rivaroxaban and Thrombophilia

To summarize the literature assessing the safety and efficacy of direct oral anticoagulants (DOACs) for the acute treatment and secondary prevention of venous thromboembolism (VTE) in select patients with hypercoagulable disorders.. An electronic PubMed literature search was conducted from January 2010 to July 2020 using the following keywords:. Articles were included if they reported clinical outcomes associated with cancer-associated VTE, antiphospholipid syndrome (APS), and other hereditary thrombophilias.. The safety and efficacy of using a DOAC is highly dependent on the type of hypercoagulable disease state. Current trials support the use of edoxaban, rivaroxaban, and apixaban for the treatment of cancer-associated thrombosis (CAT), with apixaban being preferred because of lower bleeding rates compared with standard of care. The use of DOACs, especially rivaroxaban, have been associated with worse outcomes in patients with APS, whereas data on DOAC use in hereditary thrombophilia remains scarce and limited to low-risk patients.. This review evaluates the literature assessing the safety and efficacy of DOACs in patients with various hypercoagulable disorders.. The current body of evidence supports the use of select DOACs for the treatment of CAT. In contrast, DOAC use in patients with APS and hereditary thrombophilia should be avoided at this time.

Topics: Administration, Oral; Anticoagulants; Dabigatran; Hemorrhage; Humans; Rivaroxaban; Thrombophilia; Venous Thromboembolism

COVID-19 is also manifested with hypercoagulability, pulmonary intravascular coagulation, microangiopathy, and venous thromboembolism (VTE) or arterial thrombosis. Predisposing risk factors to severe COVID-19 are male sex, underlying cardiovascular disease, or cardiovascular risk factors including noncontrolled diabetes mellitus or arterial hypertension, obesity, and advanced age. The VAS-European Independent Foundation in Angiology/Vascular Medicine draws attention to patients with vascular disease (VD) and presents an integral strategy for the management of patients with VD or cardiovascular risk factors (VD-CVR) and COVID-19. VAS recommends (1) a COVID-19-oriented primary health care network for patients with VD-CVR for identification of patients with VD-CVR in the community and patients' education for disease symptoms, use of eHealth technology, adherence to the antithrombotic and vascular regulating treatments, and (2) close medical follow-up for efficacious control of VD progression and prompt application of physical and social distancing measures in case of new epidemic waves. For patients with VD-CVR who receive home treatment for COVID-19, VAS recommends assessment for (1) disease worsening risk and prioritized hospitalization of those at high risk and (2) VTE risk assessment and thromboprophylaxis with rivaroxaban, betrixaban, or low-molecular-weight heparin (LMWH) for those at high risk. For hospitalized patients with VD-CVR and COVID-19, VAS recommends (1) routine thromboprophylaxis with weight-adjusted intermediate doses of LMWH (unless contraindication); (2) LMWH as the drug of choice over unfractionated heparin or direct oral anticoagulants for the treatment of VTE or hypercoagulability; (3) careful evaluation of the risk for disease worsening and prompt application of targeted antiviral or convalescence treatments; (4) monitoring of D-dimer for optimization of the antithrombotic treatment; and (5) evaluation of the risk of VTE before hospital discharge using the IMPROVE-D-dimer score and prolonged post-discharge thromboprophylaxis with rivaroxaban, betrixaban, or LMWH.

Topics: Anticoagulants; Cardiology; Cardiovascular Diseases; COVID-19; COVID-19 Drug Treatment; Europe; Heparin, Low-Molecular-Weight; Humans; Inflammation; Practice Guidelines as Topic; Risk Factors; Rivaroxaban; SARS-CoV-2; Societies, Medical; Thrombophilia; Thrombosis

Topics: Anticoagulants; Aspirin; Clopidogrel; Drug Synergism; Drug Therapy, Combination; Factor Xa Inhibitors; Hemorrhage; Humans; Mortality; Multicenter Studies as Topic; Myocardial Infarction; Platelet Aggregation Inhibitors; Postoperative Complications; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Rivaroxaban; Stents; Stroke; Thrombophilia; Ticlopidine

Direct oral anticoagulants (DOAC) are indicated for stroke prevention in atrial fibrillation and for the prevention and treatment of venous thromboembolism. As any anticoagulant, they are associated with a bleeding risk. Management of DOAC-induced bleeding is challenging. Idarucizumab, antidote for dabigatran, is currently available and is part of the therapeutic strategy, whereas antidotes for anti-Xa agents are under development. Activated or non-activated prothrombin concentrates are proposed, although their efficacy to reverse DOAC is uncertain. We propose an update on DOAC-associated bleeding management, integrating the availability of idarucizumab and the critical place of DOAC concentration measurements.

Topics: Administration, Oral; Antibodies, Monoclonal, Humanized; Antidotes; Antithrombins; Arginine; Blood Coagulation Factors; Blood Transfusion; Dabigatran; Factor Xa; Factor Xa Inhibitors; Hemorrhage; Hemostatics; Humans; Piperazines; Pyrazoles; Pyridones; Recombinant Proteins; Rivaroxaban; Stroke; Thrombophilia

The aim of this study is to compare effectiveness and safety profile of rivaroxaban with bemiparin in 3-week extended prophylaxis after knee arthroscopy.. Four hundred and sixty-seven patients were included in this review divided in two groups. One followed prophylaxis with rivaroxaban and the other one with bemiparin. All patients were interviewed and explored at 1 and 3 months postoperatively, looking for symptomatic signs of deep-vein thrombosis (DVT). In case of suspicion, diagnostic tests were performed. Collected data were age, sex, gender, diagnosis, time with ischemia, body mass index, concomitant diseases, concomitant therapy, DVT signs, treatment satisfaction, minor and major complications, treatment adherence and tolerability.. No thromboembolic events were observed in any of the groups. In one case treated with rivaroxaban, the drug had to be withdrawn due to epistaxis.. Our study showed that extended prophylaxis with 10 mg of rivaroxaban once daily for 3 weeks resulted as effective as bemiparin in knee arthroscopy thromboprophylaxis.

