vitamin-k-semiquinone-radical and Pulmonary-Embolism

Life-long anticoagulation is the recommended management for chronic thromboembolic pulmonary hypertension (CTEPH). Evidence regarding the use of direct oral anticoagulants (DOAC) for CTEPH is yet to be established. We performed a systematic review and meta-analysis to clarify the outcomes of CTEPH in patients who used DOAC or vitamin K antagonists (VKA).. We reviewed literature in PubMed and EMBASE through March 2023. We included studies involving patients with CTEPH where DOAC and VKA were compared. We collected data including intervention history for CTEPH, bleeding events, recurrence of VTE (venous thromboembolism), and mortality. We performed a meta-analysis using the Mantel-Haenszel method with a fixed-effects model.. We included one randomized clinical trial and six observational studies, with a total of 2969 patients. Six studies investigated major bleeding outcomes, and seven investigated all bleeding outcomes. There were no differences in major bleeding (RR 0.59, 95 % CI [0.34-1.02], I. DOAC compared to VKA was associated with a significantly lower mortality and higher risk of recurrent PE. Since most of the included studies are observational, we must consider the existence of multiple biases and confounding factors.

Topics: Administration, Oral; Anticoagulants; Blood Coagulation; Fibrinolytic Agents; Hemorrhage; Humans; Hypertension, Pulmonary; Pulmonary Embolism; Randomized Controlled Trials as Topic; Venous Thromboembolism; Vitamin K

Pulmonary embolism (PE) is characterized by occlusion of blood flow in a pulmonary artery, typically due to a thrombus that travels from a vein in a lower limb. The incidence of PE is approximately 60 to 120 per 100 000 people per year. Approximately 60 000 to 100 000 patients die from PE each year in the US.. PE should be considered in patients presenting with acute chest pain, shortness of breath, or syncope. The diagnosis is determined by chest imaging. In patients with a systolic blood pressure of at least 90 mm Hg, the following 3 steps can be used to evaluate a patient with possible PE: assessment of the clinical probability of PE, D-dimer testing if indicated, and chest imaging if indicated. The clinical probability of PE can be assessed using a structured score or using clinical gestalt. In patients with a probability of PE that is less than 15%, the presence of 8 clinical characteristics (age <50 years, heart rate <100/min, an oxygen saturation level of > 94%, no recent surgery or trauma, no prior venous thromboembolism event, no hemoptysis, no unilateral leg swelling, and no estrogen use) identifies patients at very low risk of PE in whom no further testing is needed. In patients with low or intermediate clinical probability, a D-dimer level of less than 500 ng/mL is associated with a posttest probability of PE less than 1.85%. In these patients, PE can be excluded without chest imaging. A further refinement of D-dimer threshold is possible in patients aged 50 years and older, and in patients with a low likelihood of PE. Patients with a high probability of PE (ie, >40% probability) should undergo chest imaging, and D-dimer testing is not necessary. In patients with PE and a systolic blood pressure of 90 mm Hg or higher, compared with heparin combined with a vitamin K antagonist such as warfarin followed by warfarin alone, direct oral anticoagulants such as apixaban, edoxaban, rivaroxaban, or dabigatran, are noninferior for treating PE and have a 0.6% lower rate of bleeding. In patients with PE and systolic blood pressure lower than 90 mm Hg, systemic thrombolysis is recommended and is associated with an 1.6% absolute reduction of mortality (from 3.9% to 2.3%).. In the US, PE affects approximately 370 000 patients per year and may cause approximately 60 000 to 100 000 deaths per year. First-line therapy consists of direct oral anticoagulants such as apixaban, edoxaban, rivaroxaban, or dabigatran, with thrombolysis reserved for patients with systolic blood pressure lower than 90 mm Hg.

Topics: Acute Disease; Administration, Oral; Anticoagulants; Dabigatran; Fibrin Fibrinogen Degradation Products; Heparin; Humans; Pulmonary Embolism; Risk; Rivaroxaban; United States; Vitamin K; Warfarin

Chronic thromboembolic pulmonary hypertension (CTEPH) represents the later stage consequence of at least one or more unresolved episodes of acute pulmonary embolism; thus, indefinite anticoagulation is strongly recommended by current practice guidelines. Historically, vitamin K antagonists have been widely used in these patients. However, recent data indicate a shift toward direct oral anticoagulants (DOACs), despite lack of data on the safety and efficacy in this patient population. Herein, we briefly discuss the current rationale for oral anticoagulation use in CTEPH, addressing important issues and controversies involved with the use of DOACs, opening a strategy for further clinical research in the field of oral anticoagulation.

Topics: Administration, Oral; Anticoagulants; Humans; Hypertension, Pulmonary; Pulmonary Embolism; Venous Thromboembolism; Vitamin K

Anticoagulation in patients with pulmonary embolism.. To identify how non-vitamin K antagonist oral anticoagulants are associated with multiple outcomes in patients with pulmonary embolism.. We performed a systematic search of systematic reviews via multiple electronic databases from inception to August 19th, 2019, without language restriction. Two authors independently extracted data and assessed the methodological quality of the included systematic reviews using the ROBIS tool.. We found twelve systematic reviews. Eleven SRs collected their data from randomized clinical trials and one from observational studies. All the included studies were published between 2014 and 2019 in English. The methodological quality of the 12 systematic reviews was low to high. None of the systematic reviews, which are included in our overview of systematic reviews, has evaluated the overall quality of evidence outcome using the Grading of Recommendations Assessments, Development and Evaluation (GRADE) approach.. This is the first effort to summarize evidence about non-vitamin K antagonist oral anticoagulants in an overview of systematic reviews focusing exclusively on patients with pulmonary embolism. The evidence suggests that the non-vitamin K antagonist oral anticoagulants seem to be more effective and safer than a dualdrug approach with LMWH- VKA.

Topics: Administration, Oral; Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Pulmonary Embolism; Systematic Reviews as Topic; Venous Thromboembolism; 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

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

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

Pulmonary embolism (PE) is a potentially life-threatening cardiovascular emergency with a high mortality rate. Rapid diagnosis and treatment are important in optimising clinical outcomes in patients with PE, and anticoagulants are the mainstay of treatment. Traditionally, anticoagulant therapy involves parenteral anticoagulants, overlapping with and followed by oral vitamin K antagonists. Direct oral anticoagulants (DOACs), including the factor Xa inhibitors rivaroxaban, apixaban and edoxaban, and the direct thrombin inhibitor dabigatran etexilate, have been developed to address limitations associated with traditional anticoagulant therapy. Apixaban, dabigatran and rivaroxaban have recently been approved for the treatment of acute deep vein thrombosis (DVT) and PE and prevention of recurrent DVT or PE. Edoxaban is approved in the United States but not currently in the European Union for the treatment of DVT and PE; approval of edoxaban in Europe is anticipated in the near future.. To summarise the management of patients with suspected PE in accordance with recent guidelines, and to discuss the evidence behind the recent approvals of the DOACs for the treatment of PE.. Diagnosis and treatment of PE is guided by clinical probability scoring systems and tools for prognostic stratification and early mortality risk evaluation. Anticoagulants remain the mainstay of treatment. Successful phase III trials have demonstrated the efficacy of the DOACs for the treatment of DVT and PE, with a potentially improved safety profile, leading to their recent approval in this indication, and giving the clinician greater choice of anticoagulant therapies in this setting.. DOACs offer an alternative and potentially simplified option for anticoagulation therapy in patients with PE compared with traditional anticoagulants and are likely to assist physicians in optimising management of patients with PE and improve clinical outcomes.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Clinical Trials, Phase III as Topic; Evidence-Based Medicine; Female; Humans; Male; Practice Guidelines as Topic; Prognosis; Pulmonary Embolism; Risk Assessment; Treatment Outcome; Vitamin K

Due to the nonspecific symptoms of the condition, a diagnosis of acute pulmonary embolism (PE) is frequently considered. However, PE will only be confirmed in 10-20% of patients. Because the imaging test of choice, computed tomography pulmonary angiography (CTPA), is costly and associated with radiation exposure and other complications, a validated diagnostic algorithm consisting of a clinical decision rule and D-dimer test should be used to safely exclude PE in 20-30% of patients without the need for CTPA. Recently, the age-adjusted D-dimer threshold has been validated, and this has increased the proportion of patients at older age in whom PE can be excluded without CTPA. Initial therapeutic management of PE depends on the risk of short-term PE-related mortality. Haemodynamically unstable patients should be closely monitored and receive thrombolytic therapy unless contraindicated because of an unacceptably high bleeding risk, whereas patients with low-risk PE may be safely discharged early from hospital or receive only outpatient treatment. The PESI score and Hestia decision rule are available to select patients in whom early discharge or outpatient treatment will be safe, although the safety of these strategies should be confirmed in additional studies. Standard PE therapy consists of low molecular weight heparin (LMWH) followed by vitamin K antagonists (VKAs). Recently, several nonvitamin K-dependent oral anticoagulants have been shown to be as effective as LMWH/VKAs, and maybe safer. Determining the optimal duration of treatment for a first unprovoked PE remains a challenge, although clinical prediction rules for estimating the risk of recurrence of venous thromboembolism and anticoagulation-associated haemorrhage are under investigation. Using these prediction rules may lead to both more standardized and more individualized long-term treatment of PE.

Topics: Aged, 80 and over; Anticoagulants; Diagnostic Imaging; Fibrin Fibrinogen Degradation Products; Heparin, Low-Molecular-Weight; Humans; Pulmonary Embolism; Thrombolytic Therapy; 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

Anticoagulants are beneficial for prevention and treatment of venous thromboembolism and stroke prevention in atrial fibrillation. The development of target-specific oral anticoagulants is changing the landscape of anticoagulation therapy and created growing interest on this subject. Understanding the pharmacology of different anticoagulants is the first step to adequately treat patients with best available therapy while avoiding serious bleeding complications. This article reviews the pharmacology of the main anticoagulant classes (vitamin K antagonists, direct oral anticoagulants, and heparins) and their clinical indications based on evidence-based data currently available in the literature.

Topics: Age Factors; Anticoagulants; Antithrombins; Arthroplasty, Replacement; Atrial Fibrillation; Comorbidity; Critical Illness; Drug Interactions; Drug Monitoring; Hemorrhage; Heparin; Humans; Neoplasms; Perioperative Care; Pulmonary Embolism; Stroke; Venous Thromboembolism; Vitamin K

Venous thromboembolism (VTE) is a major cause of morbidity and mortality in the western world. The approval of non-vitamin K oral anticoagulants (NOACs) as antithrombotic alternatives to vitamin K antagonists (VKAs) has offered more treatment options to physicians for the prevention of VTE recurrence, fatal pulmonary embolism (PE) and long-term complications. Four NOACs (dabigatran, rivaroxaban, apixaban and edoxaban) that have been approved for the treatment of acute VTE following large phase III trials, where NOACs demonstrated similar efficacy and superior safety profile compared to VKAs.. The purpose of this review article is to summarise current knowledge of oral anticoagulation for the treatment of acute VTE and to compare NOACs with VKAs, highlighting the factors that might influence the decisions of physicians. Data for this article were obtained through a search of PubMed for trials comparing NOACs with VKAs in acute VTE setting and articles or analyses that interpreted results from these trials.. The NOACs have changed clinical practice regarding oral anticoagulation for acute VTE. Despite their advantages, 'grey zones' still remain and more studies are needed to provide evidence and confirm the superiority (or at least non-inferiority) of NOACs over VKAs. Real world data might give additional insights.

Topics: Administration, Oral; Anticoagulants; Antifibrinolytic Agents; Fibrinolytic Agents; Humans; Pulmonary Embolism; Venous Thromboembolism; Vitamin K

Anticoagulant agents have been approved by international regulatory agencies to prevent and treat venous thromboembolism (VTE). However, chronic kidney disease (CKD) is: (1) highly frequent in VTE patients; (2) strongly linked to VTE; and (3) a risk factor for cardiovascular morbidity/mortality and fatal pulmonary embolism. Therefore, an increasing number of patients are presented with CKD and VTE and more and more physicians must face the questions of the management of these patients and that of the handling of anticoagulant agents in CKD patients because of the pharmacokinetic modifications of these drugs in this population. These modifications may lead to overdosage and dose-related side effects, such as bleeding. It is therefore necessary to screen VTE patients for CKD and to modify the doses of anticoagulants, if necessary.

