venous thromboembolism.. The objective of this review was to evaluate efficacy and safety of different durations of treatment with vitamin K antagonists in patients with symptomatic venous thromboembolism.. The Cochrane Peripheral Vascular Diseases Group searched their Specialised Register and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library Issue 3, 2005). The Specialised Register is constructed from electronic searches of MEDLINE (from inception to October 2005) and EMBASE (inception to October 2005) and through handsearching relevant journals. In addition, we also contacted colleagues for details of trials. The last searches were carried out on 11 October 2005.. Randomized controlled clinical trials comparing different durations of treatment with vitamin K antagonists in patients with symptomatic venous thromboembolism.. Two reviewers (BH and MP) extracted the data and assessed the quality of the trials independently.. Eight studies with a total of 2994 patients were included. A consistent reduction in the risk of recurrent events was observed during prolonged treatment with vitamin K antagonists (OR 0.18; 95% CI 0.13 to 0.26) independent of the period elapsed since the index thrombotic event. A 'rebound' phenomenon, i.e. an excess of recurrences shortly after cessation of the prolonged treatment was not observed (OR 1.24; 95% CI 0.91 to 1.69). In addition, a substantial increase in bleeding complications was found during the entire period after randomization (OR 2.62; 95% CI 1.48 to 4.61).. In conclusion, this meta-analysis shows that treatment with vitamin K antagonists reduces the risk of recurrent venous thromboembolism for as long as it is used. However, the absolute risk of recurrent venous thromboembolism declines over time, while the risk for major bleeding remains. Thus, the efficacy of vitamin K antagonist administration decreases over time since the index event.

Topics: Anticoagulants; Humans; International Normalized Ratio; Randomized Controlled Trials as Topic; Secondary Prevention; Thromboembolism; Venous Thrombosis; Vitamin K

Topics: Anticoagulants; Fondaparinux; Forecasting; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Pulmonary Embolism; Risk Factors; Thromboembolism; Thrombolytic Therapy; Venous Thrombosis; Vitamin K

The risk of venous thromboembolism (VTE) is increased in association with malignancy, and has a potential to produce significant morbidity and mortality. Treatment of such patients with anticoagulants is associated with both benefit and a high rate of complications. In the early phase, the treatment is usually achieved with low molecular weight heparin (LMWH), which has a number of advantages over unfractionated heparin (UFH): once or twice daily administration, no necessary laboratory monitoring, lesser risk of bleeding and no drugs interactions. Nevertheless, the UFH is the anticoagulant of choice when a rapid anticoagulant effect or stop of anticoagulant effect is required, in the treatment of massive pulmonary embolism or severe renal insufficiency. Prolonged anticoagulation with LMWH (over 3 or 6 months) appears to be beneficial on survival for such patients. The subject of anticoagulation in patients with primary or secondary brain tumours is controversial. The long-term anticoagulation mainly use LMWH or vitamin K antagonist. The last ones are more difficult to use because of an unpredictable response with higher rate of recurrence and bleeding. The optimal duration of treatment is not known but the patients should be treated for at least 6 months, even at least 12 months after a second episode of venous thromboembolism. On the primary prevention in high-risk surgical oncology, the LMWH are at least as effective and safer as UFH when the optimal dose was administered. For the medical patients, the use of prophylactic anticoagulant treatment is less clear except the patients who are bedridden for prolonged periods of time. For the secondary prevention, the LMWH seems to be more effective over vitamin K antagonists. For these patients, the anticoagulant therapy is recommended indefinitely or until cancer is resolved.

Topics: Anticoagulants; Antineoplastic Agents, Hormonal; Heparin; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Postoperative Complications; Tamoxifen; Thromboembolism; Venous Thrombosis; Vitamin K

The aim of this study was to evaluate the evidence on the optimal duration of vitamin K antagonist (VKA) therapy for venous thromboembolism (VTE).. Randomized controlled trials of VKA for VTE were identified by a computerized database search. Summary event rates for relevant outcomes were calculated using a random effects model with 95% confidence intervals (95% CI).. Ten studies met inclusion criteria. The incidence of recurrent VTE (3 months, 7.9 VTE per 100 patient-years [95% CI, 5.2 to 10] versus 4-12 months, 4.9 VTE per 100 patient-years [95% CI, 3.6 to 6.2] versus continuous therapy, 0.7 VTE per 100 patient-years [95% CI, 0.3 to 1.1]) and total adverse events (3 months, 11.2 events per 100 patient-years [95%CI, 7.1 to 15.4] versus 4-12 months, 7.4 events per 100 patient-years [95%CI, 6.2 to 8.5] versus continuous therapy 3.1 events per 100 patient-years [95%CI, 2.2 to 4.0] declined as VKA therapy duration increased. Continuous reduced intensity therapy (INR 1.5-2) was associated with more recurrent VTE (2.3 VTE per 100 patient-years [95%CI, 1.5 to 3.0]). Continuous VKA therapy (INR 2-3) was beneficial for patients with a second VTE and antiphospholipid antibodies. The incidence of recurrent VTE was similar with 6 or 12 weeks of therapy for isolated calf DVT.. Randomized controlled trials indicate that continuous VKA therapy (INR 2-3) for VTE is associated with better clinical outcomes than shorter durations. Patients with a second VTE or antiphospholipid antibodies also benefit from continuous anticoagulation. Patients with calf DVT should be treated for at least 6 weeks.

Topics: Anticoagulants; Drug Administration Schedule; Humans; MEDLINE; Randomized Controlled Trials as Topic; Thromboembolism; Time Factors; Venous Thrombosis; Vitamin K

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

Immediate anticoagulant treatment is essential to reduce morbidity and mortality in patients with acute venous thromboembolism (VTE). Currently, rapid anticoagulation can only be achieved with parenteral anticoagulants, such as heparin or low-molecular-weight heparin (LMWH). Weight-adjusted LMWH is the treatment of choice, because it produces predictable anticoagulation and does not require coagulation monitoring. If heparin is used, the activated partial thromboplastin time must be monitored and the heparin dose adjusted to ensure a therapeutic level of anticoagulation. Heparin is recommended for patients with renal impairment and for those at high risk of bleeding. The selective factor Xa inhibitor fondaparinux is a recently introduced alternative to heparin or LMWH for initial VTE treatment. Heparin, LMWH, or fondaparinux should be given for at least five to seven days. Vitamin K antagonists should be initiated on the first day, or as soon as possible, in patients who are candidates for an oral anticoagulant. An oral anticoagulant agent to be used without laboratory monitoring for both acute and long-term treatment of VTE remains an unsolved clinical need in the treatment of VTE.

Topics: Administration, Oral; Algorithms; Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Partial Thromboplastin Time; Thromboembolism; Venous Thrombosis; Vitamin K

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

Venous thromboembolism (VTE) is a common complication in cancer patients that results in significant morbidity and mortality. Long-term treatment options for cancer patients who experience VTE include vitamin K antagonists (VKAs), low molecular weight heparins (LMWHs), and inferior vena caval (IVC) filters. Cancer patients have a two- to fourfold higher risk for experiencing recurrent VTE and major bleeding during chronic VKA therapy than patients without malignancies. Recent randomized clinical trials have shown that LMWHs rather than oral VKAs are preferred for initial chronic treatment of VTE in patients with advanced cancer. One factor potentially limiting the broader use of LMWH for chronic therapy in the United States is its higher acquisition cost. Efficacy, cost, drug availability, patient comorbidities, and concomitant medications all need to be considered when selecting chronic VTE therapy. Cancer patients with VTE should be treated for as long as their disease is active to minimize the incidence of recurrence. Use of IVC filters should generally be reserved for patients at high risk for recurrent VTE who have contraindications to anticoagulation. Several new anticoagulants are being investigated that promise greater therapeutic choices and potentially better outcomes for cancer patients with VTE.

Topics: Heparin, Low-Molecular-Weight; Humans; Neoplasms; Thromboembolism; Vena Cava Filters; Venous Thrombosis; Vitamin K

To evaluate whether the incidence of recurrent venous thromboembolism (VTE) events after therapy differs for patients treated with long-term low-molecular-weight heparin (LMWH) or oral anticoagulant therapy (OAT).. All randomized studies were searched through computerized queries of MEDLINE, the Cochrane Controlled Trials Register, the American Society of Hematology abstract database, and the American Society of Clinical Oncology abstract database.. Eleven studies including 2,907 patients were identified. Seven studies evaluated a period of 3 to 9 months after cessation of the allocated treatment: 5.4% of patients in the LMWH group vs 4% in the arm allocated to OAT had an episode of recurrent symptomatic VTE. Combined analysis showed a nonsignificant trend in lowering recurrent symptomatic VTE in favor of OAT (relative risk [RR], 1.29; 95% confidence interval [CI], 0.82 to 2.02; p = 0.27). By contrast, during active treatment, a statistically significant reduction of the risk of recurrent symptomatic VTE in favor of LMWH over OAT was registered (RR, 0.63; 95% CI, 0.47 to 0.83; p = 0.001). Regarding cancer patients only, 37 of 569 patients (6.5%) in the LMWH group had recurrent symptomatic VTE vs 69 of 546 patients (12.6%) in the OAT group, with a statistically significant reduction of the risk of recurrent symptomatic VTE in favor of LMWH (RR, 0.52; 95% CI, 0.35 to 0.76; p = 0.001).. Despite the significant reduction of the risk of recurrent symptomatic VTE in favor of LMWH over OAT during treatment, patients treated with long-term LMWH do not seem to have more frequently recurrent VTE events compared with OAT after cessation of therapy. The significant difference favoring LMWH over OAT among all patients receiving treatment comes mostly from studies enrolling cancer patients.

Topics: Anticoagulants; Drug Administration Schedule; Drug Therapy, Combination; Follow-Up Studies; Heparin, Low-Molecular-Weight; Humans; Long-Term Care; Pulmonary Embolism; Randomized Controlled Trials as Topic; Secondary Prevention; Substance Withdrawal Syndrome; Venous Thrombosis; Vitamin K

Venous thromboembolism (VTE) is a major cause of morbidity and mortality worldwide and the annual incidence of VTE is 1 per 1000. The individual risk for venous thromboembolism may be substantially higher and is determined by expositional and dispositional factors. Unfractionated heparin and warfarin have been the mainstays for the prevention of VTE until the early 1980s. Bleeding complications and side effects limited the use of these agents and subsequently low molecular weight heparins (LMWH) were introduced into clinical practice. These are most commonly used for the prophylaxis and treatment of VTE today. In the last decade, the pace of development of further anticoagulants has accelerated with the introduction of new treatment regimens and new substances. In this context, novel drugs directed against clotting factor Xa (such as fondaparinux) and direct thrombin inhibitors (such as melagatran/ximelagatran) have been developed. Fondaparinux shows a favourable efficacy/safety profile and has been documented to be cost-effective compared to enoxaparin in the US and the UK.

Topics: Anticoagulants; Factor Xa Inhibitors; Heparin; Humans; Risk Assessment; Thrombin; Thromboembolism; Venous Thrombosis; Vitamin K

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

Low-molecular-weight heparins (LMWHs) are used widely in the treatment and prevention of venous thromboembolism (VTE). The LMWHs dalteparin and enoxaparin reduce the rate of VTE by at least 50% if administered for 4-5 weeks following major orthopedic surgery, compared with in-hospital prophylaxis for 7-15 days. Meta-analyses have confirmed that the size of the reduction is similar for both clinical and asymptomatic VTE. Vitamin K antagonists (VKAs) have been shown to be associated with significantly higher bleeding rates compared with LMWH when used as prolonged prophylaxis against VTE following major orthopedic surgery. Patients with cancer are a recognized group at high risk of VTE, and those undergoing major surgery for their malignancy are at particular risk. Evidence from clinical trials is amassing to show that prolonged prophylaxis with LMWH (dalteparin, enoxaparin) in these patients can significantly reduce the rate of postoperative VTE. In cancer patients with acute VTE, the traditional approach is to initiate acute treatment with unfractionated heparin or LMWH followed by long-term treatment with VKA to prevent recurrence. However, clinical trial data have confirmed that the LMWH dalteparin, when administered for 6 months, is significantly more effective than VKA in preventing recurrence, cutting the rate of VTE by 52% without increasing the risk of bleeding. A new and intriguing area of interest is whether LMWH can enhance survival in patients with cancer. Preliminary data suggest that a biological effect of LMWH may act to prolong survival in patients with cancer.

Topics: Anticoagulants; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Postoperative Complications; Premedication; Thromboembolism; Venous Thrombosis; Vitamin K

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are two manifestations of the same disorder, venous thromboembolism, and low-molecular weight heparin is the treatment of choice for both DVT and PE. Alternatively, intravenous adjusted-dose unfractionated heparin can be used in hemodynamically unstable patients with massive PE. Secondary thromboprophylaxis with vitamin K-antagonists (VKA) should be started as soon as the diagnosis is confirmed. The dose of VKA should be adjusted to a target international normalized ratio (INR) of 2.5. For most patients with PE, thrombolysis is not recommended. Vena cava filters should be restricted to patients with active bleeding or risk of serious bleeding, and to those in whom PE has recurred despite adequate anticoagulation. Several new antithrombotics with potential advantages over heparin and VKA have been evaluated in phase II and III trials, but are currently not licensed for the treatment of venous thromboembolic events.

Topics: Acute Disease; Administration, Oral; Fibrinolytic Agents; Heparin; Heparin, Low-Molecular-Weight; Humans; Infusions, Intravenous; Pulmonary Embolism; Randomized Controlled Trials as Topic; Secondary Prevention; Venous Thrombosis; Vitamin K

Topics: Anticoagulants; Azetidines; Benzylamines; Clinical Trials as Topic; Humans; Prodrugs; Stroke; Venous Thrombosis; Vitamin K

This review on the treatment of patients with venous thromboembolic disease consists of three sections. The first section describes the epidemiology, natural history and reasons for treatment of venous thromboembolism (VTE), as well as a short overview on the evaluation of the use of antithrombotic agents and the spectrum of treatment options. In the second section, the evidence from clinical studies available to us in 2005 with the various treatment modalities is summarized. This section describes the current recommendations about how to treat patients with VTE initially and long term. Finally, in the third section the challenges for the treatment of patients beyond 2005 are discussed.

Topics: Blood Coagulation; Clinical Trials as Topic; Fibrinolytic Agents; Heparin; Humans; Models, Biological; Pulmonary Embolism; Thromboembolism; Time Factors; Treatment Outcome; Venous Thrombosis; Vitamin K

Adequate initial anticoagulant treatment is required to prevent thrombus growth and recurrence. Intravenous unfractionated heparin is being replaced by low-molecular-weight heparin as the anticoagulant of choice for initial treatment of venous thromboembolism. Vitamin K antagonists remain the only oral anticoagulant available (target international normalized ratio: 2.5). The duration of therapy should be individualized according to the risk of recurrence and the risk of bleeding. Three months of treatment is usually adequate if thrombosis was provoked by a reversible risk factor such as surgery. For patients with unprovoked ("idiopathic") thrombosis, anticoagulant treatment for at least 6 months is indicated. For patients with a recurrence of venous thromboembolism or with an irreversible risk factor such as cancer, indefinite anticoagulant therapy is recommended. Long-term treatment with low-molecular-weight heparin is usually preferable for patients with active cancer. Systemic thrombolysis is indicated for patients with massive pulmonary embolism but controversy persists for those with isolated right ventricular dysfunction.

Topics: Anticoagulants; Heparin; Humans; Venous Thrombosis; Vitamin K

Anticoagulation is highly effective in the prevention and treatment of venous thromboembolism (VTE). Since decades, vitamin K antagonists (VKA) were the only available oral anticoagulants. Even though VKA are very effective, they have numerous practical problems: Due to their narrow therapeutic window, highly variable dose requirements and drug interactions, close monitoring is mandatory, aiming towards an INR of 2-3 for most indications. At present, new oral anticoagulants are being studied, such as the oral direct thrombin inhibitor Ximelagatran, which in trials for prevention and treatment of VTE appears at least equivalent to heparin and VKA. Heparins have to be administered parenterally, and low molecular-weight heparins have been able to overcome some of the shortcomings of standard heparins, such as limited bioavailability, variable dose response and heparin induced thrombocytopenia (HIT). Heparinoids and hirudins are alternative anticoagulants to treat HIT. With the development of synthetic pentasaccharides, such as Fondaparinux an increase in efficacy could be achieved in high-risk thromboprophylaxis.

Topics: Anticoagulants; Azetidines; Benzylamines; Dose-Response Relationship, Drug; Drug Therapy; Evidence-Based Medicine; Fondaparinux; Heparin; Humans; Patient Care Management; Polysaccharides; Practice Patterns, Physicians'; Thrombocytopenia; Treatment Outcome; Venous Thrombosis; Vitamin K

Topics: Anticoagulants; Azetidines; Benzylamines; Clinical Trials, Phase III as Topic; Drug Design; Factor Xa Inhibitors; Follow-Up Studies; Fondaparinux; Humans; Polysaccharides; Randomized Controlled Trials as Topic; Recurrence; Thromboembolism; Thrombophilia; Venous Thrombosis; Vitamin K

Topics: Azetidines; Benzylamines; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Orthopedic Procedures; Postoperative Complications; Therapeutic Equivalency; Thromboembolism; Venous Thrombosis; Vitamin K

The benefit-to-risk ratio of vitamin K antagonists (VKA), relative to active comparators, especially low-molecular-weight heparins (LMWH), for preventing venous thromboembolism in patients undergoing major orthopedic surgery is debated.. We performed a meta-analysis of all randomized trials in orthopedic surgery comparing adjusted doses of VKA to control treatments.. An exhaustive literature search, both manual and computer-assisted, was performed. Studies were selected on the basis of randomization procedure (VKA vs. a control group). At least one of the following outcome measures was to be evaluated: deep vein thrombosis (DVT), pulmonary embolism (PE), death, major hemorrhage or wound hematoma. Four reviewers assessed each article to determine eligibility for inclusion and outcome measures.. VKAs were more effective than placebo or no treatment in reducing DVT [567 patients, relative risk (RR) = 0.56, 95% confidence interval (CI) 0.37, 0.84, P < 0.01] and clinical PE (651 patients, RR = 0.23, 95% CI 0.09, 0.59, P < 0.01). These results were obtained at the cost of a higher rate of wound hematoma (162 patients, RR = 2.91, 95% CI 1.09, 7.75, P = 0.03). VKAs were also more effective than intermittent pneumatic compression (534 patients, RR = 0.46, 95% CI 0.25, 0.82, P = 0.009) in preventing proximal DVT. In contrast, VKAs were less effective than LMWH in preventing total DVT and proximal DVT (9822 patients, RR = 1.51, 95% CI 1.27, 1.79, P < 0.001; and 6131 patients, RR = 1.51, 95% CI 1.04, 2.17, P = 0.028, respectively). The differences between VKA and LMWH in major hemorrhage and wound hematoma were not significant.. In patients undergoing major orthopedic surgery, VKAs are less effective than LMWH, without any significant difference in the bleeding risk.

Topics: Fibrinolytic Agents; Hemorrhage; Humans; Orthopedic Procedures; Postoperative Complications; Randomized Controlled Trials as Topic; Survival Rate; Therapeutic Equivalency; Thromboembolism; Venous Thrombosis; Vitamin K

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

Long-term treatment of venous thromboembolism (VTE) focuses mainly on the duration of anticoagulant therapy, usually with vitamin K (VK) antagonists. The duration of therapy should be individualized based on the risk of recurrent VTE if treatment were stopped and the risk of bleeding if treatment were continued. The risk of recurrence is low if thrombosis was provoked by a major reversible risk factor such as surgery; 3 months of treatment is usually adequate for such patients. The risk of recurrence is high if thrombosis was unprovoked ("idiopathic") or associated with an irreversible risk factor such as cancer; anticoagulant treatment for at least 6 months, and often indefinitely, is indicated for such patients. Risk of recurrence is intermediate if thrombosis was associated with a minor transient risk factor; such patients can be treated for 3 to 6 months. Within each of these categories, presentation as pulmonary embolism, >1 previous VTE, an underlying malignancy, an antiphospholipid antibody, or selected hereditary thrombophilic states favor more prolonged therapy, whereas isolated distal deep vein thrombosis, high risk of bleeding, and patient preference favor shorter treatment. The optimal intensity of anticoagulant therapy with VK antagonists corresponds to a target international normalized ratio of 2.5 (range, 2.0 to 3.0). Long-term treatment with low-molecular-weight heparin is an alternative to VK-antagonist therapy and is usually preferable in patients with active cancer. Oral direct thrombin inhibitors also appear suitable for long-term prevention of recurrent VTE but await regulatory approval and comparison with VK antagonists.

Topics: Anticoagulants; Drug Administration Schedule; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Pulmonary Embolism; Recurrence; Thromboembolism; Venous Thrombosis; Vitamin K

This article discusses the prevention of venous thromboembolism (VTE) and is part of the Seventh American College of Chest Physicians Conference on Antithrombotic and Thrombolytic Therapy: Evidence-Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2004; 126:179S-187S). Among the key recommendations in this chapter are the following. We recommend against the use of aspirin alone as thromboprophylaxis for any patient group (Grade 1A). For moderate-risk general surgery patients, we recommend prophylaxis with low-dose unfractionated heparin (LDUH) (5,000 U bid) or low-molecular-weight heparin (LMWH) [< or = 3,400 U once daily] (both Grade 1A). For higher risk general surgery patients, we recommend thromboprophylaxis with LDUH (5,000 U tid) or LMWH (> 3,400 U daily) [both Grade 1A]. For high-risk general surgery patients with multiple risk factors, we recommend combining pharmacologic methods (LDUH three times daily or LMWH, > 3,400 U daily) with the use of graduated compression stockings and/or intermittent pneumatic compression devices (Grade 1C+). We recommend that thromboprophylaxis be used in all patients undergoing major gynecologic surgery (Grade 1A) or major, open urologic procedures, and we recommend prophylaxis with LDUH two times or three times daily (Grade 1A). For patients undergoing elective total hip or knee arthroplasty, we recommend one of the following three anticoagulant agents: LMWH, fondaparinux, or adjusted-dose vitamin K antagonist (VKA) [international normalized ratio (INR) target, 2.5; range, 2.0 to 3.0] (all Grade 1A). For patients undergoing hip fracture surgery (HFS), we recommend the routine use of fondaparinux (Grade 1A), LMWH (Grade 1C+), VKA (target INR, 2.5; range, 2.0 to 3.0) [Grade 2B], or LDUH (Grade 1B). We recommend that patients undergoing hip or knee arthroplasty, or HFS receive thromboprophylaxis for at least 10 days (Grade 1A). We recommend that all trauma patients with at least one risk factor for VTE receive thromboprophylaxis (Grade 1A). In acutely ill medical patients who have been admitted to the hospital with congestive heart failure or severe respiratory disease, or who are confined to bed and have one or more additional risk factors, we recommend prophylaxis with LDUH (Grade 1A) or LMWH

Topics: Anticoagulants; Aspirin; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Evidence-Based Medicine; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Polysaccharides; Postoperative Complications; Pulmonary Embolism; Randomized Controlled Trials as Topic; Risk Assessment; Venous Thrombosis; Vitamin K

This chapter about antithrombotic therapy for venous thromboembolic disease is part of the seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2004; 126:179S-187S). Among the key recommendations in this chapter are the following: for patients with objectively confirmed deep vein thrombosis (DVT), we recommend short-term treatment with subcutaneous (SC) low molecular weight heparin (LMWH) or, alternatively, IV unfractionated heparin (UFH) [both Grade 1A]. For patients with a high clinical suspicion of DVT, we recommend treatment with anticoagulants while awaiting the outcome of diagnostic tests (Grade 1C+). In acute DVT, we recommend initial treatment with LMWH or UFH for at least 5 days (Grade 1C), initiation of vitamin K antagonist (VKA) together with LMWH or UFH on the first treatment day, and discontinuation of heparin when the international normalized ratio (INR) is stable and > 2.0 (Grade 1A). For the duration and intensity of treatment for acute DVT of the leg, the recommendations include the following: for patients with a first episode of DVT secondary to a transient (reversible) risk factor, we recommend long-term treatment with a VKA for 3 months over treatment for shorter periods (Grade 1A). For patients with a first episode of idiopathic DVT, we recommend treatment with a VKA for at least 6 to 12 months (Grade 1A). We recommend that the dose of VKA be adjusted to maintain a target INR of 2.5 (INR range, 2.0 to 3.0) for all treatment durations (Grade 1A). We recommend against high-intensity VKA therapy (INR range, 3.1 to 4.0) [Grade 1A] and against low-intensity therapy (INR range, 1.5 to 1.9) compared to INR range of 2.0 to 3.0 (Grade 1A). For the prevention of the postthrombotic syndrome, we recommend the use of an elastic compression stocking (Grade 1A). For patients with objectively confirmed nonmassive PE, we recommend acute treatment with SC LMWH or, alternatively, IV UFH (both Grade 1A). For most patients with pulmonary embolism (PE), we recommend clinicians not use systemic thrombolytic therapy (Grade 1A). For the duration and intensity of treatment for PE, the recommendations are similar to those for DVT.

Topics: Evidence-Based Medicine; Fibrinolytic Agents; Heparin; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Long-Term Care; Pulmonary Embolism; Randomized Controlled Trials as Topic; Secondary Prevention; Venous Thrombosis; Vitamin K

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

Current antithrombotic therapy of deep vein thrombosis (DVT) consists of an initial course of heparin, followed by the secondary prevention with oral anticoagulation (OAC). Low molecular weight heparin has several advantages over unfractionated heparin, however, renal insufficiency has to be observed to avoid accumulation. The synthetic pentasaccharide Fondaparinux is a factor Xa inhibitor, that will shortly be available for the initial treatment of DVT. Oral anticoagulation with vitamin K antagonists (VKA) is highly effective, the standard target INR is 2.0-3.0. For a first episode of DVT the duration of OAC usually is six months, but has to be adjusted according to the estimated risk for recurrence. Because of the narrow therapeutic window of VKA, low molecular weight heparins are increasingly being used for secondary prevention in patients with an increased risk for bleeding, mostly in 1/2-therapeutic dose. At present, several new antithrombotic agents are being studied and may become available shortly for DVT treatment.