Topics: Adult; Aged; Arthroscopy; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Follow-Up Studies; Heparin, Low-Molecular-Weight; Humans; Knee Joint; Male; Middle Aged; Morpholines; Polypharmacy; Postoperative Complications; Postoperative Hemorrhage; Retrospective Studies; Risk Factors; Rivaroxaban; Therapeutic Equipoise; Thiophenes; Thrombophilia; Venous Thrombosis

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; Dabigatran; Elective Surgical Procedures; Emergencies; Factor Xa Inhibitors; Hemorrhage; Humans; Kidney Diseases; Morpholines; Orthopedic Procedures; Postoperative Complications; Premedication; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Risk; Rivaroxaban; Thiophenes; Thrombophilia; Vitamin K

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

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

Heparins and vitamin K antagonists (VKA) used commonly are the standard treatment of venous and arterial thromboses. They are very efficient and safe, but have some limitations: iatrogenicity, laboratory monitoring, parenteral use for heparins and fondaparinux. Nowadays, four new inhibitors of factor Xa are used orally (rivaroxaban, apixaban, edoxaban, betrixaban), and they are at least as efficient as heparins and vitamin K antagonists. The objective is to substitute these indirect inhibitors of factor Xa (heparins, low molecular weight heparins and fondaparinux) in the prevention of venous and arterial thromboembolic episodes. The new direct inhibitors do not require routine laboratory monitoring of blood coagulation. They inhibit the extrinsic and the intrinsic pathways of blood coagulation. Rivaroxaban and apixaban are efficacious and safe in the prevention of cerebral infarcts in patients with non-valvular fibrillation. Apixaban is another direct inhibitor of factor Xa used orally which is developed in the same indications as rivaroxaban. Edoxaban and betrixaban are also in development. The objective of this work is to study the pharmacodynamic, pharmacokinetic, the efficacy and safety of these four oral direct factor Xa inhibitors.

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Benzamides; Blood Coagulation; Embolism; Factor Xa Inhibitors; Hemorrhage; Hemostatics; Humans; Morpholines; Postoperative Complications; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Thiophenes; Thrombophilia; Thrombosis

New oral anticoagulants like the direct thrombin inhibitor, dabigatran (Pradaxa®), and factor Xa-inhibitors, rivaroxaban (Xarelto®) and apixaban (Eliquis®) are available for prophylaxis and treatment of thromboembolic disease. They are emerging alternatives to warfarin and provide equal or better clinical outcome together with reduced need for routine monitoring. Methods for measuring drug concentrations are available, although a correlation between plasma drug concentrations and the risk of bleeding has not been firmly established. Standard laboratory measures like prothrombin time and activated partial thromboplastin time are not sensitive enough to detect thrombin or factor Xa inhibition provided by new oral anticoagulants. Thus, these standard tests may only be used as a crude estimation of the actual anticoagulation status. Further challenges regarding patients receiving new oral anticoagulants who presents with major bleeding or need for emergency surgery pose a unique problem. No established agents are clinically available to reverse the anticoagulant effect, although preclinical data report prothrombin complex concentrate as more efficient than fresh frozen plasma or other prohaemostatic agents. This review summaries current knowledge on approved new oral anticoagulants and discusses clinical aspects of monitoring, with particular focus on the management of the bleeding patient.

Topics: Anticoagulants; Benzimidazoles; beta-Alanine; Blood Coagulation Tests; Dabigatran; Drug Monitoring; Factor Xa Inhibitors; Hemorrhage; Hemostatic Techniques; Hemostatics; Humans; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Thrombin; Thromboembolism; Thrombophilia

Chronic kidney disease and atrial fibrillation (AF) commonly coexist, and data suggest that renal patients have AF rates in excess of double that encountered in the general population. These patients are at increased risk of stroke, regardless of the presence or absence of AF. Furthermore, a lower GFR causes increased thromboembolic risk in patients with AF - independent of other risk factors. The dilemma facing clinicians treating this cohort of patients is that renal insufficiency confers both a thromboembolic and a bleeding risk. Renal disease also commonly coexists with other risk factors for stroke and bleeding such as hypertension and advanced age. Furthermore, bleeding risk tracks stroke risk and many risk factors are common to both thromboembolism and haemorrhage. Patients with severe renal impairment are also actively excluded from the majority of trials for stroke prevention in AF, including those trials which informed the development of stroke risk factor scoring schemes. Therefore, patients with renal disease and AF present a unique management challenge. The available data suggests that the benefit from warfarin in terms of stroke reduction is not as clear as in the general population, and there is an increased risk of bleeding complications and even ectopic vascular calcification. Thus, it is problematic to extrapolate the benefits of warfarin in the general population to a subgroup that has been actively excluded from clinical trials. The new oral anticoagulants have relatively little data in patients with severe renal impairment, and all have an element of renal excretion. There is a need for large randomised control trials in patients with renal insufficiency and on haemodialysis to provide a bank of high-quality scientific data on which clinicians can base their management decisions. Until then, we must adopt a pragmatic approach which involves careful consideration of the relative risk of stroke and bleeding in each individual patient.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Comorbidity; Dabigatran; Disease Management; Embolism; Female; Fibrinolytic Agents; Hemorrhage; Humans; Hypertension; Intracranial Embolism; Male; Morpholines; Patient Selection; Pyrazoles; Pyridones; Renal Insufficiency, Chronic; Risk; Risk Factors; Rivaroxaban; Severity of Illness Index; Stroke; Thiophenes; Thrombophilia; Warfarin

The vitamin K antagonists (VKA) available for stroke prevention in patients with atrial fibrillation have many drawbacks due to their difficult clinical use and high risk of bleeding. Currently, several drugs are being developed as possible substitutes for VKA that have many advantages such as the lack of monitoring requirement and scarce pharmacologic and food interactions. The present article provides an update on the new oral anticoagulants that are in a more advanced stage of clinical research, their pharmacologic properties, advantages and disadvantages and their results in recent clinical trials.