Topics: Anticoagulants; Cardiovascular Diseases; Drug Overdose; Heparin; Heparin, Low-Molecular-Weight; Humans; Kidney; Pulmonary Embolism; Renal Insufficiency, Chronic; Risk Factors; Venous Thromboembolism; 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

Direct oral anticoagulants (DOACs) specifically target factor IIa or Xa and represent a major step forward in the treatment of acute- and long-term prevention of venous thrombo-embolism (VTE). They are at least as effective and as safe as conventional therapy (heparins and vitamin-K inhibitors) and have practical advantages, such as fixed dosing and no need for laboratory monitoring. These antithrombotic agents introduce a new paradigm for the day-to-day management of VTE. Direct oral anticoagulants should streamline the management of most patients with VTE and will facilitate care in the outpatient setting. Nevertheless, it remains uncertain how to select specific DOACs for particular profiles of patients, and the optimal management of bleeding complications is evolving.

Topics: Acute Disease; Administration, Oral; Antithrombins; Benzimidazoles; beta-Alanine; Clinical Trials, Phase III as Topic; Dabigatran; Hemorrhage; Humans; Long-Term Care; Morpholines; Perioperative Care; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thiophenes; Treatment Outcome; Venous Thromboembolism; Vitamin K

Venous thrombo-embolism is the third most frequent acute cardiovascular syndrome after myocardial infarction and stroke. Recently published landmark trials paved the way for significant progress in the management of the disease and provided the evidence for the ESC Pulmonary Embolism (PE) Guidelines 2014 update. Risk stratification strategies for non-high-risk PE continue to evolve, with an increasing emphasis on clinical prediction rules and right ventricular (RV) assessment on computed tomographic pulmonary angiography. In the field of anticoagulation treatment, pharmacogenetic testing for vitamin K antagonists on top of clinical parameters was not found to offer a significant benefit during the initiation phase; on the other hand, dosing based on the patient's clinical data seems superior to fixed loading regimens. The phase 3 trial programme of new oral anticoagulants in the treatment of venous thrombo-embolism has been completed, and the results indicate that these agents are at least as effective and probably cause less major bleeding than currently standard treatment. A multicentre prospective phase 4 trial will determine whether early discharge and out-of-hospital treatment of low-risk PE with the oral factor Xa inhibitor rivaroxaban is feasible, effective, and safe. For intermediate-risk PE defined on the basis of imaging tests and laboratory biomarkers, the bleeding risks of full-dose thrombolytic treatment appear too high to justify its use, unless clinical signs of haemodynamic decompensation appear. Patients in whom PE has resulted in chronic thrombo-embolic pulmonary hypertension and who are not suitable for pulmonary endarterectomy, may be expected to benefit from emerging pharmaceutical and interventional treatment options.

Topics: Administration, Oral; Algorithms; Ambulatory Care; Anticoagulants; Biomarkers; Chronic Disease; Clinical Trials as Topic; Diagnostic Imaging; Early Diagnosis; Humans; Long-Term Care; Pulmonary Embolism; Risk Assessment; Thrombolytic Therapy; Venous Thromboembolism; Vitamin K

Novel oral anticoagulants (NOACs) have been developed as alternatives for vitamin K antagonists (VKAs) for the prevention of thromboembolic events in patients with a variety of medical conditions. In this review, we summarize the current data on NOACs safety and efficacy compared to VKAs and in specific patients' groups including heart valve replacement, venous thromboembolism, advanced renal failure and the elderly.

Topics: Administration, Oral; Anticoagulants; Chemistry, Pharmaceutical; Humans; Pulmonary Embolism; Renal Insufficiency; Thromboembolism; 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

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

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

Venous thrombosis typically involves the lower extremities. Rarely, it can occur in cerebral, splanchnic, or renal veins, with a frightening clinical impact. Other rare manifestations are upper-extremity deep vein thrombosis, that can complicate with pulmonary embolism and post-thrombotic syndrome, and retinal vein occlusion, significantly affecting the quality of life. This review is focused on venous thromboses at unusual extra-abdominal sites. Local infections or cancer are frequent in cerebral sinus-venous thrombosis. Upper-extremity deep vein thrombosis is mostly due to catheters or effort-related factors. Common risk factors are inherited thrombophilia and oral contraceptive use. Acute treatment is based on heparin; in cerebral sinus-venous thrombosis, local or systemic fibrinolysis should be considered in case of clinical deterioration. Vitamin-K antagonists are recommended for 3-6 months; indefinite anticoagulation is suggested for recurrent thrombosis or unprovoked thrombosis and permanent risk factors. However, such recommendations mainly derive from observational studies; there are no data about long-term treatment of retinal vein occlusion.

Topics: Anticoagulants; Catheters; Contraceptives, Oral; Heparin; Humans; Postthrombotic Syndrome; Pulmonary Embolism; Retinal Vein Occlusion; Risk Factors; Thrombophilia; Upper Extremity Deep Vein Thrombosis; Vitamin K; Warfarin

Acute pulmonary embolism (PE) poses a significant burden on health and survival. Its severity ranges from asymptomatic, incidentally discovered subsegmental thrombi to massive, pressor-dependent PE complicated by cardiogenic shock and multisystem organ failure. Rapid and accurate risk stratification is therefore of paramount importance to ensure the highest quality of care. This article critically reviews currently available and emerging tools for risk-stratifying acute PE, and particularly for distinguishing between elevated (intermediate) and low risk among normotensive patients. We focus on the potential value of risk assessment strategies for optimizing severity-adjusted management. Apart from reviewing the current evidence on advanced early therapy of acute PE (thrombolysis, surgery, catheter interventions, vena cava filters), we discuss recent advances in oral anticoagulation with vitamin K antagonists, and with new direct inhibitors of factor Xa and thrombin, which may contribute to profound changes in the treatment and secondary prophylaxis of venous thrombo-embolism in the near future.

Topics: Acute Disease; Aged; Ambulatory Care; Anticoagulants; Biomarkers; Cardiac Imaging Techniques; Female; Heparin; Humans; Length of Stay; Male; Middle Aged; Prognosis; Pulmonary Embolism; Randomized Controlled Trials as Topic; Recurrence; Risk Assessment; Severity of Illness Index; Thrombectomy; Thrombolytic Therapy; Vena Cava Filters; 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

Dabigatran etexilate is the first oral anticoagulant to be approved in the United States in decades. It works directly by inhibiting clot-bound and free factor IIa (ie, thrombin) and indirectly by inhibiting platelet aggregation induced by thrombin. It is approved in the United States for stroke prophylaxis in nonvalvular atrial fibrillation. There is evidence to suggest that it is also effective for the treatment of acute venous thromboembolism and venous thromboembolism prophylaxis after knee and hip replacement surgery. Dabigatran etexilate therapy does not require laboratory monitoring, an advantage over warfarin. Unlike the earlier direct thrombin inhibitor, ximelagatran, it has demonstrated no potential for serious hepatotoxicity. It is also subject to a much lower degree of interpatient variability in dose response, has no diet-drug interactions, and has fewer clinically significant drug-drug interactions compared with warfarin. Dabigatran etexilate appears to be a valuable addition to our anticoagulant armamentarium.

Topics: Administration, Oral; Anticoagulants; Arthroplasty, Replacement; Atrial Fibrillation; Benzimidazoles; Clinical Trials as Topic; Dabigatran; Drug Interactions; Heparinoids; Humans; Pulmonary Embolism; Pyridines; Stroke; Venous Thromboembolism; 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 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

Topics: Acute Disease; Algorithms; Anticoagulants; Echocardiography, Transesophageal; Fibrin Fibrinogen Degradation Products; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Pulmonary Embolism; Risk Assessment; Tomography, X-Ray Computed; Vitamin K

There is some uncertainty about the management of pulmonary embolism in nonagenarians.. Immobility plays an important role in the pathogenesis of venous thromboembolism in the elderly. Of 858 nonagenarians with acute venous thromboembolism enrolled in Registro Informatizado de la Enfermedad TromboEmbolica venosa registry, 41% had recent immobility and only 7.7% had recent surgery. Comorbidity is common: 19% of patients had chronic heart failure, 9.8% chronic lung disease, 14% cancer, and 63% had abnormal creatinine levels. Most (92%) of the patients were initially treated with low-molecular-weight heparin and then 46% switched to antivitamin K drugs. During follow-up, the proportion of patients who developed recurrent venous thromboembolism (4.9%) or major bleeding complications (6.2%) was similar, but the 5.9% of fatal pulmonary embolisms by far exceeded the 2.2% of fatal bleeding events. The most common clinical symptoms are isolated dyspnea and syncope, and presentation as pulmonary infarction (with hemoptysis and pleuritic chest pain) is rare.. In patients aged at least 90 years presenting with acute pulmonary embolism, the incidence of fatal pulmonary embolism by far outweighs the incidence of fatal bleeding, and pulmonary embolism is the most common cause of death. Thus, there seems to be more reason to be concerned about fatal pulmonary embolism than about bleeding in elderly patients presenting with pulmonary embolism.

Topics: 4-Hydroxycoumarins; Age Factors; Aged, 80 and over; Anticoagulants; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Incidence; Indenes; Male; Pulmonary Embolism; Risk Factors; Spain; Vitamin K

The clinical presentation of pulmonary embolism (PE) varies widely, ranging from only limited symptoms to severe cardiogenic shock. Treatment of PE comprises initial therapy--with low-molecular-weight heparin (LMWH), fondaparinux, or unfractionated heparin--and long-term treatment, most commonly with vitamin-K antagonists (VKAs). Methods of risk stratification, to determine whether a patient will benefit from thrombolysis, are currently under investigation. However, at present, insufficient evidence exists that hemodynamically stable patients who demonstrate echocardiographic right ventricular strain (submassive PE) benefit from thrombolysis. By contrast, thrombolysis is a widely accepted treatment strategy for patients with hemodynamic shock (massive PE). The duration of VKA treatment is commonly 3-12 months and depends on the type of PE and on the balance between the risks of recurrent PE, major bleeding, and the patient's preference. In patients with a malignancy, treatment with LMWH during the first 6 months after diagnosis of PE is recommended. Several new oral anticoagulants, such as factor IIa and factor Xa inhibitors, are now being investigated. For prevention of recurrent PE in situations where anticoagulation is contraindicated, a temporary inferior vena cava filter might be useful. Some patients with PE can be safely treated at home, but few outcome studies in this setting have been published.

Topics: Acute Disease; Anticoagulants; Biomarkers; Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Prothrombin; Pulmonary Embolism; Risk Assessment; Shock, Cardiogenic; Vitamin K

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

To discuss new features that were published during the past few years on diagnosis and treatment of venous thromboembolism (VTE). Progress has been made in assessing clinical probability of pulmonary embolism (PE), in addressing the particular aspects of PE diagnosis in the elderly, in evaluating the diagnostic performance of single- and multi-detector row helical computed tomography (hCT), and in looking at the role of D-dimer measurement and lower limb venous compression ultrasonography in the diagnostic work-up of PE. New therapeutic options have also been proposed. Diagnosing VTE depends upon several, mainly non-invasive diagnostic tools that must be used sequentially, depending on the clinical situation and the local expertise. In the vast majority of patients, a noninvasive work-up is feasible and the diagnostic algorithms are becoming simpler. We focused on new developments of clinical probability assessment, PE in the elderly, potential new uses of D-dimer measurement, advent of multidetector row helical computed tomography and utility of ultrasonography to detect deep vein thrombosis in PE suspected patients. Treatment of acute venous thromboembolism consists of parenteral administration of heparin (usually low-molecular-weight heparin or, more recently, fondaparinux) overlapped and followed by oral vitamin K antagonists that will be administered for a certain period of time (usually 3 to 12 months), depending upon the estimated risks of recurrence and bleeding in each individual patient. Contemporary features include the controversial possibility of reducing the intensity of oral anticoagulant treatment (INR 1.5-2) after an initial full-intensity treatment (INR 2-3) period of 3 to 12 months, and the emergence of new anticoagulant drugs such as direct oral synthetic inhibitors of thrombin or factor Xa.

Topics: Administration, Oral; Age Factors; Anticoagulants; Biomarkers; Blood Coagulation; Drug Administration Schedule; Fibrin Fibrinogen Degradation Products; Health Status Indicators; Humans; Predictive Value of Tests; Pulmonary Embolism; Risk Assessment; Tomography, Spiral Computed; Ultrasonography; Venous Thromboembolism; Vitamin K

The overall thromboembolic risk is the resultant of patient-related risk and surgical risk. The surgical risk is decreasing, especially with the introduction of new procedures (fast-track surgery). The value of prophylaxis has been firmly established. Mechanical prophylaxis is to be used as first-line prophylaxis when there is a risk of bleeding. Combining this with drugs increases the antithrombotic efficacy. However, the effectiveness of prophylaxis on pulmonary embolism and mortality has not been demonstrated. Renal function needs to be evaluated when low molecular weight heparins, fondaparinux, rivaroxaban or dabigatran are prescribed. An age of over 75 years and low body weight (<50 kg) have to be taken into account. There is a risk of spinal or epidural hematoma in patients receiving anticoagulants. Caution should be taken especially when administering the newer agents. Patients undergoing surgery that involves a moderate or high overall risk should receive prophylaxis until full mobilization. Patients who have undergone a total hip replacement, surgery for hip fracture, or major abdominal surgery should receive prophylaxis for about 5 weeks longer. The relevance of distal vein thromboses is debated. Surrogate venographic end-points should be gradually replaced by a combination of ultrasound and clinical criteria. The new antithrombotic agents will probably modify prevention in the years to come but currently there are very few long-term data for these products for which - it should be reminded - no antagonists are available.