Topics: Administration, Oral; Anticoagulants; Fibrinolytic Agents; Heparin; Heparin, Low-Molecular-Weight; Humans; Practice Guidelines as Topic; Practice Patterns, Physicians'; Treatment Outcome; Venous Thrombosis; Vitamin K

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

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

After a first episode of venous thromboembolism, patients are treated with vitamin K (phytonadione) antagonists. There are indications that the risk of recurrence after treatment with vitamin K antagonists decreases relative to the time since the first event. The aim of the present meta-analysis is to describe the risk of recurrent venous thromboembolism after treatment with vitamin K antagonist in relation to the time since the index event.. Computerized searches in MEDLINE and EMBASE databases; reference checks of pertinent articles; personal communication with colleagues to find randomized clinical trials and cohort studies in which patients with venous thromboembolism were treated with vitamin K antagonists. Per treatment arm, 2 reviewers independently extracted data on the number of recurrent events and the duration of follow-up per time period of 3 months.. A total of 135 potentially eligible studies were identified. Of these, 18 studies could be included, comprising 25 treatment arms that could be analyzed. Treatment arms were divided into 3 groups based on treatment duration (short, medium, and long). For all 3 groups, the monthly incidence immediately after discontinuation of treatment was high and declined rapidly thereafter. The monthly incidence after 9 months seemed independent of the treatment duration.. There is a diminishing risk of recurrent venous thromboembolism over time and a stabilization after 9 months independent of the duration of the initial treatment with vitamin K antagonists. These findings have important implications for decision making about the optimal duration of treatment with vitamin K antagonists.

Topics: Anticoagulants; Humans; Pulmonary Embolism; Recurrence; Risk Factors; Time Factors; Venous Thrombosis; Vitamin K

Thrombin has long been a target for development of oral anticoagulants but it has been difficult to find synthetic inhibitors with a desirable combination of pharmacodynamic and pharmacokinetic properties. However, there are now two oral direct thrombin inhibitors (DTIs) in clinical development, ximelagatran (ExantaTM) and BIBR 1048. Both are prodrugs with two protecting groups that are eliminated after absorption from the gastrointestinal tract. Their main active substances, melagatran and BIBR 953, are both potent and selective DTIs. In experimental models of thrombosis, melagatran has been shown to have a shallower dose-response curve than warfarin and, therefore, a better separation between efficacy and bleeding. Oral bioavailability, measured as the plasma concentration of the active metabolite, seems to be higher for ximelagatran (20%) than for BIBR 1048 (estimated to 5%). BIBR 953 has a longer half-life (about 12 h) than does melagatran (3-5 h) after oral administration of BIBR 1048 and ximelagatran, respectively. Both melagatran and BIBR 953 are mainly eliminated via the renal route. The variability of the plasma concentration of melagatran after oral administration of ximelagatran is low. There are no clinically relevant interactions with food or cytochrome P450 metabolized drugs and ximelagatran. In clinical studies, ximelagatran has been administered in a twice-daily fixed-dose regimen without coagulation monitoring. Results of published clinical studies are encouraging, both with regard to efficacy and bleeding. Major indications in Phase III studies with ximelagatran are the prevention of venous thromboembolism (VTE) in hip and knee replacement surgery, treatment and long-term secondary prevention of VTE and prevention of stroke in patients with nonvalvular atrial fibrillation. It is anticipated that with a favourable outcome of the Phase III clinical studies new oral DTIs, with the oral fixed-dose regimen without routine coagulation monitoring, will ease the use of today's anticoagulant therapy.

Topics: Anticoagulants; Azetidines; Benzimidazoles; Benzylamines; Dabigatran; Glycine; Hemostasis; Humans; Prodrugs; Pyridines; Stroke; Thrombin; Thrombosis; Venous Thrombosis; Vitamin K

Unfractionated heparin, low molecular weight heparin and vitamin K antagonists are anticoagulants currently used for the prevention and treatment of deep vein thrombosis and pulmonary embolism. Considerable limitations of these agents, such as a narrow therapeutic window, a variable dose response or lack of oral bioavailability, created the need for new anticoagulants. Numerous new compounds with different mechanisms of action have been developed and some have been already approved for clinical use. Quite recently, fondaparinux, an indirect anti-factor Xa inhibitor, has been licensed in Europe and in the US for prevention of VTE in patients undergoing hip or knee replacement surgery. In addition, lepirudin, a recombinant hirudin derivative, and the heparinoid danaparoid, have been approved in Austria for treatment of heparin-induced thrombocytopenia. Recombinant nematode anticoagulant protein c2, the orally available thrombin inhibitor ximelagatran and ART-123, a recombinant soluble thrombomodulin, are in advanced stages of clinical development. This article reviews mechanisms and sites of action, and the current state of preclinical and clinical research of these and various other agents with respect to the prevention and treatment of venous thromboembolism).

Topics: Anticoagulants; Azetidines; Benzylamines; Blood Coagulation Factors; Drugs, Investigational; Fondaparinux; Glycine; Heparin; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Pulmonary Embolism; Research; Thrombin; Venous Thrombosis; Vitamin K

Oral anticoagulation with vitamin-K-antagonists is very effective in secondary prevention of venous thromboembolism. In Germany, most commonly Phenprocoumon is used, while most of the evidence-based data are available for Warfarin. The initial treatment of acute venous thromboembolism requires immediate anticoagulation with heparin and a subsequent overlapping treatment with oral anticoagulants. During this phase, anticoagulation may be unstable with increased risk for bleeding. An INR target range between 2 and 3 provides effective protection with minimal risk for major bleeding. The individual risk for bleeding may be estimated by a clinical score. Six months of oral anticoagulation is the standard duration for a first episode of venous thromboembolism, while recurrencies are treated for at least one to two years. The duration may be tailored to the individual patient according to underlying risk factors for recurrencies and for bleeding. Because of a plethora of practical problems and the narrow therapeutic window, there is a need for new antithrombotic agents. These may allow a longer duration of secondary prevention with improved protection against recurrencies without sacrificing safety.

Topics: Administration, Oral; Anticoagulants; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Infant, Newborn; International Normalized Ratio; Male; Pregnancy; Pulmonary Embolism; Risk Factors; Secondary Prevention; Venous Thrombosis; Vitamin K

Anticoagulants are widely used for the prevention and treatment of venous and arterial thrombosis. Current treatment strategies often employ a combination of parenteral and oral agents because the only available orally active anticoagulants, vitamin K antagonists, have a delayed onset of action. Furthermore, vitamin K antagonists have a narrow therapeutic window that necessitates careful anticoagulation monitoring, and dosing is problematic because of multiple food and drug interactions. These limitations highlight the need for oral anticoagulants that produce a more predictable anticoagulant response than vitamin K antagonists, thereby obviating the need for laboratory monitoring. Ximelagatran has the potential to meet this need. A prodrug of melagatran, an agent that targets thrombin, ximelagatran exhibits many of the characteristics of an ideal anticoagulant. This article (1). reviews the limitations of vitamin K antagonists, (2). lists the characteristics of an ideal anticoagulant, (3). rationalizes thrombin as a target for new anticoagulants, (4). reviews the preclinical and clinical data with ximelagatran, and (5). provides clinical perspective as to the future of ximelagatran and other orally active anticoagulants currently under development.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Azetidines; Benzylamines; Blood Coagulation; Drug Monitoring; Glycine; Humans; International Normalized Ratio; Postoperative Complications; Prodrugs; Stroke; Thrombin; Thrombosis; Venous Thrombosis; Vitamin K

People with venous thromboembolism are generally treated for five days with intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin followed by three months of vitamin K antagonists treatment. Treatment with vitamin K antagonists requires regular laboratory measurements and some patients have contraindications for treatment.. To evaluate the efficacy and safety of long-term treatment of venous thromboembolism with low-molecular-weight heparins compared to vitamin K antagonists.. Searches of MEDLINE, EMBASE and ISI Web of Science, the Specialised Trials Register of the Cochrane Peripheral Vascular Disease Group and the Cochrane Controlled Trials Register were made and relevant journals were hand-searched. Additional trials were sought through communication with colleagues and pharmaceutical companies.. Two reviewers evaluated studies independently for methodological quality.. Two reviewers extracted data independently. Primary analysis concerned all trial participants during the period of randomized treatment. Separate analyses were performed for category I and category II studies; i.e. studies using similar treatments initially in both study arms, and those that did not; and the different periods of follow-up.. All seven studies fulfilling our criteria combined, a statistically non-significant reduction in the risk of recurrent venous thromboembolism favoring low-molecular-weight heparin treatment (OR 0.70; 95% CI [0.42, 1.16]) was found. Analysis of pooled data for category I studies showed a non-significant reduction in the risk of recurrent venous thromboembolism favoring low-molecular-weight heparin treatment (OR 0.75; 95% CI [0.40, 1.39]). Omitting a potentially-confounded study, a statistically non-significant reduction in the risk of recurrent venous thromboembolism favoring vitamin K antagonist treatment remained (OR 1.95; 95% CI [0.74, 5.19]). All studies combined, the difference in bleeding significantly favored treatment with low-molecular-weight heparin (OR 0.38; 95% CI [0.15, 0.94]), however, considering only category I studies a non-significant trend favoring low-molecular-weight heparin remained (OR 0.80; 95% CI [0.21, 3.00]). No difference was observed in mortality (OR 1.13; 95% CI [0.47, 2.69]).. Low-molecular-weight heparins are possibly as effective as vitamin K antagonists in preventing symptomatic venous thromboembolism after an episode of symptomatic deep venous thrombosis, but are much more expensive. Treatment with low-molecular-weight heparin is significantly safer than treatment with vitamin K antagonists and is possibly a safe alternative in some patients; especially those in geographically inaccessible places, reluctant to visit the thrombosis service regularly, or with contraindications to vitamin K antagonists. However, treatment with vitamin K antagonists remains the treatment of choice for the majority of patients.

Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Odds Ratio; Randomized Controlled Trials as Topic; Venous Thrombosis; Vitamin K

Topics: Anticoagulants; Blood Coagulation; Drug Interactions; Female; Fibrinolytic Agents; Heparin; Heparin, Low-Molecular-Weight; Humans; Postoperative Complications; Pregnancy; Pregnancy Complications, Cardiovascular; Thromboembolism; Time Factors; Venous Thrombosis; Vitamin K

The optimal duration of oral anticoagulant therapy after a first episode of venous thromboembolism is still a matter of debate. It is essential to balance the desired effect of the anticoagulants in reducing recurrences against the risk of major bleeding. The aims of this paper are to describe the current concepts in this field.. Recent data, based on randomised controlled trials, suggest that it is necessary to tailor the duration of anticoagulation individually according to the topography of venous thromboembolism and the presence of risk factors. A 6-week treatment for patients with isolated calf vein thrombosis is sufficient. For proximal thrombosis and/or pulmonary embolism, a short anticoagulant course seems sufficient in patients with temporary risk factors (3 months) and a longer anticoagulant course (6 months at least) is recommended for cases with permanent risk factors or idiopathic venous thromboembolism. The inherited or acquired hypercoagulable states can be divided into those that are common and associated with a modest risk of recurrence (i.e., isolated factor V Leiden or G20210A prothrombin gene) and those that are uncommon but associated with a high risk of recurrence (i.e., antithrombin, protein C or S deficiencies and anticardiolipin antibodies). Thus, the presence of one of these last abnormalities favours more prolonged anticoagulant therapy.. 1) For patients at high risk of recurrence, there is a paucity of evidence-based medicine, particularly for patients with biological thrombophilia, and randomised controlled trials in this population are required. An assessment of low- or fixed-dose oral anticoagulation is also necessary in order to reduce the bleeding risk. 2) It is not always possible to precisely determine the optimal duration with the available data. We have performed a meta-analysis on summary data which suggests that a long course of oral anticoagulant therapy is superior to a short course. An individual meta-analytic approach is needed to draw more precise conclusions on an interesting and important clinical topic and we propose to perform this analysis in a international collaborative group.

Topics: Administration, Oral; Aged; Anticoagulants; Humans; Iatrogenic Disease; Meta-Analysis as Topic; Prospective Studies; Pulmonary Embolism; Randomized Controlled Trials as Topic; Recurrence; Risk Factors; Thromboembolism; Thrombophilia; Time Factors; Venous Thrombosis; Vitamin K

The necessity of anticoagulant treatment after a pulmonary embolus or a deep venous thrombosis has been demonstrated. The modalities of this treatment have been well established, especially the usefulness of initial heparin therapy followed by a period of antivitamin K treatment with an "ideal target INR" between 2 and 3. One of the last questions in this therapeutic protocol is the duration of antivitamin K treatment. The choice of duration of treatment must be made on numerous criteria. It is necessary to distinguish the circumstances of the occurrence of the DVT or the PE and the context. It is thus possible for less than 3 months treatment in secondary venous thrombo-embolic disease, which occurs in precise, recognised circumstances for which the cause will have been controlled. Otherwise, in so-called idiopathic venous thrombo-embolic disease, which is distinguished by a higher prevalence of recurrences, it is known that long-term antivitamin K treatment is effective for the thrombo-embolic recurrences but at the price of a risk of haemorrhage. Finally thrombo-embolic recurrences also benefit from a long treatment. These circumstances of occurrence are thus important in order to decide the choice of treatment duration. But, in our opinion, the compliance to antivitamin K treatment remains the primary criterion to consider. The dilemma facing the prescriber is to evaluate the risk-benefit ratio of each patient, asking especially if the antivitamin K treatment surveillance of a particular patient will be done as well as in the randomised studies. For the future, long-term antivitamin K does not perhaps represent the only therapeutic option. The results of studies evaluating the durations of long-term treatment with less intense levels of anticoagulation (INR < 2) as well as therapeutic alternatives to antivitamin K (antiaggregants or other antithrombins) are awaited.

Topics: 4-Hydroxycoumarins; Anticoagulants; Decision Making; Drug Administration Schedule; Hemorrhage; Humans; Indenes; Patient Compliance; Recurrence; Risk Factors; Venous Thrombosis; Vitamin K

Currently the most frequently used secondary treatment for patients with venous thromboembolism are vitamin K antagonists targeted at an INR of 2.5 (range 2.0 - 3.0). However, based on the continuing risk of bleeding and uncertainty regarding the risk of recurrent venous thromboembolism, there is discussion on the proper duration of treatment with vitamin K antagonists for these patients. Recently, several studies were published in which the risk and benefits of different durations of oral anticoagulants were compared in patients with venous thromboembolism.. The objective of this review was to evaluate efficacy and safety of different durations of treatment with vitamin K antagonists in patients with symptomatic venous thromboembolism.. The reviewers sought publications through computerized searches of MEDLINE and EMBASE, and by hand-searching relevant journals, using the search strategy described by the Cochrane Review Group on Peripheral Vascular Diseases. They also contacted colleagues.. Randomized controlled clinical trials comparing different durations of treatment with vitamin K antagonists in patients with symptomatic venous thromboembolism.. Two reviewers extracted the data and assessed the quality of the trials independently.. Four studies with a total of exactly 1500 patients were included. A consistent reduction for the risk of recurrent events was observed during prolonged treatment with vitamin K antagonists (OR 0.15; 95% CI [0.10 - 0.23]) independent of the period elapsed since the index thrombotic event. A 'rebound' phenomenon, i.e. an excess of recurrences shortly after cessation of the prolonged treatment was not observed (OR 1.11; 95% CI [0.71 - 1.75]). In addition, a substantial increase in bleeding complications was found during the entire period after randomization (OR 7.75; 95% CI [1.08 - 55.57]).. In conclusion this meta-analysis shows that treatment with vitamin K antagonists reduces the risk of recurrent venous thromboembolism as long as it is used. However, the absolute risk of recurrent venous thromboembolism declines over time, while the risk for major bleeding remains. Thus, the efficiency of vitamin K antagonist administration decreases over time since the index event.

Topics: Anticoagulants; Drug Administration Schedule; Humans; Pulmonary Embolism; Randomized Controlled Trials as Topic; Time Factors; Venous Thrombosis; Vitamin K

Patients who have had an episode of symptomatic venous thromboembolism are usually treated for at least five days with intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin. Thereafter, they received a three month course of a vitamin K antagonist, with a dose adjusted to achieve an International Normalized Ratio between 2.0 and 3.0. Some patients have contraindications to vitamin K antagonists. In addition, treatment with vitamin K antagonists has the disadvantage of regular laboratory measurements.. The objective of this review was to evaluate the efficacy and safety of long-term treatment of symptomatic venous thromboembolism with low-molecular-weight heparins compared with vitamin K antagonists.. Computerized searches of MEDLINE, EMBASE and Current Contents were made and relevant journals were hand-searched using the search strategy described by the Cochrane Peripheral Vascular Disease Group. In addition, randomized clinical trials were located through personal communication with colleagues. Where necessary, the reviewers contacted pharmaceutical companies for further information.. Two reviewers evaluated studies independently for methodological quality.. Two reviewers reviewed and extracted data independently using a standard form. Primary analysis concerned all patients in the studies during the period of randomized treatment. Additional separate analyses were performed for category I and category II studies; studies that used similar initial treatments in both study arms and those that used different treatment regimes during the initial treatment; and the total period of follow-up in the different studies.. Five studies were identified that fulfilled our predefined criteria (three category I and two category II studies). When all five studies were combined, a statistically non-significant reduction of the risk of recurrent symptomatic venous thromboembolism in favor of low-molecular-weight heparin treatment (OR 0.72; 95% CI [0.42, 1.23]) was found. In category I studies, analysis of the pooled data showed a statistically non-significant reduction of the risk of recurrent symptomatic venous thromboembolism in favor of low-molecular-weight heparin treatment (OR 0.75; 95% CI [0.40, 1.39]). This OR was mainly due to one possibly confounded study, and after omitting this study from the analysis a statistically non-significant reduction of the risk of recurrent symptomatic venous thromboembolism in favor of vitamin K antagonist treatment remained (OR 1.95; 95% CI [0.74, 5.19]). No differences in the risk of bleeding (OR 0.63; 95% CI [0.21, 1.88]) and mortality (OR 1.13; 95% CI [0.47, 2.69] were observed.. Low-molecular-weight heparins are possibly as effective and safe as vitamin K antagonists in the prevention of recurrent symptomatic venous thromboembolism after an episode of symptomatic deep venous thrombosis, but have the disadvantage of much higher medicinal costs. Treatment with low-molecular-weight heparin is possibly a safe alternative in some patients; for example patients who live in geographically inaccessible places; patients who are reluctant to go to the thrombosis service on a regular basis; and patients with contraindications to vitamin K antagonists (e.g. pregnant women). Therefore, in the absence of definitive evidence on the safety and efficacy of low-molecular-weight heparins compared with vitamin K antagonists, we believe that treatment with vitamin K antagonists is still the treatment of choice in the prevention of recurrent symptomatic venous thromboembolism after an episode of deep venous thrombosis, in the majority of patients.

Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Odds Ratio; Randomized Controlled Trials as Topic; Venous Thrombosis; Vitamin K

The optimal anticoagulant following catheter-based therapy of acute iliofemoral deep vein thrombosis (IFDVT) is unknown.. From the Swiss Venous Stent registry, an ongoing prospective cohort study, we performed a subgroup analysis of patients with acute IFDVT who underwent catheter-based early thrombus removal followed by nitinol stent placement. Duplex ultrasound and Villalta scores were used to determine patency rates and incidence of the post-thrombotic syndrome (PTS) in patients treated with either rivaroxaban (n = 73) or a vitamin K-antagonist (VKA; n = 38) for a minimum duration of 3 months.. Mean follow-up duration was 24 ± 19 months (range 3 to 77 months). Anticoagulation therapy was time-limited (3 to 12 months) in 56% of patients (47% in the rivaroxaban group and 58% in the VKA group, p = 0.26), with shorter mean duration of anticoagulation in the rivaroxaban group (180 ± 98 days versus 284 ± 199 days, p = 0.01). Overall, primary and secondary patency rates at 24 months were 82% (95%CI, 71-89%) and 95% (95%CI, 87-98%), respectively, with no difference between the rivaroxaban (87% [95%CI, 76-94%] and 95% [95%CI, 85-98%]) and the VKA group (72% [95%CI, 52-86%] and 94% [95%CI, 78-99%]; p > 0.10 for both). Overall, 86 (86%) patients were free from PTS at latest follow-up, with no difference between the rivaroxaban and the VKA groups (57 [85%] versus 29 [88%]; p = 0.76). Two major bleeding complications (1 in each group) occurred in the peri-interventional period, without any major bleeding thereafter.. In patients with acute IFDVT treated with catheter-based early thrombus removal and venous stent placement, the effectiveness and safety of rivaroxaban and VKA appear to be similar.. The study is registered on the National Institutes of Health website (ClinicalTrials.gov; identifier NCT02433054).

Topics: Adult; Aged; Anticoagulants; Catheterization; Endovascular Procedures; Factor Xa Inhibitors; Female; Femoral Vein; Humans; Iliac Vein; Male; Middle Aged; Postthrombotic Syndrome; Prospective Studies; Rivaroxaban; Stents; Thrombolytic Therapy; Treatment Outcome; Vascular Patency; Venous Thrombosis; Vitamin K

Essentials Prospective studies of pharmacogenetic-guided (PG) coumarin dosing produced varying results. EU-PACT acenocoumarol and phenprocoumon trials compared PG and non-PG dosing algorithms. Sub-analysis of EU-PACT identified differences between trial arms across VKORC1-CYP2C9 groups. Adjustment of the PG algorithm might lead to a higher benefit of genotyping.. Background The multicenter, single-blind, randomized EU-PACT trial compared the safety and efficacy of genotype-guided and non-genetic dosing algorithms for acenocoumarol and phenprocoumon in patients with atrial fibrillation or deep vein thrombosis. The trial showed no differences in the primary outcome between the two dosing strategies. Objectives To explore possible reasons for the lack of differences between trial arms by performing a secondary analysis of EU-PACT data in order to evaluate the performance of both dosing algorithms across VKORC1-CYP2C9 genetic subgroups. Patients/Methods Anticoagulation control measured according to an International Normalized Ratio (INR) below (INR of < 2), within (INR of 2-3) and above (INR of > 3) the therapeutic range was compared across VKORC1-CYP2C9 subgroups. Owing to a low number of patients in each subgroup, trials for acenocoumarol and phenprocoumon were combined for analysis. Results Four weeks after therapy initiation, genotype-guided dosing increased the mean percentage of time in the therapeutic INR range (PTIR) in the VKORC1 GG-CYP2C9*1*1 subgroup as compared with the non-genetic dosing (difference of 14.68%, 95% confidence interval [CI] 5.38-23.98). For the VKORC1 AA-CYP2C9*1*1 subgroup, there was a higher risk of under-anticoagulation with the genotype-guided algorithm (difference of 19.9%; 95% CI 11.6-28.2). Twelve weeks after therapy initiation, no statistically significant differences in anticoagulation control between trial arms were noted across the VKORC1-CYP2C9 genetic subgroups. Conclusions EU-PACT genetic-guided dose initiation algorithms for acenocoumarol and phenprocoumon could have predicted the dose overcautiously in the VKORC1 AA-CYP2C9*1*1 subgroup. Adjustment of the genotype-guided algorithm could lead to a higher benefit of genotyping.

Topics: Acenocoumarol; Aged; Algorithms; Anticoagulants; Atrial Fibrillation; Cytochrome P-450 CYP2C9; Data Interpretation, Statistical; Female; Genotype; Humans; International Normalized Ratio; Male; Middle Aged; Pharmacogenetics; Phenprocoumon; Prospective Studies; Single-Blind Method; Treatment Outcome; Venous Thrombosis; Vitamin K; Vitamin K Epoxide Reductases

Deep vein thrombosis (DVT) and pulmonary embolisms (PEs) are common complications after surgical procedures. The influence of prescribed blood products on the occurrence of DVT and PE was evaluated in postsurgical patients in this retrospective case-control study. The records of 286 surgical patients were analyzed: DVT (n = 52), PE (n = 92), and a control group (n = 142). The amounts of prescribed blood, blood products, and vitamin K were reviewed, together with appropriate prescribing of low-molecular-weight heparins. The influence of prescribed blood products on the occurrence of DVT or PE was analyzed using multinomial logistic regression. We demonstrated a significant difference between the test and control groups ( P < .05) in relation to receiving packed red blood cells. Treatment with red blood cells was associated with an increased risk of PE but not DVT. Patients who developed PE after surgery were hospitalized for longer (median 10 days) than patients with DVT (median 6 days). There was no difference between the test and control groups concerning treatment with fresh frozen plasma. Inadequate thromboprophylaxis significantly increased the likelihood of DVT. There is a connection between receiving packed red blood cells and occurrence of postoperative PE in surgical patients. Thus, patients receiving red blood cells should be monitored more closely after surgery, as they are more likely to develop PE postoperatively.

Topics: Aged; Aged, 80 and over; Erythrocyte Transfusion; Female; Heparin, Low-Molecular-Weight; Humans; Incidence; Male; Middle Aged; Plasma; Postoperative Complications; Pulmonary Embolism; Retrospective Studies; Venous Thrombosis; Vitamin K

Pulmonary embolism (PE) is a life-threatening manifestation of venous thromboembolism. Rivaroxaban is an oral anticoagulant, which directly inhibits Factor Xa. The objective of the current study was, in comparison to the standard-therapy method, to investigate the potential of rivaroxaban to improve the treatment of patients with PE, and to reduce hemorrhage in the standard-therapy group through adjusting the dose of warfarin by CYP2C9 and VKORC1 genotypes.. Sixty-two PE patients with or without deep venous thrombosis (DVT) was randomized to rivaroxaban mono-therapy or standard-therapy with enoxaparin followed by vitamin K antagonist (VKA). Concentration of the anticoagulants was adjusted according to the results of CYP2C9 and VKORC1 genotypes in order to stabilize the international normalized rate (INR) at 2.0-3.0 range. Length of hospital stay at initial hospitalization was compared, therapeutic efficacy was examined by computed tomographic pulmonary angiography (CTPA) and ventilation/perfusion (V/Q) scan, and side-effect of anti-coagulants was monitored at 1-month, and 3- or 6-months follow-up check points.. We found that, overall, patients who received rivaroxaban mono-therapy had a significantly shorter length of hospital stay compared with patients who received standard-therapy of enoxaparin followed by VKA (9.29±3.70 versus 11.38±3.12days, P=0.021). The therapeutic efficacy was of no marked difference between these two groups. However, after one month treatment, 50% (16/32) of the standard-therapy group had mild hemorrhage, which was significantly higher than that of rivaroxaban mono-therapy group (16.7%, 5/30, P=0.006). Moreover, a significantly higher rate in the standard-therapy group (22.2% versus 3.4%, P=0.032) was found after 3 or 6months therapy. Major bleeding was slightly but not significantly higher in the standard-therapy group than that in the rivaroxaban therapy group. In addition, 2 (6.3%) patients died from Life-threatening bleeding in the standard-therapy group.. Findings of the current study suggested that rivaroxaban mono-therapy result in shorter hospital stay compared to the standard-therapy. Implication of CYP2C9 and VKORC1 genotypes in determining dose of warfarin, however, remains to be further examined in larger cohort studies.