Topics: Administration, Oral; Anticoagulants; Azetidines; Benzimidazoles; Benzylamines; beta-Alanine; Clinical Trials as Topic; Dabigatran; Drug Monitoring; Drugs, Investigational; Hemorrhage; Humans; Morpholines; Multicenter Studies as Topic; Patient Care Planning; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Thiophenes; Thrombophilia; Vitamin K

New oral anticoagulant drugs are emerging as alternatives to warfarin for the prevention of stroke in patients with non-valvular atrial fibrillation. Two agents are direct factor Xa inhibitors (rivaroxaban and apixaban), and the third is a direct thrombin inhibitor (dabigatran). They have been separately compared to warfarin in large randomised trials. Our objective was to indirectly compare the three agents to each other for major efficacy and safety outcomes. Studies were assessed for comparability and the odds ratios of selected outcomes for each anticoagulant versus one another were estimated indirectly. The three cohorts differed significantly in terms of CHADS(2) score and the number of individuals with a past history of stroke, transient ischemic attack or systemic embolism. The estimated odds ratio of stroke or systemic embolism was 1.35 for rivaroxaban vs dabigatran 150 mg (p=0.04), 0.97 for rivaroxaban versus dabigatran 110 mg (p=0.81), 1.22 for apixaban versus dabigatran 150 mg (p=0.18), 0.88 for apixaban versus dabigatran 110 mg (p=0.34) and 0.90 for apixaban versus rivaroxaban (p=0.43). The estimated odds ratio of major bleeding was 1.10 for rivaroxaban versus dabigatran 150 mg (p=0.36), 1.28 for rivaroxaban versus dabigatran 110 mg (p=0.02), 0.74 for apixaban versus dabigatran 150 mg (p=0.004), 0.87 for apixaban versus dabigatran 110 mg (p=0.17) and 0.68 for apixaban versus rivaroxaban (p<0.001). In conclusion, the available data indicate no significant difference in efficacy between dabigatran 150 mg and apixaban for the prevention of stroke or systemic embolism in patients with non-valvular atrial fibrillation. It appears however that apixaban is associated with less major bleeding than dabigatran 150 mg or rivaroxaban and that rivaroxaban is less effective than dabigatran 150 mg in preventing stroke or systemic embolism. Such an indirect comparison should be used only to generate hypotheses which need to be tested in a dedicated randomised trial comparing the three drugs directly.

Topics: Aged; Anticoagulants; Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Clinical Trials, Phase III as Topic; Dabigatran; Embolism; Factor Xa Inhibitors; Female; Heart Valve Diseases; Hemorrhage; Humans; Ischemic Attack, Transient; Male; Morpholines; Multicenter Studies as Topic; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Secondary Prevention; Severity of Illness Index; Stroke; Thiophenes; Thrombophilia; Vitamin K; Warfarin

The use of antithrombotic drugs for the prevention of venous thromboembolism (VTE) in patients undergoing surgery is presently based on solid principles and high-level scientific evidence. This article reviews current strategies of pharmacological thromboprophylaxis. The level of VTE risk following surgery depends on a variety of factors that the surgeon should take into account, including the type of surgery and the presence of additional risk factors, such as elderly age and cancer. In patients undergoing minor general surgery, early mobilization is sufficient as prophylaxis, whereas in those undergoing major general surgery, thromboprophylaxis with low molecular weight heparin (LMWH), low-dose unfractionated heparin, or the pentasaccharide fondaparinux is recommended. Patients undergoing major orthopedic surgery have a particularly high risk of VTE, and routine thromboprophylaxis with LMWH, fondaparinux, or a vitamin K antagonist (international normalized ratio target: 2.0 to 3.0) is the standard of care in this group of patients. Recently, two new oral anticoagulants, rivaroxaban (a factor Xa inhibitor) and dabigatran etexilate (a direct thrombin inhibitor) have been licensed to be used for thromboprophylaxis after orthopedic surgery in Europe. Mechanical methods of thromboprophylaxis (compression stockings, intermittent pneumatic compression, vena cava filters), not discussed in detail in this review, should always be considered in patients at high thrombotic risk, in association with the pharmacological strategies, or in cases of contraindications to anticoagulants, as in patients or procedures at high risk of bleeding.

Topics: Aged; Anticoagulants; Antithrombins; Arthroscopy; Bariatric Surgery; Benzimidazoles; Blood Coagulation Disorders, Inherited; Dabigatran; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Hip Fractures; Humans; Kidney; Knee; Laparoscopy; Morpholines; Neoplasms; Orthopedic Procedures; Polysaccharides; Postoperative Complications; Pyridines; Rivaroxaban; Thiophenes; Thrombophilia; Venous Thromboembolism