Topics: Adult; Aged; Anticoagulants; Combined Modality Therapy; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Middle Aged; Morpholines; Polysaccharides; Postoperative Complications; Preanesthetic Medication; Pulmonary Embolism; Risk Factors; Rivaroxaban; Stockings, Compression; Thiophenes; Thromboembolism; Thrombophlebitis; Vitamin K

Topics: Aerospace Medicine; Aircraft; Anticoagulants; Drug Therapy, Combination; Humans; Pulmonary Embolism; Risk Factors; Time Factors; Travel; Treatment Outcome; Venous Thromboembolism; 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

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

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

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

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

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

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

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

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

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

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

Anticoagulants (unfractionated heparin UFH, low-molecular-weight heparins LMWH, coumarins) are mainly used to prevent (prophylactic dosage) or treat (therapeutic dosage) deep-vein thrombosis and pulmonary embolism. After surgery, prophylactic regimens of UFH and LMWH induce a doubling of the hemorrhagic risk which is observed under placebo. At therapeutic dosages, UFH and LMWH are associated with a risk of major bleeding of about 5%, with a trend favouring LMWH for a similar antithrombotic efficacy. At therapeutic levels, coumarins induce major bleeding at a rate of approximately 1%/month. This figure is proportional to the duration and the intensity (INR) of the treatment. It appears to be the major determinant of an optimal duration of anticoagulant treatment following deep-vein thrombosis.

Topics: 4-Hydroxycoumarins; Anticoagulants; Blood Loss, Surgical; Contraindications; Hemorrhage; Heparin; Humans; Indenes; Pulmonary Embolism; Risk Factors; Thrombophlebitis; Vitamin K

Topics: 4-Hydroxycoumarins; Anesthesia, Spinal; Anticoagulants; Dextrans; Digestive System Diseases; Female; Genital Diseases, Female; Hemodilution; Heparin; Humans; Indenes; Leg Injuries; Male; Postoperative Complications; Pulmonary Embolism; Thrombophlebitis; Vitamin K

Topics: Anesthesia; Aspirin; Bandages; Dextrans; Female; France; Heparin, Low-Molecular-Weight; Humans; Male; Postoperative Complications; Pulmonary Embolism; Thrombosis; Vitamin K

Clinical indications of vena cava interruption are reviewed. During the last few years pulmonary embolism frequency remained high and many new percutaneous vena caval filters became available. These facts probably explain the increasing use of these filters reaching about 10,000 filters each year in France. Existing data show that: embolic risk with antithrombotic agents is less than 5%, probably not far greater than embolic risk with cava filters (about 2%); complications encountered with the filters are caval thrombosis in 8%, and more or less than 4% other major complications; there is no controlled study comparing antithrombotic treatment associated with caval filters to antithrombotic treatment alone; there is no controlled study comparing new cava filters among them or to the Greenfield filter; economical implications of caval filters are mostly unknown. The only admitted indications of vena cava interruption, in case of proximal venous thrombosis, are contraindications to anticoagulation. In other situations no data allow to recommend a cava filter; indication will be discussed on a case by case basis. Prospective controlled studies are greatly encouraged.

Topics: Heparin; Humans; Ligation; Pulmonary Embolism; Recurrence; Thrombosis; Vena Cava Filters; Vena Cava, Inferior; Vitamin K

The administration of warfarin requires careful attention. The concurrent intake of drugs can either enhance or compete with its anticoagulant effect. Less frequently encountered are the effects from vitamin K added to food, intake of foods with naturally occurring high levels of vitamin K and diets deficient in vitamin K. We report a case in which loss of anticoagulant control was caused by a dietary supplement taken during a weight reducing diet by a patient who was receiving warfarin following a pulmonary embolus. A review of the literature reveals several similar cases. Amounts of vitamin K in food supplements and in foods with large amounts of naturally occurring vitamin K are tabulated along with suggestions for surveillance of patients taking anticoagulants.

Topics: Adult; Female; Food, Fortified; Humans; Pulmonary Embolism; Vitamin K; Warfarin

Oral anticoagulants are used extensively, although their risks are not always fully recognized. The prophylaxis of venous thrombosis after hip surgery, the prevention of deep venous thrombosis and pulmonary emboli after an acute episode of these, the prevention of arterial emboli from the heart in patients at risk, and the prophylaxis of thrombosis in patients with congenital deficiency of antithrombin III, protein C, or protein S are some of the indications for oral anticoagulant use. Warfarin sodium is contraindicated in pregnancy, however. The recommended prothrombin time is 1 1/2 to two times control, lower than previously. The major risk of oral anticoagulant therapy, bleeding, is treated with vitamin K or plasma, depending on its severity. Warfarin necrosis and the "purple-toe" syndrome are seen more frequently than realized.

Topics: Absorption; Administration, Oral; Biological Availability; Drug Interactions; Hemorrhage; Hip Fractures; Humans; Myocardial Infarction; Necrosis; Postoperative Complications; Protein Binding; Prothrombin Time; Pulmonary Embolism; Thrombophlebitis; Thrombosis; Vitamin K; Warfarin

The major clinical importance of plasma protein C is attested to by the strong association between inherited protein C deficiencies of half normal levels and recurrent venous thromboembolic disease. Homozygous protein C deficient individuals do not survive beyond infancy without continuous therapeutic intervention. The spectrum of protein C deficiency is becoming broader and includes patients with both abnormal molecules and half normal levels of functionally active molecules. Rarely, a few young adults with thrombosis have been identified with protein C levels below 25%. Studies of protein C activity have been hampered until the very recent developments of functional assays of plasma protein C. Application of these assays to a wide variety of clinical situations involving thrombotic complications is just beginning and may lead to an explosive proliferation of new data that should prove most fascinating and give much further insight into the contributions of protein C in the regulation of thrombosis.

Topics: Anticoagulants; Blood Coagulation Factors; Disseminated Intravascular Coagulation; Glycoproteins; Half-Life; Humans; Infant, Newborn; Liver Diseases; Male; Necrosis; Protein C; Pulmonary Embolism; Purpura; Skin Diseases; Thromboembolism; Thrombophlebitis; Vitamin K

Topics: Adenosine Diphosphate; Anticoagulants; Blood Coagulation; Blood Coagulation Factors; Coumarins; Disseminated Intravascular Coagulation; Heart Valve Prosthesis; Hemostasis; Heparin; Humans; Intracranial Embolism and Thrombosis; Myocardial Infarction; Postoperative Care; Pulmonary Embolism; Rheumatic Heart Disease; Thromboembolism; Vitamin K

Topics: Acute Disease; Anticoagulants; Atrial Fibrillation; Cell Transformation, Neoplastic; Disseminated Intravascular Coagulation; Dose-Response Relationship, Drug; Embolization, Therapeutic; Female; Hemorrhage; Heparin; Humans; Mitral Valve; Postoperative Complications; Pregnancy; Pulmonary Embolism; Thrombocytopenia; Thromboembolism; Thrombophlebitis; Vitamin K; Warfarin

Topics: Administration, Oral; Ancrod; Anticoagulants; Blood Coagulation Tests; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fibrinolysis; Heparin; Humans; Infusions, Parenteral; Injections, Intravenous; Plasminogen Activators; Pregnancy; Pulmonary Embolism; Streptokinase; Thrombophlebitis; Urokinase-Type Plasminogen Activator; Vitamin K

Topics: Administration, Oral; Anticoagulants; Blood Coagulation Tests; Coumarins; Heparin; Humans; Indenes; Infusions, Parenteral; Poisoning; Protamines; Prothrombin Time; Pulmonary Embolism; Thromboembolism; Vitamin K

Topics: Blood Coagulation; Blood Coagulation Factors; Blood Coagulation Tests; Embolism; Factor IX; Factor VII; Factor X; Heparin; Humans; Myocardial Infarction; Prothrombin; Prothrombin Time; Pulmonary Embolism; Thromboembolism; Thrombophlebitis; Vitamin K; Warfarin

Topics: Angina Pectoris; Arteriosclerosis; Blood Coagulation; Cerebral Hemorrhage; Chemical Phenomena; Chemistry; Coumarins; Drug Antagonism; Drug Synergism; Female; Hemorrhage; Humans; Intracranial Embolism and Thrombosis; Ischemic Attack, Transient; Myocardial Infarction; Pregnancy; Pregnancy Complications, Cardiovascular; Pulmonary Embolism; Thrombophlebitis; Vitamin K

Vitamin K antagonists (VKA) such as warfarin or phenprocoumon have been the mainstay of therapy for long-term oral anticoagulant therapy (OAT) in patients with atrial fibrillation or with pulmonary embolism. Due to interferences with matrix Gla-protein, an important vitamin K-dependent local calcification inhibitor in cardiovascular structures, VKA antagonists stimulate cardiovascular calcification (CVC). In contrast, rivaroxaban, a nonvitamin K-dependent oral anticoagulant (NOAC), should be neutral in terms of CVC. We seek to investigate these potential differences in CVC development between VKA versus NOACs in a randomized controlled trial (RCT).. The influence of rivaroxaban compared to vitamin K antagonist treatment upon development of cardiovascular calcification in patients with atrial fibrillation and/or pulmonary embolism trial (NCT02066662) is a multicenter, prospective RCT with a two-arm, open-label study design. The primary endpoint is the progression of coronary and aortic valve calcification (quantified as calcification volume score) as assessed by cardiac computed tomography (CT) at 24 months in patients either treated by rivaroxaban or VKA. A total of 192 patients were randomized in a 1:1 fashion. The main inclusion criteria were the presence of atrial fibrillation and/or pulmonary embolism with the indication for OAT and pre-existent coronary calcification. The development of CVC will be assessed by follow-up CT at 12 and 24 months.. In total 192 patients (median age 70, 72% male) were enrolled over a period of 5 years and followed up for 2 years.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Female; Fibrinolytic Agents; Humans; Male; Pulmonary Embolism; Rivaroxaban; Stroke; Vitamin K

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

Bleeding-prediction scores may help guiding management of patients with pulmonary embolism (PE), although no such score has been validated. We aimed to externally validate and compare two bleeding-prediction scores for venous thromboembolism to three scores developed for patients with atrial fibrillation in a real-world cohort of PE patients. We performed a prospective observational cohort study in 448 consecutive PE patients who were treated with heparins followed by vitamin-K-antagonists. The Kuijer, RIETE, HEMORR2HAGES, HAS-BLED and ATRIA scores were assessed at baseline. All patients were followed for the occurrence of major bleeding over a 30-day period. The accuracies of both the overall, original 3-level and newly defined optimal 2-level outcome of the scores were evaluated and compared, both for the 30-day period as well as for bleeding occurring in versus after the first week of treatment. 20 of 448 patients suffered major bleeding resulting in a cumulative incidence of 4.5 % (95 % CI 2.5-6.5). The predictive power of all five scores for bleeding was poor (c-statistics 0.57-0.64), both for the 3-level and 2-level score outcomes. No individual score was found to be superior. The HAS-BLED score had a good c-statistic for bleedings occurring after the first week of treatment (0.75, 95 % CI 0.47-1.0). Current available scoring systems have insufficient accuracy to predict overall anticoagulation-associated bleeding in patients treated for acute PE. To optimally target bleeding-prevention strategies, the development of a high quality PE-specific risk score is urgently needed.