Topics: Administration, Oral; Anticoagulants; Cytochrome P-450 CYP2C9; Enoxaparin; Genotype; Humans; Pulmonary Embolism; Rivaroxaban; Venous Thrombosis; Vitamin K; Vitamin K Epoxide Reductases

Post-thrombotic syndrome (PTS) is a common complication of deep-vein thrombosis (DVT). Poor quality treatment with vitamin K antagonists (VKA) is a risk factor for PTS. We hypothesised that treatment with the direct oral anticoagulant (DOAC) rivaroxaban may lower PTS incidence as compared to enoxaparin/VKA, as DOACs have a more stable pharmacologic profile than VKA. We performed a post-hoc subgroup analysis of the Einstein DVT trial (n=3449). Kaplan-Meier survival analysis was performed to compare the cumulative incidence of PTS between the rivaroxaban and enoxaparin/VKA groups. Hazard ratios (HR) and 95 % confidence intervals (CI) were calculated using Cox proportional hazards models. We included 336 patients with a mean age of 58 ± 16 years and a median follow-up after index DVT of 57 months (interquartile range 48-64). Of these, 162 (48 %) had been treated with rivaroxaban and 174 (52 %) with enoxaparin/VKA. The cumulative PTS incidence at 60 months follow-up was 29 % in the rivaroxaban group and 40 % in the enoxaparin/VKA group. After adjusting for age, gender, body mass index, previous VTE, ipsilateral recurrent DVT, extent of DVT, idiopathic DVT, duration of anticoagulant treatment, compliance to assigned study medication, elastic compression stocking use and active malignancy, the HR of PTS development for rivaroxaban was 0.76 (95 % CI: 0.51-1.13). In conclusion, treatment of acute DVT with rivaroxaban was associated with a numerically lower but statistically non-significant risk of PTS compared to enoxaparin/VKA treatment. The potential effect on reducing PTS deserves evaluation in a large randomised trial.

Topics: Adult; Aged; Anticoagulants; Enoxaparin; Female; Follow-Up Studies; Humans; Male; Middle Aged; Postthrombotic Syndrome; Recurrence; Rivaroxaban; Survival Analysis; Treatment Outcome; Venous Thrombosis; Vitamin K

The impact of residual vein thrombosis (RVT) on the long-term outcome of patients with deep vein thrombosis (DVT) is unknown. We assessed the incidence of recurrent venous thromboembolism (VTE), postthrombotic syndrome (PTS), arterial thrombotic events, and cancer in patients with DVT with and without RVT. For this purpose, we evaluated up to 3 years 869 consecutive patients with acute proximal DVT who had conventional anticoagulation. RVT, defined as ultrasound incompressibility of at least 4 mm in the common femoral and/or the popliteal vein after 3 months, was detected in 429 (49.4%) patients, and was more likely in males (adjusted odds ratio [OR], 1.82; 95% confidence interval [CI], 1.37-2.04), in patients with previous VTE (OR, 1.64; 95% CI, 1.06-2.54), and in those with extensive thrombosis (OR, 3.58; 95% CI, 2.19-5.86). During the 3-year follow-up, recurrent VTE developed in 84 (19.6%) patients with RVT and 43 (9.8%) patients without RVT (adjusted hazard ratio [HR], 2.03; 95% CI, 1.40-2.94); PTS in 225 (52.4%) and 118 (26.8%), respectively (HR, 2.34; 95% CI, 1.87-2.93); arterial thrombosis in 29 (6.7%) and 14 (3.2%), respectively (HR, 2.05; 95% CI, 1.08-3.88); and cancer in 21 (4.9%) and 8 (1.8%), respectively (HR, 3.09; 95% CI, 1.31-7.28). In conclusion, in patients treated with vitamin K antagonists for prevention of recurrent VTE, RVT doubles the risk of recurrent VTE, PTS, arterial thrombosis, and cancer. Males, patients with previous VTE, and those with extensive thrombosis are independent risk factors of RVT development. Studies addressing the impact of the novel direct anticoagulants on the development of RVT as well as the long-term complications of DVT are needed.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasms; Postthrombotic Syndrome; Recurrence; Venous Thromboembolism; Venous Thrombosis; Vitamin K

Rivaroxaban is a new oral anticoagulant (NOAC) that can be prescribed in a fixed dose, making regular monitoring and dose adjustments unnecessary. It has been proven to be safe and effective in comparison with enoxaparin/vitamin K antagonists (LMWH/VKA) for the (extended) treatment of venous thromboembolism in the EINSTEIN studies. Nevertheless, there is a need for information regarding the clinical impact of (major) bleeding events with NOACs such as rivaroxaban.. A post-hoc analysis was performed to compare the severity of clinical presentation and subsequent clinical course of major bleeding with rivaroxaban vs. LMWH/VKA.. Two investigators performed a blinded classification of major bleeding using a priori defined criteria. During the EINSTEIN studies, data concerning the clinical course and measures applied were prospectively collected for each major bleed.. Treatment with LMWH/VKA caused more major bleeding events (1.7%) than rivaroxaban (1.0%; hazard ratio, 0.54; 95% confidence interval [CI], 0.37-0.79). Major bleeding events during rivaroxaban therapy had a milder presentation (23% were adjudicated to the worst categories vs. 38% for LMWH/VKA; hazard ratio or HR, 0.35; 95% CI, 0.17-0.74; P = 0.0062). The clinical course was severe in 25% of all major bleeding events associated with rivaroxaban, compared with 33% of LMWH/VKA-associated bleeds (HR, 0.46; 95% CI, 0.22-0.96; P = 0.040).. Rivaroxaban-associated major bleeding events occurred less frequently, had a milder presentation and appeared to take a less severe clinical course compared with major bleeding with LMWH/VKA.

Topics: Anticoagulants; Blood Coagulation Factors; Factor VIIa; Factor Xa Inhibitors; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Kaplan-Meier Estimate; Plasma; Prospective Studies; Pulmonary Embolism; Recombinant Proteins; Rivaroxaban; Severity of Illness Index; Single-Blind Method; Thrombophilia; Venous Thrombosis; Vitamin K

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

Treatment of splanchnic vein thrombosis (SVT) is a clinical challenge due to heterogeneity of clinical presentations, increased bleeding risk, and lack of evidences from clinical trials. We performed an international registry to describe current treatment strategies and factors associated with therapeutic decisions in a large prospective cohort of unselected SVT patients. A total of 613 patients were enrolled (mean age 53.1 years, standard deviation ± 14.8); 62.6% males; the majority (468 patients) had portal vein thrombosis. Most common risk factors included cirrhosis (27.8%), solid cancer (22.3%), and intra-abdominal inflammation/infection (11.7%); in 27.4% of patients, SVT was idiopathic. During the acute phase, 470 (76.7%) patients received anticoagulant drugs, 136 patients (22.2%) remained untreated. Incidental diagnosis, single vein thrombosis, gastrointestinal bleeding, thrombocytopenia, cancer, and cirrhosis were significantly associated with no anticoagulant treatment. Decision to start patients on vitamin K antagonists after an initial course of parenteral anticoagulation was significantly associated with younger age, symptomatic onset, multiple veins involvement, and unprovoked thrombosis. Although a nonnegligible proportion of SVT patients did not receive anticoagulant treatment, the majority received the same therapies recommended for patients with usual sites thrombosis, with some differences driven by the site of thrombosis and the pathogenesis of the disease.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Female; Fibrinolytic Agents; Fibrosis; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Neoplasms; Registries; Retrospective Studies; Risk Factors; Splanchnic Circulation; Venous Thrombosis; Vitamin K

Direct oral anticoagulants (DOACs) were developed for the treatment of thromboembolic diseases to overcome limitations of vitamin K antagonists (VKA). International guidelines on atrial fibrillation acknowledge patients' for antiembolic therapy with VKA or DOAC as relevant decision criteria. The objective assessment of patients' preference social interactions and psychological factors are hard to measure albeit representing important contributors. After a series of structured interviews and pilot studies assessing the preparedness to use DOAC as an anticoagulant and the motivation of patients to participate in clinical studies with DOAC, seven items were identified from several questionnaires by regression analysis. Those items were seen the best to describe the willingness to change anticoagulation from VKA to DOAC. By their use, we aim to develop a tool for the objective identification of the patients' preferences for VKA or for DOAC to increase adherence to therapy and to reduce anticoagulant undertreatment. German-speaking patients were asked to fill out a questionnaire consisting of biographic data and the seven selected items, and 180 patients completed the questionnaire so far. Of these, 90 patients were on treatment with VKA (group 1), 57 patients changed anticoagulation from VKA to DOAC (group 2), 29 patients were DOAC naive patients (group 3), and 4 patients changed from DOAC to VKA (group 4). Overall, 94 patients received VKA, 29 patients received dabigatran, 50 patients received rivaroxaban, and 7 patients received apixaban as an anticoagulant. Eight patients were younger than 40 years, 35 patients were aged between 40 and 59 years, 53 patients were aged between 60 and 70 years, and 84 patients were aged older than 70 years. Indication for anticoagulation were atrial fibrillation (n = 106), pulmonary embolism (n = 24), deep vein thrombosis (n = 40), artificial heart valve replacement (n = 8), or other diseases (n = 2). Based on the results of the analysis, a score will be suggested to identify the preference of patients for anticoagulation with VKA or DOAC. This tool may be useful for practitioners and health-care professionals to support patient adherence to therapy, and thereby increase treatment effectiveness.

Topics: Administration, Oral; Adult; Aged; Anticoagulants; Atrial Fibrillation; Female; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Practice Guidelines as Topic; Pulmonary Embolism; Surveys and Questionnaires; Venous Thrombosis; Vitamin K

The phase III EINSTEIN DVT and EINSTEIN PE trials demonstrated the potential of oral rivaroxaban for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). The length of initial hospitalization in patients presenting with either symptomatic DVT or PE was assessed using hospitalization records from these trials.. Analyses were carried out in the intention-to-treat population, using non-parametric and parametric statistical methods.. Overall, 52% (1781/3434) of EINSTEIN DVT patients and 90% (4328/4821) of EINSTEIN PE patients were admitted to hospital. The proportion of hospitalized patients with a length of stay of five or fewer days receiving rivaroxaban was 54% compared with 31% for enoxaparin/vitamin K antagonist (VKA) in patients with DVT. For patients with PE, the corresponding values were 45% and 33%. Stays of 6-10 days were observed in 29% of rivaroxaban-treated patients compared with 45% of enoxaparin/VKA-treated patients for DVT. For patients with PE, these values were 39% and 46% in the rivaroxaban and enoxaparin/VKA groups, respectively. Overall, length of stay was significantly shorter in the rivaroxaban group, compared with the enoxaparin/VKA group across all analyses performed (p < 0.0001). Across regions, the observed admission rates and length of stay duration varied greatly: Asia had the longest overall hospitalization rates, whereas the lowest rates were reported in North America, Australia and New Zealand. Nevertheless, a consistent trend was observed: length of hospital stay in patients with DVT or PE receiving rivaroxaban was shorter than, or at least similar to, patients receiving enoxaparin/VKA.. A single-drug regimen with rivaroxaban may reduce the burden on healthcare systems and patients, and provides effective and well tolerated treatment. The studies shared an open-label design that allowed comparison of initial hospitalization, but limitations include the well monitored clinical trial setting in which decisions on admission and discharge could vary from real-world management.

Topics: Anticoagulants; Enoxaparin; Female; Humans; Length of Stay; Male; Middle Aged; Morpholines; Pulmonary Embolism; Rivaroxaban; Thiophenes; Venous Thrombosis; Vitamin K

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

The optimal duration of anticoagulation after recurrent venous thromboembolism(VTE) is poorly established [1,2]. Recent studies suggested that D-dimer may identify patients at low risk of recurrence after a first VTE [3,4]. In a pilot, prospective, cohort study we aimed to assess the negative predictive value of D-dimer in patients with recurrent VTE. Patients with negative D-dimer while on treatment stopped anti coagulation and underwent repeated testing after 7, 15, and 30 days; treatment was resumed if D-dimer turned positive and permanently stopped if it remained negative. The study was interrupted after the enrolment of 75 patients. At that time, treating physicians decided treatment resumption in 12.2% of the patients, but the majority of events were distal or superficial vein thromboses. The rate of objectively documented recurrent proximal deep vein thrombosis (DVT) and/or pulmonary embolism (PE) was 2.56% (95% CI 0.13, 15.07%) in the 39 patients with persistently negative D-dimer at 30 days, for an annual incidence of VTE of 5.65 events/100 patient/years. These preliminary findings suggest that negative D-dimer may identify patients with history of previous VTE at low risk of recurrences, but this approach should be tested in larger trials in highly selected patients.

Topics: Aged; Anticoagulants; Cohort Studies; Drug Monitoring; Early Termination of Clinical Trials; Female; Fibrin Fibrinogen Degradation Products; Follow-Up Studies; Humans; Incidence; Italy; Male; Middle Aged; Pilot Projects; Pulmonary Embolism; Risk Factors; Secondary Prevention; Venous Thromboembolism; Venous Thrombosis; Vitamin K

The stimulation of cells by thrombin is associated with the release of microparticles (MPs) from cell membranes. These MPs can express procoagulant activity. As vitamin K antagonists (VKA) decrease the generation of thrombin, we compared plasma procoagulant phospholipids (PPL) levels in patients with a previous history of venous thrombosis who were being treated with VKA and compared them with an untreated group.. Plasma PPL were measured using a factor Xa-based coagulation assay. sGPV, a marker of platelet activation by thrombin, was measured by ELISA. Platelet MPs were also evaluated using standard flow cytometric techniques. Ninety-six VKA-treated patients and 80 patients not undergoing VKA therapy were tested and the results compared.. PPL activity was significantly reduced (p<0.0001) in VKA-treated patients compared with the untreated group. PPL were correlated with platelet and white blood cell count and with sGPV levels in the untreated group, but not in VKA-treated patients. PPL were correlated with fibrinogen levels in both groups, but not with C-reactive protein. Polymorphonuclear neutrophils (PMN) were significantly lower (p=0.01) in VKA-treated patients than in untreated patients.. The difference between PPL levels in VKA-treated patients and patients without treatment could be related to the decrease in PMN count. It remains to be established if this decrease of PPL is directly related to the capacity of activated PMN to generate MPs, or indirectly by reducing the amount of pro-inflammatory cytokines or reactive oxygen species produced by PMN.

Topics: Adult; Aged; Anticoagulants; Blood Coagulation Factors; Female; France; Humans; Male; Middle Aged; Phospholipids; Reproducibility of Results; Sensitivity and Specificity; Venous Thrombosis; Vitamin K; Young Adult

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

About 20% of patients with unprovoked venous thromboembolism have a recurrence within 2 years after the withdrawal of oral anticoagulant therapy. Extending anticoagulation prevents recurrences but is associated with increased bleeding. The benefit of aspirin for the prevention of recurrent venous thromboembolism is unknown.. In this multicenter, investigator-initiated, double-blind study, patients with first-ever unprovoked venous thromboembolism who had completed 6 to 18 months of oral anticoagulant treatment were randomly assigned to aspirin, 100 mg daily, or placebo for 2 years, with the option of extending the study treatment. The primary efficacy outcome was recurrence of venous thromboembolism, and major bleeding was the primary safety outcome.. Venous thromboembolism recurred in 28 of the 205 patients who received aspirin and in 43 of the 197 patients who received placebo (6.6% vs. 11.2% per year; hazard ratio, 0.58; 95% confidence interval [CI], 0.36 to 0.93) (median study period, 24.6 months). During a median treatment period of 23.9 months, 23 patients taking aspirin and 39 taking placebo had a recurrence (5.9% vs. 11.0% per year; hazard ratio, 0.55; 95% CI, 0.33 to 0.92). One patient in each treatment group had a major bleeding episode. Adverse events were similar in the two groups.. Aspirin reduced the risk of recurrence when given to patients with unprovoked venous thromboembolism who had discontinued anticoagulant treatment, with no apparent increase in the risk of major bleeding. (Funded by the University of Perugia and others; WARFASA ClinicalTrials.gov number, NCT00222677.).

Topics: Aged; Anticoagulants; Aspirin; Double-Blind Method; Female; Follow-Up Studies; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Pulmonary Embolism; Secondary Prevention; Venous Thromboembolism; Venous Thrombosis; Vitamin K

Traditionally, patients with pulmonary embolism (PE) are initially treated in the hospital with low molecular weight heparin (LMWH). The results of a few small non-randomized studies suggest that, in selected patients with proven PE, outpatient treatment is potentially feasible and safe.. To evaluate the efficacy and safety of outpatient treatment according to predefined criteria in patients with acute PE.. A prospective cohort study of patients with objectively proven acute PE was conducted in 12 hospitals in The Netherlands between 2008 and 2010. Patients with acute PE were triaged with the predefined criteria for eligibility for outpatient treatment, with LMWH (nadroparin) followed by vitamin K antagonists. All patients eligible for outpatient treatment were sent home either immediately or within 24 h after PE was objectively diagnosed. Outpatient treatment was evaluated with respect to recurrent venous thromboembolism (VTE), including PE or deep vein thrombosis (DVT), major hemorrhage and total mortality during 3 months of follow-up.. Of 297 included patients, who all completed the follow-up, six (2.0%; 95% confidence interval [CI] 0.8-4.3) had recurrent VTE (five PE [1.7%] and one DVT [0.3%]). Three patients (1.0%, 95% CI 0.2-2.9) died during the 3 months of follow-up, none of fatal PE. Two patients had a major bleeding event, one of which was fatal intracranial bleeding (0.7%, 95% CI 0.08-2.4).. Patients with PE selected for outpatient treatment with predefined criteria can be treated with anticoagulants on an outpatient basis. (Dutch Trial Register No 1319; http://www.trialregister.nl/trialreg/index.asp).

Topics: Acute Disease; Adult; Aged; Ambulatory Care; Anticoagulants; Female; Hemorrhage; Humans; Male; Middle Aged; Nadroparin; Netherlands; Patient Selection; Prospective Studies; Pulmonary Embolism; Risk Assessment; Risk Factors; Secondary Prevention; Time Factors; Treatment Outcome; Venous Thrombosis; Vitamin K

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

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

Patients with first venous thromboembolism (VTE) and high factor VIII (FVIII) are at increased risk of recurrence. It is unknown whether these patients benefit from prolonged secondary thrombophrophylaxis. In a prospective trial patients with first spontaneous VTE and FVIII levels >230 IU/dl were randomized to discontinue vitamin K Antagonist (VKA) after 6 months or to continue VKA for additional 24 months. Patients were excluded if they had a natural inhibitor deficiency, lupus anticoagulant, cancer, were pregnant, required long-term antithrombotic therapy or had acute-phase reaction. Primary study endpoints were symptomatic recurrent VTE or major bleeding within 2 years. Follow-up was continued beyond 2 years. Of 3,219 screened patients 34 met the inclusion criteria. Mean observation time was 37 months. Two of 17 patients allocated to discontinue VKA and two of 17 patients randomized to prolonged anticoagulation had recurrent VTE within 2 years. In the prolonged treatment group, one patient had recurrence during VKA therapy and one patient 4 weeks after voluntary discontinuation of VKA. One major nonfatal bleeding (severe epistaxis) after 10 months of VKA occurred in the prolonged treatment group. Five patients allocated to prolonged anticoagulation had recurrent VTE after discontinuation of VKA. The probability of recurrence at 2 years after discontinuation of VKA was 30% (95% CI 13-46%). Patients with high FVIII are at increased risk of recurrence. Our findings in a small number of patients indicate that prolonged anticoagulation seems to be effective but that the benefit is not maintained after discontinuation of anticoagulation.

Topics: Adult; Aged; Anticoagulants; Factor VIII; Female; Follow-Up Studies; Hemorrhage; Humans; Male; Middle Aged; Secondary Prevention; Time Factors; Venous Thrombosis; Vitamin K

Apixaban, an oral potent reversible direct inhibitor of activated factor X, has shown promise in the prevention of venous thromboembolism following major orthopedic surgery. We conducted a dose-ranging study in patients with deep vein thrombosis.. Consecutive patients with symptomatic deep vein thrombosis were included and randomized to receive 84-91 days of apixaban 5 mg twice-daily, 10 mg twice-daily, or 20 mg once-daily, or low molecular weight heparin (LMWH) followed by a vitamin K antagonist (VKA). The primary efficacy outcome was the composite of symptomatic recurrent venous thromboembolism and asymptomatic deterioration of bilateral compression ultrasound or perfusion lung scan. The principal safety outcome was the composite of major and clinically relevant, non-major bleeding.. The mean age of the 520 included patients was 59 years, and 62% were male. The primary outcome occurred in 17 of the 358 apixaban-treated patients [4.7%, 95% confidence interval (CI) 2.8-7.5%] and in five of the 118 LMWH/VKA-treated patients (4.2%, 95% CI 1.4-9.6%) who were evaluable. The incidence in all three apixaban groups was low and comparable without evidence of a dose response. The principal safety outcome occurred in 28 (7.3%) of the 385 apixaban-treated patients and in 10 (7.9%) of the 126 LMWH/VKA-treated patients. No dose response for apixaban was observed.. These observations warrant further evaluation of apixaban in phase III studies. The attractive fixed-dose regimen of this compound may meet the demand to simplify anticoagulant treatment in patients with established venous thromboembolism.

Topics: Administration, Oral; Adult; Aged; Anticoagulants; Dose-Response Relationship, Drug; Double-Blind Method; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Recurrence; Safety; Treatment Outcome; Venous Thrombosis; Vitamin K

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

Topics: Cardiolipins; Factor V; Genetic Predisposition to Disease; Humans; Mutation; Phlebography; Plasminogen Activator Inhibitor 1; Polymorphism, Single Nucleotide; Prothrombin; Pulmonary Embolism; Risk; Thrombophilia; Venous Thrombosis; Vitamin K

Venous thromboembolism is treated with unfractionated heparin or low-molecular-weight heparin, followed by a vitamin K antagonist. We investigated the potential use of idraparinux, a long-acting inhibitor of activated factor X, as a substitute for standard therapy.. We conducted two randomized, open-label noninferiority trials involving 2904 patients with deep-vein thrombosis and 2215 patients with pulmonary embolism to compare the efficacy and safety of idraparinux versus standard therapy. Patients received either subcutaneous idraparinux (2.5 mg once weekly) or a heparin followed by an adjusted-dose vitamin K antagonist for either 3 or 6 months. The primary efficacy outcome was the 3-month incidence of symptomatic recurrent venous thromboembolism (nonfatal or fatal).. In the study of patients with deep venous thrombosis, the incidence of recurrence at day 92 was 2.9% in the idraparinux group as compared with 3.0% in the standard-therapy group (odds ratio, 0.98; 95% confidence interval [CI], 0.63 to 1.50), a result that satisfied the prespecified noninferiority requirement. At 6 months, the hazard ratio for idraparinux was 1.01. The rates of clinically relevant bleeding at day 92 were 4.5% in the idraparinux group and 7.0% in the standard-therapy group (P=0.004). At 6 months, bleeding rates were similar. In the study of patients with pulmonary embolism, the incidence of recurrence at day 92 was 3.4% in the idraparinux group and 1.6% in the standard-therapy group (odds ratio, 2.14; 95% CI, 1.21 to 3.78), a finding that did not meet the noninferiority requirement.. In patients with deep venous thrombosis, once-weekly subcutaneous idraparinux for 3 or 6 months had an efficacy similar to that of heparin plus a vitamin K antagonist. However, in patients with pulmonary embolism, idraparinux was less efficacious than standard therapy. (ClinicalTrials.gov numbers, NCT00067093 [ClinicalTrials.gov] and NCT00062803 [ClinicalTrials.gov].).

Topics: Anticoagulants; Female; Follow-Up Studies; Hemorrhage; Heparin; Humans; Incidence; Male; Middle Aged; Oligosaccharides; Pulmonary Embolism; Recurrence; Treatment Outcome; Venous Thrombosis; Vitamin K

The extended use of vitamin K antagonists for prophylaxis against venous thromboembolism is often constrained by risk-benefit limitations and inconvenience. We evaluated the efficacy and safety of a 6-month extension of prophylaxis against recurrent venous thromboembolism with idraparinux in patients who had initially received 6 months of prophylaxis with an anticoagulant.. We randomly assigned patients who had completed 6 months of prophylaxis with idraparinux or a vitamin K antagonist and in whom extended anticoagulation was warranted to receive once-weekly injections of 2.5 mg of idraparinux or placebo for 6 months without monitoring. The primary efficacy and safety outcomes were recurrent venous thromboembolism and major bleeding.. Of 1215 patients, 6 of 594 (1.0%) in the idraparinux group and 23 of 621 (3.7%) in the placebo group had recurrent venous thromboembolism (P=0.002). Major bleeding occurred in 11 patients (1.9%) in the idraparinux group and in none in the placebo group (P<0.001). Of these 11 episodes, 3 were fatal intracranial hemorrhages. As compared with patients whose initial treatment was a vitamin K antagonist, patients whose initial treatment was idraparinux who were assigned to 6 months in the placebo group had a lower incidence of recurrent thromboembolism (0.7% vs. 5.9%); patients who received 6 additional months of idraparinux therapy had a higher incidence of major bleeding (3.1% vs. 0.9%).. During a 6-month extension of thromboprophylaxis, idraparinux was effective in preventing recurrent thromboembolism but was associated with an increased risk of a major hemorrhage. (ClinicalTrials.gov number, NCT00071279 [ClinicalTrials.gov].).

Topics: Aged; Anticoagulants; Double-Blind Method; Drug Administration Schedule; Factor Xa Inhibitors; Female; Follow-Up Studies; Hemorrhage; Humans; Injections, Subcutaneous; Kaplan-Meier Estimate; Male; Middle Aged; Oligosaccharides; Pulmonary Embolism; Secondary Prevention; Treatment Outcome; Venous Thrombosis; Vitamin K

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

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

In a randomized trial in patients with proximal deep-vein thrombosis, permanent vena cava filters reduced the incidence of pulmonary embolism but increased that of deep-vein thrombosis at 2 years. An 8-year follow-up was performed to assess their very long-term effect.. Four hundred patients with proximal deep-vein thrombosis with or without pulmonary embolism were randomized either to receive or not receive a filter in addition to standard anticoagulant treatment for at least 3 months. Data on vital status, venous thromboembolism, and postthrombotic syndrome were obtained once a year for up to 8 years. All documented events were reviewed blindly by an independent committee. Outcome data were available in 396 patients (99%). Symptomatic pulmonary embolism occurred in 9 patients in the filter group (cumulative rate 6.2%) and 24 patients (15.1%) in the no-filter group (P=0.008). Deep-vein thrombosis occurred in 57 patients (35.7%) in the filter group and 41 (27.5%) in the no-filter group (P=0.042). Postthrombotic syndrome was observed in 109 (70.3%) and 107 (69.7%) patients in the filter and no-filter groups, respectively. At 8 years, 201 (50.3%) patients had died (103 and 98 patients in the filter and no-filter groups, respectively).. At 8 years, vena cava filters reduced the risk of pulmonary embolism but increased that of deep-vein thrombosis and had no effect on survival. Although their use may be beneficial in patients at high risk of pulmonary embolism, systematic use in the general population with venous thromboembolism is not recommended.