For years, prevention and treatment of thromboembolic events have been restricted to the use of heparins and vitamin K antagonists. These treatments, in spite of their unquestioned efficacy, present numerous limits (hemorrhagic risk, need for regular laboratory controls). These limits call for the development of new antithrombotic drugs. This review briefly reports on three new molecules, in very advanced phases of clinical research: dabigatran (Pradaxa®), rivaroxaban (Xarelto®) and apixaban. These molecules represent new oral anticoagulants, which directly inhibit a coagulation factor (thrombin for dabigatran, factor Xa for rivaroxaban and apixaban) and do not need regular anticoagulant monitoring or dose adjustment. The approval is still restricted in France to the prophylaxis of venous thromboembolism in orthopaedics. Dabigratran will be soon available in the prevention of stroke in atrial fibrillation. With the forthcoming phase III studies to prevent and treat venous thromboembolism, anticoagulant therapy management will be most probably improved in the coming years.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Dabigatran; Drug Approval; Drug Monitoring; Factor Xa Inhibitors; Fibrinolytic Agents; Forecasting; France; Humans; Morpholines; Orthopedic Procedures; Postoperative Complications; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Thrombin; Thromboembolism; Thrombophilia; Venous Thromboembolism

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

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

Vitamin K antagonists and heparins have been standard anticoagulation drugs over the past decades. They are effective and safe but they have several drawbacks which has led to the development of new oral anticoagulants. Dabigatran etexilate is a specific oral thrombin inhibitor and rivaroxaban and apixaban are oral inhibitors of factor Xa. These agents produce a predictable anticoagulant response after fixed-dose administration so that routine coagulation monitoring is unnecessary. Currently, dabigatran etexilate, rivaroxaban and apixaban are licensed for thromboprophylaxis after elective total hip or knee replacement surgery. Since august 2011, dabigatran etexilate is licensed for patients with atrial fibrillation, rivaroxaban will follow. However, indications will be expanded e.g. for therapy of venous thromboembolism. It is important to be aware of the pharmacokinetic and pharmacodynamic profiles of these new agents. The drugs considerably influence the global test of coagulation thus making an interpretation of test results difficult. Currently, there is a lack of suitable coagulation tests to monitor anticoagulation in emergency cases, such as bleeding. Specific antidotes are not yet available.

Topics: Administration, Oral; Antithrombins; Arthroplasty, Replacement, Hip; Atrial Fibrillation; Benzimidazoles; Blood Coagulation Tests; Critical Care; Dabigatran; Drug Approval; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Heparin; Humans; Morpholines; Postoperative Complications; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiophenes; Thrombophilia; Vitamin K

Topics: Angina, Unstable; Anticoagulants; Azetidines; Benzimidazoles; Benzylamines; Brain Ischemia; Clinical Trials as Topic; Coumarins; Dabigatran; Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Forecasting; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Morpholines; Myocardial Infarction; Peptide Fragments; Polysaccharides; Prothrombin; Pyrazoles; Pyridines; Pyridones; Recombinant Proteins; Rivaroxaban; Thiophenes; Thrombin; Thrombophilia; Thrombosis; Warfarin

Despite rapid clinical adoption of novel anticoagulants, it is unknown whether outcomes differ among patients with worsening renal function (WRF) taking these new drugs compared with warfarin. We aimed to determine whether the primary efficacy (stroke or systemic embolism) and safety (major bleeding and nonmajor clinically relevant bleeding) end points from the ROCKET AF trial (Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation trial) differed among participants with WRF taking rivaroxaban and those taking warfarin.. After excluding patients without at least 1 follow-up creatinine measurement (n=1624), we included all remaining patients (n=12 612) randomly assigned to either rivaroxaban or dose-adjusted warfarin. On-treatment WRF (a decrease of >20% from screening creatinine clearance measurement at any time point during the study) was evaluated as a time-dependent covariate in Cox proportional hazards models.. Baseline characteristics were generally similar between patients with stable renal function (n=9292) and WRF (n=3320). Rates of stroke or systemic embolism, myocardial infarction, and bleeding were also similar, but WRF patients experienced a higher incidence of vascular death versus stable renal function (2.21 versus 1.41 events per 100 patient-years; P=0.026). WRF patients who were randomized to receive rivaroxaban had a reduction in stroke or systemic embolism compared with those taking warfarin (1.54 versus 3.25 events per 100 patient-years) that was not seen in patients with stable renal function who were randomized to receive rivaroxaban (P=0.050 for interaction). There was no difference in major or nonmajor clinically relevant bleeding among WRF patients randomized to warfarin versus rivaroxaban.. Among patients with on-treatment WRF, rivaroxaban was associated with lower rates of stroke and systemic embolism compared with warfarin, without an increase in the composite bleeding end point.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00403767.

Topics: Aged; Atrial Fibrillation; Creatinine; Double-Blind Method; Embolism; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Kidney; Male; Middle Aged; Proportional Hazards Models; Rivaroxaban; Stroke; Thrombophilia; Warfarin

Use of vitamin K antagonists for the prevention of stroke and systemic embolism in dialysis patients with nonvalvular atrial fibrillation is controversial. However, no good alternatives presently are available. The anti-factor Xa antagonist rivaroxaban is contraindicated for lack of pharmacokinetic, pharmacodynamic, and clinical data. This study aims to characterize the pharmacokinetics/pharmacodynamics of rivaroxaban in maintenance hemodialysis patients.. Pharmacokinetic and pharmacodynamic study.. 18 maintenance hemodialysis patients without residual kidney function at 2 centers. DRUG ADMINISTRATION, OUTCOMES, & MEASUREMENTS: (1) A single dose of 10mg of rivaroxaban was administered at the end of each of 3 consecutive dialysis sessions and area under the curve (AUC) and the effect on coagulation parameters were measured for 44 hours thereafter. (2) A single dose of 10mg of rivaroxaban was given 6 to 8 hours before a dialysis session and the effect of dialysis on rivaroxaban concentrations was evaluated. (3) To assess potential accumulation, 10mg of rivaroxaban was given once daily and AUC was measured during 24 hours on days 1 and 7.. Mean AUC0-44 of rivaroxaban plasma concentrations after a single dose of 10mg was 2,072μg/L/h, mean maximum concentration was 172.6μg/L, and mean terminal elimination half-life was 8.6 hours. Dialysis had no appreciable effect on rivaroxaban plasma concentrations. Mean trough concentration after multiple daily doses of 10mg was 20.2μg/L.. Higher rivaroxaban doses and patients with substantial residual kidney function were not studied.. A 10-mg dose of rivaroxaban in hemodialysis patients without residual kidney function results in drug exposure similar as published for 20mg in healthy volunteers. Rivaroxaban is not eliminated by dialysis. There is no accumulation after multiple daily dosing. The efficacy and safety of rivaroxaban in hemodialysis patients should be the subject of a large randomized trial.