Topics: Acute Disease; Aged; Aged, 80 and over; Female; Hemorrhage; Heparin; Humans; Male; Predictive Value of Tests; Prospective Studies; Pulmonary Embolism; Registries; Risk Assessment; 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

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

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

A fixed-dose regimen of rivaroxaban, an oral factor Xa inhibitor, has been shown to be as effective as standard anticoagulant therapy for the treatment of deep-vein thrombosis, without the need for laboratory monitoring. This approach may also simplify the treatment of pulmonary embolism.. In a randomized, open-label, event-driven, noninferiority trial involving 4832 patients who had acute symptomatic pulmonary embolism with or without deep-vein thrombosis, we compared rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with standard therapy with enoxaparin followed by an adjusted-dose vitamin K antagonist for 3, 6, or 12 months. The primary efficacy outcome was symptomatic recurrent venous thromboembolism. The principal safety outcome was major or clinically relevant nonmajor bleeding.. Rivaroxaban was noninferior to standard therapy (noninferiority margin, 2.0; P=0.003) for the primary efficacy outcome, with 50 events in the rivaroxaban group (2.1%) versus 44 events in the standard-therapy group (1.8%) (hazard ratio, 1.12; 95% confidence interval [CI], 0.75 to 1.68). The principal safety outcome occurred in 10.3% of patients in the rivaroxaban group and 11.4% of those in the standard-therapy group (hazard ratio, 0.90; 95% CI, 0.76 to 1.07; P=0.23). Major bleeding was observed in 26 patients (1.1%) in the rivaroxaban group and 52 patients (2.2%) in the standard-therapy group (hazard ratio, 0.49; 95% CI, 0.31 to 0.79; P=0.003). Rates of other adverse events were similar in the two groups.. A fixed-dose regimen of rivaroxaban alone was noninferior to standard therapy for the initial and long-term treatment of pulmonary embolism and had a potentially improved benefit-risk profile. (Funded by Bayer HealthCare and Janssen Pharmaceuticals; EINSTEIN-PE ClinicalTrials.gov number, NCT00439777.).

Topics: Administration, Oral; Aged; Anticoagulants; Drug Therapy, Combination; Enoxaparin; Female; Follow-Up Studies; Hemorrhage; Humans; International Normalized Ratio; Kaplan-Meier Estimate; Male; Middle Aged; Morpholines; Pulmonary Embolism; Recurrence; Rivaroxaban; Thiophenes; Treatment Outcome; Vitamin K

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

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

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

After stopping a 3 to 6 months course of oral anticoagulation for a first episode of idiopathic venous thromboembolism (VTE), the risk of recurrent VTE is high (10% per year). In this setting, international guidelines recommend at least 6 months treatment. However, this recommendation is not satisfactory for the following reasons: (1) no randomized trial has compared 6 months to extended duration (2 years) anticoagulation; and (2), even though the frequency of recurrent VTE is similar after pulmonary embolism (PE) and deep vein thrombosis (DVT), the fatality rate of recurrent VTE after PE is higher than that after DVT.. A French multicentre double blind randomized trial. The main objective is to demonstrate, after a first episode of symptomatic idiopathic PE treated for 6 months using a vitamin K antagonist, that extended anticoagulation for 18 months (INR between 2 and 3) is associated with an increased benefit / risk ratio (recurrent VTE and severe anticoagulant-related bleeding) compared to placebo. The double blind evaluation is ensured using by active warfarin and placebo, and blinded INR. The protocol was approved by the ethics board of the Brest Hospital on the 7th of March 2006. For an alpha risk of 5% and a beta risk of 20%, the estimated sample size is 374 patients.. This study has the potential to: (1) demonstrate that the benefit / risk ratio of extended anticoagulation for 18 months is higher than that observed with placebo in patients with a first episode of idiopathic PE initially treated for 6 months, during and after the treatment period; and (2) to validate or invalidate the contribution of isotope lung scans, lower limb Doppler ultrasound and D-Dimer at 6 months of treatment as predictors of recurrent VTE (medico-economic analysis included).

Topics: Anticoagulants; Chi-Square Distribution; Data Interpretation, Statistical; Double-Blind Method; Hemorrhage; Humans; Placebos; Practice Guidelines as Topic; Prognosis; Pulmonary Embolism; Recurrence; Risk Assessment; Time Factors; Venous Thromboembolism; Vitamin K; Warfarin

Prothrombin complex concentrate (PCC) can substantially shorten the time needed to reverse antivitamin K oral anticoagulant therapy (OAT). OBJECTIVES. To determine the effectiveness and safety of emergency OAT reversal by a balanced pasteurized nanofiltered PCC (Beriplex P/N) containing coagulation factors II, VII, IX, and X, and anticoagulant proteins C and S.. Patients receiving OAT were eligible for this prospective multinational study if their International Normalized Ratio (INR) exceeded 2 and they required either an emergency surgical or urgent invasive diagnostic intervention or INR normalization due to acute bleeding. Stratified 25, 35, or 50 IU kg(-1) PCC doses were infused based on initial INR. Study endpoints included INR normalization (

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Coumarins; Drug Combinations; Emergencies; Europe; Factor IX; Factor VII; Factor X; Female; Hemorrhage; Hemostatics; Humans; International Normalized Ratio; Israel; Male; Middle Aged; Prospective Studies; Prothrombin; Pulmonary Embolism; Vitamin K

The assessment of the risk of recurrent venous thromboembolism (VTE) is important to determine the optimal duration of secondary prophylaxis. The risk can be estimated by measuring individual parameters reflecting hypercoagulability. Because of the large numbers of such putative parameters, the assessment in individual patients is complex. Application of global assays reflecting the pro-/anti-coagulant balance in vivo would be desirable.. To investigate the relationship between recurrent VTE and thrombin generation (TG).. Two hundred and fifty-four patients were followed-up after a first episode of unprovoked, objectively documented VTE for a period of 2.7 years after discontinuation of treatment with vitamin K antagonists. TG was measured 1 month after discontinuation of treatment as endogenous thrombin potential (ETP), peak thrombin and lag-time in the presence or absence of thrombomodulin. The study outcome was objectively documented symptomatic recurrent VTE.. Patients with ETP or peak (measured in the presence of thrombomodulin) of >960 nm(*)min or >193 nm had hazard ratios (HR) (95% CI) for recurrent VTE of 3.41 (1.34-8.68) or 4.57 (1.70-12.2) as compared with those with an ETP <563 nm(*)min or peak <115 nm. Patients with lag-time <14.5 min had HR of 3.19 (1.29-7.89) as compared with those with lag-time >20.8 min. HR for ETP, peak or lag-time measured in the absence of thrombomodulin were smaller than those measured in the presence of thrombomodulin.. The measurement of TG helps to identify patients at higher risk of VTE recurrence. The increased risk may be better appreciated if the test is performed in the presence of thrombomodulin.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Female; Humans; Male; Middle Aged; Prospective Studies; Pulmonary Embolism; Recurrence; Risk Factors; Thrombin; Thrombomodulin; Venous Thromboembolism; Vitamin K

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 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

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

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

A double blind cross over study with suloctidil (Sulocton, Continental Pharma) and placebo was carried out for 6 months in 31 patients with idiopathic recurrent vein thrombosis. They were previously unsuccessfully treated with vitamin K antagonists (VKA) (18 patients) or acetylsalicylic acid (ASA) (13 patients) combined or not the a fibrinolysis activator (theophylline nicotinate). Clinical features, ultrasonic venous flow and biological parameters were controlled monthly during the 6 month treatment. Relevant improvement of clinical, ultrasonic and biological parameters was only observed under suloctidil therapy: during placebo administration 12 patients developed new thrombotic events complicated in 2 by pulmonary embolism while none occurred under suloctidil therapy.

Topics: Adult; Aged; Antigens; beta-Thromboglobulin; Blood Platelets; Cell Survival; Factor VIII; Female; Humans; Male; Middle Aged; Platelet Factor 4; Platelet Function Tests; Propanolamines; Pulmonary Embolism; Recurrence; Suloctidil; Thrombophlebitis; Ultrasonography; Vitamin K

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 pathophysiology of chronic thromboembolic pulmonary hypertension (CTEPH) is not fully understood. Poor-quality anticoagulation may contribute to a higher risk of CTEPH after acute pulmonary embolism (PE), partly explaining the transition from acute PE to CTEPH. We assessed the association between the time in therapeutic range (TTR) of vitamin-K antagonist (VKA) treatment and incidence of CTEPH after a PE diagnosis.. Case-control study in which the time spent in, under and above therapeutic range was calculated in 44 PE patients who were subsequently diagnosed with CTEPH (cases). Controls comprised 150 consecutive PE patients in whom echocardiograms two years later did not show pulmonary hypertension. All patients were treated with VKA for at least 6 months after the PE diagnosis. Time in (TTR), under and above range were calculated. Mean differences between cases and controls were estimated by linear regression.. Mean TTR during the initial 6-month treatment period was 72% in cases versus 78% in controls (mean difference -6%, 95%CI -12 to -0.1), mainly explained by more time above the therapeutic range in the cases. Mean difference of time under range was 0% (95%CI -6 to 7) and 2% (95CI% -3 to 7) during the first 3 and 6 months, respectively. In a multivariable model, adjusted odds ratios (ORs) for CTEPH were around unity considering different thresholds for 'poor anticoagulation', i.e. TTR <50%, <60% and <70%.. Subtherapeutic initial anticoagulation was not more prevalent among PE patients diagnosed with CTEPH than in those who did not develop CTEPH.

Topics: Aged; Anticoagulants; Case-Control Studies; Female; Humans; Hypertension, Pulmonary; Incidence; Male; Middle Aged; Pulmonary Embolism; Risk; Treatment Outcome; Vitamin K

Topics: Arabidopsis Proteins; Asbestos; Blood Platelets; Congresses as Topic; Construction Materials; Germany; Humans; Pseudopodia; Pulmonary Embolism; Thrombosis; Vitamin K; Vitamin K Epoxide Reductases; Warfarin

Venous thromboembolism (VTE) is an important cause of morbidity and mortality in Western countries. The incidence rate of VTE is estimated at 1-2 cases per 1000 annually. This study was a population-based cohort study of previously treatment naïve patients with a first occurrence of venous thromboembolism (VTE), using data from the administrative health data register of the Stockholm Region 2011-2018. Data on anticoagulant treatment was taken from the Swedish Prescribed Drug Register. We also analyzed all VTE events between 2011 and 2018. Altogether 14,849 naïve incident VTE cases were identified. In 2011 the majority of patients with a first episode of VTE were prescribed warfarin versus non-vitamin K antagonist oral anticoagulants (NOACs), 1144 versus 5. In contrast in 2018, the majority of patients were treated with NOACs, 1049 versus 59 treated with warfarin. Treatment with low molecular weight heparin only decreased from 814 to 683 patients. The frequency of all VTE events in the population increased over time from 1.88/1000 to 1.93/1000 (p = 0.072), and PE diagnoses increased from 0.69/1000 to 0.76/1000 (p = 0.003). In conclusion, during 2011-2018 there has been a shift of prescription of warfarin to a clear predominance of NOACs in the treatment of VTE in the Stockholm Region, in line with current recommendations. In the clinical situation, treatment has been simplified as monitoring of warfarin has decreased substantially. PE events increased during the time period in the population even if the increase was rather modest, while all VTE events did not increase significantly.

Topics: Administration, Oral; Anticoagulants; Demography; Drug Prescriptions; Female; Heparin, Low-Molecular-Weight; Humans; Male; Pulmonary Embolism; Registries; Sweden; Venous Thromboembolism; Vitamin K; Warfarin

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

Chronic thromboembolic pulmonary hypertension is one of the most prevalent forms of pulmonary hypertension and is a major complication of acute pulmonary embolism. One mainstay of chronic thromboembolic pulmonary hypertension treatment is lifelong anticoagulation. The recent advent of direct oral anticoagulants for acute pulmonary embolism treatment has provided a viable and effective alternative for treating this condition. However, little is known about the efficacy of this new class of drugs for treating chronic thromboembolic pulmonary hypertension. We aimed to evaluate the safety and efficacy of direct oral anticoagulants in the treatment of chronic thromboembolic pulmonary hypertension.. A cohort of chronic thromboembolic pulmonary hypertension patients who initiated treatment with direct oral anticoagulants between June 2015 and November 2016 were enrolled in this study.. Sixteen patients used rivaroxaban, three used dabigatran and one used apixaban for a mean follow-up of 20.9 months. The mean age was 51 years, and eighteen patients were classified as functional class II/III. Eight patients underwent a pulmonary endarterectomy and exhibited clinical, hemodynamic and functional improvement and currently continue to use direct oral anticoagulants. No episode of venous thromboembolism recurrence was identified during the follow-up period, but there was one episode of major bleeding after a traumatic fall.. Although direct oral anticoagulants appear to be a safe and effective alternative for treating chronic thromboembolic pulmonary hypertension, larger studies are needed to support their routine use.