Topics: Aged; Anticoagulants; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pulmonary Embolism; Recurrence; Vena Cava Filters; Venous Thrombosis; Vitamin K

Vitamin K antagonists for secondary prevention in patients with deep vein thrombosis (DVT) require monitoring and dose adjustments. The synthetic factor Xa inhibitor, SanOrg34006, has predictable pharmacokinetics and may be administered once weekly without dose adjustments.. After 5-7 days of enoxaparin treatment, patients with proximal DVT were randomized to receive 2.5, 5.0, 7.5 or 10 mg of SanOrg34006 subcutaneously once weekly or warfarin (INR, 2.0-3.0) for 12 weeks. The primary efficacy outcome was the composite of change in thrombotic burden, as assessed by ultrasonography and perfusion lung scanning at baseline and week 12 +/- 1, and clinical thromboembolic events. This outcome was classified as normalization, no relevant change, or deterioration. Other outcomes were major and other clinically relevant bleeding.. A total of 659 patients were randomized and treated. In 614 (93%) patients the primary efficacy outcome was evaluable. The rates of normalization and deterioration were similar in all SanOrg34006 groups (P = 0.4) and did not differ from the warfarin group. There was a clear dose-response for major bleeding among patients treated with SanOrg34006 (P = 0.003). Patients receiving 2.5 mg SanOrg34006 had less bleeding than did warfarin recipients (P = 0.03).. SanOrg34006 dosed at 2.5 mg appears as effective as higher dosages and warfarin for secondary prevention in DVT and was not associated with major bleeding. Therefore, 2.5 mg of SanOrg34006 administered subcutaneously once weekly might be a suitable alternative to dose-adjusted oral vitamin K antagonist.

Topics: Antithrombins; Factor Xa Inhibitors; Hemorrhage; Humans; Oligosaccharides; Safety; Treatment Outcome; Ultrasonography; Venous Thrombosis; Vitamin K

The current standard initial therapies for deep venous thrombosis are low-molecular-weight heparin and unfractionated heparin. In a dose-ranging study of patients with symptomatic deep venous thrombosis, fondaparinux had efficacy and a safety profile similar to those of low-molecular-weight heparin (dalteparin).. To evaluate whether fondaparinux has efficacy and safety similar to those of enoxaparin in patients with deep venous thrombosis.. Randomized, double-blind study.. 154 centers worldwide.. 2205 patients with acute symptomatic deep venous thrombosis.. Fondaparinux, 7.5 mg (5.0 mg in patients weighing <50 kg and 10.0 mg in patients weighing >100 kg) subcutaneously once daily, or enoxaparin, 1 mg/kg of body weight, subcutaneously twice daily for at least 5 days and until vitamin K antagonists induced an international normalized ratio greater than 2.0.. The primary efficacy outcome was the 3-month incidence of symptomatic recurrent venous thromboembolic complications. The main safety outcomes were major bleeding during initial treatment and death. An independent, blinded committee adjudicated all outcomes.. 43 (3.9%) of 1098 patients randomly assigned to fondaparinux had recurrent thromboembolic events compared with 45 (4.1%) of 1107 patients randomly assigned to enoxaparin (absolute difference, -0.15 percentage point [95% CI, -1.8 to 1.5 percentage points]). Major bleeding occurred in 1.1% of patients receiving fondaparinux and 1.2% of patients receiving enoxaparin. Mortality rates were 3.8% and 3.0%, respectively.. Follow-up was incomplete in 0.4% of fondaparinux-treated patients and 1.0% of enoxaparin-treated patients.. Once-daily subcutaneous fondaparinux was at least as effective (not inferior) and safe as twice-daily, body weight-adjusted enoxaparin in the initial treatment of patients with symptomatic deep venous thrombosis.

Topics: Aged; Body Weight; Cause of Death; Double-Blind Method; Drug Administration Schedule; Enoxaparin; Female; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Humans; Kidney; Male; Middle Aged; Polysaccharides; Recurrence; Treatment Outcome; Venous Thrombosis; Vitamin K

Because only limited evidence suggests that elastic stockings prevent the post-thrombotic syndrome in patients with symptomatic deep venous thrombosis (DVT), these stockings are not widely used.. To evaluate the efficacy of compression elastic stockings for prevention of the post-thrombotic syndrome in patients with proximal DVT.. Randomized, controlled clinical trial.. University hospital.. 180 consecutive patients with a first episode of symptomatic proximal DVT who received conventional anticoagulant treatment.. Before discharge, patients were randomly assigned to wear or not wear below-knee compression elastic stockings (30 to 40 mm Hg at the ankle) for 2 years. Follow-up was performed for up to 5 years.. The presence and severity of the post-thrombotic syndrome were scored by using a standardized scale.. Post-thrombotic sequelae developed in 44 of 90 controls (severe in 10) and in 23 of 90 patients wearing elastic stockings (severe in 3). All but 1 event developed in the first 2 years. The cumulative incidence of the post-thrombotic syndrome in the control group versus the elastic stockings group was 40.0% (95% CI, 29.9% to 50.1%) versus 21.1% (CI, 12.7% to 29.5%) after 6 months, 46.7% (CI, 36.4% to 57.0%) versus 22.2% (CI, 13.8% to 30.7%) after 1 year, and 49.1% (CI, 38.7% to 59.4%) versus 24.5% (CI, 15.6% to 33.4%) after 2 years. After adjustment for baseline characteristics, the hazard ratio for the post-thrombotic syndrome in the elastic stockings group compared with controls was 0.49 (CI, 0.29 to 0.84; P = 0.011).. This study lacked a double-blind design.. Post-thrombotic sequelae develop in almost half of patients with proximal DVT. Below-knee compression elastic stockings reduce this rate by approximately 50%.

Topics: Adult; Aged; Anticoagulants; Bandages; Female; Follow-Up Studies; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Patient Compliance; Postphlebitic Syndrome; Risk Factors; Venous Thrombosis; Vitamin K

In clinical practice, decisions on the duration of treatment with vitamin K antagonists are usually based on the presence of persistent risk factors, the risk of bleeding and centre policy. Little is known about the influence of patients' experienced quality of life. The objectives of this study were: 1). to explore the course of quality of life in patients with venous thrombosis treated for 3 months versus patients treated for 6 months with vitamin K antagonists; 2). to investigate the factors that were associated with the duration of treatment with vitamin K antagonists. The study sample comprised patients participating in a multi-centre clinical trial. Quality of life was assessed at study entry, after 10-14 days, 3 and 6 months in 360 patients. Overall, no differences in quality of life were found between the 2 patient groups. An interaction effect between group and time was found for physical functioning. Regression analyses indicated that the presence of one or more permanent risk factors, duration of hospitalisation, mobility prior to deep-vein thrombosis and study centre were associated with the duration of treatment with vitamin K antagonists. Interestingly, quality of life was not associated with treatment duration. Since study centre was the most important factor associated with treatment duration, local policy appears to have a great influence on decisions regarding the duration of treatment with vitamin K antagonists.

Topics: Activities of Daily Living; Adaptation, Psychological; Adult; Aged; Anticoagulants; Australia; Europe; Female; Humans; Male; Middle Aged; New Zealand; Organizational Policy; Quality of Life; Risk Factors; Severity of Illness Index; Time Factors; Venous Thrombosis; Vitamin K

Low-molecular-weight and unfractionated heparins are frequently used to treat venous thromboembolism, but it is not known whether they are equally effective in inhibiting in vivo generation of thrombin. In this multicenter trial, 1048 patients were randomized to intravenous unfractionated heparin (group A), twice daily low-molecular-weight heparin (reviparin) for 1 week (group B), or once daily reviparin for 4 weeks (group C). All patients received vitamin K antagonists. Blood samples withdrawn at the baseline and at weeks 1 and 3 were analyzed using markers of in vivo thrombin generation and other coagulation parameters. During the first 3 weeks symptomatic recurrent deep vein thrombosis-pulmonary embolism (DVT/PE) occurred in 17 (4.5%) of 375 patients in group A compared with 4 (1.0%) of 388 patients in group B, and 9 (2.4%) of 374 patients in group C. Forty percent of patients in group A, 53.4% in group B, and 53.5% in group C showed 30% or greater reduction in thrombus size assessed by venography. Patients in group B had significantly greater reduction in D-dimer, prothrombin fragments 1 and 2 (F1 + 2), endogenous thrombin potential (ETP), and thrombin-antithrombin (TAT) complexes compared to groups A and C. Greater release of tissue factor pathway inhibitor (TFPI) and reduction in levels of thrombin activatable fibrinolysis inhibitor (TAFI) and fibrinogen were significantly more pronounced in group C patients. Reviparin administered twice daily plus vitamin K antagonist is more effective in inhibiting in vivo thrombin generation compared to intravenous unfractionated heparin plus vitamin K antagonist, and reviparin once daily produced significantly higher TFPI release and greater reduction in TAFI and fibrinogen levels.

Topics: Acute Disease; Anticoagulants; Biomarkers; Blood Coagulation Factors; Heparin; Heparin, Low-Molecular-Weight; Humans; Partial Thromboplastin Time; Prospective Studies; Pulmonary Embolism; Recurrence; Thrombin; Venous Thrombosis; Vitamin K

To investigate the risk of ipsilateral versus contralateral recurrent deep vein thrombosis in the leg.. An open prospective long term follow-up multicentre trial. Patients were followed by frequent outpatient visits at each centre during the first 12 months after inclusion and thereafter annually.. Sixteen hospitals in central Sweden.. A total of 790 consecutive patients with objectively verified first episode of acute deep vein thrombosis and without diagnosed malignant disease were recruited from a randomized study comparing 6 weeks with 6 months of oral antivitamin K therapy as secondary thromboprophylaxis.. Deep vein thrombosis in the contralateral leg was confirmed by venography or ultrasound. With regard to the ipsilateral leg, venography was required.. A recurrent episode of venous thromboembolism was documented in 192 patients after a mean (+/-SD) period of 31(+/-29) months. In 26 additional patients with ipsilateral symptoms the diagnostic critera were not fulfilled. One hundred and eleven patients have deceased and 69 patients withdrew from the study. The 392 patients without recurrent episodes were followed for a median of 96 months with 90% for at least 48 months. An objectively verified recurrent contralateral and ipsilateral deep vein thrombosis occurred in 95 and 54 cases, respectively, and in 41 patients pulmonary embolism was documented. In two patients thromboses with unusual locations were registered. The risk of contralateral versus ipsilateral recurrence was significantly increased with a risk ratio of 1.6 (95% confidence interval 1.4-1.9) in a time to event model. In a multivariate analysis none of the investigated variables were significantly associated with the side of recurrent thrombosis.. The risk of a recurrent deep vein thrombosis is increased in the contralateral leg. This brings into question the importance of an impaired venous flow for recurrent episodes of thrombosis.

Topics: Aged; Data Interpretation, Statistical; Female; Follow-Up Studies; Humans; Leg; Longitudinal Studies; Male; Middle Aged; Prospective Studies; Pulmonary Embolism; Recurrence; Risk; Sweden; Treatment Outcome; Venous Thrombosis; Vitamin K

Body weight-adjusted subcutaneous low-molecular-weight heparin (LMWH) has been proven to be at least as effective and safe as dose-adjusted intravenous unfractionated heparin (UFH) for the treatment of patients with venous thromboembolism. However, body weight-adjusted dosage of low-molecular-weight heparin may be cumbersome and could lead possibly to incorrect dosing. Therefore a fixed LMWH dose, independent of body-weight, might rationalize initial treatment for venous thromboembolism.. Patients with proven proximal deep-vein thrombosis were randomly assigned to fixed dose subcutaneous LMWH Certoparin (8,000 anti-factor Xa U b.i.d.; 265 patients) or to adjusted dose i.v. UFH (273 patients) for 12 days. Vitamin K antagonists were started between day 3 and 7 and continued for up to 6 months. The primary outcome measure was a 30 percent or greater improvement in the Marder Score, as revealed by repeated venography on day 12 (end of the initial treatment). The secondary composite outcome measure included death, recurrent venous thromboembolism and major bleeding and was assessed at day 12 and after 6 months by a blinded adjunction committee.. The Marder score improved by 30% or more in 30.3% and 25.0% of patients assigned to LMWH (198 paired venograms) and UFH (192 paired venograms), respectively (2p = 0.26). At the end of the initial treatment, the composite outcome was observed in 4 of the 265 patients (1.5%) randomized to LMWH, as compared with 14 of the 273 patients (5.1%) randomized to UFH (2p = 0.03). At 6 months these figures were 6.8% and 12.8%, respectively (risk reduction 0.53, confidence interval 0.31-0.90, 2p = 0.02).. Fixed dose subcutaneous LMWH certoparin is at least as efficacious as UFH in resolving proximal vein thrombosis.

Topics: Acute Disease; Adult; Aged; Anticoagulants; Body Weight; Cohort Studies; Female; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Humans; Injections, Intravenous; Injections, Subcutaneous; Male; Middle Aged; Phlebography; Popliteal Vein; Postoperative Complications; Recurrence; Treatment Outcome; Venous Thrombosis; Vitamin K

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

It is yet unclear whether vitamin K antagonist treatment should be stopped abruptly or gradually after an episode of venous thromboembolism. The mode of withdrawal might influence a potential development of a hypercoagulable state, which could influence the risk for recurrent disease.. We prospectively studied 37 consecutive patients in whom acenocoumarol was discontinued either abrupt (18) or gradually (19) (2/3 and 1/3 of the initial dose for one week). Blood sampling was performed at various time points up to 18 days after complete withdrawal and was analysed for INR, prothrombin fragment F1 + 2 and D-dimer. All patients were clinically followed-up for the assessment of the association between hypercoagulability and occurrence of disease such as recurrent venous thromboembolism or malignancy.. An approximately fourfold increase was observed (median increase from 0.3 to 1.3 nmol/l) in the F1 + 2 levels after both abrupt and gradual withdrawal and in the D-dimer concentrations in the abrupt withdrawal group (0.10 to 0.44 mg/l), while those in whom acenocoumarol was discontinued gradually showed a less pronounced increase of the D-dimer levels (0.11 to 0.29 mg/L) (not significant). During follow-up one recurrent venous thromboembolic event occurred in each group, and a diagnosis of cancer was made four times. All these patients had the highest D-dimer concentrations measured in the entire study group.. This study indicates the potential for a hypercoagulable state after acenocoumarol discontinuation, which was not prevented by tapering the acenocoumarol dose. D-dimer, measured 2 to 3 weeks after acenocoumarol withdrawal, might be an important tool to identify patients at risk for recurrent venous thromboembolism and/or for the presence of an underlying malignancy.

Topics: Acenocoumarol; Adolescent; Adult; Aged; Anticoagulants; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Thromboembolism; Thrombophilia; Venous Thrombosis; Vitamin K

Deep venous thromboses can be divided into two groups according to their pathogenesis, anatomical features and differing responses to therapy. The first and most frequent consists of so-called simple venous thrombosis while the second group, which is less common, comprises severe or recurrent venous thrombosis characterised by a multifactorial pathogenesis, a mixed thrombus rich in platelets and by an incomplete response to both prophylactic and therapeutic treatment with anticoagulants (heparin or vitamin K antagonist). In a randomized, prospective blind study in patients with severe or recurrent venous thrombosis, which included 6 groups each of 100 patients, co-administration of anticoagulants with various types of antiplatelet agent, either with rheological effects (piracetam, buflomedil, pentoxifylline) or without them (dipyridamole), has shown a beneficial potentiating antithrombotic effect with those drugs possessing rheological effects and the absence of this effect with dipyridamole.

Topics: Adult; Anticoagulants; Biomarkers; Blood Coagulation Tests; Blood Viscosity; Dipyridamole; Drug Therapy, Combination; Female; Hemorheology; Heparin; Humans; Male; Middle Aged; Pentoxifylline; Piracetam; Platelet Aggregation Inhibitors; Pyrrolidines; Recurrence; Severity of Illness Index; Single-Blind Method; Treatment Outcome; Venous Thrombosis; Vitamin K

Direct oral anticoagulants (DOAC) are advocated as equally effective to vitamin K antagonists (VKA) for the treatment of patients with cerebral sinus and venous thrombosis (CSVT). However, data concerning the real-life management practices in CSVT patients are is lacking.. Prospective CSVT databases from four large academic medical centers were retrospectively studied. Demographics, clinical presentations, risk factors, radiological and outcome parameters were compared between CSVT patients treated with DOAC and VKA.. Out of 504 CSVT patients, 43 (8.5%) were treated with DOAC, and the remaining 461 (91.5%) were treated with VKA. All patients with antiphospholipid syndrome (APLA) were treated with VKA (61 vs. 0, p=0.013). Patients with a history or presence of malignancy were also more often treated with VKA (16% vs. 5%, p=0.046). Other risk factors for thrombosis did not differ between the groups. There were no differences in clot extent or location and no differences in the percentage of favorable outcomes or mortality were observed.. Our data suggests that only malignancy and antiphospholipid antibodies significantly influenced physician's decisions towards choosing VKA rather than DOAC. DOAC appear to be as effective and safe as VKA in patients with CSVT.

Topics: Administration, Oral; Anticoagulants; Fibrinolytic Agents; Humans; Prospective Studies; Retrospective Studies; Venous Thrombosis; Vitamin K

Venous thromboembolic disease (VTD) is currently the second leading cause of death in cancer patients with a prevalence of approximately 20% compared with that of 5% in the entire adult population. Cancer patients are a heterogeneous group with significant differences in the risk of VTD which is, in particular, determined by the type of tumour, its extent, location, and the presence of metastases. Some tumours represent a mean 3- to 5-fold increase in risk, while in others the risk of developing VTD is even several times higher. In comparison with non-cancer patients, those with a tumour are not only at an increased risk of an initial thromboembolic event, but also of its recurrence, regardless of ongoing anticoagulation which is associated with a higher risk of bleeding, particularly in mucosal involvement. Venous thrombosis and its treatment may interfere with the ongoing diagnosis and treatment. In cancer patients, VTD is a frequent incidental finding on imaging studies. Primary thromboprophylaxis (apixaban, rivaroxaban, LMWH) is currently recommended in selected groups of cancer patients who are either hospitalized for acute internal disease or immobilized and have an active malignancy, undergo outpatient systemic chemotherapy for a tumour with a high risk of VTD (a Khorana score of 2) or surgery and are not at high risk of bleeding. DOACs should be administered six months after the initiation of chemotherapy. If there is a risk of drug interactions or mucosal bleeding, LMWHs are recommended. At present, DOACs (apixaban, edoxaban, rivaroxaban) and LMWHs are the first-choice drugs in treating VTD. LMWHs are preferred in mucosal tumours, when there is a high risk of bleeding, in progressive malignancy, concomitant emetogenic therapy, and dyspeptic difficulties. In severe renal insufficiency (CrCl < 15 ml/min), vitamin K antagonists may be of value. Individualized treatment should take into consideration the patients general condition, prognosis, and personal preferences.

Topics: Administration, Oral; Adult; Anticoagulants; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Randomized Controlled Trials as Topic; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis; Vitamin K

Protein S is a vitamin K-dependent protein that acts as a break in secondary hemostasis by inactivating activated factor V and activated factor VIII. We report a case of a 40 years old male who had the first episode of deep vein thrombosis of the left lower limb 10 years back, which despite treatment, reoccurred 3 months later in the bilateral lower limb. Thrombophilic screening showed severe protein S deficiency. The patient then developed deep vein thrombosis of both upper limbs. The patient was advised to place an inferior vena cava filter, which he denied. The patient is now presenting with multiple episodes of post-thrombotic syndrome. Such attacks are treated with elastic compression stockings, rivaroxaban, and morphine. However, despite medication, the pain has not yet subsided. Hence, even though protein S deficiency is the rare cause of deep vein thrombosis when recurrent should be considered despite its rare occurrence.. deep vein thrombosis; protein S deficiency; rivaroxaban.

Topics: Adult; Humans; Male; Postthrombotic Syndrome; Protein S Deficiency; Rivaroxaban; Venous Thrombosis; Vitamin K

The evidence regarding the use of anticoagulant (AC) agents in portal vein thrombosis (PVT) is increasing and, most patients undergo chronic treatment with low molecular weight heparin (LMWH) or vitamin K antagonists (VKA). Nevertheless, there are no clear data about who should receive antithrombotic therapy, when to initiate it, how long and what dose should be used for this set of patients. The aim of the study was to assess the outcome of patients with cirrhosis and portal vein thrombosis who received AC therapy, in terms of thrombus regression, bleeding events and survival rates.. This observational and retrospective study included 107 cirrhotic patients diagnosed with PVT in a single tertiary center between 2010-2019. 54 received low molecular weight heparin or vitamin K antagonist (AC treatment group) and 53 were untreated. All patients were periodically follow-up to assess the evolution of PVT (regression, progression, stable thrombus) and potential occurrence of bleeding events.. The regression of portal vein thrombosis was significantly higher in the AC treatment group (OR=2.430; 95% CI=1.11-6.167; p=0.026), more than 50% of on-treatment patients experiencing regression of the thrombus. However, bleeding events were significantly more frequent in the AC treatment group (18.5% vs. 7.5%) and the risk of bleeding was associated with thrombocytes less than 50x103/mm3 (OR=8.266; 95%CI: 2.310-39.211; p=0.002). Survival was better in the AC treatment group (68.4% vs 48.7% at 5 years and 92.7% vs 77.8% at 1 year, p=0.038) and was lower in patients that experienced bleeding events (37.22% survival at 5 years, mean time survival 44 months, p=0.008).. In our cohort of cirrhotic patients with PVT more than 50% of patients receiving AC therapy presented regression of the thrombus; most of them obtained partial recanalization. The bleeding complication rate was higher than expected, reaching 18%. The overall mortality was lower in the treated group.

Topics: Anticoagulants; Fibrinolytic Agents; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Liver Cirrhosis; Portal Vein; Retrospective Studies; Thrombosis; Venous Thrombosis; Vitamin K

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

This is the 2nd update to the 9th edition of these guidelines. We provide recommendations on 17 PICO (Population, Intervention, Comparator, Outcome) questions, four of which have not been addressed previously.. We generate strong and weak recommendations based on high-, moderate-, and low-certainty evidence, using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology.. The panel generated 29 guidance statements, 13 of which are graded as strong recommendations, covering aspects of antithrombotic management of VTE from initial management through secondary prevention and risk reduction of postthrombotic syndrome. Four new guidance statements have been added that did not appear in the 9th edition (2012) or 1st update (2016). Eight statements have been substantially modified from the 1st update.. New evidence has emerged since 2016 that further informs the standard of care for patients with VTE. Substantial uncertainty remains regarding important management questions, particularly in limited disease and special patient populations.

Topics: Drug Therapy, Combination; Evidence-Based Medicine; Fibrinolytic Agents; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Injections, Intravenous; Injections, Subcutaneous; International Normalized Ratio; Pulmonary Embolism; Risk Assessment; Thrombolytic Therapy; Venous Thrombosis; Vitamin K

The novel direct oral anticoagulants (DOAC) have been shown to be at least as effective as and safer than conventional anticoagulants for the initial and long-term treatment of venous thromboembolic disorders. However, the rate of post-thrombotic syndrome (PTS) in patients with deep-vein thrombosis (DVT) treated with the DOACs is unknown. With the adoption of the Villalta scale, we assessed the rate of PTS at the end of the follow-up period in a consecutive series of 309 outpatients with acute proximal DVT who had received at least 3 months of treatment with a DOAC and had been followed-up for up to 3 years. The rate of PTS development was compared with that recorded in a historical cohort of 1036 consecutive patients who had been treated with vitamin K antagonists (VKA) and had received a similar follow-up examination. Logistic regression analysis, including propensity scoring to adjust for differing probabilities of undergoing VKA/DOAC, was used to identify predictors of PTS. PTS developed in 87 patients (28.2%) treated with the DOACs (severe in 12), and in 443 patients (42.8%) treated with VKAs (severe in 61). After adjusting for estimated propensity score, age, gender, concomitant symptoms of pulmonary embolism, duration of anticoagulation and development of residual vein thrombosis, the risk of PTS in the DOAC-treated patients was reduced by 54% in comparison to patients treated with conventional anticoagulation (odds ratio 0.46; 95% CI 0.33 to 0.63). We conclude that in comparison to VKAs, the use of the direct oral anticoagulants has the potential to offer a more favorable prognosis in terms of PTS development.

Topics: Adult; Factor Xa Inhibitors; Female; Humans; Logistic Models; Male; Middle Aged; Postthrombotic Syndrome; Risk Factors; Venous Thrombosis; Vitamin K

Oral anticoagulants are the first-line drugs for treating thrombotic disorders related to nonvalvular atrial fibrillation and for treating deep vein thrombosis, diseases that increase in prevalence with age. Older patients have a greater risk of thrombotic and hemorrhagic events and are more prone to drug interactions. Given this backdrop, we wanted to determine the factors associated with the prescription of direct oral anticoagulants and vitamin K antagonists in older patients.. We performed a cross-sectional observational study using a hospital prescription database. The study population consists of 405 older patients who were given oral anticoagulants. The 2 variables of interest were the prescription of 1 of the 2 classes of oral anticoagulants (direct oral anticoagulants vs vitamin K antagonists) and appropriateness of oral anticoagulant prescribing according to Summary of Product Characteristics (potentially inappropriate vs appropriate).. The factors associated with direct oral anticoagulant prescribing were the female gender (odds ratio [OR]: 1.87, 95% confidence interval [CI]: 1.22-2.88) and initiation during hospital stay (OR: 2.56, 95% CI: [1.52-4.32]). Stage 4 and 5 chronic kidney diseases (OR: 0.39, 95% CI: [0.19-0.79] and OR: 0.07, 95% CI: [0.01-0.53]) were factors favoring vitamin K antagonist prescription. Being 90 years of age or more (OR: 2.05, 95% CI: [1.06-3.98]) was a factor for potentially inappropriate anticoagulant prescribing. The gastroenterology department (OR: 2.91, 95% CI: [1.05-8.11]) was associated with potentially inappropriate anticoagulant prescribing.. Direct oral anticoagulants are the drugs of choice for anticoagulant treatment, including in older adults. The female gender and the initiation during hospital stay increased the chances of being prescribed a direct oral anticoagulant in older adults. Stage 4 and 5 chronic kidney disease increased the likelihood of having a vitamin K antagonist prescribed. Our study also revealed a persistence of potentially inappropriate oral anticoagulant prescriptions in older patients.