Topics: Administration, Oral; Area Under Curve; Atrial Fibrillation; Dose-Response Relationship, Drug; Drug Monitoring; Factor Xa Inhibitors; Female; Half-Life; Hemorrhage; Humans; Kidney Failure, Chronic; Male; Morpholines; Renal Dialysis; Rivaroxaban; Thiophenes; Thromboembolism; Thrombophilia

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

Heart failure (HF) is associated with a hypercoagulable state that predisposes to thromboembolism and anti-coagulation may improve clinical outcomes. The oral, direct Factor Xa inhibitor, rivaroxaban, has not been studied in patients with HF. We hypothesized that rivaroxaban would also reduce biomarkers of hypercoagulability in patients with HF.. This study consisted of two cohorts: Cohort 1, open-label, actively controlled with enoxaparin 40 mg once daily, included 8 patients with acute decompensated HF; Cohort 2, double-blind and placebo-controlled, included 18 patients with stable, severe New York Heart Association Class III/IV HF.. The pharmacokinetics (PK) and pharmacodynamics (PD) of rivaroxaban were similar across both cohorts. Biomarker assessments were performed in Cohort 2; prothrombin fragment 1.2 (F1.2) mean concentration decreased by 2.7 ng/ml over 7 days with rivaroxaban, and increased by 11.6 ng/ml with placebo, an absolute difference of 14.3 ng/ml (p = 0.0009). A non-significant reduction in rate of increase of D-dimer (DD) and thrombin-anti-thrombin complex (TAT) levels with rivaroxaban was observed over 7 days (p = 0.31 and p = 0.77, respectively).. Rivaroxaban has similar PK/PD in patients with either acute or chronic HF. In vivo, hypercoagulability biomarkers appear to increase over time. Rivaroxaban reversed this trend for F1.2, and may reduce the rate of increase of DD and TAT in patients with stable, severe HF.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Antithrombin III; Biomarkers; Chronic Disease; Double-Blind Method; Enoxaparin; Factor Xa Inhibitors; Female; Fibrin Fibrinogen Degradation Products; Fibrinolytic Agents; Heart Failure; Humans; Male; Middle Aged; Morpholines; Peptide Fragments; Peptide Hydrolases; Prothrombin; Rivaroxaban; Thiophenes; Thrombophilia

Measurement of protein S (PS) activity in patients taking direct oral anticoagulants (DOACs) using reagents based on a clotting assay results in falsely high PS activity, thus masking inherited PS deficiency, which is most frequently seen in the Japanese population. In this study, we investigated the effect of factor Xa (FXa) inhibitors on PS activity using the reagent on the basis of the chromogenic assay, which was recently developed in Japan.. The study enrolled 152 patients (82 males and 70 females; the average age: 68.5±14.0 years) receiving three FXa inhibitors (rivaroxaban, edoxaban, and apixaban). PS activity was measured using the reagents on the basis of the clotting and chromogenic assays.. PS activity measured by the clotting assay reagents exhibited falsely high values depending on the plasma concentrations of FXa inhibitors in patients taking either rivaroxaban or edoxaban. However, none of the three FXa inhibitors affected PS activity when measured using the chromogenic assay.. In patients taking rivaroxaban or edoxaban, inherited PS deficiency is likely missed because the levels of PS activity measured using the reagents based on the clotting assay are falsely high. However, we report that three FXa inhibitors do not affect PS activity measured by the chromogenic assay. When measuring the levels of PS activity in patients undergoing DOACs, the principles of each reagent should be understood. Furthermore, plasma samples must be collected at the time when plasma concentrations of DOACs are lowest or the DOAC-Stop reagent should be used.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation; Factor Xa; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Protein S; Rivaroxaban; Thrombophilia

It is unclear if stopping treatment with dabigatran, a new oral anticoagulant (NOAC), induces a paradoxical rebound prothrombotic state. We investigated if short-term (1-3 days) dabigatran cessation is associated with a higher thrombus volume than expected from a simple reversal of the anticoagulant effect.. Ten-week-old C57Bl/6 mice (n = 338) received one of the following oral treatments: phosphate-buffered saline (PBS), dabigatran for 7 days with or without 1 to 4 day cessation, and aspirin in either a single dose or daily for 7 days. Some of the animals that ceased dabigatran for 1 to 3 days received single-dose aspirin. Thereafter, we induced FeCl. We observed a ~ 40% higher volume of carotid thrombus after dabigatran cessation at 1 to 3 days than after vehicle treatment and showed that this effect could be prevented by single-dose aspirin pretreatment. Dabigatran cessation unduly increased platelet aggregability for 2 days after drug cessation, an effect mediated through thrombin or arachidonic acid, which effect was significantly attenuated by single-dose aspirin pretreatment. In patients, short-term (≤ 3 days) cessation of NOAC therapy, compared with longer-term (≥ 5 days) cessation, tended to be associated with relatively high stroke severity.. We provide the first preclinical evidence that a rebound prothrombotic state follows short-term cessation of dabigatran therapy. ANN NEUROL 2021;89:444-458.