Topics: Administration, Oral; Adult; Aged; Antithrombins; Chronic Disease; Dabigatran; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Pulmonary Embolism; Pyrazoles; Pyridones; Reproducibility of Results; Treatment Outcome; Vitamin K

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

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

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

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

Since first used in 2009, non-vitamin K oral anticoagulants (NOAC) have gained world-wide acceptance. Two groups of NOAC are currently used: the direct thrombin antagonist dabigatran and three direct factor  Xa antagonists apixaban, edoxaban, and ricaroxaban. With their increasing use for prevention of thromboembolism, the probability increases that NOAC-pretreated patients are admitted to emergency departments or intensive care units.The clinical challenge in NOAC preanticoagulated patients is to adequately cope with the given anticoagulated status of such patients. Because of their short half-life, many patients will be adequately treated with a "wait and see" approach, and surgeries and interventions are postponed until anticoagulant activities have totally subsided. In the few cases where immediate action is mandated, based on appropriate risk assessments it can be decided either to take the increased hemorrhagic risk of early intervention or to transfuse factor concentrates like PPSB or FEIBA which can safely reverse the anticoagulant activities of the three factor Xa antagonists (and potentially also of dabigatran). Recently a humanized Fab antibody fragment for dabigatran, idarucizumab, has been introduced onto the market, that can immediately reverse the anticoagulant effects of dabigatran. For the reversal of dabigatran, idarucizumab is therefore the drug of choice.In addition, in some specific indications of emergency and intensive care medicine, the primary use of a NOAC can be considered advantageous. Such indications are early cardioversion in patients admitted for new episodes of atrial fibrillation and patients with acute pulmonary embolism. For the widespread use of low-molecular-weight heparins in such indications, however, the decision to use a NOAC for anticoagulant therapy is frequently postponed to the treatment phase when the stabilized patient is already treated on the general ward.

Topics: Antibodies, Monoclonal, Humanized; Anticoagulants; Dabigatran; Electric Countershock; Emergency Service, Hospital; Factor Xa Inhibitors; Hemorrhage; Humans; Intensive Care Units; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thrombin; Thromboembolism; Vitamin K

ESSENTIALS: We performed a pooled analysis of 926 patients with cancer-associated incidental pulmonary embolism (IPE). Vitamin K antagonists (VKA) are associated with a higher risk of major hemorrhage. Recurrence risk is comparable after subsegmental and more proximally localized IPE. Our results support low molecular weight heparins over VKA and similar management of subsegmental IPE.. Incidental pulmonary embolism (IPE) is defined as pulmonary embolism (PE) diagnosed on computed tomography scanning not performed for suspected PE. IPE has been estimated to occur in 3.1% of all cancer patients and is a growing challenge for clinicians and patients. Nevertheless, knowledge about the treatment and prognosis of cancer-associated IPE is scarce. We aimed to provide the best available evidence on IPE management.. Incidence rates of symptomatic recurrent venous thromboembolism (VTE), major hemorrhage, and mortality during 6-month follow-up were pooled using individual patient data from studies identified by a systematic literature search. Subgroup analyses based on cancer stage, thrombus localization, and management were performed.. In 926 cancer patients with IPE from 11 cohorts, weighted pooled 6-month risks of recurrent VTE, major hemorrhage and mortality were 5.8% (95% confidence interval [CI] 3.7-8.3%), 4.7% (95% CI 3.0-6.8%), and 37% (95% CI 28-47%). VTE recurrence risk was comparable under low molecular weight heparins (LMWH) and vitamin K antagonists (VKAs) (6.2% vs. 6.4%; hazard ratio [HR] 0.9; 95% CI 0.3-3.1), while 12% in untreated patients (HR 2.6; 95% CI 0.91-7.3). Risk of major hemorrhage was higher under VKAs than under LMWH (13% vs. 3.9%; HR 3.9; 95% CI 1.6-10). VTE recurrence risk was comparable in patients with an subsegmental IPE and those with a more proximally localized IPE (HR 1.1; 95% CI 0.50-2.4).. These results support the current recommendation to anticoagulate cancer-associated IPE with LMWH and argue against different management of subsegmental IPE.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Cohort Studies; Data Interpretation, Statistical; Female; Follow-Up Studies; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Incidence; Male; Middle Aged; Neoplasms; Pulmonary Embolism; Recurrence; Registries; Risk Factors; Tomography, X-Ray Computed; Treatment Outcome; Venous Thromboembolism; Vitamin K; Young Adult

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

Chronic inflammatory diseases predispose for development of a first pulmonary embolism (PE). Previous studies showed that corticosteroids, which are the mainstay of treatment for inflammatory diseases, enhance the risk of a first venous thromboembolism. Yet, it is unknown whether corticosteroids also predispose for recurrent events. Therefore, we investigated the association between oral and/or inhaled corticosteroid use and the risk of recurrent PE.. We performed a nested case-control study using the PHARMO Database. Adult patients who had suffered from a first PE for which vitamin K antagonists were prescribed, were eligible. Of these, 384 patients with recurrent PE were matched to 1030 patients without recurrent PE.. We showed that oral or inhaled corticosteroids was ever used by 22.7% and 20.6% of patients with recurrent PE, and 23.5% and 21.5% of the patients without recurrent PE. There was an overall association between oral corticosteroid use and the risk of recurrent PE (p=0.02). Current use of oral corticosteroids increased the risk of recurrent PE (OR 3.74; 95% CI 2.04-6.87), whereas past use reduced the risk (OR 0.46; 95% CI 0.28-0.74). A similar pattern was observed for inhaled corticosteroids, although less strong (p=0.10).. Current use of oral corticosteroids is associated with increased risk of recurrent PE. Whether this increased risk is caused by oral corticosteroids themselves, or by the underlying disease, or both, needs further investigation. Nevertheless, given the frequent use of corticosteroids in clinical practice, clinicians should be aware of this risk.

Topics: Administration, Inhalation; Administration, Oral; Adrenal Cortex Hormones; Adult; Aged; Anticoagulants; Case-Control Studies; Female; Humans; Male; Middle Aged; Pulmonary Embolism; Recurrence; Risk Factors; Vitamin K

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

The optimal duration of treatment with vitamin K antagonists (VKA) after venous thromboembolism (VTE) in patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) is uncertain. To tackle this issue, we retrospectively studied 206 patients with MPN-related VTE (deep venous thrombosis of the legs and/or pulmonary embolism). After this index event, we recorded over 695 pt-years 45 recurrences, venous in 36 cases, with an incidence rate (IR) of 6.5 per 100 pt-years (95% confidence interval (CI): 4.9-8.6). One hundred fifty-five patients received VKA; the IR of recurrent thrombosis per 100 pt-years was 4.7 (95% CI: 2.8-7.3) on VKA and 8.9 (95% CI: 5.7-13.2) off VKA (P=0.03). In patients receiving VKA, the IR of recurrent thrombosis per 100 pt-years was 5.3 (95% CI: 3.2-8.4) among 108 patients on long-term VKA and 12.8 (95% CI: 7.3-20.7) after discontinuation among the 47 who ceased treatment (P=0.008), with a doubled risk of recurrence after stopping VKA (hazard ratio: 2.21, 95% CI: 1.19-5.30). The IR of major bleeding per 100 pt-years was 2.4 (95%: CI: 1.1-4.5) on VKA and 0.7 (95% CI: 0.08-2.5) off VKA (P=0.08). In conclusion, in MPN patients with VTE recurrent thrombosis is significantly reduced by VKA and caution should be adopted in discontinuation; however, the incidence of recurrence on treatment remains high, calling for clinical trials aimed to improve prophylaxis in this setting.

Topics: Adult; Aged; Aged, 80 and over; Bone Marrow Neoplasms; Cohort Studies; Female; Fibrinolytic Agents; Humans; Male; Middle Aged; Myeloproliferative Disorders; Premedication; Pulmonary Embolism; Recurrence; Retrospective Studies; Venous Thromboembolism; Vitamin K

Topics: Administration, Oral; Anticoagulants; Antithrombins; Humans; Pulmonary Embolism; 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

Spontaneous hematoma of transverse mesocolon is a rare complication of anticoagulant treatment with vitamin K. We report the case of spontaneous hematoma of right angle of the transverse mesocolon associated with a hemoperitoneum in a 32-year-old patient treated by fluindione for pulmonary embolism. The diagnosis must be made urgently. The abdominal ultrasound and the scanning confirm the diagnosis. It is important to note that surgery is indicated only in the case of complications such as the risk of rupture of the hematoma.

Topics: Adult; Anticoagulants; Female; Hematoma; Hemoperitoneum; Humans; Mesocolon; Phenindione; Pulmonary Embolism; Vitamin K

The aetiology of chronic thromboembolic pulmonary hypertension (CTEPH) is not clearly understood. In some patients, the disease is preceded by acute pulmonary embolism (APE), and is characterised by intravascular thrombosis, vasoconstriction, inflammation and remodelling of pulmonary arteries. Ensuing pulmonary hypertension leads to potentially fatal chronic right ventricle failure. Both inborn and acquired risk factors were identified. Pathogenesis of haemostatic disorders is not completely explained, and extrinsic coagulation pathway disorders may play a role in CTEPH aetiology.. To evaluate levels of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in CETPH, and to delineate their role in the disease pathogenesis.. Plasma concentrations of TF and TFPI were evaluated in 21 CTEPH patients, in 12 patients with pulmonary arterial hypertension (PAH), in 55 APE survivors without persistent pulmonary hypertension after at least 6 months from the acute episode, and in 53 healthy volunteers (control group C). Most patients were treated with vitamin K antagonists (VKA), and some with unfractionated or low molecular weight heparin. Exclusion criteria included malignancy, inflammation, and recent operation.. Tissue factor concentration was lower in CTEPH and in post-APE patients, not stratified by anticoagulation modality, as compared to control group (p = 0.042; p = 0.011) and PAH group (p = 0.024, p = 0.014). Patients with CTEPH and post-APE on adequate VKA-anticoagulation had similar TF concentration to group C. TFPI concentration was similar in CETPH and post-APE patients irrespective of anticoagulation, and higher as compared to group C (respectively, p = 0.012; p = 0.024; p = 0.004). TFPI concentration was similar in patients with CETPH and in post-APE group, both on adequate VKA-anticoagulation when compared to group C. In the post-APE group, there was no significant difference in TFPI concentration between patients receiving adequate and subjects without anticoagulation. Group C was significantly (p = 0.000) younger than any other group, and showed correlation (r = 0.31) between age and TFPI concentration.. In CTEPH there is a high consumption of TF, leading to reduction in plasma concentration of TF and increase in TFPI. Adequate VKA-anticoagulation normalises TF and TFPI plasma concentrations, as is the case of APE survivors.

Topics: Adult; Aged; Anticoagulants; Humans; Hypertension, Pulmonary; Lipoproteins; Middle Aged; Pulmonary Embolism; Thromboplastin; Vitamin K; Young Adult

Benefits and harms of long-term anticoagulant therapy (AT) after acute pulmonary embolism (PE) are poorly known. The aim of this study was to investigate the outcome of patients with PE treated with AT for 5 years according to American College of Chest Physicians (ACCP) guidelines.Patients with both unprovoked and secondary PE were consecutively enrolled in a "real life" study. After a 12-month AT, they continued or stopped the treatment according to ACCP guidelines, and were followed-up for 5 years. Outcomes were all-cause mortality, recurrence, and fatal recurrence under AT.Of the original consecutive 585 patients, 471 were included (83 dead, 31 lost during the 1st year). Of these, 361 (76.6%) continued AT. During 5 years, death occurred in 109 (30.2%) patients, with a mortality rate of 8.00 events/100 person-years of follow-up; recurrence in 34 (9.4%), with an incidence rate of 2.58 events/person-years; fatal recurrence in 13 (3.6%), with an incidence rate of 0.95 events/person-years. The case fatality rate for recurrence was 38.2%. In the subgroup of patients with unprovoked PE, the chance of dying was significantly lower (RR 0.35; 95% confidence interval 0.24-0.53) and the tendency to fatal recurrence (not significantly) greater (0.11 events/100 person-years vs 0.07 events/100 person-years) than in the remaining patients. Major bleeding occurred in 5 (1.3%) patients. The case fatality rate for bleeding was 14.3%.During 5-year AT, 30% of patients dies, 10% experiences recurrences, and 5% has fatal recurrences. According to guidelines, most patients need to continue AT; the case fatality rate for bleeding is lower than that for recurrence.

Topics: Aged; Aged, 80 and over; Anticoagulants; Cause of Death; Female; Follow-Up Studies; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Incidence; Male; Middle Aged; Practice Guidelines as Topic; Prospective Studies; Pulmonary Embolism; Recurrence; Risk Factors; Secondary Prevention; Time Factors; Vitamin K

The aim of this case report is to discuss the issue of nutritional therapy in patients taking warfarin. Patients are often prescribed vitamin K free diets without nutritional counseling, leading to possible health consequences.. A 52-year-old woman with obesity and hypertension was prescribed a low calorie diet by her family doctor in an effort to promote weight loss. After a pulmonary embolism, she was placed on anticoagulant therapy and on hospital discharge she was prescribed a vitamin K free diet to avoid interactions. Given poor control of her anticoagulant therapy, she was referred to our Nutritional Unit outpatients' service.. This case illustrates the importance of a thorough medical nutrition assessment in the management of patients with obesity and the need for a change in the dietary approach of nutritional therapy in the management of vitamin K anticoagulant therapy. In patients taking warfarin, evidence suggest that the aim of nutritional therapy should be to keep dietary intake of vitamin K constant.