Topics: Administration, Oral; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Clinical Decision-Making; Cross-Sectional Studies; Databases, Factual; Drug Interactions; Factor Xa Inhibitors; Female; France; Hemorrhage; Humans; Inappropriate Prescribing; Male; Prevalence; Renal Insufficiency, Chronic; Retrospective Studies; Risk Assessment; Risk Factors; Sex Factors; Treatment Outcome; Venous Thrombosis; Vitamin K

Anticoagulation therapy is the cornerstone of treatment in acute vein thrombosis (DVT) and it aims to reduce symptoms, thrombus extension, DVT recurrences, and mortality. The treatment for DVT depends on its anatomical extent, among other factors. Anticoagulation therapy for proximal DVT is clearly recommended (at least for 3 months), while AT for isolated distal DVT should be considered, especially in the presence of high thromboembolic risk factors. The optimal anticoagulant and duration of therapy are determined by the clinical assessment, taking into account the thromboembolic and bleeding risk in each patient in a case-by-case decision making. Non-Vitamin K antagonists oral anticoagulants (NOACs) were a revolution in the anticoagulation management of DVT. Nowadays, NOACs are considered as first-line therapy in the anticoagulation therapy for DVT and are recommended as the preferred anticoagulant agents by most scientific societies. NOACs offer a simple route of administration (oral agents), a rapid onset-offset of their action along with a good efficacy and safety profile in comparison with Vitamin K Antagonists (VKAs). However, there are issues about their efficacy and safety profile in specific populations with high thromboembolic and bleeding risks, such as renal failure patients, active-cancer patients, and pregnant women, in which VKAs and heparins were the standard care of treatment. Since the available data are promising for the use of NOACs in end-stage chronic kidney disease and cancer patients, several ongoing randomized trials are currently trying to solve that issues and give evidence about the safety and efficacy of NOACs in these populations.

Topics: Administration, Oral; Anticoagulants; Female; Humans; Pregnancy; Venous Thromboembolism; Venous Thrombosis; Vitamin K

Topics: Erythrocyte Transfusion; Humans; Infant; Intracranial Thrombosis; Magnetic Resonance Imaging; Male; Plasma; Venous Thrombosis; Vitamin K; Vitamin K Deficiency

Thromboembolic vein disease (TVD) comprises of deep vein thrombosis (DVT) and pulmonary embolism (PE). Standard therapy consists of the administration of low molecular weight heparin (LMWH) imbricated with antivitamin K agonists (AVK). Recently a new series of oral anticoagulants known as the direct oral anticoagulants (DOACs) has been introduced. CHEST 2016 guidelines recommend the use of DOACs rather then AVKs for the treatment of TVD.. The aim of this study was to analise the choice of antithrombotic treatment and to see if CHEST 2016 guidelines were used in the ASL TO3 district for TVD therapy.. Data obtained from the SISR archives was used to perform a cohort retrospective study. Patients who had been recovered for TEVD were selected 6 months after dismissal. Based on Chest guidelines, the period that ranged from 01/01/2014 to 30/06/2017 was divided into two parts. The cohort was classified according to antithrombotic therapy administered to these patients.. 475 patients that had been dismissed after recovery for TVD were identified and enrolled into this study. 1st period: from 275 patients, 247 had a prescription: 132 TAO, 73 DOACs, 42 eparine, 0 ASA. 2nd period: from 200 patients, 185 had a prescription: 55 TAO, 95 DOACs, 34 eparine, 1 ASA.. Our analysis shows a significant difference between the choice of antithrombotic therapy during both periods, this difference is greater among males. We can conclude that antithrombotic prescriptions carried out in the ASL TO3 area have been adherent to Chest guidelines.

Topics: Aged; Anticoagulants; Cohort Studies; Female; Fibrinolytic Agents; Guideline Adherence; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Practice Guidelines as Topic; Pulmonary Embolism; Retrospective Studies; Sex Factors; Venous Thrombosis; Vitamin K

Venous thromboembolism (VTE), which includes pulmonary embolism and deep vein thrombosis, is a leading cause of morbidity and mortality worldwide. Based on new evidence, the management and treatment of VTE have changed over the years. For several decades, low molecular weight heparin and vitamin K antagonists have been the two cornerstones of anticoagulant therapy for VTE. Recently, the introduction in clinical practice of the new oral anticoagulants has radically changed the management of VTE for their easy use and their better efficacy and safety profile. Here, we report on recent evidence of 10 still controversial clinical questions concerning common diagnostic and therapeutic aspects of VTE.

Topics: Anticoagulants; Humans; Pulmonary Embolism; Venous Thromboembolism; Venous Thrombosis; Vitamin K

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

Venous thromboembolism (VTE) comprises deep vein thrombosis (DVT) and pulmonary embolism (PE) and is associated with significant recurrence and mortality risk. Standard VTE treatment includes at least 3 months anticoagulation. The objective was to describe time trends in the duration of oral anticoagulation in patients initially treated with vitamin K antagonists (VKAs).. A retrospective cohort study was conducted on patients with first VTE and VKA treatment initiation within 30 days, identified from the UK Clinical Practice Research Datalink from 2001 to 2014. VKA users were followed for the duration of oral anticoagulation which included switching to non-VKA oral anticoagulants. The probability of remaining on anticoagulation treatment (persistence) was estimated using Kaplan-Meier survival functions.. A total of 16,018 patients with VTE initiated VKA; 48.2% males, mean age 62.1 years, median VKA treatment duration 6.5 months. The 90-day persistence increased from 75.6% in 2001 to 91.2% in 2013 (p < .0001) and the 180-day persistence from 39.3% in 2001 to 61.1% in 2013 (p < .0001). This time trend was also shown for patients with DVT, PE, provoked VTE, unprovoked VTE, provoked DVT, unprovoked DVT, provoked PE and unprovoked PE. There were no major differences in persistence between patients with provoked and unprovoked VTE, but persistence was lower following DVT than PE (p < .0001).. The increase in persistence was independent of the presentation of the first VTE (provoked or unprovoked), but higher for first PE. Whether the increasing persistence resulted in decreasing risk of recurrent VTE needs to be confirmed.

Topics: Anticoagulants; Antithrombins; Cohort Studies; Drug Substitution; Female; Humans; Male; Medication Therapy Management; Middle Aged; Needs Assessment; Pulmonary Embolism; Recurrence; Retrospective Studies; Time Factors; United Kingdom; Venous Thrombosis; Vitamin K

Portal vein thrombosis (PVT) is a frequent and serious complication in patients with liver cirrhosis (LC). Recently, a new classification of PVT was proposed, although the functional component was not completed included. The status of liver disease (compensated/decompensated) should be added to this classification. Reduced portal flow velocity and the acquired hypercoagulable status associated with LC are the main risk factors for PVT development, although endothelial dysfunction may play an important role that needs to be further evaluated. The European Association for the Study of the Liver and the American Association for the Study of Liver Disease recommend that the anticoagulant treatment should be consider in cirrhotic patients with PVT. Low molecular weight heparin and vitamin K antagonists proved their efficacy and relatively safety in PVT treatment, although in addition to recanalization rates, more complex end-points such as mortality and decompensation rate should be evaluated. The new oral anticoagulant therapies offers the advantage of oral administration in the absence of laboratory monitoring, however, there are a few reports regarding their use in cirrhotic patients, most of them referring to compensated isolated cases. Transjugular intrahepatic portosystemic shunt could be an alternative if thrombosis progresses despite anticoagulatant therapy and/or when PVT is associated with portal hypertension complications. The aim of this editorial is to discuss the different aspects of pathophysiology, clinical relevance, diagnosis and management of PVT in patients with LC.

Topics: Administration, Oral; Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Hypertension, Portal; Liver Cirrhosis; Portal Vein; Portasystemic Shunt, Transjugular Intrahepatic; Severity of Illness Index; Venous Thrombosis; Vitamin K

Multifocal avascular osteonecrosis (AON) is a serious manifestation of systemic lupus erythematosus (SLE). Prothrombotic factors, especially antiphospholipid antibodies (aPL), have been associated with the development of AON; therefore, attenuating the procoagulant state while balancing the haemorrhagic risks might have a rationale when managing this condition. We report a case of a 37-year-old patient with SLE, treated with low doses of corticosteroids and immunosuppressive therapy, who was started on vitamin K antagonist following an episode of deep vein thrombosis while having persistent positivity for aPL. After 2 years, he presented with multifocal AON, involving both femurs and shoulders. The patient underwent a bilateral hip replacement, but despite appropriate anticoagulation therapy after 2 years, he developed another episode of AON at both distal epiphyses of the femurs and proximal epiphyses of the tibias. Multifocal AON should be suspected, especially in the presence of aPL positivity. Its aetiology is still unknown and is most likely multifactorial. Its management is challenging and requires combined approaches.

Topics: Adult; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Diagnosis, Differential; Humans; Lupus Erythematosus, Systemic; Male; Osteonecrosis; Rare Diseases; Treatment Outcome; Venous Thrombosis; Vitamin K

Until recently, vitamin K antagonists (VKAs) were the only form of anticoagulation for the prevention of thromboembolic complications in patients with atrial fibrillation or venous thromboembolisms. Various caregivers are involved in anticoagulation care. Criticism of the support by the thrombosis department focused mainly on the lack of guarantees regarding the interinstitutional anticoagulation chain of care. Initiatives have now been deployed to improve this support, as described in the national integrated anticoagulation care standard (LSKA, Landelijke Standaard Ketenzorg Antistolling) and the national primary care anticoagulation agreement (LESA, Landelijke Eerstelijns Samenwerkingsafspraken). However, rapidly increasing use of direct oral anticoagulants (DOACs) has dramatically altered anticoagulation care. Patients and caregivers are more often confronted with uncertainty about treatment coordination. This article aims to sketch frameworks for responsible anticoagulation care. We examine different topics, such as coordination, organisation of follow-up, availability for answering questions and switching from VKA to DOAC.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Thromboembolism; Thrombolytic Therapy; Venous Thrombosis; Vitamin K

The recanalization rate in patients with deep venous thrombosis (DVT) of the legs treated with the direct oral anticoagulants (DOAC) is unknown.. In an Italian cohort, we investigated the rate of residual vein thrombosis (RVT) after three and/or six months in 352 patients with proximal DVT who had been treated with the DOACs as a stand-alone therapy or lead-in parenteral anticoagulants, and compared it to that recorded in a historical cohort of 1094 patients in which vitamin K antagonists (VKAs) had been employed. In both cohorts, RVT was defined as the ultrasound persistence of thrombotic material resulting in a diameter of at least 4mm of incompressibility of the proximal veins.. RVT was detected in 143 patients treated with DOACs (41.2%) after three months and in 58 patients (21.1%) after six months; the corresponding figure in patients treated with conventional anticoagulation was 52.3% and 54.5%, respectively. After adjusting for the baseline characteristics, the odds ratio of RVT in patients treated with the DOACs as compared with those treated with conventional anticoagulation was 0.63 (95% CI, 0.48-0.81) after three months, and 0.17 (95% CI; 0.11-0.26) after six months.. In patients with proximal DVT treated with the DOACs, the persistence of ultrasound detectable RVT is likely to occur less frequently than in patients treated with conventional anticoagulation. These results may have implications for the prognosis of patients with DVT.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Cohort Studies; Female; Humans; Italy; Male; Middle Aged; Prognosis; Venous Thrombosis; Vitamin K

Essentials Low-molecular-weight-heparins (LMWH) kinetics differ which may result in different bleeding risks. A cohort of 12 934 venous thrombosis patients on LMWH was followed until major bleeding. The absolute major bleeding risk was low among patients registered at the anticoagulation clinic. Once-daily dosing was associated with a lower bleeding risk as compared with twice-daily.. Background Low-molecular-weight heparins (LMWHs) are considered members of a class of drugs with similar anticoagulant properties. However, pharmacodynamics and pharmacokinetics between LMWHs differ, which may result in different bleeding risks. As these agents are used by many patients, small differences may lead to a large effect on numbers of major bleeding events. Objectives To determine major bleeding risks for different LMWH agents and dosing schedules. Methods A cohort of acute venous thrombosis patients from four anticoagulation clinics who used an LMWH and a vitamin K antagonist were followed until they ceased LMWH treatment or until major bleeding. Exposures were classified according to different types of LMWHs and for b.i.d. and o.d. use. Cumulative incidences for major bleeding per 1000 patients and risk ratios were calculated and adjusted for study center. Results The study comprised 12 934 patients with a mean age of 59 years; 6218 (48%) were men. The cumulative incidence of major bleeding was 2.5 per 1000 patients (95% confidence interval [CI], 1.7-3.5). Enoxaparin b.i.d. or o.d. was associated with a relative bleeding risk of 1.7 (95% CI, 0.2-17.5) compared with nadroparin o.d. In addition, a nadroparin b.i.d. dosing schedule was associated with a 2.0-fold increased major bleeding risk (95% CI, 0.8-5.1) as compared with a nadroparin o.d. dosing schedule. Conclusions Absolute major bleeding rates were low for all LMWH agents and dosing schedules in a large unselected cohort. Nevertheless, twice-daily dosing with nadroparin appeared to be associated with an increased major bleeding risk as compared with once-daily dosing, as also suggested in a meta-analysis of controlled clinical trials.

Topics: Acute Disease; Adult; Aged; Anticoagulants; Cohort Studies; Drug Administration Schedule; Female; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Humans; Incidence; Male; Middle Aged; Nadroparin; Pulmonary Embolism; Risk; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis; Vitamin K

Topics: Antithrombins; Dabigatran; Humans; Practice Guidelines as Topic; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Review Literature as Topic; Rivaroxaban; Thiazoles; Venous Thromboembolism; Venous Thrombosis; Vitamin K

Peripherally inserted central catheters (PICCs) are frequently used for prolonged drug administration, but their use is commonly complicated by the development of upper extremity deep venous thrombosis (UEDVT) requiring anticoagulation. Here, we compared the efficacy and safety profile of rivaroxaban (20 mg/d) with low molecular weight (LMW) heparin and vitamin K antagonists in the treatment of PICC-associated UEDVT.. Patients (N = 84) with PICC-associated UEDVT were studied. All had UEDVT identified by ultrasound scanning. Further ultrasound images were obtained at 1, 2, and 3 months after the start of treatment. Forty-four patients were treated with rivaroxaban and 40 with initial LMW heparin and vitamin K antagonist with continuation of vitamin K antagonists alone once international normalized ratio was therapeutic FINDINGS: In the rivaroxaban group mean (SD) age was 51 (16) years and 57% were men, whereas in the other group respective values were 50 (16) years and 56%. All patients were receiving treatment for cancer. Resolution of thrombus had occurred in 53.5% at 1 month, 76.1% at 2 months, and 92.6% at 3 months in the rivaroxaban-treated patients. Corresponding values in the LMW heparin/vitamin antagonist-treated patients were 34.2%, 55.5%, and 88.5%, respectively. Differences between groups were significant at 1 month (P < 0.01) and 2 months (P < 0.05). There were no major bleeds in either group, and cumulative bleeding rates by 3 months were 7.3% in the rivaroxaban group and 11.4% in the LMW heparin/vitamin K antagonist group.. Rivaroxaban led to faster resolution of PICC-associated UEDVT than LMW/vitamin K antagonists without any increase in bleeding.

Topics: Adult; Aged; Blood Coagulation; Catheterization, Peripheral; Factor Xa Inhibitors; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Rivaroxaban; Upper Extremity; Venous Thrombosis; Vitamin K

Topics: Abdominal Injuries; Accidents, Traffic; Adult; Anticoagulants; Computed Tomography Angiography; Female; Hematoma; Humans; Lacerations; Liver; Pulmonary Embolism; Tomography, X-Ray Computed; Vena Cava, Inferior; Venous Thrombosis; Vitamin K; Wounds, Nonpenetrating

DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) is a rare syndrome triggered by an immunological reaction to certain drugs and which may be life-threatening as a result of the onset of severe organ involvement. It is characterised by a long period from the time of drug therapy to the onset of actual signs. Herein, we report the case of 42-year-old female patient who developed DRESS one month after beginning allopurinol treatment.. A 42-year-old woman was hospitalised for febrile exanthema with facial oedema, polyadenopathy, mononucleosis syndrome, major hypereosinophilia and hepatic cytolysis. A diagnosis was made of DRESS with a RegiSCAR score of 5. The implicated drug was allopurinol, which had been initiated one month earlier. HHV-6 IgM serology was positive. Two days after the start of systemic corticosteroids, the patient developed thrombosis of the internal jugular vein. Other than major hypereosinophilia, no other factors favouring thrombosis were detected. A favourable outcome was achieved under effective anticoagulants and corticosteroids.. They have been rare reports of venous thrombosis during DRESS. Hypereosinophilia can be involved in the onset of this condition. Prophylaxis with systemic anticoagulants may be necessary in DRESS involving major hypereosinophilia.

Topics: Adrenal Cortex Hormones; Adult; Allopurinol; Drug Hypersensitivity Syndrome; Drug Therapy, Combination; Female; Heparin; Humans; Oxypurinol; Patch Tests; Venous Thrombosis; Vitamin K

Direct-acting oral anticoagulants (DOACs) are used in patients with splanchnic vein thrombosis (SVT) and cirrhosis, but evidence for safety and efficacy in this setting is limited. Our aim was to identify indications and reasons for starting or switching to DOACs and to report adverse effects, complications and short-term outcome.. Data collection including demographic information, laboratory values, treatment and complications through the Vascular Liver Disease Interest Group Consortium.. Forty-five centres (90%) of the consortium completed the initial eCRF. We report here a series of 94 patients from 17 centres. Thirty-six patients (38%) had cirrhosis. Child-Pugh score was 6 (range 5-8), and MELD score 10.2 (range 6-19). Indications for anticoagulation were splanchnic vein thrombosis (75%), deep vein thrombosis (5%), atrial fibrillation (14%) and others (6%). DOACs used were rivaroxaban (83%), dabigatran (11%) and apixaban (6%). Patients were followed up for a median duration of 15 months (cirrhotic) and 26.5 months (non-cirrhotic). Adverse events occurred in 17% of patients and included one case of recurrent portal vein thrombosis and five cases of bleeding. Treatment with DOACs was stopped in three cases. The major reasons for choosing DOACs were no need for monitoring or inadequacy of INR to guide anticoagulation in cirrhotic patients. Renal and liver function did not change during treatment.. A consistent number of patients with SVT and/or cirrhosis are currently treated with DOACs, which seem to be effective and safe. These data provide a basis for performing randomized clinical trials of DOACs vs. low molecular weight heparin or vitamin K antagonists.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Europe; Female; Gastrointestinal Hemorrhage; Humans; Liver Cirrhosis; Male; Middle Aged; Splanchnic Circulation; Venous Thrombosis; Vitamin K; Young Adult

The therapeutic management of venous thromboembolism (VTE) is rapidly evolving. Following the positive results of pivotal large-scale randomised trials, the non-vitamin K antagonist oral anticoagulants (NOACs) represent an important alternative to standard anticoagulation. In phase III studies, dabigatran was as effective as, and significantly safer than warfarin. Additional information on real-world data of dabigatran is now warranted. RE-COVERY DVT/PE is a multi-centre, international, observational (i. e. non-interventional) study enrolling patients with acute DVT and/or PE within 30 days after objective diagnosis. The study is designed with two phases. Phase 1 has a cross-sectional design, enrolling approximately 6000 patients independently of treatment choice, with the aim of providing a contemporary picture of the management of VTE worldwide. Phase 2 has a prospective cohort design, with follow-up of one year, enrolling 8000 patients treated with dabigatran or vitamin K antagonists (VKAs) with the aim of comparing their safety, defined by the occurrence of major bleeding, and effectiveness, defined by the occurrence of symptomatic recurrent VTE. RE-COVERY DVT/PE will complement both the results of other observational studies in this field and the results of phase III studies with dabigatran, in particular by assessing its clinical benefit in various patient subgroups treated in routine clinical practice.

Topics: Acute Disease; Anticoagulants; Antithrombins; Blood Coagulation; Cross-Sectional Studies; Dabigatran; Hemorrhage; Humans; Prospective Studies; Pulmonary Embolism; Research Design; Risk Factors; Time Factors; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis; Vitamin K

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: Anticoagulants; Blood Coagulation Factors; Child; Enoxaparin; Female; Headache; Hemorrhage; Heparin Antagonists; Humans; Protamines; Treatment Outcome; Venous Thrombosis; Vitamin K; Warfarin

Outpatient treatment of acute venous thromboembolism (VTE) requires the selection of patients with a low risk of bleeding during the first few weeks of anticoagulation. The accuracy of four systems, originally derived for predicting bleeding in VTE treated with vitamin K antagonists (VKAs), was assessed in VTE patients treated with rivaroxaban.. All patients treated with rivaroxaban in the multinational EINSTEIN deep vein thrombosis (DVT) and pulmonary embolism (PE) trials were included. Major bleeding was defined as ≥2 g/dL drop in hemoglobin or ≥2-unit blood transfusion, bleeding in critical area, or bleeding contributing to death. The authors examined the incidence of major bleeding in patients with low-risk assignment by the systems of Ruiz-Gimenez et al. (score = 0 to 1), Beyth et al. (score = 0), Kuijer et al. (score = 0), and Landefeld and Goldman. (score = 0). For clinical relevance, the definition of low risk for all scores except Kuijer includes all patients < 65 years with no prior bleeding history and no comorbid conditions (current cancer, renal insufficiency, diabetes mellitus, anemia, prior stroke, or myocardial infarction).. A total of 4,130 patients (1,731 with DVT only, 2,399 with PE with or without DVT) were treated with rivaroxaban for a mean (±SD) duration of 207.6 (±95.9) days. Major bleeding occurred in 1.0% (40 of 4,130; 95% confidence interval [CI] = 0.7% to 1.3%) overall. Rates of major bleeding for low-risk patients during the entire treatment period were similar: Ruiz-Gimenez et al., 12 of 2,622 (0.5%; 95% CI = 0.2% to 0.8%); Beyth et al., nine of 2,249 (0.4%; 95% CI = 0.2% to 0.8%); Kuijer et al., four of 1,186 (0.3%; 95% CI = 0.1% to 0.9%); and Landefeld and Goldman, 11 of 2,407 (0.5%; 95% CI = 0.2% to 0.8%). At 30 days, major bleed rates for low-risk patients were as follows: Ruiz-Gimenez et al., five of 2,622 (0.2%; 95% CI = 0.1% to 0.4%); Beyth et al., five of 2,249 (0.2%; 95% CI = 0.1% to 0.5%); Kuijer et al., three of 1,186 (0.3%; 95% CI = 0.1% to 0.7%); and Landefeld and Goldman, seven of 2,407 (0.3%; 95% CI = 0.1% to 0.6%). No low-risk patient had a fatal bleed.. Four scoring systems that use criteria obtained in routine clinical practice, derived to predict low bleeding risk with VKA treatment for VTE, identified patients with less than a 1% risk of major bleeding during full-course treatment with rivaroxaban.

Topics: Aged; Anticoagulants; Clinical Decision-Making; Emergency Service, Hospital; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Predictive Value of Tests; Pulmonary Embolism; Risk Assessment; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis; Vitamin K

Topics: Humans; Long-Term Care; Pulmonary Embolism; Pyrazoles; Pyridones; Venous Thromboembolism; Venous Thrombosis; Vitamin K

Cancer and venous thrombo-embolic disease (VTE) are closely related. Indeed, cancer can reveal VTE and VTE can be the first sign of cancer. Low molecular weight heparin (LWMH) is now the first line treatment in cancer patients. Compliance with marketing authorizations and guidelines are crucial for patient-centered decision-making. This work deals with the prescription of LWMH in patients who develop VTE during cancer in order to better recognize what should or should not be done. The patient's wishes must be taken into consideration when making the final therapeutic decision. The other treatments are discussed: vitamin K antagonists and direct oral anticoagulants (DOACs) may be useful.

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

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

Topics: Administration, Oral; Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Liver Cirrhosis; Portal Vein; Venous Thrombosis; Vitamin K

Information on coagulation for cirrhotics on anticoagulants is scanty. We investigated plasma from 23 cirrhotics treated with low-molecular-weight-heparin (LMWH) followed by vitamin K antagonists (VKA).. On days 1-4 patients received full-dose LMWH. On day-5 VKA was started and LMWH was terminated when INR therapeutic-interval was reached. Blood was collected at peak and trough during LMWH, LMWH+VKA and VKA. Non-cirrhotics on VKA were included as controls.. Anti-factor Xa increased from baseline-to-peak during LMWH. During LMWH+VKA was high and reverted to zero during VKA. INR was slightly high at baseline, trough or peak during LMWH and increased to 2.2 during LMWH+VKA or VKA. Mean VKA weekly-doses for cirrhotics and controls were 28.5mg and 28.6mg. Protein C decreased upon VKA, but not to the expected extent. Endogenous-thrombin-potential (ETP) decreased from baseline (1436nMmin) to trough (1258nMmin) and peak (700nMmin) during LMWH and was further reduced during LMWH+VKA (395nMmin).. Target-INR for cirrhotics can be reached by VKA dosages similar to those for non-cirrhotics. ETP reduction parallels the effect of LMWH and/or VKA. Whether these parameters represent the antithrombotic action elicited by these drugs remains to be determined by clinical-trials and laboratory-measurements. ETP, being a global-test reflecting both pro- and anti-coagulants targeted by antithrombotic drugs, seems the candidate for these trials.

Topics: Aged; Anticoagulants; Blood Coagulation Factors; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Italy; Liver Cirrhosis; Male; Middle Aged; Portal Vein; Ultrasonography, Doppler; Venous Thrombosis; Vitamin K

Risk scores for patients who are at high risk for major bleeding complications during treatment with vitamin K antagonists (VKAs) do not perform that well. BLEEDS was initiated to search for new biomarkers that predict bleeding in these patients.. To describe the outline and objectives of BLEEDS and to examine whether the study population is generalizable to other VKA treated populations.. A cohort was created consisting of all patients starting VKA treatment at three Dutch anticoagulation clinics between January-2012 and July-2014. We stored leftover plasma and DNA following analysis of the INR.. Of 16,706 eligible patients, 16,570 (99%) were included in BLEEDS and plasma was stored from 13,779 patients (83%). Patients had a mean age of 70 years (SD 14), 8713 were male (53%). The most common VKA indications were atrial fibrillation (10,876 patients, 66%) and venous thrombosis (3920 patients, 24%). 326 Major bleeds occurred during 17,613 years of follow-up (incidence rate 1.85/100 person years, 95%CI 1.66-2.06). The risk for major bleeding was highest in the initial three months of VKA treatment and increased when the international normalized ratio increased. These results and characteristics are in concordance with results from other VKA treated populations.. BLEEDS is generalizable to other VKA treated populations and will permit innovative and unbiased research of biomarkers that may predict major bleeding during VKA treatment.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Fibrinolytic Agents; Follow-Up Studies; Hemorrhage; Humans; International Normalized Ratio; Longitudinal Studies; Male; Middle Aged; Phenprocoumon; Prognosis; Risk Factors; Venous Thrombosis; Vitamin K

Guidelines describing the perioperative management of antithrombotic therapy in patients requiring temporary interruption of vitamin K antagonists (VKAs) were first published in 2008. The objective of this study is to evaluate the perioperative management of anticoagulation of patients on chronic VKA and the incidence of bleeding and thrombotic complications pre and postpublication of the 2008 American College of Chest Physicians (ACCP) guidelines. A retrospective review of 40 patients on chronic VKA requiring temporary discontinuation of VKA due to an invasive or surgical procedure who were referred to a single haematology practice from January 2006 to June 2010. Demographics, indications of VKA, risk factors for thrombosis, type of procedure, bridging regimen and bleeding complications were recorded pre and post-2008 ACCP guidelines. Sixty-one procedures were performed in 40 patients; 60% were women. Indications for anticoagulation were secondary prevention of venous thrombosis (n = 27), arterial thrombosis (n = 8) or both arterial thrombosis and venous thrombosis (n = 4), and primary prevention of arterial thrombosis (n = 1). Twenty patients (50%) had thrombophilia. The most common surgical and invasive procedures were gastrointestinal (33%), gynaecological (15%) and orthopaedic (11%). Bridging regimen with therapeutic-dose subcutaneous low molecular heparin (LMWH) was used in 27 (67.5%) patients, prophylactic-dose LMWH in 12 (30%) and a combination of LMWH therapeutic and prophylactic-dose doses in 11 (27.5%). Three bleeding complications occurred prepublication of the 2008 ACCP practice guidelines, although no bleeding complications occurred after the guidelines were published. Adherence to the 2008 ACCP guidelines for the perioperative management of anticoagulation reduced bleeding complications in patients on chronic VKA treatment.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Patient Compliance; Perioperative Care; Practice Guidelines as Topic; Retrospective Studies; Risk Factors; Thrombophilia; Thrombosis; Venous Thrombosis; Vitamin K; Young Adult

Calciphylaxis is associated with a poor prognosis in dialysis patients, and its pathogenesis remains incompletely understood. Although the use of vitamin K antagonists (VKA) has been implicated, previous reports are conflicting. We aimed to determine if vitamin K antagonists conferred an increased risk of calciphylaxis in patients on dialysis.. We performed a single-centre, retrospective cohort study of 2,234 patients receiving dialysis, and compared the characteristics of those with and without calciphylaxis.. We identified 5 cases of calciphylaxis (all female) between January 2009 and December 2013. Overall, 142 patients (6.4%) were treated with VKA during the study period. Calciphylaxis was more common in the VKA group (4 of 142 patients, OR = 61, 95% CI 6.7-546, p = 0.0001). VKA was withdrawn in all cases and treatment instituted with sodium thiosulphate, cinacalcet and supportive measures. All patients recovered, although there was one sudden cerebrovascular death during follow-up.. Treatment with VKA predisposes to the development of calciphylaxis.