Topics: Aged; Aged, 80 and over; Animals; Antithrombins; Arachidonic Acid; Aspirin; Carotid Artery Thrombosis; Cerebral Infarction; Chlorides; Computed Tomography Angiography; Dabigatran; Deprescriptions; Factor Xa Inhibitors; Female; Ferric Compounds; Humans; Ischemic Stroke; Magnetic Resonance Angiography; Male; Mean Platelet Volume; Mice; Noxae; Pilot Projects; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Count; Pyrazoles; Pyridones; Rivaroxaban; Severity of Illness Index; Substance Withdrawal Syndrome; Thrombin; Thrombophilia; X-Ray Microtomography

Topics: Administration, Oral; Anticoagulants; Counseling; COVID-19; Drug Monitoring; Drug Substitution; Hospitals, University; Humans; Informed Consent; London; Pandemics; Patient Acceptance of Health Care; Patient Education as Topic; Pyridines; Quarantine; Rivaroxaban; SARS-CoV-2; Telemedicine; Tertiary Care Centers; Thiazoles; Thrombophilia; Warfarin

To explore the clinical and prognostic features of CVT caused by PROS1 gene mutations and to provide clinical experience for new oral anticoagulants, such as rivaroxaban, in the treatment of CVT with a high risk of thrombosis.. The CVT patient's clinical symptoms were described, and the brain imaging and blood coagulation tests were performed to confirm the diagnosis of CVT. The patient's family members were recruited to receive blood coagulation tests and ultrasonic examination of lower limb vessels. Genetic analysis on the pedigree was carried out to identify the responsible gene for PS deficiency. We followed-up with this patient for 24 months to evaluate the clinical outcomes, laboratory results and imaging performances of CVT.. The patient presented with typical CVT symptoms, including headache and epilepsy. Brain CT showed hemorrhage in the bilateral frontal lobe and left occipital lobe, while MRV demonstrated that thrombus had occurred. It was reviewed that the patient and his mother had a history of bilateral leg deep vein thrombosis. Gene tests revealed that the patient and two family members carried a heterozygous mutation of PROS1 (c.751_752delAT, p.M251Vfs*17). During 24 months of follow-up study, the patient was treated with rivaroxaban continuously and recovered well, supported by an mRS score that remained below 2. Blood coagulation tests were within normal limits, and MRV revealed partial recanalization of the cerebral venous sinus.. The frame shift mutation in the PROS1 gene (c.751_752delAT) may greatly affect the function of protein S and lead to a severe phenotype of CVT. Rivaroxaban showed a satisfying therapeutic effect in this CVT patient with hereditary thrombophilia.

Topics: Administration, Oral; Adult; Anticoagulants; Blood Coagulation; Follow-Up Studies; Humans; Male; Mutation; Pedigree; Protein S; Protein S Deficiency; Rivaroxaban; Thrombophilia; Venous Thrombosis

Topics: Female; Humans; Pregnancy; Pregnant Women; Purpura; Rivaroxaban; Thrombophilia

Patients treated with direct Xa inhibitors may require urgent surgery. Administration of prothrombin complex concentrate (PCC) in this setting is common; however, it is based on limited experience in healthy volunteers.. To characterize the population receiving PCC for apixaban/rivaroxaban reversal prior to an urgent surgery and evaluate its efficacy and safety.. This was a retrospective study in 2 tertiary hospitals. Bleeding was evaluated based on surgical reports, hemoglobin drop, and the use of blood products or additional PCC during 48 h. Safety measures were thrombotic complications and 30-day mortality.. Sixty-two patients aged 80.7 ± 9 years, treated with apixaban (39.63%) or rivaroxaban (23.37%), received PCC before an urgent surgery/procedure. Most underwent abdominal operation (61%), orthopedic surgery (13%), or transhepatic cholecystostomy insertion (10%). Bleeding during surgery was reported in 3 patients (5%), no patient required additional PCC, and 16 patients (26%) received packed cells (median: 1 unit, range: 1-5). The 30-day mortality and thrombosis rates were 21% (n = 13) and 3% (n = 2), respectively. The cause of death was related to the primary disease, most commonly sepsis. No patient died due to bleeding/thrombosis.. Our results support the use of PCC to achieve hemostasis in patients treated with Xa inhibitors prior to an urgent surgery.

Topics: Academic Medical Centers; Aged; Aged, 80 and over; Atrial Fibrillation; Blood Coagulation Factors; Blood Component Transfusion; Blood Loss, Surgical; Emergencies; Factor Xa Inhibitors; Female; Hemostatics; Humans; Male; Postoperative Hemorrhage; Preoperative Care; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Surgical Procedures, Operative; Tertiary Care Centers; Thrombophilia; Thrombosis; Tranexamic Acid

: We herein report the case of a young patient who presented with premature thromboembolic venous disease secondary to combined heterozygous G20210A prothrombin mutation, dual homozygosity for Factor V Leiden, and severe protein S deficiency. This association has never been reported to date and is likely to be exceptional, even in populations wherein these thrombophilia traits are more common. Long-term antithrombotic prophylaxis with rivaroxaban has proven successful in preventing clinical recurrence under prolonged treatment.