Topics: Anticoagulants; Caloric Restriction; Female; Humans; Hypertension; Middle Aged; Nutrition Assessment; Obesity; Pulmonary Embolism; Vitamin K; Warfarin; Weight Loss

The relative effectiveness of vitamin K antagonists compared with novel oral anticoagulants in treating pulmonary embolism remains unclear. Recent trials comparing the efficacy of vitamin K antagonists with factor Xa inhibitors for the treatment of pulmonary emboli have been non-inferiority studies based primarily on risk reduction (such as bleeding events), rather than resolution of specific diseases such as pulmonary embolism. Consequently, there is a lack of evidence indicating which of these agents are more effective. Here, we present a case where pulmonary emboli were treated with novel oral anticoagulants followed by warfarin to discuss the potential limitations in the use of novel oral anticoagulants as prevention or treatment of thromboembolism and the continued role for warfarin in this setting.. A 34-year-old African American woman presented to our clinic with shortness of breath and pleuritic chest pain several months post-surgery. She was identified as having multiple bilateral pulmonary embolisms and was treated with several novel oral anticoagulants, which failed to resolve the clots. Complete resolution was achieved upon switching to warfarin.. The patient described in this report failed to respond to novel oral anticoagulant therapy, but her emboli resolved when she was treated with warfarin. This study challenges the notion that factor Xa inhibitors are better alternatives to vitamin K anticoagulants in the treatment of pulmonary emboli based on their safety profile and ease of use alone. As a result, further post-marketing investigations into the efficacy of these agents in the management of pulmonary emboli may be warranted.

Topics: Administration, Oral; Adult; Angiography; Anticoagulants; Chest Pain; Dyspnea; Female; Humans; Pulmonary Embolism; Treatment Failure; Vitamin K; Warfarin

Venous thromboembolism (VTE) impacts ∼900,000 individuals annually in the US, causing up to 100,000 deaths. Patients experiencing VTE have heightened risk of recurrence. Initial parenteral anti-coagulation is standard therapy for acute VTE followed by ≥3 months of warfarin, which introduces the risk of major bleeding. Balancing increased risks of bleeding and recurrent VTE remains challenging. Recent clinical trials suggest that rivaroxaban, an oral direct inhibitor of factor Xa, provides an effective, safe, simplified approach to treatment. This study considers the economic implications of these data.. This study modeled inpatient, acute, and 1-year VTE costs for a hypothetical commercial plan with 1 million members. At baseline, all VTE patients receive standard therapy. Alternatively, 25% are instead treated with rivaroxaban. Model inputs are trial- and literature-based.. Standard therapy for VTE consumes 9474 inpatient days ($31.6 million). Added to that is treatment for 74 recurrences ($1.4 million); major and non-major bleed events ($1 million); and direct costs of anti-coagulation ($5.3 million). Alternatively, a 25% shift to oral anti-coagulation with rivaroxaban reduces inpatient days (by 5%); associated acute-care costs (by 2%); recurrences and costs (by 6%). Four major bleeding events are prevented, at the cost of one additional non-major bleeding event, which, taken together, reduce net utilization by 9%. Direct costs of anti-coagulation increase by 5%.. The reduction in inpatient utilization, recurrences, and major bleeding resulting from a 25% shift from standard therapy to rivaroxaban following acute VTE would conserve ∼$860,475 for every 1 million commercial health plan enrollees.

Topics: Anticoagulants; Computer Simulation; Cost-Benefit Analysis; Drug Therapy, Combination; Enoxaparin; Hemorrhage; Hospitalization; Humans; Models, Econometric; Pulmonary Embolism; Recurrence; Rivaroxaban; United States; Venous Thromboembolism; Vitamin K

The initial management or venous thromboembolism (VTE) corresponds to the first 3 months of treatment. Pulmonary embolism (PE) are mostly hospitalized. Serious PE associated with hemodynamic instability has to be admitted in intensive care unit due to the need for fibrinolytics. PE without any risk factor for VTE recurrences or death could be followed as outpatient. Conversely, deep vein thrombosis (DVT), including proximal DVT are not hospitalized with the xception of patients with serious risk factors. The therapeutic strategy is identical between DVT and PE treatment with an acute phase with either parenteral anticoagulants, especially low molecular weight heparins or fondaparinux, or by an intensive dose of direct oral anticoagulant such as rivaroxaban or apixaban. Then maintenance therapy has to be prescribed either with vitamin K antagonists with overlapping parenteral anticoagulants for at least 72 hours, or with a maintenance dose of apixaban or rivaroxaban.

Topics: Anticoagulants; Blood Coagulation Tests; Fibrinolytic Agents; Humans; Pulmonary Embolism; Risk Assessment; Venous Thromboembolism; Vitamin K

Venous thromboembolism occurs in up to 10% of patients with cancer. The incidence of thrombosis is varying with the nature, the histologic type and the stage of the disease. The risk of thrombosis is also increased by most of anticancer treatments and supportive care. Although long-term prophylactic treatment is able to decrease the rate of venous thromboembolism in patients with cancer, the absolute reduction is too low to give long-term prophylaxis, except for some rare exceptions. The treatment of cancer associated thrombosis is based on the use of low-molecular weight heparin for at least three to six months. In most cases, anticoagulation should be given for a longer period but the choice of the drug should be indi- vidualized on the basis of the evolution of the underlying cancer, overall prognosis, tolerance of injections and patient's preference. Recurrent venous thromboembolism during treatment with low-molecular weight heparin can be treated with a 10% dose escalation. Dose should be adjusted during periods of thrombocytopenia. Finally, the direct oral anticoagulants have not been compared with low-molecular weight heparins for the treatment of cancer associated thrombosis.

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

Topics: Acute Disease; Anticoagulants; Guideline Adherence; Heparin; Humans; Morpholines; Pulmonary Embolism; Risk Assessment; Rivaroxaban; Thiophenes; 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

Topics: 4-Hydroxycoumarins; Adult; Anticoagulants; Humans; Indenes; Pulmonary Embolism; Randomized Controlled Trials as Topic; Risk Assessment; Secondary Prevention; Vitamin K

Venous thromboembolism (VTE) is a common complication in patients with cancer. Because of their improved subcutaneous bioavailability and reliable antithrombotic efficiency low-molecular-weight heparins (LMWH) are preferably used for prevention and treatment of cancer-related VTE. Thromboprophylaxis with LMWH is well established in patients undergoing cancer surgery and hospitalized cancer patients, while outpatient prophylaxis remains contentious. LMWH are recommended over unfractionated heparins and vitamin K antagonists for initial treatment and secondary prophylaxis (3-6 months) after cancer-related VTE. Long-term secondary prophylaxis should be considered for patients with ongoing active malignancy and low bleeding risk. Due to absence of clinical studies in cancer patients, the use of novel oral anticoagulants is currently not recommended.

Topics: Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Neoplasms; Postoperative Complications; Pulmonary Embolism; Randomized Controlled Trials as Topic; Risk Factors; Thrombocytopenia; Venous Thromboembolism; Vitamin K

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

Few studies have assessed treatment patterns of acute venous thromboembolism (VTE) in a real-world population. We aimed to describe anticoagulant treatment patterns for acute VTE using healthcare databases of Québec, Canada.. We used linked healthcare databases of the province of Québec, Canada to identify all incident cases of deep vein thrombosis (DVT) and pulmonary embolism (PE) between 2000 and 2009. We formed two patient cohorts, one with definite cases (definite VTE cohort, N=40,776) and the other including cases with definite or probable VTE (any VTE cohort, N=54,803) that were followed until death, end of health coverage, or end of study (December 31, 2009).. In the definite cohort, 73.6% of subjects were dispensed an anticoagulant following the diagnosis of VTE. Of those who were dispensed a vitamin K antagonist (VKA), median duration of use was 61days (interquartile range 89). VKA initiation was more likely in patients with pulmonary embolism than deep vein thrombosis alone (HR 1.62, 95% CI (1.58-1.66)). Among outpatients, those managed initially in the outpatient setting were less likely to initiate VKA therapy (HR 0.75, 95% CI (0.68-0.77)), while those requiring admission to hospital for VTE management were more likely to initiate (HR 1.81, 95% CI (1.76-1.87)). Findings were similar in the any VTE cohort.. Our study describes VTE treatment patterns in a real-world setting and suggests that there may be important gaps. These may include significant numbers of patients who did not initiate oral anticoagulant therapy, particularly in the outpatient setting, and shorter duration of oral anticoagulant use than recommended.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Child; Child, Preschool; Cohort Studies; Female; Humans; Infant; Male; Middle Aged; Pulmonary Embolism; Quebec; Venous Thromboembolism; Vitamin K; Young Adult

Topics: Administration, Oral; Algorithms; Anticoagulants; Biomarkers; Chronic Disease; Clinical Laboratory Techniques; Diagnostic Imaging; Embolectomy; Endovascular Procedures; Female; Fibrin Fibrinogen Degradation Products; Fibrinolytic Agents; Heart Failure; Home Care Services; Humans; Hypertension, Pulmonary; Long-Term Care; Neoplasms; Pregnancy; Pregnancy Complications, Cardiovascular; Prognosis; Pulmonary Embolism; Risk Factors; Vasoconstrictor Agents; Vasodilator Agents; Vitamin K

Since 2004, guidelines recommend long-term treatment with low-molecular-weight heparin (LMWH) in patients with cancer and pulmonary embolism (PE). We assessed the proportion of cancer patients with PE actually treated with LMWH and the duration of anticoagulant treatment in the Netherlands.. A retrospective cohort study in patients that were hospitalised for PE between 1998-2008. Patients with PE were selected from national hospital discharge records, after linkage to a national pharmacy database. Cancer patients with PE were matched for age, sex and year of diagnosis of PE to subjects with PE without cancer.. 600 cancer patients with PE were matched to 1200 patients with PE without cancer. Long-term LMWH was prescribed in 82 (13.7%) of the cancer patients and in eight (0.7%) of the cancer-free patients (p < 0.001); all the other patients received vitamin K antagonists (VKA). From 1998-2008, there was an increase in the use of LMWH in cancer patients: in 2007-2008, LMWH was prescribed in 42 (32%) cases, compared with one (1.7%) of the cancer patients with PE in 1998-1999. Median duration of treatment was 5.8 months (interquartile range 3.1-8.8) in cancer patients, compared with 7.0 months (4.9-11) in patients without cancer (p < 0.001), a difference that persisted after adjustment for mortality.. Although the use of LMWH in patients with cancer and PE is increasing, in 2008, patients in the Netherlands are still mostly treated with VKA, and not with LMWH as recommended by guidelines. Cancer patients with PE on average receive shorter treatment than matched patients without cancer.

Topics: Aged; Anticoagulants; Female; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Neoplasms; Netherlands; Practice Guidelines as Topic; Pulmonary Embolism; Retrospective Studies; Time Factors; Vitamin K

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

Topics: Anticoagulants; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Pulmonary Embolism; Vitamin K

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

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

Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Meta-Analysis as Topic; Pulmonary Embolism; Secondary Prevention; Vitamin K

Patients with idiopathic venous thromboembolism (VTE) have a high recurrence risk during and after stopping anticoagulant treatment. Several studies suggest that treatment with statins reduces the incidence of a first episode of VTE, but data on the effects in patients with a previous episode are lacking. We examined the effect of statin therapy on the risk of recurrent pulmonary embolism (PE).. Using the PHARMO Record Linkage System, a Dutch population-based registry of pharmacy records linked with hospital discharge records, patients hospitalized with an acute episode of PE were identified between 1998 and 2008. Prescription-based use of statins and vitamin K antagonist (VKA) were identified starting at hospital discharge and during follow-up. The association between statin use (time-varying) and the incidence of recurrences, cardiovascular events, and death was assessed using Cox regression analysis. The mean (standard deviation) age was 61 (17) years. The median (range) duration of VKA treatment after acute PE was 199 (45-3793) days. Twenty-four per cent of the patients (n = 737) had at least one prescription of statins during the follow-up period and the median duration of statin therapy was 1557 (5-4055) days. During a median follow-up of 1529 (1-4155) days, 285 (9.2%) patients experienced a recurrence. Treatment with statins was associated with a reduced risk of recurrent PE [adjusted hazard ratio (HR) 0.50, 95% CI: 0.36-0.70], both during and after stopping VKA treatment. A dose-response relationship was shown for potency, with the largest reduction in those with the most potent statins. Finally, statin treatment also reduced the risk for cardiovascular events and all-cause mortality.. Statin treatment decreases the risk of recurrent PE, irrespective of VKA treatment. Treatment with statins may be an attractive alternative for anticoagulant treatment in the long-term treatment of PE.