Topics: Adult; Aged; Amputation Stumps; Anticoagulants; Arterioles; Calciphylaxis; Cohort Studies; Diabetes Mellitus, Type 2; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Renal Replacement Therapy; Retrospective Studies; Venous Thrombosis; Vitamin K

Topics: Administration, Oral; Anticoagulants; Humans; Incidence; Myocardial Infarction; Thromboembolism; Venous Thromboembolism; Venous Thrombosis; Vitamin K

The treatment of splanchnic vein thrombosis (SVT) is challenging, due to the increased risk of bleeding and potentially life-threatening complications. Current recommendations are based on evidence from the treatment of venous thrombosis in usual sites, but small observational studies in SVT population suggest that the bleeding risk may offset the benefit of anticoagulant treatment in this setting. The aim of this study was to evaluate the safety of vitamin K antagonists (VKAs) in SVT patients.. We retrospectively included SVT patients treated with VKAs followed by 37 Italian anticoagulation clinics, until June 2013. The primary outcome was the incidence of major bleeding (MB), according to the ISTH definition, during VKA treatment. Vascular events, including both arterial and venous thrombosis, and mortality were also documented.. Three hundred and seventy-five patients were included (median age 53 years; 54.7% males). During a median VKA treatment duration of 1.98 years, 15 MB events occurred, corresponding to an incidence rate of 1.24 (95% confidence interval [CI], 0.75-2.06) per 100 patient-years. Gastrointestinal bleeding represented 40% of all MB events. At multivariate analysis, the presence of esophageal varices emerged as independent predictor of MB (hazard ratio 5.4; 95% CI, 1.4-21.1). The incidence rate of vascular events on treatment was 1.37 (95% CI, 0.84-2.23) per 100 patient-years and the mortality rate was 0.83 (95% CI, 0.44-1.54) per 100 patient-years.. Selected SVT patients followed by anticoagulation clinics for the management of VKA treatment show a low rate of major bleeding and vascular events.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Chi-Square Distribution; Esophageal and Gastric Varices; Female; Gastrointestinal Hemorrhage; Humans; Incidence; Italy; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Patient Safety; Proportional Hazards Models; Retrospective Studies; Risk Factors; Splanchnic Circulation; Time Factors; Treatment Outcome; Venous Thrombosis; Vitamin K; Young Adult

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

Topics: Anticoagulants; Atrial Fibrillation; Cohort Studies; Humans; Retrospective Studies; Venous Thrombosis; Vitamin K

Is long-term (≥3 months) vs short-term therapy with vitamin K antagonists (VKAs) associated with differences in the incidence of recurrent venous thromboembolism (VTE), major bleeding, and mortality in patients with symptomatic VTE?. Long-term treatment with VKAs is associated with a reduced risk for recurrent VTE and an increased risk for major bleeding compared with short-term treatment in patients with VTE, but is not associated with differences in mortality.

Topics: Anticoagulants; Humans; Thromboembolism; Venous Thrombosis; Vitamin K

Vitamin-K antagonists (VKAs) present an effective anticoagulant treatment in deep venous thrombosis (DVT). However, the use of VKAs is limited because of the risk of bleeding and the necessity of frequent and long-term laboratory monitoring. Therefore, new oral anticoagulant drugs (NOACs) such as dabigatran, with lower rates of (major) intracranial bleeding compared to VKAs and not requiring monitoring, may be considered.. To estimate resource utilization and costs of patients treated with the VKAs acenocoumarol and phenprocoumon, for the indication DVT. Furthermore, a formal cost-effectiveness analysis of dabigatran compared to VKAs for DVT treatment was performed, using these estimates.. A retrospective observational study design in the thrombotic service of a teaching hospital (Deventer, The Netherlands) was applied to estimate real-world resource utilization and costs of VKA monitoring. A pooled analysis of data from RE-COVER and RE-COVER II on DVT was used to reflect the probabilities for events in the cost-effectiveness model. Dutch costs, utilities and specific data on coagulation monitoring levels were incorporated in the model. Next to the base case analysis, univariate probabilistic sensitivity and scenario analyses were performed.. Real-world resource utilization in the thrombotic service of patients treated with VKA for the indication of DVT consisted of 12.3 measurements of the international normalized ratio (INR), with corresponding INR monitoring costs of €138 for a standardized treatment period of 180 days. In the base case, dabigatran treatment compared to VKAs in a cohort of 1,000 DVT patients resulted in savings of €18,900 (95% uncertainty interval (UI) -95,832, 151,162) and 41 (95% UI -18, 97) quality-adjusted life-years (QALYs) gained calculated from societal perspective. The probability that dabigatran is cost-effective at a conservative willingness-to pay threshold of €20,000 per QALY was 99%. Sensitivity and scenario analyses also indicated cost savings or cost-effectiveness below this same threshold.. Total INR monitoring costs per patient were estimated at minimally €138. Inserting these real-world data into a cost-effectiveness analysis for patients diagnosed with DVT, dabigatran appeared to be a cost-saving alternative to VKAs in the Netherlands in the base case. Cost savings or favorable cost-effectiveness were robust in sensitivity and scenario analyses. Our results warrant confirmation in other settings and locations.

Topics: Anticoagulants; Antithrombins; Cost Savings; Cost-Benefit Analysis; Dabigatran; Decision Support Techniques; Health Resources; Humans; Netherlands; Pulmonary Embolism; Quality-Adjusted Life Years; Retrospective Studies; Venous Thrombosis; Vitamin K

Topics: Anticoagulants; Aspirin; Drug Therapy, Combination; Early Ambulation; Heparin, Low-Molecular-Weight; Humans; Pulmonary Embolism; Stockings, Compression; Thrombocytopenia; Venous Thrombosis; Vitamin K; Warfarin

Venous thromboembolism (VTE), comprised of deep vein thrombosis (DVT) and pulmonary embolism (PE), is commonly treated with a low-molecular-weight heparin such as enoxaparin plus a vitamin K antagonist (VKA) to prevent recurrence. Administration of enoxaparin + VKA is hampered by complexities of laboratory monitoring and frequent dose adjustments. Rivaroxaban, an orally administered anticoagulant, has been compared with enoxaparin + VKA in the EINSTEIN trials. The objective was to evaluate the cost-effectiveness of rivaroxaban compared with enoxaparin + VKA as anticoagulation treatment for acute, symptomatic, objectively-confirmed DVT or PE.. A Markov model was built to evaluate the costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios associated with rivaroxaban compared to enoxaparin + VKA in adult patients treated for acute DVT or PE. All patients entered the model in the 'on-treatment' state upon commencement of oral rivaroxaban or enoxaparin + VKA for 3, 6, or 12 months. Transition probabilities were obtained from the EINSTEIN trials during treatment and published literature after treatment. A 3-month cycle length, US payer perspective ($2012), 5-year time horizon and a 3% annual discount rate were used.. Treatment with rivaroxaban cost $2,448 per-patient less and was associated with 0.0058 more QALYs compared with enoxaparin + VKA, making it a dominant economic strategy. Upon one-way sensitivity analysis, the model's results were sensitive to the reduction in index VTE hospitalization length-of-stay associated with rivaroxaban compared with enoxaparin + VKA. At a willingness-to-pay threshold of $50,000/QALY, probabilistic sensitivity analysis showed rivaroxaban to be cost-effective compared with enoxaparin + VKA approximately 76% of the time.. The model did not account for the benefits associated with an oral and minimally invasive administration of rivaroxaban. 'Real-world' applicability is limited because data from the EINSTEIN trials were used in the model. Also, resource utilization and costs were based on the US healthcare system.. Rivaroxaban is a cost-effective option for anticoagulation treatment of acute VTE patients.

Topics: Anticoagulants; Cost-Benefit Analysis; Drug Therapy, Combination; Enoxaparin; Humans; Markov Chains; Middle Aged; Morpholines; Quality-Adjusted Life Years; Rivaroxaban; Thiophenes; United States; Venous Thrombosis; Vitamin K

The optimal initial treatment of splanchnic vein thrombosis is uncertain. Anticoagulant therapy has been shown to be associated with vessel recanalization and decreased recurrence. Furthermore, information regarding potential predictors of chronic complications is not well understood.. A retrospective cohort study involving consecutive patients diagnosed with first-episode noncirrhotic splanchnic vein thrombosis referred to the thrombosis clinic of the authors' institution between 2008 and 2011 was conducted. Demographic and clinical information was collected. The response to initial anticoagulant therapy was evaluated by determining radiographic recanalization of vessels and clinical resolution (defined as the absence of ongoing splanchnic vein thrombosis symptoms or complications requiring treatment beyond anticoagulant therapy).. Twenty-two patients were included. Anticoagulant therapy alone resulted in vessel recanalization in 41% of patients and 68% achieved clinical resolution. Two patients experienced bleeding events. Factors associated with a lack of clinical resolution included signs of portal hypertension⁄liver failure on presentation, complete vessel occlusion at diagnosis, presence of a myeloproliferative disorder or JAK2V617F tyrosine kinase mutation and the absence of a local⁄transient predisposing factor.. Anticoagulant therapy appeared to be an effective initial treatment in patients with splanchnic vein thrombosis. Clinical factors may help to identify patients who are at risk for developing complications thus requiring closer monitoring. These findings were limited by the small sample size and need to be explored in larger prospective studies.

Topics: Abdominal Pain; Adult; Aged; Anticoagulants; Female; Heparin, Low-Molecular-Weight; Humans; Hypertension, Portal; Janus Kinase 2; Liver Failure; Male; Middle Aged; Mutation; Myeloproliferative Disorders; Portal Vein; Retrospective Studies; Splanchnic Circulation; Splenic Vein; Treatment Outcome; Venous Thrombosis; Vitamin K

Post-thrombotic syndrome (PTS) is the most common complication of deep vein thrombosis (DVT), but few data are available on the risk factors for PTS.. To assess whether the time-course of D-dimer, FVIII, and thrombotic burden are related to PTS development.. Patients (n=59) with proximal DVT of the lower limbs (age 64; range:20-88years; male 56%) were enrolled on the day of diagnosis (D0) and all received heparin for 5-7days, overlapped and followed by vitamin K antagonists (VKA) for 3months. Whole-leg compression ultrasound examination was conducted on D0 and 7 (D7), 30 (D30), and 90 (D90) days afterwards, when blood samples were also taken for D-dimer (STA Liatest) and FVIII (chromogenic assay) testing. Thrombotic burden was defined at each time point according to a score, which considered thrombosis extent and occlusion degree. Villalta score was evaluated at D30, D90, and D180.. At D90, 12 patients developed PTS (Villalta score ≥5) and the median Villalta score was 1 (IQR 0.3-3.0) and was not correlated with either D-dimer or FVIIII time course. At D180, 13 patients had PTS and they had similar thrombotic score at D0, D30 to those without PTS, but higher at D90 (7.6±5.1 vs. 3.2±3.6; p=0.011). Thrombotic score at D90 was correlated with Villalta score at D90 (rho=0.374, p=0.009) and at D180 (rho=0.436, p=0.006).. Thrombotic burden after 90days of VKA is correlated with PTS.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Anticoagulants; Factor VIII; Female; Fibrin Fibrinogen Degradation Products; Heparin; Humans; Leg; Male; Middle Aged; Postthrombotic Syndrome; Risk Factors; Ultrasonography; Venous Thrombosis; Vitamin K; Young Adult

Venous thromboembolism (VTE) (deep vein thrombosis [DVT] and pulmonary embolism [(PE]) represents a substantial economic burden to the healthcare system. Using data from the randomized EINSTEIN DVT and PE trials, this North American sub-group analysis investigated the potential of rivaroxaban to reduce the length of initial hospitalization in patients with acute symptomatic DVT or PE.. A post-hoc analysis of hospitalization and length-of-stay (LOS) data was conducted in the North American sub-set of patients from the randomized, open-label EINSTEIN trial program. Patients received either rivaroxaban (15 mg twice daily for 3 weeks followed by 20 mg once daily; n = 405) or dose-adjusted subcutaneous enoxaparin overlapping with (guideline-recommended 'bridging' therapy) and followed by a vitamin K antagonist (VKA) (international normalized ratio = 2.0-3.0; n = 401). The open-label study design allowed for the comparison of LOS between treatment arms under conditions reflecting normal clinical practice. LOS was evaluated using investigator records of dates of admission and discharge. Analyses were carried out in the intention-to-treat population using parametric tests. Costs were applied to the LOS based on weighted mean cost per day for DVT and PE diagnoses obtained from the Healthcare Cost and Utilization Project dataset.. Of 382 patients hospitalized, 321 (84%), had acute symptomatic PE; few DVT patients required hospitalization. Similar rates of VTE patients were hospitalized in the rivaroxaban and enoxaparin/VKA treatment groups, 189/405 (47%) and 193/401 (48%), respectively. In hospitalized VTE patients, rivaroxaban treatment produced a 1.6-day mean reduction in LOS (median = 1 day) compared with enoxaparin/VKA (mean = 4.5 vs 6.1; median = 3 vs 4), translating to total costs that were $3419 lower in rivaroxaban-treated patients.. In hospitalized North American patients with VTE, treatment with rivaroxaban produced a statistically significant reduction in LOS. When treating DVT and PE patients, clinicians should consider newer anti-coagulants with less complex treatment regimens.

Topics: Adolescent; Adult; Aged; Anticoagulants; Enoxaparin; Female; Humans; Length of Stay; Male; Middle Aged; Morpholines; Pulmonary Embolism; Rivaroxaban; Thiophenes; United States; Venous Thrombosis; Vitamin K; Young Adult

Topics: Anticoagulants; Hemorrhage; History, 20th Century; History, 21st Century; Humans; International Normalized Ratio; Ontario; Prothrombin Time; Venous Thrombosis; Vitamin K; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Humans; India; Pulmonary Embolism; Stroke; Venous Thrombosis; Vitamin K

Rivaroxaban is one of the new oral anticoagulants (NOACs). It has many potential advantages in comparison with Vitamin K Antagonists (VKA). It has a predictable anticoagulant effect and does not theoretically require biological monitoring. It is also characterized by less food and drug interactions. However, due to major risks associated with over- and under-dosage, its optimal use in patients should be carefully followed by health care professionals. The aim of this article is to provide recommendations for pharmacists on the practical use of Xarelto in its different approved indications. This document is adapted from the practical user guide of rivaroxaban which was developed by an independent group of Belgian experts in the field of thrombosis and haemostasis.

Topics: Anticoagulants; Humans; Morpholines; Pharmacists; Rivaroxaban; Thiophenes; Venous Thrombosis; Vitamin K

The focus of DVT treatment is the prevention of recurrence and thrombus migration by treatment with anticoagulants. The aim is to improve outcomes by reducing clot burden and by preventing thrombus propagation, in order to prevent PE and the development of long-term complication. Actually, initial therapy is parenteral anticoagulation, mainly with low molecular weight heparin followed by a vitamin K antagonist (VKA) for triggered and idiopathic DVT. The long term treatment suggestion with a VKA is for sure the most challenging therapeutic scenario, showing all the disadvantages of VKA especially in the onset phase when therapeutic levels of VKA are difficult to achieve. The difference between VKAs and NOACs is the fact, that NOACs target a specific factor in the coagulation cascade. At time now two pathways have been chosen for treatment options, the direct inhibition of active sites of thrombin and factor Xa. Routine monitoring is not required and the drugs can be administered in fixed doses, which should increase patient adherence to long term treatment. At time now, four novel anticoagulants are called to be options for DVT treatment. Rivaroxaban, apixaban and edoxaban are direct FXa inhibitors, whereas dabigtran etexilate is a direct thrombin inhibitor.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Factor Xa Inhibitors; Humans; Secondary Prevention; Treatment Outcome; Venous Thrombosis; Vitamin K

Despite the recent emergence of new oral anticoagulants, vitamin K antagonists remain the primary therapy in patients with atrial fibrillation and the only therapy licensed for use in patients with artificial heart valves.. The aim of this study was (a) to assess the impact of clinical and genetic factors on acenocoumarol (AC) dose requirements and the percentage of time in therapeutic range (%TTR) and (b) to develop pharmacogenetic-guided AC dose calculation algorithm.. We included 235 outpatients of the Institute of Cardiology (Warsaw), mean age 69.3, 46.9% women, receiving AC for artificial heart valves and/or atrial fibrillation. A multiple linear-regression analysis was performed using log-transformed effective AC dose as the dependent variable, and combining CYP2C9 and VKORC1 genotyping with other clinical factors as independent predictors.. We identified factors that influenced the AC dose: CYP2C9 polymorphisms (P=0.004), VKORC1 polymorphisms (P<0.0001), age (P<0.0001), creatinine clearance lower than 40 ml/min (P=0.035), body mass (P=0.02), and dietary vitamin K intake (P=0.026). Clinical and genetic factors explained 49.0% of AC dose variability. We developed a dosing calculation algorithm that is, to the best of our knowledge, the first one to assess the effect of such clinical factors as creatinine clearance and dietary vitamin K intake on the AC dose. The clinical usefulness of the algorithm was assessed on separate validation group (n=50) with 70% accuracy. Dietary vitamin K intake higher than 200 mcg/day improved international normalized ratio control (%TTR 73.3±17 vs. 67.7±18, respectively, P=0.04).. Inclusion of a variety of genetic and clinical factors in the dosing calculation algorithm allows for precise AC dose estimation in most patients and thus improves the efficacy and safety of the therapy.

Topics: Acenocoumarol; Adult; Aged; Aged, 80 and over; Algorithms; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Atrial Fibrillation; Body Mass Index; Creatinine; Cytochrome P-450 CYP2C9; Dose-Response Relationship, Drug; Drug Dosage Calculations; Female; Genetic Markers; Genetic Variation; Genotype; Heart Valve Prosthesis; Humans; Linear Models; Male; Middle Aged; Poland; Polymorphism, Single Nucleotide; Venous Thrombosis; Vitamin K; Vitamin K Epoxide Reductases

Venous thromboembolism is an increasingly recognised complication in the community and in hospital in-patients. Nowadays, most physicians are familiar with the algorithmic approach to the management of suspected deep vein thrombosis. However, a lack of understanding remains with regard to certain aspects of the diagnostic and treatment pathways, which has resulted in the wrong information being imparted to patients. Some of these issues are discussed in this paper, with considerations for changes in management.

Topics: Anticoagulants; Biomarkers; Diet; Fibrin Fibrinogen Degradation Products; Hemorrhage; Humans; Patient Education as Topic; Physician-Patient Relations; Risk Factors; Venous Thrombosis; Vitamin K

Topics: Administration, Oral; Anticoagulants; Hemorrhage; Humans; Pulmonary Embolism; Pyridines; Randomized Controlled Trials as Topic; Secondary Prevention; Thiazoles; Venous Thrombosis; Vitamin K; Warfarin

For more than a decade, the only treatments available for the prevention of recurrent venous thromboembolism, were vitamin K inhibitors, or low molecular weight heparins (LMWH). Both have been very useful for this purpose; however, with the inconvenience of required frequent laboratory tests and the risk of provoking major hemorrhages. LMWH also carry the risk for immune reactions and the high cost of using it for an extended period of time. With the advent of the new anticoagulants, there is no need for laboratory tests, but there is no way to individualize the dose, or to neutralize their effect. They are also very expensive. Several recent articles have shown that aspirin, as the only treatment for the prevention of recurrent venous thromboembolism, gave good results in comparison to placebo. It has also been found that, after hip replacement surgery, the frequency of thromboembolism was similar in those patients treated with aspirin and those treated with LMWH. These results could open a new path in the search for the ideal treatment for the prevention of recurrent venous thromboembolism.

Topics: Anticoagulants; Antithrombins; Aspirin; Clinical Trials as Topic; Factor Xa Inhibitors; Heparin, Low-Molecular-Weight; Humans; Multicenter Studies as Topic; Pyrazoles; Pyridones; Recurrence; Thromboembolism; Thrombophilia; Venous Thrombosis; Vitamin K

Topics: Aged; Anticoagulants; Colonoscopy; Diagnosis, Differential; Female; Gastrointestinal Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Pulmonary Embolism; Sigmoid Neoplasms; Venous Thrombosis; Vitamin K

Topics: Aged; Anticoagulants; Antitubercular Agents; Comorbidity; Cyclosporine; Drug Substitution; Drug Therapy, Combination; Female; Hemorrhage; Heparin; Humans; Immunosuppressive Agents; Kidney Transplantation; Lung Diseases, Interstitial; Pericarditis; Phenindione; Polypharmacy; Postoperative Complications; Rifampin; Sirolimus; Venous Thrombosis; Vitamin K

Topics: 4-Hydroxycoumarins; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Fibric Acids; France; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indenes; Meta-Analysis as Topic; Pancreatitis; Pharmacoepidemiology; Pharmacovigilance; Pneumonia; Randomized Controlled Trials as Topic; Treatment Outcome; Venous Thrombosis; Vitamin K

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

This article addresses the treatment of VTE disease.. We generated strong (Grade 1) and weak (Grade 2) recommendations based on high-quality (Grade A), moderate-quality (Grade B), and low-quality (Grade C) evidence.. For acute DVT or pulmonary embolism (PE), we recommend initial parenteral anticoagulant therapy (Grade 1B) or anticoagulation with rivaroxaban. We suggest low-molecular-weight heparin (LMWH) or fondaparinux over IV unfractionated heparin (Grade 2C) or subcutaneous unfractionated heparin (Grade 2B). We suggest thrombolytic therapy for PE with hypotension (Grade 2C). For proximal DVT or PE, we recommend treatment of 3 months over shorter periods (Grade 1B). For a first proximal DVT or PE that is provoked by surgery or by a nonsurgical transient risk factor, we recommend 3 months of therapy (Grade 1B; Grade 2B if provoked by a nonsurgical risk factor and low or moderate bleeding risk); that is unprovoked, we suggest extended therapy if bleeding risk is low or moderate (Grade 2B) and recommend 3 months of therapy if bleeding risk is high (Grade 1B); and that is associated with active cancer, we recommend extended therapy (Grade 1B; Grade 2B if high bleeding risk) and suggest LMWH over vitamin K antagonists (Grade 2B). We suggest vitamin K antagonists or LMWH over dabigatran or rivaroxaban (Grade 2B). We suggest compression stockings to prevent the postthrombotic syndrome (Grade 2B). For extensive superficial vein thrombosis, we suggest prophylactic-dose fondaparinux or LMWH over no anticoagulation (Grade 2B), and suggest fondaparinux over LMWH (Grade 2C).. Strong recommendations apply to most patients, whereas weak recommendations are sensitive to differences among patients, including their preferences.

Topics: Administration, Oral; Anticoagulants; Diagnostic Imaging; Drug Administration Schedule; Evidence-Based Medicine; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Infusions, Intravenous; International Normalized Ratio; Long-Term Care; Polysaccharides; Pulmonary Embolism; Risk Factors; Societies, Medical; United States; Venous Thrombosis; Vitamin K

Topics: Administration, Oral; Anticoagulants; Dose-Response Relationship, Drug; Drug Administration Schedule; Guideline Adherence; Humans; Injections, Subcutaneous; Ultrasonography, Doppler, Color; Venous Thrombosis; Vitamin K

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: Adult; Anticoagulants; Antithrombin III; Antithrombin III Deficiency; Factor IX; Hematoma; Humans; Male; Muscular Diseases; Mutation; Phenprocoumon; Protein Precursors; Venous Thrombosis; Vitamin K

Perioperative management of anticoagulants and antiplatelet agents is based on a compromise between the risk of hemorrhage induced by maintaining (or substituting for) them and the risk of thrombosis if they are discontinued. The hemorrhage risk in major spinal surgery is clear (50-81% incidence of transfusion), and the incidence of postoperative symptomatic spinal hematoma varies between 0.4% and 0.2% depending on whether low-molecular-weight heparin (LMWH) is prescribed postoperatively. The French Health Authority, in 2008, published guidelines on the management of patients treated with vitamin K antagonists. Treatment may be stopped without preoperative replacement in certain cases of atrial fibrillation or venous thromboembolic disease; otherwise, preoperative replacement by curative dose unfractionated heparin (UFH) or LMWH is recommended, with withdrawal early enough to avoid peroperative bleeding. Postoperative care should take account of hemorrhagic risk following surgery. The management of patients treated with antiplatelets is delicate, as maintenance is preferable in most of the situations in which they are prescribed (bare or active stenting, or secondary prevention of myocardial infarction, stroke or peripheral ischemia), although they are liable to increase the risk of perioperative hemorrhage, especially when associated to antithrombotic prophylaxis. If surgery cannot be performed under treatment continuation, the interruption should be as short as possible. New guidelines are presently being drawn up under the auspices of the French Health Authority. In both types of treatment, the strategy should be jointly determined by surgeon, anesthesiologist and cardiologist, to optimize individualized care taking account of each party's requirements, with the patient in the central role. The selected strategy should be clearly stated in the patient's file.. V.