Topics: Child; Factor Xa Inhibitors; Humans; Male; Risk Factors; Rivaroxaban; Thrombophilia

To conduct a survey of diagnostic facility and therapeutic capability of Pulmonary thromboembolism (PE) in 90 hospitals throughout China.. It was a cross-sectional study among the participating hospitals of the National Key Research & Development Program of China-the Precision Research of Standardized Management and Application of Pulmonary Thromboembolism to obtain the equipment and application of radiological facility to diagnose PE, laboratory tests for thrombophilia, coagulation function and the availability of anticoagulants and thrombolysis agents.. CT pulmonary arteriography is capable in all 90 hospitals, 71.11% of the hospitals could perform ventilation/perfusion scintigraphy, 24.44% of the hospitals do not routinely perform right heart evaluation by echocardiography. Protein C and protein S activity can be detected in half of the hospitals and warfarin pharmacogenomics tests can be conducted in 40 hospitals. Immune turbidimetry was used as the detection method of D-dimer in 72.37% hospitals. About 81.11% of participating hospitals were equipped with new novel oral anticoagulants, all of which were equipped with Rivaroxaban.. The hospitals are capable for standardized diagnosis and management PE, while the capability of precise stratification, coagulation function tests, thrombophilia screening and pharmacogenomics requires further improvement.

Topics: Angiography; Anticoagulants; Blood Coagulation Tests; China; Cross-Sectional Studies; Echocardiography; Factor Xa Inhibitors; Fibrin Fibrinogen Degradation Products; Fibrinolytic Agents; Hospital Bed Capacity; Hospitals; Humans; Nephelometry and Turbidimetry; Patient Care Management; Pharmacogenetics; Pulmonary Embolism; Rivaroxaban; Surveys and Questionnaires; Thrombophilia; Ventilation-Perfusion Scan; Warfarin

Evidence for the efficacy of direct oral anticoagulants (DOACs) to prevent cardiovascular (CV) events and mortality in older individuals with a low estimated glomerular filtration rate (eGFR) is lacking. We sought to characterize the association of oral anticoagulant use with CV morbidity in elderly patients with or without reductions in eGFRs, comparing DOACs with vitamin K antagonists (VKAs).. Population-based retrospective cohort study.. All individuals 66 years or older with an initial prescription for oral anticoagulants dispensed in Ontario, Canada, from 2009 to 2016.. DOACs (apixaban, dabigatran, and rivaroxaban) compared with VKAs by eGFR group (≥60, 30-59, and<30mL/min/1.73m. The primary outcome was a composite of a CV event (myocardial infarction, revascularization, or ischemic stroke) or mortality. Secondary outcomes were CV events alone, mortality, and hemorrhage requiring hospitalization.. High-dimensional propensity score matching of DOAC to VKA users and Cox proportional hazards regression.. 27,552 new DOAC users were matched to 27,552 new VKA users (median age, 78 years; 49% women). There was significantly lower risk for CV events or mortality among DOAC users compared with VKA users (event rates of 79.78 vs 99.77 per 1,000 person-years, respectively; HR, 0.82 [95% CI, 0.75-0.90]) and lower risk for hemorrhage (event rates of 10.35 vs 16.77 per 1,000 person-years, respectively; HR, 0.73 [95% CI, 0.58-0.91]). There was an interaction between eGFR and the association of anticoagulant class with the primary composite outcome (P<0.02): HRs of 1.01 [95% CI, 0.92-1.12], 0.83 [95% CI, 0.75-0.93], and 0.75 [95% CI, 0.51-1.10] for eGFRs of≥60, 30 to 59, and<30mL/min/1.73m. Retrospective observational study design limits causal inference; dosages of DOACs and international normalized ratio values were not available; low event rates in some subgroups limited statistical power.. DOACs compared with VKAs were associated with lower risk for the composite of CV events or mortality, an association for which the strength was most apparent among those with reduced eGFRs. The therapeutic implications of these findings await further study.

Topics: Aged; Aged, 80 and over; Antithrombins; Brain Ischemia; Cause of Death; Comorbidity; Dabigatran; Female; Glomerular Filtration Rate; Hemorrhage; Humans; Male; Mortality; Myocardial Infarction; Myocardial Revascularization; Ontario; Procedures and Techniques Utilization; Propensity Score; Proportional Hazards Models; Pyrazoles; Pyridones; Renal Insufficiency, Chronic; Retrospective Studies; Rivaroxaban; Thrombophilia; Vitamin K

Topics: 4-Hydroxycoumarins; Adult; Aftercare; Anticoagulants; Antiphospholipid Syndrome; England; Factor Xa Inhibitors; Fibrin Fibrinogen Degradation Products; Heparin, Low-Molecular-Weight; Humans; Incidence; Indenes; International Normalized Ratio; Neoplasms; Pyrazoles; Pyridones; Risk Assessment; Rivaroxaban; State Medicine; Systematic Reviews as Topic; Thrombophilia; Vena Cava Filters; Venous Thromboembolism; Vitamin K

Topics: Administration, Oral; Anticoagulants; Factor Xa Inhibitors; Humans; Pyrazoles; Pyridones; Rivaroxaban; Thrombophilia; Venous Thromboembolism

Topics: Aged; Aged, 80 and over; Antidotes; Factor Xa; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Postoperative Hemorrhage; Practice Guidelines as Topic; Pyrazoles; Pyridones; Recombinant Proteins; Rivaroxaban; Thrombophilia; Thrombosis; Treatment Outcome

We and others have previously highlighted the potential problems with testing of lupus anticoagulants (LA) in patients on anticoagulant therapy, including most recently as related to the direct oral anticoagulants (DOACs). Thus, current DOACs in use (e.g., dabigatran, a direct thrombin inhibitor, and apixaban and rivaroxaban, both direct Xa inhibitors), affect a wide variety of coagulation assays, including those used in LA investigation. The Russell viper venom time (RVVT) assay in particular, key to the investigation of LA, is highly sensitive to DOACs. LA is a marker of thrombophilia, and patients who have had a thrombosis may be placed on a DOAC. Thus, there is a high likelihood that LA testing will be requested on patients whilst they are on DOACs. In the current report, we have assessed data from our facility for the past two and a half years for all LA tests performed by RVVT testing, and have evaluated this data with respect to patient anticoagulant status. In total, there were 7170 test requests for RVVT associated testing during the period of data capture. Most LA-RVVT screen results (5008; ∼70%) were within normal limits, thereby excluding LA by RVVT method in most of the patient cohort. All DOACs led to a prolongation in both RVVT screen and confirm assays. However, rivaroxaban affected the screen more than the confirm, leading to higher RVVT ratios, whereas apixaban affected the confirm more than the screen, leading to lower RVVT ratios. LA testing in the presence of DOACs also led to lower intra-patient consistency in LA test results. We conclude that ex-vivo data appears to confirm the potential for false positive (with rivaroxaban) and potential for false negative (with apixaban) identification of LA in patients on DOAC treatment. We also make some recommendations in regards to such testing.