Topics: Aged; Anticoagulants; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Pulmonary Embolism; Registries; Regression Analysis; Risk Factors; Secondary Prevention; Treatment Outcome; Vitamin K

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: Anticoagulants; Drug Administration Schedule; Evidence-Based Medicine; Heparin; Heparin, Low-Molecular-Weight; Humans; Long-Term Care; Neoplasms; Practice Guidelines as Topic; Pulmonary Embolism; Randomized Controlled Trials as Topic; Risk Factors; Secondary Prevention; Venous Thromboembolism; Vitamin K

Topics: Anticoagulants; Heart Diseases; Humans; International Normalized Ratio; Nutritional Requirements; Pulmonary Embolism; Thrombophlebitis; Vitamin K; Vitamin K Deficiency

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

The rate of resolution of a first episode of pulmonary embolism (PE) is uncertain. A baseline test indicating any residual PE is pivotal in aiding a more accurate diagnosis of recurrent PE. This study aimed to assess the rate and risk factors of residual PE with either multidetector computed tomography imaging (MDCT) or lung perfusion scan (LPS) using a cross-sectional study in which consecutive patients were enrolled with a first objectively documented episode of symptomatic PE, and who were considered for possible treatment withdrawal after at least 3 months of anticoagulation. A first cohort of patients (n = 80) underwent MDCT, while the subsequent cohort (n = 93) underwent LPS. The two cohorts had similar characteristics, and 98.3% of patients had non high-risk index PE. MDCT detected residual PE in 15% of subjects (12/80, 95% CI 8-25%) after a mean of 9 months of anticoagulation. No clinical characteristics were significantly associated with residual PE at MDCT. LPS detected residual PE in 28% (26/93, 95% CI 19-38%) of patients after a period of a mean of 9 months of anticoagulation with a significant association with increasing age and known pulmonary disease. Resolution of PE was high after a first episode of non high-risk PE treated with heparin followed by at least 3 months of anticoagulation. Age and coexistent pulmonary disease influence the presence of residual PE detected by LPS, but not by MDCT. Further studies are warranted in which the presence of residual embolism is detected by repetition of the same test that had been initially carried out.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Antifibrinolytic Agents; Cross-Sectional Studies; Female; Humans; Logistic Models; Male; Middle Aged; Perfusion Imaging; Predictive Value of Tests; Pulmonary Embolism; Tomography, X-Ray Computed; Vitamin K; Young Adult

Massive pulmonary embolism is a life threatening pathology with a high mortality over 20%. Thrombolysis is one of therapy ways that leads to a lower rate of death. The aim of the study is to show interest, limits and complications of thrombolytic therapy in massive pulmonary embolism.. This descriptive study presents 8 cases of pulmonary embolism admitted to the Cardiology Division of Grand-Yoff from March 2003 to March 2006. All cases confirmed by Tomodensitometry (TDM) with massive pulmonary embolism were included in this study.. We used thrombolytic only in 8 cases of massive pulmonary embolism about 32. In-hospital prevalence was 25%. The average age was 49.8 ± 19.1 (from 15 to 72) and sex-ratio 0.33. Seven patients had a moderate clinical probability Well's score and one of them 1 had a high clinical probability. The clinical signs were: cardio-vascular collapse (7 cases), syncope (1) and cardio-vascular arrest. The electrocardiogram showed a sub-epicardial ischemia (4 cases), a right bundle branch block and a Mac Ginn White's sign. Two patients had a right-basal opacification at the chest X ray. The echocardiography found 5 cases of right ventricular dilatation, 1 case of paradoxal septum, 1 case of multiple thrombi in the right ventricule. The TDM confirmed diagnosis with 3 cases of bilateral pulmonary embolism, 1 case of pulmonary aneurysm. The treatment used thrombolytic : 1,500,000 IU of streptokinase, sympathomimetic drugs, anticoagulation with heparins and vitamin K antagonists.

Topics: Adolescent; Adult; Aged; Anticoagulants; Echocardiography; Electrocardiography; Female; Fibrinolytic Agents; Humans; Male; Middle Aged; Pulmonary Embolism; Vitamin K; Young Adult

We present the case of a 19-year-old male athlete with protein C deficiency who developed proximal deep venous thrombosis and pulmonary embolism while abusing anabolic-androgenic steroids. Anabolic-androgenic steroids have been reported to have anticoagulatory and profibrinolytic effects in patients with protein C deficiency. Despite these antithrombotic effects, the patient developed repeated venous thromboembolism during treatment with low-molecular-weight heparin. The net effect of anabolic-androgenic steroids on the haemostatic system may change from antithrombotic to prothrombotic in male abusers of anabolic steroids with protein C deficiency.

Topics: Anticoagulants; Blood Coagulation Factors; Dalteparin; Doping in Sports; Enoxaparin; Hematoma, Subdural; Humans; Male; Methandrostenolone; Pleural Effusion; Protein C Deficiency; Pulmonary Embolism; Substance-Related Disorders; Thrombophilia; Thrombophlebitis; Vena Cava Filters; Vitamin K; Young Adult

Few studies have examined the clinical course of pulmonary embolism (PE) in patients anticoagulated continuously for 1 year.. We sought to determine the incidence of death, recurrent PE and bleeding during anticoagulation in the first year after acute PE, and to assess associated risk factors.. All consecutive PE patients who were referred to our center in Pisa, Italy between 2001 and 2005 received a conventional initial treatment, followed by vitamin K antagonists [international normalized ratio (INR), 2.0-3.0] for 1 year. They were followed-up at scheduled times at the study center. The development of recurrent PE was objectively documented and recorded.. Out of 497 patients, 48 (9.6%) developed recurrent PE, which was fatal in 36. Of these 48 events, 39 occurred within 10 days of diagnosis and only two patients had a non-fatal recurrent PE between 6 and 12 months. Risk factors associated with the risk for overall recurrent PE were persistent severe dyspnoea (P = 0.007), a high perfusion defect score index (PDI) (P = 0.003) and cardiopulmonary co-morbidities (P = 0.005). Unprovoked presentation (P = 0.030), persistent severe dyspnoea (P = 0.011) and a high PDI (P = 0.001) predicted the risk for fatal PE. Overall bleeding incidence was 3.4%, no cases of bleeding occurred between 180 and 360 days post-diagnosis.. In spite of conventional anticoagulation, a proportion of patients with PE experience both a fatal and non-fatal recurrent embolism within the first year. The large majority of these occur within the days proceeding diagnosis, with only a small minority occurring in the last 6 months. No bleeding was observed after 6 months. Therefore, prolonging anticoagulation for 1 year represents both a safe and effective treatment.

Topics: Aged; Anticoagulants; Drug Administration Schedule; Female; Follow-Up Studies; Hemorrhage; Humans; International Normalized Ratio; Italy; Kaplan-Meier Estimate; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Pulmonary Embolism; Recurrence; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Vitamin K

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

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

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

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

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

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

Topics: Acute Disease; Anticoagulants; Critical Care; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Practice Guidelines as Topic; Practice Patterns, Physicians'; Pulmonary Embolism; Triage; Vitamin K

Topics: Anticoagulants; Embolectomy; Evidence-Based Medicine; Female; Heparin; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Pulmonary Embolism; Thrombectomy; Thromboembolism; Thrombolytic Therapy; Vitamin K

The diagnosis of pulmonary embolism (PE) remains a considerable challenge to any physician. Irrespective of the diagnostic progress, the prevalence of fatal PE in autopsy studies is still about one third. Introducing sufficient anticoagulant therapy, mortality due to PE can be decreased from about 30% to 2-8%. Therefore, immediate anticoagulant therapy should be given, if PE is clinically suspected. Initial anticoagulation by low-molecular-weight heparins is as effective as unfractionated heparin in non-massive PE. In patients suffering from massive PE, thrombolytic treatment is indicated. Whether patients with submassive PE and/or elevated cardial troponins should also receive thrombolytic treatment, is still under debate. After PE has been established, vitamin-k-antagonists are the current standard of secondary prophylaxis.

Topics: Acute Disease; Anticoagulants; Critical Care; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Patient Care Management; Pulmonary Embolism; Triage; 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

Antivitamin K treatments (AVK) are related to increased morbidity and mortality, notably in elderly patients. The International Normalized Ratio (INR) should be well controlled and its stabilisation within the therapeutic range help to prevent the haemorrhagic complications.. A one-year prospective survey on all the cases of excess AVK was conducted in hospitalised patients aged over 70.. During the study period, 225 hospitalised patients treated with AVK (mean age 84 years) were identified: 62% received warfarin, 19% fluindione, 8% acenocoumarol and 11% received several successive AVK. During this period, 1.904 INR measurements were recorded: 97 (5.1%) were > or =5.0 and 12 (0.63%) were > or =9.0. In all, 59 patients (23.1%) exhibited one or several episodes of excess AVK (INR > or =5.0) and 57 exhibited a target INR of 2.5. Three patients died of accidental haemorrhage--two of them due to intra-cerebral bleeding--among the 59 patients with excess AVK. In three cases, the INR was greater than 7.0 at the time of the accident.. In half of the cases of excess, the episode occurred during the month following initiation of treatment with AVK. In nearly two thirds of cases, a change had been made in drug therapy in the 10 days preceding the excess, with the prescription of a drug enhancing the effect of the AVK: anti-infection agents (antibiotics and anti-fungals) and amiodarone were the drugs most frequently involved. Oral or intravenous vitamin K1 was administered in only 19% of cases.. In very old patients treated with oral anticoagulants, certain risk factors must be identified: the initiation period of treatment, the occurrence of an intercurrent disease and the subsequent change in the drug therapy. INR monitoring should be intensified in order to detect any excess and, if detected, ensure the optimal management of the patient.

Topics: 4-Hydroxycoumarins; Aged; Aged, 80 and over; Amiodarone; Anti-Arrhythmia Agents; Anti-Bacterial Agents; Anticoagulants; Antifungal Agents; Coma; Drug Administration Schedule; Drug Overdose; Drug Synergism; Female; Hematoma, Subdural; Hemorrhage; Hospitalization; Humans; Indenes; International Normalized Ratio; Male; Prospective Studies; Pulmonary Embolism; Thrombocytopenia; Vitamin K; Warfarin

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

Can the biochemical evidence for "new thrombophilic factors" influence the duration of AVK treatment following the occurrence of a first pulmonary embolus? Certainly for the classic but very rare antithrombin defects as well as for the existence of circulating anticoagulant. Possibly for protein C and S defects. On the other hand, the existence of a heterozygotic "Leiden" mutation of factor V, or factor II, and an increase of factors VIII, IX, or XI, do not at present warrant a change in AVK prescription. In effect, in the case where the existence of a thrombogenic state implies a prolongation of AVK treatment with its significant potential complications, it is indispensable that the risk/benefit ratio is well founded, which is not the case for these "new" thrombophilic states. The coexistence of several of these new biochemical anomalies (for example the association of a factor V and factor II mutation) probably represents an excess risk of thrombosis, but in this situation the reasoning remains the same. On the other hand, faced with a confirmed recurrence, the studies in the literature tell us that very long term treatment should be debated independently from the biochemical results. It is conceivable that there are biochemical anomalies (sometimes quite frequent which should be viewed as "normal variants") which, although they have great significance for improving the understanding of venous thrombo-embolic disease, do not at present warrant a change in our therapeutic protocols. Another facet of the problem concerns the use of D-dimers following the first months of AVK treatment in order to possibly distinguish patients at low risk of recurrence. The first results of this approach are interesting, but require confirmation before they can be used in practice.

Topics: 4-Hydroxycoumarins; Anticoagulants; Humans; Indenes; Pulmonary Embolism; Recurrence; Time Factors; 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: 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

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

Topics: Aged; Aged, 80 and over; Anticoagulants; Female; Heparin, Low-Molecular-Weight; Humans; Male; Pulmonary Embolism; Recurrence; Risk Factors; Thrombophlebitis; Vitamin K

We analyzed the clinical and biological characteristics as well as the clinical course and outcome observed in 20 patients with antiphospholipid antibodies and clinical signs including thrombosis or repeated spontaneous abortion to better identify the recently described antiphospholipid syndrome.. We retrospectively studied all patients observed in our unit from 1981 to 1992 who fulfilled the following inclusion criteria: a) at least one episode of arterial or venous thrombosis and/or repeated spontaneous abortions, b) positive for antiphospholipid antibodies.. Twenty patients were included, 3 with systemic lupus erythematosus (according to the American Rheumatism Association criteria). Arterial or venous thrombosis occurred in 9 and 16 respectively, including exceptional cases of cerebral phlebitis and thrombosis of dermal capillaries. High blood pressure was recorded in 8. Only 1 or 2 types of antiphospholipid antibodies were found in most patients. Anticardiolipin, a circulating anticoagulant and a false-positive Bordet-Wassermann reaction were found together in only 3 out of 16. In addition, the antibody level varied independently from the thrombotic events. There was no case with a clinical course from primary antiphospholipid syndrome to systemic erythromatosus lupus. The effect to treatment on occurrence of new thrombotic events was studied. Three patients suffered one or more haemorrhagic events during antivitamin K treatment.. It is difficult to establish a differentiation between primary antiphospholipid syndrome, systemic lupus erythematosus and lupus-like syndromes, and precise methods of identifying antiphospholipid antibodies should be further developed.