Topics: Anticoagulants; Blood Loss, Surgical; Hemorrhage; Humans; Orthopedic Procedures; Perioperative Care; Platelet Aggregation Inhibitors; Postoperative Care; Practice Guidelines as Topic; Risk Assessment; Spine; Venous Thrombosis; Vitamin K

Neonatal renal venous thrombosis (NRVT) is a rare disease, with variable consequences on kidney function. We report a retrospective study of 9 newborns with NRVT admitted to our hospital from 1996 to 2005. The median age at diagnosis was 2 days (range, 1-10 days). In 7 patients, diagnosis was suspected based on one classical clinical or biological sign and was confirmed by ultrasound. Seven newborns had at least one known obstetrical or neonatal risk factor. NRVT was unilateral in three cases, was bilateral in 6 cases, and was associated with inferior vena cava thrombosis in 5 patients, with surrenal hemorrhage in 3 patients. Three patients did not receive specific treatment. The median delay between diagnosis and specific treatment was 20 h (range, 3-36 h). Three patients were treated by fibrinolysis, including 2 with bilateral NRVT, 2 newborns received heparins, and 1 patient was treated with a vitamin K antagonist. With a median evaluation time of 5 years and 2 months for 6 patients, 5 patients recovered their kidney function completely and the 6th child has moderate renal failure. It seems illusory to wait for randomized control studies to appreciate the potential long-term benefit of treatments on kidney function after a NRVT, whose bilateral forms appear to be more severe. A case-by-case approach appears better adapted. These results reinforce recommendations that suggest an early pediatric nephrologic follow-up for all newborns with a NRVT.

Topics: Drug Therapy, Combination; Female; Fibrinolytic Agents; Follow-Up Studies; Heparin; Hospitals, Maternity; Humans; Infant, Newborn; Infant, Newborn, Diseases; Kidney; Male; Paris; Renal Veins; Retrospective Studies; Risk Factors; Survival Rate; Treatment Outcome; Ultrasonography; Vena Cava, Inferior; Venous Thrombosis; Vitamin K

Topics: Anticoagulants; Azetidines; Benzylamines; France; Hemorrhage; Humans; Pulmonary Embolism; Thromboembolism; Thrombosis; Venous Thrombosis; Vitamin K

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

Vitamin K-antagonists (VKA) decreases vitamin K coagulation factors. To counterbalance this effect, it has been postulated that non-vitamin K proteins increase during VKA treatment. To investigate if VKA affect FVIII, a cohort of 1772 patients referred from Jan 1997 to Oct 2008 to our Thrombosis Center for a thrombophilia screening after at least 3 months from diagnosis of first venous thrombosis was studied. At the time of blood sampling, 1303 patients had discontinued VKA for at least one month, whereas the remaining 469 were still taking VKA. FVIII was significantly higher in patients on VKA than in those who had discontinued VKA (mean+/-SD: 144+/-41 IU/dL and 134+/-40 IU/dL, respectively, p<0.0001), also after adjustment for sex, age, body mass index, thrombophilia and time elapsed from thrombosis in a multiple linear regression analysis. In order to avoid overestimation of FVIII levels, patients should be preferentially tested after VKA discontinuation.

Topics: Adult; Anticoagulants; Biomarkers; Blood Coagulation; Blood Coagulation Tests; Chi-Square Distribution; Drug Administration Schedule; Factor VIII; Female; Humans; Italy; Linear Models; Male; Middle Aged; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Venous Thrombosis; Vitamin K

Venous thrombosis typically involves the lower extremity circulation. Rarely, it can occur in the cerebral or splanchnic veins and these are the most frightening manifestations because of their high mortality rate. A third site of rare venous thrombosis is the deep system of the upper extremities that, as for the lower extremity, can be complicated by pulmonary embolism and post-thrombotic syndrome. The authors conducted a narrative review focused on clinical manifestations, risk factors, and treatment of rare venous thromboses. Local risk factors such as infections or cancer are frequent in thrombosis of cerebral or portal veins. Upper extremity deep-vein thrombosis is mostly due to local risk factors (catheter- or effort-related). Common systemic risk factors for rare venous thromboses are inherited thrombophilia and oral contraceptive use; chronic myeloproliferative neoplasms are closely associated with splanchnic vein thrombosis. In the acute phase rare venous thromboses should be treated conventionally with low-molecular-weight heparin. Use of local or systemic fibrinolysis should be considered in the case of clinical deterioration in spite of adequate anticoagulation. Anticoagulation with vitamin K-antagonists is recommended for 3-6 months after a first episode of rare venous thrombosis. Indefinite anticoagulation is recommended for Budd-Chiari syndrome, recurrent thrombosis or unprovoked thrombosis and permanent risk factors. In conclusion, the progresses made in the last couple of decades in diagnostic imaging and the broadened knowledge of thrombophilic abnormalities improved the recognition of rare venous thromboses and the understanding of pathogenic mechanisms. However, the recommendations for treatment mainly derive from observational studies.

Topics: Anticoagulants; Cerebral Veins; Contraceptive Agents; Diagnostic Imaging; Hematologic Neoplasms; Heparin; Humans; Intracranial Thrombosis; Regional Blood Flow; Risk Factors; Splanchnic Circulation; Upper Extremity; Venous Thrombosis; Vitamin K

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

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

Topics: Abdominal Pain; Anticoagulants; Decompression Sickness; Diving; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Portal Vein; Venous Thrombosis; Vitamin K

Statins [3-hydroxymethyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors] and antiplatelet therapy reduce the risk of atherosclerotic disease. Besides a reduction of lipid levels, statins might also have antithrombotic and anti-inflammatory properties, and anti-platelet therapy reduces clot formation. We have studied the risk of venous thrombosis with use of statins, other lipid-lowering medication, and antiplatelet therapy.. Patients with a first episode of deep vein thrombosis in the leg or pulmonary embolism between March 1999 and September 2004 were included in a large population-based case-control study (MEGA study). Control subjects were partners of patients (53%) or recruited via a random-digit-dialing method (47%). Participants reported different all-medication use in a questionnaire.. Of 4538 patients, 154 used statins (3.3%), as did 354 of 5914 control subjects (5.7%). The use of statins [odds ratio (OR) 0.45; 95% confidence interval (CI) 0.36-0.56] but not other lipid-lowering medications (OR 1.22; 95% CI 0.62-2.43), was associated with a reduced venous thrombosis risk as compared with individuals who did not use any lipid-lowering medication, after adjustment for age, sex, body mass index, atherosclerotic disease, antiplatelet therapy and use of vitamin K antagonists. Different types and various durations of statin therapy were all associated with a decreased venous thrombosis risk. Antiplatelet therapy also reduced venous thrombosis risk (OR 0.56; 95% CI 0.42-0.74). However, sensitivity analyses suggested that this effect is most likely explained by a so-called 'healthy user effect'. Simultaneous use of medication most strongly reduced venous thrombosis risk.. These results suggest that the use of various types of statins is associated with a reduced risk of venous thrombosis, whereas antiplatelet therapy and other lipid-lowering medications are not.

Topics: Adolescent; Adult; Aged; Case-Control Studies; Drug Therapy, Combination; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypolipidemic Agents; Male; Middle Aged; Platelet Aggregation Inhibitors; Risk; Surveys and Questionnaires; Treatment Outcome; Venous Thrombosis; Vitamin K; Young Adult

Cerebral venous thrombosis is an uncommon disease characterized by expansive cerebral edema, venous infarction and massive intracerebral hemorrhage. Magnetic resonance imaging and angiography are useful for diagnosis of cerebral venous thrombosis. A 54-year-old man was admitted with headache, vomiting and right hemiparesis. Computed tomography (CT) revealed subcortical hematoma in the left parietal lobe. Digital subtraction angiography (DSA) demonstrated occlusion of the left Labbé vein with dilation of cortical veins and deep cerebral veins. He also suffered from pulmonary embolization and deep vein thrombosis in the lower extremities. Anticoagulant and thrombolytic agents were administered, then respiratory condition and hemiparesis were improved. However, his condition deteriolated 7 months after the initial attack. CT revealed huge subcortical hematoma in the same site. He underwent craniotomy and intracerebral hematoma was evacuated during treatment with vitamin K. His symptom gradually improved and he was discharged with moderate disability 2 months after operation. Dicision of surgical treatment is difficult because there is a risk of rebleeding due to thrombolytic therapy and progressive venous congestion. Since anticoagulant and thrombolytic therapy are inevitable, surgical indication for refractory intracerebral hemorrhage associated with cerebral venous thrombosis should be considered carefully.

Topics: Cerebral Hemorrhage; Diagnostic Imaging; Fibrinolytic Agents; Humans; Male; Middle Aged; Perioperative Care; Venous Thrombosis; Vitamin K

The current approach for deciding the duration of vitamin K antagonist (VKA) treatment after an episode of venous thrombo-embolism (VTE) is mainly based on the characteristic of the index event (3 months or longer in case of unknown/persistent risk factors, 3 months or less in case of removable causes). However, the length of anticoagulation should be tailored on the patient's risk for recurrent thrombosis as well as for bleeding, but such 'time for decision' is often unclear and the optimal duration of VKA remains debatable. The presence of persistent residual vein thrombosis and increased D-dimer levels after stopping therapy are predictors for recurrent deep vein thrombosis (DVT). Management strategies based on these parameters have been demonstrated to optimize the decision for VKA duration, as they establish the patient's intrinsic risk for recurrent events. This annotation discusses current practice and upcoming approaches regarding the length of VKA treatment after a first episode of DVT.

Topics: Biomarkers; Drug Administration Schedule; Fibrin Fibrinogen Degradation Products; Fibrinolytic Agents; Humans; Neoplasms; Recurrence; Risk Assessment; Time Factors; Venous Thrombosis; Vitamin K; Vitamins

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

In the initial treatment of venous thromboembolism (VTE) fondaparinux, a pentasaccharide, is a good alternative to heparin. Whether this is also true for cancer patients is unknown. We performed two post-hoc analyses of two randomized studies to compare efficacy, safety and overall survival of fondaparinux to standard initial (low-molecular-weight) heparin (LMWH) treatment in cancer patients with venous thromboembolism. Two hundred thirty-seven cancer patients with deep venous thrombosis (DVT) were initially treated with fondaparinux or enoxaparin. Two hundred forty cancer patients with pulmonary embolism (PE) received fondaparinux or unfractionated heparin. The initial treatment was followed by vitamin K antagonists. In DVT patients, the three-month recurrence rate was 5.4% in the enoxaparin recipients compared to 12.7% in those treated with fondaparinux [absolute difference 7.3%, 95% CI 0.1, 14.5]. A recurrence was observed in 8.9% of the PE patients treated with fondaparinux compared to 17.2% in the unfractionated heparin recipients [absolute difference -8.3, 95% CI -16.7, 0.1]. In both studies no difference in bleeding and overall survival was observed. Regarding overall survival and bleeding fondaparinux is comparable to enoxaparin and unfractionated heparin in cancer patients. No significant differences in recurrent VTE were observed when comparing fondaparinux with unfractionated or LMWH. Because of study limitations these results should be considered hypothesis-generating.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Double-Blind Method; Enoxaparin; Female; Fondaparinux; Hemorrhage; Heparin; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasms; Polysaccharides; Proportional Hazards Models; Pulmonary Embolism; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Assessment; Secondary Prevention; Time Factors; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis; Vitamin K; Young Adult

(1) The standard anticoagulant for preventing thromboembolic events after hip or knee replacement surgery is a subcutaneous low-molecular-weight heparin such as enoxaparin; (2) Dabigatran, a specific thrombin inhibitor, was recently licensed for oral prophylaxis in this setting, as dabigatran etexilate (mesilate), a prodrug; (3) The clinical evaluation of dabigatran in this indication is based on two comparative double-blind trials with similar protocols, comparing dabigatran 150 mg or 220 mg/day versus enoxaparin in 3494 patients undergoing hip replacement surgery and 2101 patients undergoing knee replacement surgery. The results were virtually identical: compared with enoxaparin, dabigatran did not reduce overall mortality (almost zero in the different groups), the frequency of symptomatic pulmonary embolism (almost zero in the different groups), or the frequency of symptomatic deep venous thrombosis (0.1% to 1.2%); (4) There was no difference between the groups with respect to the frequency of severe bleeding (about 1.5%), hepatic disorders (about 4%), or acute coronary events (a few cases). But dabigatran was associated with surgical wound seepage in 7% of patients, versus 4.7% with enoxaparin; (5) The anticoagulant effect of dabigatran, and therefore the frequency of haemorrhage, increases with age and in cases of renal failure. However, clinical trials included relatively few elderly patients and/or patients with renal failure, who nonetheless represent a large proportion of the candidates for hip or knee replacement; (6) Dabigatran becomes more potent when combined with P-glycoprotein inhibitors or with drugs that impair renal function. Combination with other antithrombotic drugs should be avoided. (7) Dabigatran is administered orally, while enoxaparin requires daily subcutaneous injections. Dabigatran therapy does not necessitate laboratory monitoring, while the platelet count must be monitored with enoxaparin. There is no known antidote for dabigatran overdose; (8) In summary, for the prevention of venous thromboembolic events after orthopaedic surgery, it is better to continue to use heparins, at least pending more thorough evaluation of dabigatran.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; Dabigatran; Drug Approval; Enoxaparin; Factor Xa Inhibitors; Fibrinolytic Agents; France; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hirudin Therapy; Humans; Prodrugs; Pyridines; Randomized Controlled Trials as Topic; Thrombin; Thromboembolism; Venous Thrombosis; Vitamin K

Factor V Leiden (R506Q) mutation is the most commonly observed inherited genetic abnormality related to vein thrombosis. Lebanon has one of the highest frequencies of this mutation in the world with a prevalence of 14.4% in the general population. The aim of this study is to define risk factors including inherited genetic abnormalities among Lebanese patients with lower extremity deep vein thrombosis. We report the clinical outcome of patients with thrombophilia.. From January 1998 to January 2008, 162 patients (61 males and 101 females) were diagnosed with lower extremity deep vein thrombosis. Mean age was 61 years (range: 21 to 95 years).. The most frequent risk factors for vein thrombosis were surgery, advanced age, obesity, and cancer. Twenty-five patients had thrombophilia, 16 patients had factor V Leiden (R506Q) mutation, and seven patients had MTHFR C677T mutation. Ninety-two percent of patients screened for thrombophilia were positive. Screening was requested in young patients (16), patients with recurrent (11), spontaneous (8), and extensive (5) venous thrombosis, familial history (5), pregnancy (4), estroprogestative treatment (3), and air travel (1). Nine patients had one, 11 patients had two, and five had three of these conditions. Follow-up (6 to 120 months) of these 25 patients treated with antivitamin K did not reveal recurrences or complications related to venous thromboembolism.. Factor V Leiden mutation followed by MTHFR mutation are the most commonly observed genetic abnormalities in these series. Defining risk factors and screening for thrombophilia when indicated reduce recurrence rate and complications. Recommendations for thrombophilia screening will be proposed.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Asian People; Factor V; Female; Gene Frequency; Genetic Predisposition to Disease; Humans; Incidence; Lebanon; Lower Extremity; Male; Mass Screening; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Mutation; Neoplasms; Obesity; Recurrence; Risk Assessment; Risk Factors; Surgical Procedures, Operative; Thrombophilia; Treatment Outcome; Venous Thrombosis; Vitamin K; Young Adult

Knowledge on the natural history of mesenteric vein thrombosis (MVT) and of the efficacy and safety of long-term oral anticoagulant therapy (OAT) in this setting is based on small uncontrolled series of patients with a limited follow-up. It was the aim of the study to assess the natural history of MVT in a cohort of patients treated with OAT. The charts of all MVT patients currently attending or who have attended four anticoagulation clinics were reviewed. Information on risk factors, treatment, recurrence, major bleeding and mortality was collected. Seventy-seven patients (mean age 49.2 years; 45 males) were included with a median follow-up of 36 months (range 2-204 months). Forty-six patients were treated with long-term OAT. Seven patients had venous thromboembolism (VTE) recurrence (5 splanchnic vein thromboses and two pulmonary emboli) for an incidence rate of 23.4 events /1,000 year patients. In two patients recurrent VTE occurred during OAT, for an incidence rate of 10.5 events /1,000 year patient. Five patients had VTE recurrence when OAT was suspened for an incidence rate of 45.9 events /1,000 year patient. Two patients (2.6%) had a major bleeding event. 97.3% of patients were alive at one year, and seven patients (9.1%) died during follow up. In conclusion, patients with MTV seem to have a low risk of recurrent VTE while receiving OAT. This risk appears increased after treatment is stopped.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Cohort Studies; Female; Humans; Male; Mesenteric Arteries; Middle Aged; Retrospective Studies; Risk; Risk Factors; Venous Thrombosis; Vitamin K

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

This chapter about treatment for venous thromboembolic disease is part of the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do or do not outweigh risks, burden, and costs. Grade 2 suggests that individual patient values may lead to different choices (for a full understanding of the grading, see "Grades of Recommendation" chapter). Among the key recommendations in this chapter are the following: for patients with objectively confirmed deep vein thrombosis (DVT) or pulmonary embolism (PE), we recommend anticoagulant therapy with subcutaneous (SC) low-molecular-weight heparin (LMWH), monitored IV, or SC unfractionated heparin (UFH), unmonitored weight-based SC UFH, or SC fondaparinux (all Grade 1A). For patients with a high clinical suspicion of DVT or PE, we recommend treatment with anticoagulants while awaiting the outcome of diagnostic tests (Grade 1C). For patients with confirmed PE, we recommend early evaluation of the risks to benefits of thrombolytic therapy (Grade 1C); for those with hemodynamic compromise, we recommend short-course thrombolytic therapy (Grade 1B); and for those with nonmassive PE, we recommend against the use of thrombolytic therapy (Grade 1B). In acute DVT or PE, we recommend initial treatment with LMWH, UFH or fondaparinux for at least 5 days rather than a shorter period (Grade 1C); and initiation of vitamin K antagonists (VKAs) together with LMWH, UFH, or fondaparinux on the first treatment day, and discontinuation of these heparin preparations when the international normalized ratio (INR) is > or = 2.0 for at least 24 h (Grade 1A). For patients with DVT or PE secondary to a transient (reversible) risk factor, we recommend treatment with a VKA for 3 months over treatment for shorter periods (Grade 1A). For patients with unprovoked DVT or PE, we recommend treatment with a VKA for at least 3 months (Grade 1A), and that all patients are then evaluated for the risks to benefits of indefinite therapy (Grade 1C). We recommend indefinite anticoagulant therapy for patients with a first unprovoked proximal DVT or PE and a low risk of bleeding when this is consistent with the patient's preference (Grade 1A), and for most patients with a second unprovoked DVT (Grade 1A). We recommend that the dose of VKA be adjusted to maintain a target INR of 2.5 (INR range, 2.0 to 3.0) for all treatment durations (Grade 1A). We recommend at

Topics: Drug Therapy, Combination; Evidence-Based Medicine; Fibrinolytic Agents; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Injections, Intravenous; Injections, Subcutaneous; International Normalized Ratio; Polysaccharides; Pulmonary Embolism; Risk Assessment; Venous Thrombosis; Vitamin K

This chapter about antithrombotic therapy in neonates and children is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs, and Grade 2 suggests that individual patient values may lead to different choices (for a full understanding of the grading, see Guyatt et al in this supplement, pages 123S-131S). In this chapter, many recommendations are based on extrapolation of adult data, and the reader is referred to the appropriate chapters relating to guidelines for adult populations. Within this chapter, the majority of recommendations are separate for neonates and children, reflecting the significant differences in epidemiology of thrombosis and safety and efficacy of therapy in these two populations. Among the key recommendations in this chapter are the following: In children with first episode of venous thromboembolism (VTE), we recommend anticoagulant therapy with either unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) [Grade 1B]. Dosing of IV UFH should prolong the activated partial thromboplastin time (aPTT) to a range that corresponds to an anti-factor Xa assay (anti-FXa) level of 0.35 to 0.7 U/mL, whereas LMWH should achieve an anti-FXa level of 0.5 to 1.0 U/mL 4 h after an injection for twice-daily dosing. In neonates with first VTE, we suggest either anticoagulation or supportive care with radiologic monitoring and subsequent anticoagulation if extension of the thrombosis occurs during supportive care (Grade 2C). We recommend against the use of routine systemic thromboprophylaxis for children with central venous lines (Grade 1B). For children with cerebral sinovenous thrombosis (CSVT) without significant intracranial hemorrhage (ICH), we recommend anticoagulation initially with UFH, or LMWH and subsequently with LMWH or vitamin K antagonists (VKAs) for a minimum of 3 months (Grade 1B). For children with non-sickle-cell disease-related acute arterial ischemic stroke (AIS), we recommend UFH or LMWH or aspirin (1 to 5 mg/kg/d) as initial therapy until dissection and embolic causes have been excluded (Grade 1B). For neonates with a first AIS, in the absence of a documented ongoing cardioembolic source, we recommend against anticoagulation or aspirin therapy (Grade 1B).

Topics: Aspirin; Child; Drug Therapy, Combination; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Infant, Newborn; Partial Thromboplastin Time; Risk Assessment; Risk Factors; Venous Thrombosis; Vitamin K

Little is known about the consequences of a first venous thrombosis in the upper extremity. We studied the incidence of, survival, and risk factors for recurrence in a follow-up study.. We followed up 224 patients 18 to 70 years of age after a first venous thrombosis of the arm. Information was collected through anticoagulation clinics, the national death registry, discharge letters, and questionnaires. The median follow-up was 3 years, during which time 30 patients experienced a recurrent event, yielding an incidence rate of 43.2 per 1000 person-years. Survival was reduced: 55 of 224 patients died, which was 5.4-fold higher than age- and sex-adjusted population rates (standardized mortality ratio, 5.4; 95% CI, 4.2 to 7.0). The risk of recurrence was 2-fold higher in women than in men (hazard ratio, 1.8; 95% CI, 0.9 to 3.9). A central venous catheter at the time of first thrombosis was associated with a reduced risk of recurrence. A body mass index > or =25 kg/m(2) and a first nonsubclavian thrombosis appeared to increase the risk of a recurrent event. Prothrombotic mutation carriers did not appear to have an increased recurrence risk.. The risk of recurrence was high, with women, patients with body mass index > or =25 kg/m(2), and patients with a first nonsubclavian vein thrombosis having a higher risk of recurrence. Patients with a first venous thrombosis of the arm have a poor vital prognosis.

Topics: Adolescent; Adult; Aged; Axillary Vein; Blood Coagulation Tests; Female; Follow-Up Studies; Humans; Incidence; Jugular Veins; Male; Middle Aged; Neoplasms; Recurrence; Risk Factors; Sex Distribution; Subclavian Vein; Survival Analysis; Upper Extremity; Veins; Venous Thrombosis; Vitamin K

To assess the predictive value of D-dimer (D-d) and Factor VIII (FVIII) in combination for recurrent venous thromboembolism (VTE) after vitamin K antagonist (VKA) therapy suspension.. Consecutive outpatients with a first episode of idiopathic proximal deep vein thrombosis of the lower limbs were enrolled on the day of VKA suspension. After 30+/-10 days, D-d (cut-off value: 500 ng/mL), chromogenic FVIII activity and inherited thrombophilia were determined. Follow-up was 2 years.. Overall recurrence rate was 16.4% (55/336; 95% CI:13-21%). The multivariate hazard ratio (HR) for recurrence was 2.45 (95% CI: 1.24-4.99) for abnormal D-d and 2.76 (95% CI:1.57-4.85) for FVIII above the 75th percentile (2.42 U/mL) after adjustment for age, sex, thrombophilia, VKA duration and residual venous obstruction. When compared with normal D-d and FVIII, the multivariate HR was 4.5 (95% CI: 1.7-12.2) for normal D-d with FVIII above 2.42 U/mL and 2.7 (95% CI: 1.2-6.6) and 7.1 (95% CI:2.8-17.6) for abnormal D-d with FVIII, respectively, below and above 2.42 U/mL.. D-d and FVIII at 30+/-10 days after VKA withdrawal are independent risk factors for recurrent VTE.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Factor VIII; Female; Fibrin Fibrinogen Degradation Products; Humans; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Recurrence; Risk Factors; Venous Thrombosis; Vitamin K

Topics: Administration, Oral; Anticoagulants; Heparin; Humans; Pulmonary Embolism; Recurrence; Venous Thromboembolism; Venous Thrombosis; Vitamin K

Topics: Anticoagulants; Blood Chemical Analysis; Fibrin Fibrinogen Degradation Products; Humans; Pulmonary Embolism; Venous Thrombosis; Vitamin K

Topics: Ambulatory Care; Anticoagulants; Cost-Benefit Analysis; Female; Heparin; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Pregnancy; Pregnancy Complications, Hematologic; Pulmonary Embolism; Secondary Prevention; Stockings, Compression; Thromboembolism; Thrombolytic Therapy; Vena Cava Filters; Venous Thrombosis; Vitamin K

Venous thromboembolism is a common condition affecting 7.1 persons per 10,000 person-years among community residents. Incidence rates for venous thromboembolism are higher in men and African Americans and increase substantially with age. It is critical to treat deep venous thrombosis at an early stage to avoid development of further complications, such as pulmonary embolism or recurrent deep venous thrombosis. The target audience for this guideline is all clinicians caring for patients who have been given a diagnosis of deep venous thrombosis or pulmonary embolism. The target patient population is patients receiving a diagnosis of pulmonary embolism or lower-extremity deep venous thrombosis.

Topics: Ambulatory Care; Anticoagulants; Cost-Benefit Analysis; Female; Heparin; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Pregnancy; Pregnancy Complications, Hematologic; Pulmonary Embolism; Secondary Prevention; Stockings, Compression; Thromboembolism; Thrombolytic Therapy; Vena Cava Filters; Venous Thrombosis; Vitamin K

Making decisions about any modality of secondary prophylaxis in patients with venous thromobembolism (VTE) has to balance the risk of bleeding induced by anticoagulants against the benefit of reducing the risk of recurrent disease. It has to be kept in mind that the magnitude of risk is not only defined by the number of events per time period but also by the impact of the event on the fate of the patient. With standard intensity vitamin K antagonists (VKA), the risk of bleeding is more closely related to comorbidities than to other factors, eg age. The risk of VTE recurrence differs largely between patient groups. The criterion of presence or absence of a permanent or transient clinical trigger factor for the actual VTE episode has a greater impact than an abnormal result in thrombophilia testing. The standard period of secondary prophylaxis for proximal DVT and for PE is three to six months. The concept of prolonging this period for several months according to the risk of recurrence is seriously challanged by the observation that the prolongation period seems to delay recurrencies rather than truly avoiding them. For this reason, patients who clearly are threatened by recurrent episodes should receive indefinitive secondary prophylaxis. This is the case for cancer patients, patients with the antiphospholipid syndrome, and those who belong to families with severe and symptomatic protein C, protein S, or antithrombin deficiencies. Patients with recurrent VTE, with idiopathic VTE, or with combined thrombophilic conditions may only benefit from indefinitive secondary prophylaxis if the bleeding risk of the anticoagulant regimen under consideration is very low.