Topics: 4-Hydroxycoumarins; Adrenal Cortex Hormones; Adult; Anticoagulants; Antiphospholipid Syndrome; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Indenes; Intracranial Embolism and Thrombosis; Male; Middle Aged; Pregnancy; Pulmonary Embolism; Retrospective Studies; Thrombophlebitis; Vitamin K

Gammacarboxyglutamic acid (gla) is a non essential amino acid synthesized in presence of vitamin K, predominantly found in coagulation and bone proteins. In 14 cases of deep vein thrombosis and in 11 cases of disseminated intravascular coagulation, compared to 19 normal subjects and 9 patients hospitalized for leg pain, free plasma gla levels were found significantly elevated (respectively 372 +/- 244 and 559 +/- 361 versus 146 +/- 34 and 120 +/- 40 pmol/mL). In six paired plasma and serum, gla levels were similar. These results suggest an involvement of blood coagulation in gla generation with need of a catabolism of the activated factors. A significant decrease was noticed during vitamin K antagonist therapy and liver disease, both instances in which the synthesis of gla containing coagulation factors is affected. During hepatocellular carcinoma with elevated desgamma carboxyprothrombin, gla was found normal, denying an global impairement of the vitamin K metabolism.

Topics: 1-Carboxyglutamic Acid; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Carcinoma, Hepatocellular; Chronic Disease; Disseminated Intravascular Coagulation; Female; Hemangioma; Humans; Leg; Liver Diseases; Liver Neoplasms; Male; Middle Aged; Pain; Pulmonary Embolism; Skin Neoplasms; Thrombophlebitis; Vitamin K

This study reports the efficacy in the prevention of thromboembolic complications of adapted low-dose oral anticoagulants following total hip replacement. 750 patients undergoing total hip replacement received oral anticoagulants as exclusive drug prophylaxis for thromboembolic complications. These patients were considered preoperatively not to present any particular risk for the development of postoperative thrombosis. Anticoagulant therapy was commenced on the evening of the operation. Eleven pulmonary embolisms (1.5 per cent) were observed, but none of them were fatal. The risk of thrombosis was evaluated in 100 of these 750 patients by means of bilateral venography of the lower limbs: 21 patients developed distal thrombosis (sural veins) and 2 patients developed proximal femoral thrombosis. Only one haemorrhagic complication occurred in the 750 patients of this series. The prothrombin profile determined in the patients developing thrombosis or pulmonary embolism was not significantly different from that of the patients free of any thromboembolic complications. Although oral anticoagulants appear to be particularly effective for the prevention of fatal pulmonary embolism, it is not clear that their efficacy is directly related to the prothrombin time.

Topics: 4-Hydroxycoumarins; Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Female; Hemorrhage; Hip Prosthesis; Humans; In Vitro Techniques; Indenes; Male; Middle Aged; Prothrombin; Pulmonary Embolism; Retrospective Studies; Risk Factors; Thromboembolism; Vitamin K

Topics: Adolescent; Adult; Cerebral Infarction; Female; Humans; Pregnancy; Pregnancy Complications, Hematologic; Pulmonary Embolism; Vegetables; Vitamin K; Warfarin

Anticoagulants constitute the rational treatment of thromboembolic accidents occurring in elderly people, but they are often not prescribed because of the risk of haemorrhage. The chronological age by itself is not a contra-indication, the limitations being the diseases associated with ageing. Anticoagulants may be used as curative treatment in atrial fibrillation with dilated left atrium (greater than 45 mm at echocardiography), in myocardial infarction, embolic strokes and complicated arteritis. They may also be used as preventive and curative treatment in phlebitis and pulmonary embolism. The complications of anticoagulant therapy will be better prevented by using the international normalized ratio and by prescribing doses that are adequate for each indication.

Topics: 4-Hydroxycoumarins; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dose-Response Relationship, Drug; Heparin; Humans; Indenes; Intracranial Embolism and Thrombosis; Myocardial Infarction; Phlebitis; Pulmonary Embolism; Risk Factors; Vitamin K

Deep venous thrombosis and pulmonary embolism are frequently diagnosed in patients encountered in a primary-care practice. Poor prognosis is related to acute sudden death and to recurrent thromboembolic disease. Anticoagulant therapy with heparin followed by coumarin derivatives is highly effective in preventing such recurrences, but the intensity of anticoagulation must be strictly monitored. Treatment with heparin, sufficient to prolong the activated partial prothrombin time to 1.5 to 2.0 times the control, should be continued for five to ten days, and oral anticoagulation should be overlapped with heparin for four to five days. The recommended therapeutic range for the prothrombin time during coumarin therapy is an INR of 2.0 to 3.0. The duration of anticoagulant treatment must be tailored to the individual patient. Patients with slowly resolving risk factors must be treated for at least three months after an acute deep vein thrombosis and for six months after a pulmonary embolism. Patients with tumors, antithrombin III, protein C or S deficiency should be treated indefinitely.

Topics: Anticoagulants; Heparin; Humans; Prothrombin Time; Pulmonary Embolism; Recurrence; Thromboembolism; Vitamin K

Although the antithrombotic potential of oral anticoagulants is undisputed, bleeding complications constitute a serious problem. One of the main causes for these complications has been a lack of standardization of the prothrombin time. The introduction of the International Normalized Ratio (INR) has led to a better standardization of prothrombin time. Thus, the same level of anticoagulation can be reached using different reagents and therefore over- and undercoagulation can be avoided. Furthermore, the benefit/risk ratio can be improved by adapting the intensity of anticoagulation to the indication. The following clinical conditions are established indications for treatment with oral anticoagulants: Prevention of cardiac emboli in acute anterior myocardial infarction with atrial thrombus, in patients with atrial fibrillation with or without mitral valve disease, in patients with prosthetic heart valves and in patients with dilated cardiomyopathy. Furthermore, oral anticoagulants should be given to patients after femoropopliteal bypass. A relatively mild oral anticoagulant treatment (INR 2-3) is sufficient to prevent recurrences of venous thrombosis and pulmonary emboli. The duration of treatment in patients with venous thromboembolism depends on some clinical features and the results of clotting tests which indicate an increased tendency to thrombosis.

Topics: Administration, Oral; Anticoagulants; Blood Coagulation Factors; Blood Coagulation Tests; Heart Diseases; Humans; Pulmonary Embolism; Thromboembolism; Thrombophlebitis; Vitamin K

Among the various methods to diagnose deep venous thrombosis in the lower limbs, the radiofibrinogen uptake test has been mainly used in clinical studies. Physical means to accelerate venous return are of limited use and only in patients at a low thrombotic risk. Antivitamins K are efficient, but surgeons hesitate to use them because of the postoperative hemorrhagic risk. Dextran infusions are quite effective and without real risk of bleeding. The same holds for low dose heparin administered subcutaneously, particularly when combined with dihydroergotamine. Among the various anti-aggregating agents only aspirin may be effective in the prevention of venous thrombosis.

Topics: Blood Circulation; Dextrans; Humans; Platelet Aggregation; Postoperative Complications; Pulmonary Embolism; Thrombophlebitis; Vitamin K

Topics: 4-Hydroxycoumarins; Adult; Aged; Anticoagulants; Female; Fibrinolytic Agents; Heparin; Humans; Indenes; Male; Middle Aged; Phlebography; Prognosis; Pulmonary Embolism; Recurrence; Thrombosis; Vitamin K

Topics: Electrocardiography; Heparin; Humans; Pulmonary Embolism; Vitamin K

Topics: Dextrans; Heparin; Humans; Postoperative Complications; Pulmonary Embolism; Vitamin K

Some aspects of the use of anticoagulants to prevent or treat thromboembolic disorders remain controversial after more than 40 years of clinical trial and experience. This review describes the mode of action of heparin and the oral anticoagulants and examines their practical use for the prevention and treatment of venous thromboembolism.

Topics: Administration, Oral; Anticoagulants; Drug Administration Schedule; Drug Interactions; Female; Hemorrhage; Heparin; Humans; Injections, Intravenous; Middle Aged; Pregnancy; Pulmonary Embolism; Thromboembolism; Thrombosis; Vitamin K; Warfarin

Topics: Dextrans; Heparin; Humans; Platelet Aggregation; Postoperative Complications; Pulmonary Embolism; Thrombophlebitis; Vitamin K

Topics: Heparin; Male; Postoperative Complications; Pulmonary Embolism; Thromboembolism; Thrombophlebitis; Urologic Diseases; Vitamin K

Topics: Angina Pectoris; Anticoagulants; Arterial Occlusive Diseases; Arteriosclerosis; Coumarins; Disseminated Intravascular Coagulation; Fibrinolytic Agents; Heparin; Humans; Myocardial Infarction; Pulmonary Embolism; Streptokinase; Thromboembolism; Thrombophlebitis; Thrombosis; Urokinase-Type Plasminogen Activator; Vitamin K

Topics: Aged; Blood Coagulation; Calcium; Female; Hemorrhage; Heparinoids; Humans; Injections, Subcutaneous; Middle Aged; Myocardial Infarction; Postoperative Complications; Pulmonary Embolism; Thromboembolism; Time Factors; Urologic Diseases; Vitamin K

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Clofibrate; Hemorrhage; Humans; Male; Methods; Middle Aged; Prothrombin Time; Pulmonary Embolism; Sodium; Vitamin E; Vitamin K; Vitamin K Deficiency; Warfarin

Topics: Aged; Arrhythmias, Cardiac; Blood Transfusion; Coronary Disease; Diverticulum, Colon; Gastrointestinal Hemorrhage; Hematocrit; Humans; Hypertension; Intracranial Embolism and Thrombosis; Middle Aged; Prothrombin Time; Pulmonary Embolism; Thrombophlebitis; Vitamin K; Warfarin

Topics: Adult; Angiography; Electrocardiography; Ethambutol; Hematoma; Heparin; Humans; Isoniazid; Male; Phlebitis; Phlebography; Pulmonary Embolism; Radionuclide Imaging; Rifamycins; Streptokinase; Tachycardia; Tuberculosis, Pulmonary; Vena Cava, Inferior; Vitamin K

Topics: Administration, Oral; Anticoagulants; Coumarins; Hemorrhage; Heparin; Humans; Indenes; Injections, Intravenous; Injections, Subcutaneous; Leg; Prothrombin Time; Pulmonary Embolism; Recurrence; Thromboembolism; Thrombophlebitis; Vitamin K

Topics: Anticoagulants; Fibrinolytic Agents; Heparin; Humans; Myocardial Infarction; Peptide Hydrolases; Pulmonary Embolism; Streptokinase; Thromboembolism; Thrombophlebitis; Thrombosis; Vitamin K

Topics: Angiography; Blood Chemical Analysis; Blood Coagulation Disorders; Blood Platelets; Cardiac Catheterization; Electrocardiography; Fibrinolytic Agents; Heparin; Humans; Middle Aged; Pulmonary Embolism; Radionuclide Imaging; Resuscitation; Thromboembolism; Venoms; Vitamin K

Topics: Adult; Femoral Vein; Heparin; Humans; Iliac Vein; Male; Middle Aged; Phlebography; Pulmonary Embolism; Thrombophlebitis; Time Factors; Vitamin K

Topics: Anticoagulants; Blood Coagulation Tests; Fibrinolytic Agents; Humans; Postoperative Complications; Pulmonary Embolism; Thromboembolism; Thrombophlebitis; Thrombosis; Vitamin K

Topics: Adult; Anesthesia, Spinal; Antibodies; Autoimmune Diseases; Blood Coagulation Tests; Blood Protein Electrophoresis; Dicumarol; Eosinophilia; Fibrinogen; Heparin; Humans; Jaundice; Male; Pneumonia; Priapism; Pulmonary Embolism; Steroids; Thrombophlebitis; Vitamin K

Topics: Angiography; Animals; Anticoagulants; Chromium Isotopes; Dogs; Heparin; Humans; Iodine Isotopes; Pulmonary Embolism; Radionuclide Imaging; Thrombophlebitis; Vitamin K