Topics: Anticoagulants; Hemorrhage; Humans; Incidence; Recurrence; Risk Factors; Thromboembolism; Venous Thrombosis; Vitamin K

Topics: Anticoagulants; Drug Administration Schedule; Factor Xa Inhibitors; Female; Fibrin; Fondaparinux; Humans; Middle Aged; Perioperative Care; Phenprocoumon; Polysaccharides; Postoperative Hemorrhage; Surgical Procedures, Operative; Thromboembolism; Thrombophilia; Venous Thrombosis; Vitamin K

Topics: Aged; Coumarins; Female; Humans; Male; Middle Aged; Pulmonary Embolism; Recurrence; Registries; Venous Thrombosis; Vitamin K

Initial treatment of venous thromboembolic events is currently based on antithrombotics. This treatment is validated and identical for deep vein thrombosis (DVT) and pulmonary embolism. For distal DVT, this treatment has still to be validated. This reference therapeutic strategy is firstly parenteral and based on low-molecular-weight heparins (LMWH) or fondaparinux, subcutaneously prescribed at fixed dosage based on body weight without any systematic dose adjustment on hemostasis tests. Unfractionated heparin is steel the reference treatment in case of severe renal insufficiency. This parenteral treatment has to be relieved by vitamin K antagonists (VKA). VKA has to be co-administrated for at least 3 days, without any loading dose and can be early initiated. VKA dose needs to be adjusted in order to maintain INR between 2 and 3. However, in case of cancer, LMWH have to be carried on for 6 months. A part this antithrombotic treatment, thrombolytics are recommended in case of massive PE and vena cava filter should be used in case of recurrence despite adequate antithrombotic treatment or in case of contraindication to antithrombotic.

Topics: Anticoagulants; Antifibrinolytic Agents; Factor X; Fibrinolytic Agents; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Injections, Intravenous; Injections, Subcutaneous; International Normalized Ratio; Polysaccharides; Pulmonary Embolism; Renal Insufficiency; Thromboembolism; Vena Cava Filters; Venous Thrombosis; Vitamin K

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

The antiphospholipid syndrome had been rarely reported as a cause of mesenteric venous thrombosis.. We report two exceptional cases of primary antiphospholipid syndrome associated with mesenteric venous thrombosis in 51 years old man and 27 years old women.. Identifying the underlying process is very important to try to propose a specific treatment.

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Female; Fibrinolytic Agents; Follow-Up Studies; Heparin, Low-Molecular-Weight; Humans; Male; Mesenteric Vascular Occlusion; Mesenteric Veins; Middle Aged; Time Factors; Treatment Outcome; Venous Thrombosis; Vitamin K

Topics: Acute Disease; Algorithms; Anticoagulants; Drug Monitoring; Hemorrhage; Heparin; Humans; Long-Term Care; Patient Selection; Risk Factors; Thromboembolism; Venous Thrombosis; Vitamin K

LMWHs are the major anticoagulant/antithrombotic treatment given to pregnant women to prevent and treat venous thromboembolism despite the absence of specific clinical trials. An emerging indication, the prevention of adverse pregnancy outcomes, is under investigation. During pregnancy, LMWHs seem to be safe and efficient. Some uncertainties remain about the management of rare potential side effects, particularly in the event of heparin intolerance and with cross-reactivity to danaparoid sodium.

Topics: Abnormalities, Drug-Induced; Anticoagulants; Contraindications; Dermatitis, Allergic Contact; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Humans; Pregnancy; Pregnancy Complications, Hematologic; Thrombocytopenia; Thrombophilia; Venous Thrombosis; Vitamin K

Topics: Anticoagulants; Biomarkers; Drug Administration Schedule; Drug Monitoring; Fibrin Fibrinogen Degradation Products; Humans; Practice Guidelines as Topic; Predictive Value of Tests; Randomized Controlled Trials as Topic; Risk Factors; Secondary Prevention; Venous Thrombosis; Vitamin K

Renal vein thrombosis is a rare pathology difficult to diagnose. It has quite various clinical expressions and biological consequences. The diagnosis is based upon radiologic explorations. This entity may have various causes. Detecting this condition may lead to restoration of renal function compromised by renal vein thrombosis. The treatment of renal vein thrombosis is mainly medical and based on anticoagulants. The role of fibrinolytic treatment is controversial. Surgery is exceptional. We report two cases of idiopathic thrombosis of the renal vein in adult patient. Also, we have done a review of the literature on this clinical syndrome and its diagnostic and therapeutic aspects.

Topics: Anticoagulants; Female; Fibrinolytic Agents; Follow-Up Studies; Heparin; Humans; Male; Middle Aged; Radiography, Abdominal; Renal Veins; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Ultrasonography, Doppler; Urography; Venous Thrombosis; Vitamin K

Topics: Anticoagulants; Budd-Chiari Syndrome; Contraception; Contraindications; Female; Heparin; Humans; Hypertension, Portal; Liver; Liver Transplantation; Male; Myeloproliferative Disorders; Portal System; Portal Vein; Portasystemic Shunt, Transjugular Intrahepatic; Pregnancy; Retrospective Studies; Risk Factors; Sclerosis; Stents; Venous Thrombosis; Vitamin K

Protein Z is a vitamin K-dependent glycoprotein that plays a role in the regulation of coagulation. A nucleotide substitution of G by C in exon II of the protein Z gene, resulting in the replacement of Glu-30 with Gln (E30Q), and a G to A transition at the 79th nucleotide in intron F (IntF79G/A) were heterozygously identified in a patient with a severe thrombotic tendency, whose plasma protein Z level was about 15% of normal. Other vitamin K-dependent coagulation factors were within normal ranges. Glu-30 is one of 13 gamma-carboxylation sites in protein Z and is well conserved among vitamin K-dependent proteins. Expression studies revealed that the E30Q mutant was not released from synthesizing cells, although wild-type protein Z was readily secreted in a vitamin K-dependent fashion. The E30Q mutant was N-glycosylated, gamma-carboxylated, and translocated from the endoplasmic reticulum (ER) to the Golgi in the presence of vitamin K, as was the wild type. Coexpression of E30Q with wild-type protein Z interfered with the secretion of the wild type, while only a minor or no effect was observed on the secretion of factor X and plasminogen. The IntF79A allele has been reported to be also associated with lowered protein Z levels.

Topics: Amino Acid Substitution; Animals; Blood Proteins; Cell Line; Cricetinae; DNA, Complementary; Female; Glycosylation; Humans; Kidney; Point Mutation; Protein Structure, Tertiary; Transfection; Venous Thrombosis; Vitamin K

The efficacy and safety of vitamin K antagonists (VKA) are related to the actual level of anticoagulation (given as the international normalized ratio, INR). It is often difficult to maintain an optimal INR over time. We assessed the clinical impact of the individual time spent within INR target range (ITTR) in 2304 consecutive patients with venous thromboembolism. Annual incidences of recurrent thromboembolism and major bleeding were 6.2% and 2.8% respectively. The relative risk (RR) of thromboembolism was 4.5 [95% confidence interval (CI) 3.1-6.6, P < 0.001] at INR < 2.0, for major bleeding it was 6.4 (2.5-16.1, P < 0.001) at INR > 5.0, compared with INR 2.0-3.0. Patients with ITTR < 45% were at higher risk than those with ITTR > 65% (RR 2.8, 1.9-4.3, P < 0.001), while no difference was demonstrated comparing ITTR 45-65% and ITTR > 65% (RR 1.2, 0.7-1.8, P = 0.54). Annual incidences of recurrent thromboembolism were 16.0%, 4.9% and 4.6% at ITTR < 45%, 45-60% and >65% respectively. For major bleeding these were 8.7%, 2.1% and 1.9% respectively. ITTR < 37% during the first 30 treatment days was highly predictive for the total treatment time ITTR < 45% (RR 24.2, 13.5-43.1, P < 0.001). In conclusion, ITTR can be used to identify patients on VKA at risk of recurrent thromboembolism or major bleeding. Since the 30-d ITTR is highly predictive for total treatment ITTR, these patients can be identified soon after start of treatment.

Topics: Anticoagulants; Drug Administration Schedule; Drug Monitoring; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Prothrombin Time; Pulmonary Embolism; Recurrence; Retrospective Studies; Treatment Outcome; Venous Thrombosis; Vitamin K

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

Making decisions about any modality of secondary prophylaxis in patients with venous thromobembolism (VTE) has to balance the risk of bleeding induced by anticoagulants against the benefit of reducing the risk of recurrent disease. It has to be kept in mind that the magnitude of risk is not only defined by the number of events per time period but also by the impact of the event on the fate of the patient. With standard intensity Vitamin K antagonists, the risk of bleeding is more closely related to comorbidities than to other factors, e.g. age. The risk of VTE recurrence differs largely between patient groups. The criterion of presence, or absence of a permanent or transient clinical trigger factor for the actual VTE episode has a greater impact than an abnormal result in thrombophilia testing. The standard period ofsecondary prophylaxis for proximal deep vein thrombosis and for pulmonary embolism is three to six months. The concept of prolonging this period for several months according to the risk of recurrence is seriously challanged by the observation that the prolongation period seems to delay recurrencies rather than truly avoiding them. For this reason, patients who clearly are threatened by recurrent episodes should receive indefinitive secondary prophylaxis. This is the case for cancer patients, patients with the antiphospholipid syndrome, and those who belong to families with severe and symptomatic protein C, protein S, or antithrombin deficiencies. Patients with recurrent VTE, with idiopathic VTE, or with combined thrombophilic conditions may only benefit from indefinitive secondary prophylaxis if the bleeding risk of the anticoagulant regimen under consideration is very low.

Topics: Anticoagulants; Comorbidity; Hemorrhage; Humans; Pulmonary Embolism; Risk Factors; Secondary Prevention; Thrombophilia; Venous Thrombosis; Vitamin K

About 30% of patients with an episode of adequately treated deep venous thrombosis (DVT) develop the postthrombotic syndrome (PTS) within 2 years. During treatment with vitamin K antagonists (VKA) patients spend only 60% of time between an International Normalized Ratio (INR) of 2.0 and 3.0. We hypothesized that patients who spend a large amount of their time beneath this range will have an increased risk of the PTS.. To investigate the relation between the quality of anticoagulant therapy with VKA and the risk of the development of the PTS.. The time spent beneath the therapeutic range was calculated for patients with a first episode of DVT, who were treated with VKA for at least 3 months. At follow-up assessments for a maximum of 5 years, presence and severity of signs and symptoms of PTS were recorded.. A total of 244 patients, with a median duration of follow-up of 4.9 years were included for analysis. Of these, 81 patients (33%) developed the PTS. The multivariate model showed that patients who spend more than 50% of their time beneath an INR level of 2.0 are at higher risk for PTS [odds ratio (OR): 2.71, 95% CI: 1.44-5.10].. Low quality treatment with VKA, which is a common condition, is related to the occurrence of the PTS in patients with DVT. Strategies aimed at improving the quality of long-term anticoagulation might have the potential to reduce the incidence of this complication.

Topics: Aged; Anticoagulants; Bandages; Clinical Trials as Topic; Cohort Studies; Female; Humans; International Normalized Ratio; Male; Middle Aged; Multivariate Analysis; Neoplasms; Odds Ratio; Postphlebitic Syndrome; Quality Control; Retrospective Studies; Risk; Time Factors; Venous Thrombosis; Vitamin K

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

We assessed the predictive value of D-dimer levels in combination with residual venous obstruction (RVO) for recurrent venous thromboembolism (VTE) in a prospective cohort of outpatients after oral anticoagulant therapy (OAT) suspension for a first episode of idiopathic proximal deep vein thrombosis of the lower limbs during a 2-year follow-up. Patients (n=400) were enrolled on the day of OAT suspension when RVO was determined by compression ultrasonography (present in 48.6% of patients). D-dimer (cut-off value: 500 ng/mL) was measured 30+/-10 days afterwards (abnormal in 56.4% of patients). The overall recurrence rate was 16.7% (67/400; 95% confidence intervals - CI -: 13-21 %). The multivariate hazard ratio (HR) for recurrence was 3.32 (95% CI: 1.78-6.75; p<0.0001) for abnormal D-dimer compared to normal D-dimer and 1.2 (95% CI:0.72-2.07; p>0.05) for RVO compared to absent RVO. The recurrence rate was 5.7% (95% CI:2-13%) and 10.4% (95% CI:6-18%), respectively, for normal D-dimer either without or with RVO, 22.9% (95% CI: 14-33%) and 25.9% (95% CI: 18-35%), respectively, for abnormal D-dimer, either without or with RVO. When compared with normal D-dimer without RVO, the multivariate HR for recurrence was similar for abnormal D-dimer either with RVO (4.76 - 95% CI:1.78-12.8) or without RVO (4.3-95%:1.56-11.88). Abnormal D-dimer at one month after OAT withdrawal is an independent risk factor for recurrent VTE, while RVO at the time of OAT withdrawal, either with normal or abnormal D-dimer after one month, does not influence the risk of recurrence.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Biomarkers; Female; Fibrin Fibrinogen Degradation Products; Follow-Up Studies; Humans; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Recurrence; Risk Factors; Thrombophilia; Venous Thrombosis; Vitamin K

The risk of thromboembolic events related to travel is not exclusively due to air travel. We report the case of a patient who presented pulmonary embolism after prolonged train travel.. An 82 Year-old patient had a significant past history of ischemic heart disease. He traveled by train, in a sitting position, for around 12 hours from Barcelona (Spain) to Paris (France). Approximately 24 hours after the journey, he presented pain in the right leg and dyspnea, which increased during the following 48 hours. Ultrasonographic cardiac examination revealed pulmonary arterial hypertension (54mm Hg), acute right ventricular failure and showed a thrombus located in the pulmonary artery, confirming the diagnosis of pulmonary embolism. Ultrasonography diagnosed deep venous thrombosis of the right leg. Treatment with heparin and oral anticoagulant was initiated. Evolution was favorable and the patient was discharged home 14 days later. No further medical event occurred during the Year that followed.. The mechanisms that precede the development of a venous thrombosis are not specific to the method of transport. Blood vessel wall lesions, venous stasis and blood clotting component abnormalities, principle elements in the development of thrombosis according to Virchow's triad, are enhanced by prolonged sitting position, during travel, whether in planes or not. The role of other risk factors, personal or depending on the condition of travel, remains unknown. Simple prophylactic measures should be widely proposed during long travel, whatever the mode of transport.. The development of a venous thrombosis, enhanced by prolonged sitting position, can occur whatever the form of travel. Prophylactic measures should be widely prescribed for prolonged travel, taking in consideration personal thromboembolic risk factors and circumstances of travel.

Topics: Aged; Aged, 80 and over; Anticoagulants; Echocardiography; Follow-Up Studies; Heparin; Humans; Hypertension, Pulmonary; Male; Pulmonary Embolism; Railroads; Risk Factors; Travel; Venous Thrombosis; Ventricular Dysfunction, Right; Vitamin K

Topics: Aged; Body Weight; Cause of Death; Double-Blind Method; Drug Administration Schedule; Enoxaparin; Female; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Humans; Kidney; Male; Middle Aged; Polysaccharides; Recurrence; Treatment Outcome; Venous Thrombosis; Vitamin K

Determining the optimal duration of vitamin K antagonist (VKA) therapy for patients with venous thromboembolism (VTE) requires a weighting of the benefits and risks of treatment. The objectives of our study were to investigate patient variability in health state valuations associated with VKA therapy and treatment preferences, and to investigate the extent to which valuations and treatment preferences are associated with prior experience with these health states and other patient characteristics. Valuations of outcomes after VTE scaled from 0 (tantamount to death) to 1 (tantamount to perfect health) were elicited from 53 patients who had experienced VTE, 23 patients who had experienced major bleeding during treatment, and 48 patients with the post-thrombotic syndrome. In addition, patients' treatment preferences were evaluated using treatment trade-off questions. Median health state valuations ranged from 0.33 for 'non-fatal haemorrhagic stroke' to 0.96 for 'no VKA treatment'. Variability between patients was substantial. Patients' treatment preferences also varied: 25% of patients chose cessation of treatment, regardless of the probability of recurrent VTE presented, whereas 23% of patients were never willing to choose cessation of treatment. Differences in valuations and treatment preferences were not associated with type of event experienced. Due to the substantial and unpredictable variability in valuations and treatment preferences, recommendations regarding treatment duration should be tailored to patients' specific values and concerns.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Attitude to Health; Female; Health; Health Status Indicators; Humans; Male; Middle Aged; Quality of Life; Thromboembolism; Venous Thrombosis; Vitamin K

Topics: Administration, Oral; Anticoagulants; Hemorrhage; Humans; Recurrence; Risk Factors; Time Factors; Venous Thrombosis; Vitamin K

Topics: Anticoagulants; Drug Administration Schedule; Humans; Pulmonary Embolism; Secondary Prevention; Venous Thrombosis; Vitamin K; Warfarin

Topics: Anticoagulants; Contraindications; Creatinine; Drug Interactions; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Platelet Count; Renal Insufficiency; Thrombocytopenia; Venous Thrombosis; Vitamin K

The established initial treatment of patients with deep vein thrombosis (DVT) or pulmonary embolism (PE) consists of the administration of subcutaneous, weight adjusted, low-molecular weight heparin (LMWH). However, the use of the same LMWH dosages for patients with either DVT or PE is not supported by data from comparative studies.. 1,000 consecutive patients with acute, proximal DVT were prospectively evaluated. All patients underwent a ventilation-perfusion lung scan on admission, and remained in hospital for at least 7 days. Patients with silent PE received once daily 10,000 to 15,000 IU subcutaneous LMWH dalteparin according to body weight for 7 days, and then vitamin K antagonists. Patients with DVT alone received LMWH in a fixed dose of 10,000 IU once daily for at least 5 days, and then vitamin K antagonists. The rate of both, major bleeding and symptomatic PE episodes during the 7-day study period was evaluated.. Thirteen patients (1.3%) developed recurrent PE (1 died) and 16 patients (1.6%) had major bleeding (7 died). Recurrent PE was significantly more common in patients with silent PE (9 of 258 patients, 3.5%) than in those with DVT alone (4 of 742 patients, 0.5%. Odds ratio: 6.5; p <0.001). There were no significant differences in bleeding rate between patients with silent PE and those with DVT alone. However, the use of a fixed 10,000 IU dose in patients with DVT alone led to a significantly lower bleeding rate in patients weighing over 70 kg: 1 of 349 patients (0.3%) as compared to 9 of 393 patients (2.3%) in those weighing less than 70 kg (odds ratio: 0.12; p = 0.018).. Fixed-dose 10,000 IU of LMWH dalteparin once daily proved to be both effective and safe in patients with DVT alone. The observed recurrence rate of 0.5% in these patients compares favourably with the 3.5% rate in patients with silent PE. Furthermore, this fixed-dosage was also safe. Patients weighing over 70 kg had a significant decrease in the rate of major bleeding, and no compensatory increase in the rate of recurrent PE.

Topics: Anticoagulants; Cohort Studies; Dalteparin; Hemorrhage; Humans; Prospective Studies; Pulmonary Embolism; Recurrence; Safety; Venous Thrombosis; Vitamin K

Topics: 4-Hydroxycoumarins; Anticoagulants; Diagnosis, Differential; Heparin, Low-Molecular-Weight; Humans; Indenes; Prognosis; Pulmonary Embolism; Venous Thrombosis; Vitamin K

Topics: 4-Hydroxycoumarins; Administration, Oral; Anticoagulants; Clinical Trials as Topic; Hemorrhage; Humans; Indenes; Risk Factors; Venous Thrombosis; Vitamin K

Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Venous Thrombosis; Vitamin K

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Chemoprevention; Drug Monitoring; Heart Valve Diseases; Heart Valve Prosthesis; Hemorrhage; Humans; International Normalized Ratio; Myocardial Infarction; Pulmonary Embolism; Risk Factors; Thromboembolism; Venous Thrombosis; Vitamin K; Warfarin

Lupus anticoagulant (antiphospholipid antibodies) is associated with venous and arterial thrombosis in patients with and without autoimmune disorders. Vitamin K antagonists are the treatment of choice in patients with thrombosis, of which the dose is titrated by INR monitoring. Several recent reports suggest that the presence of the lupus anticoagulant disturbs the INR test and may lead to unreliable results with a large variation in INR values, dependent on the reagents used.. We studied 11 lupus anticoagulant positive patients and 11 lupus anticoagulant negative patients, all using vitamin K antagonists. The INR value was determined using seven different tests and the variation in INR values was compared between the two groups. The amidolytic Factor X levels were used as an phospholipid independent measure for intensity of warfarin therapy. Factor VII and X activity were measured to assess the stability of warfarin therapy.. The variation of the results with different INR tests within one patient was minimal and comparable in the two groups for INR's in the therapeutic range. The coefficient of variation for the cases and control group was 10.43 and 9.35, respectively. Variation in both groups increased at supratherapeutic levels of anticoagulation and when the anticoagulation was unstable (measured with Factor X/Factor VII ratio). The relationship between INR values and Factor X analysis revealed no influence of the lupus anticoagulant.. In this study, lupus anticoagulant antibodies do not disturb INR laboratory tests. Differences in INR measurements are seen in patients with a high intensity of anticoagulation and in patients who either just started or in whom no stable anticoagulation has been achieved. Abbreviated Abstract. This study investigates the influence of lupus anticoagulant on INR determination tests in patients treated with warfarin. Eleven cases and eleven lupus anticoagulant negative control patients, also on warfarin therapy, were included. Seven INR results per patient were obtained using different laboratory tests. A factor X assay was performed to obtain an independent measure for the intensity of warfarin therapy. The variation of INR results between the cases and controls revealed no difference in these groups. In addition, the relationship between INR values and Factor X analysis indicated no influence of the lupus anticoagulant. What was observed was an increased difference in INR values in patients with a high intensity of anticoagulation and in patients who either just started or in whom no stable anticoagulation has been achieved

Topics: Factor VII; Factor X; Humans; International Normalized Ratio; Lupus Coagulation Inhibitor; Reagent Kits, Diagnostic; Statistics, Nonparametric; Thromboembolism; Thromboplastin; Venous Thrombosis; Vitamin K; Warfarin

In order to study the effect of different intensities of anti-vitamin K treatment on coagulation parameters, 23 patients with venous thromboembolism were given, after the initial treatment period, warfarin at doses giving an International Normalised Ratio of 1.3-2.0 for 4 weeks, and of 1.1-1.3 for another 4 weeks. Blood samples were taken at the end of each of these periods and 4 weeks after the end of warfarin treatment. The vitamin K-dependent coagulation factors VII, IX, and X, as well as the inhibitor protein C and its cofactor protein S, all showed a highly significant correlation with treatment intensity. This was to some extent also true for the coagulation activation markers, prothrombin fragment 1+2 and thrombin-antithrombin complex. Ratios of pro- and anticoagulant factors in some instances showed a decrease at therapeutical (International Normalised Ratio) levels, and also sometimes with reduced warfarin treatment intensity. Taken together, our results encourage further research addressing issues of varying treatment intensity with warfarin and alternative methods for monitoring of anti-vitamin K treatment.

Topics: Adult; Aged; Anticoagulants; Antithrombin III; Biomarkers; Blood Coagulation Factors; Dose-Response Relationship, Drug; Factor IX; Factor VII; Factor X; Female; Humans; International Normalized Ratio; Male; Middle Aged; Peptide Fragments; Peptide Hydrolases; Plasminogen Activator Inhibitor 1; Protein C; Protein S; Prothrombin; Thromboembolism; Venous Thrombosis; Vitamin K; Warfarin

Initial heparinization followed by vitamin K antagonists is the treatment of choice for patients with venous thromboembolism. There is controversy whether known malignancy is a risk factor for recurrences and bleeding complications during this treatment. Furthermore, the incidence of such events in these patients is dependent on the achieved International Normalized Ratio (INR). The aim of this study was to assess the incidence of venous thromboembolic recurrence and major bleeding among patients with venous thromboembolism in relation to both malignancy and the achieved INR.. In a retrospective analysis, the INR-specific incidence of venous thromboembolic and major bleeding events during oral anticoagulant therapy was calculated separately for patients with and without malignancy. Eligible patients participated in two multicenter, randomized clinical trials on the initial treatment of venous thromboembolism. Patients were initially treated with heparin (standard or low-molecular weight). Treatment with vitamin K antagonists was started within 1 day and continued for 3 months, with a target INR of 2.0 to 3.0.. In 1,303 eligible patients (264 with malignancy), 35 recurrences and 12 bleeds occurred. Patients with malignancy, compared with nonmalignant patients, had a clinically and statistically significantly increased overall incidence of recurrence (27.1 v 9.0, respectively, per 100 patient-years) as well as bleeding (13.3 v 2.1, respectively, per 100 patient-years). In both groups of patients, the incidence of recurrence was lower when the INR was above 2.0 compared with below 2.0.. Although adequately dosed vitamin K antagonists are effective in patients with malignant disease, the incidence of thrombotic and bleeding complications remains higher than in patients without malignancy.

Topics: Aged; Anticoagulants; Female; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Humans; Incidence; International Normalized Ratio; Male; Middle Aged; Multicenter Studies as Topic; Neoplasms; Pulmonary Embolism; Randomized Controlled Trials as Topic; Recurrence; Retrospective Studies; Risk Factors; Venous Thrombosis; Vitamin K

Studies have shown that in most patients with venous thromboembolism (VTE), continuation of treatment with vitamin K antagonists for up to 27 months significantly reduces the probability of recurrence. Likewise, prolongation of oral anticoagulation beyond 6 months is believed to be of benefit in patients with certain forms of hereditary thrombophilia. Very prolonged periods of treatment with vitamin K antagonists at standard doses, although conferring benefit regarding the risk of recurrence of VTE, are associated with an increased incidence of major bleeds and require intensive monitoring. Use of a lower intensity of anticoagulation may reduce these negative aspects and enable anticoagulation to be carried out for longer.

Topics: Administration, Oral; Anticoagulants; Humans; Time Factors; Venous Thrombosis; Vitamin K

Topics: Anticoagulants; Blood Coagulation Tests; Coumarins; Exercise Therapy; Fibrinolysin; Heparin; Heparin Antagonists; Humans; Phenindione; Thrombophlebitis; Vascular Surgical Procedures; Venous Thrombosis; Vitamin K

Topics: Anemia; Anemia, Hypochromic; Chlorpromazine; Heparin; Humans; IgA Vasculitis; Iron; Methenamine; Nandrolone; Neurosurgery; Nitrofurantoin; Paraplegia; Phenindione; Postoperative Care; Prednisolone; Purpura; Rehabilitation; Subarachnoid Hemorrhage; Thrombophlebitis; Urinary Tract Infections; Venous Thrombosis; Vitamin K