Topics: Anticoagulants; Antiphospholipid Syndrome; Blood Coagulation; Blood Coagulation Tests; Dabigatran; False Negative Reactions; False Positive Reactions; Humans; Lupus Coagulation Inhibitor; Prothrombin Time; Rivaroxaban; Thrombophilia

: Thrombelastography (TEG) parameters and prothrombin time (PT), activated partial thromboplastin time (APTT) are compared and analysed. According to change of TEG parameters and assessment of haemostatic state of each patient, we try to explore the feasibility of individualized anticoagulant therapies. 87 people with hip or knee diseases awaiting arthroplasty were recruited. Haemoglobin levels and TEG parameters including R, K, α-angle, maximum amplitude, coagulation index were assessed in perioperative period. PT and APTT were assessed preoperatively. For 65 patients with normal TEG parameters, PT and APTT, we use tranexamic acid (TXA) to reduce blood loss during operation. As hypercoagulability group, 12 patients awaiting unilateral total knee arthroplasty with hypercoagulable state assessed by TEG parameters or risks for venous thromboembolism received daily 10-mg rivaroxaban until 24 h preoperatively and did not receive TXA during operation. All patients received intravenous administration of argatroban after 8 h postoperatively until day 3 and oral administration of rivaroxaban (10 mg) subsequently to prevent deep vein thrombosis or/and pulmonary embolism until 35 days postoperatively. TEG parameters have significant relationships with fibrinogen, platelet and APTT. The number of patients with abnormal haemostatic state assessed by TEG parameters is higher than that assessed by PT, APTT. TEG show hypercoagulability develops throughout perioperative period. There was no significant difference in haemoglobin concentration between hypercoagulability group and normal group in patients receiving unilateral total knee arthroplasty. TEG have higher sensitivity of perioperative abnormal haemostatic state than PT, APTT in primary arthroplasty. For patients with hypercoagulability, individualized anticoagulant therapies such as preoperative administration of rivaroxaban and not using TXA in operation is safe and effective.

Topics: Anticoagulants; Arginine; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Female; Humans; Male; Middle Aged; Partial Thromboplastin Time; Perioperative Care; Pipecolic Acids; Postoperative Care; Preoperative Care; Prospective Studies; Prothrombin Time; Pulmonary Embolism; Rivaroxaban; Sulfonamides; Thrombelastography; Thrombophilia; Venous Thrombosis

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

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

Antithrombin (AT) activity tests are used for diagnosing hereditary AT deficiency, a main genetic determinant of thrombophilia. They are either based on inhibition of thrombin (FIIa) or activated factor X (FXa). FXa-based assays have been suggested to be preferable to FIIa-based assays due to their higher sensitivity for certain AT deficiency causing mutations. To assess the performance of these two methods in a real-world scenario, 745 consecutively collected samples from patients referred to our institute during a 3-month period for thrombophilia testing were analysed. In samples from patients not receiving direct-acting oral anticoagulants or heparins (

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Antithrombin III; Antithrombins; Blood Coagulation; Blood Coagulation Tests; Child; Child, Preschool; Dose-Response Relationship, Drug; Factor Xa; Factor Xa Inhibitors; Female; Heparin; Heparin, Low-Molecular-Weight; Humans; Infant; Male; Middle Aged; Mutation; Pyrazoles; Pyridones; Rivaroxaban; Thrombin; Thrombophilia; Young Adult

Topics: Aged, 80 and over; Atrial Fibrillation; Factor Xa Inhibitors; Heart Failure; Humans; Male; Nephritis, Interstitial; Rivaroxaban; Thrombophilia

BACKGROUND Thrombophilia is a predisposition to thrombosis. Genetic causes include antithrombin III, protein C, protein S, factor V Leiden, prothrombin 20210A allele, and MTHFR mutations. Other genetic factors causing thrombosis and pulmonary embolism have been identified in recent studies, including 4G/4G polymorphism of the PAI-1 gene. CASE REPORT A patient with a personal and family history of recurrent thrombosis and pulmonary embolism was admitted to our Internal Medicine Department. After the most common acquired risk factors for thromboembolism were ruled out, the patient and her family members underwent genetic diagnostic testing. These tests showed homozygous 4G/4G polymorphism of the PAI-1 gene in 14 subjects, homozygous 4G/4G polymorphism of the PAI-1 gene and C677T/A1298C polymorphism of the MTHFR gene in 4 subjects, and heterozygous 4G/4G polymorphism of the PAI-1 gene and C677T/A1298C polymorphism of the MTHFR gene in 3 subjects. Afterwards, we initiated the administration of Rivaroxaban, with beneficial results. CONCLUSIONS No thrombotic recurrence has been observed in the patient since 2014. This case report shows the efficacy and superiority of Rivaroxaban over traditional anticoagulants in the treatment of hereditary thrombophilia. Further studies are clearly needed before Rivaroxaban can be recommended as a standard treatment in patients with inherited thrombophilia.

Topics: Factor Xa Inhibitors; Female; Humans; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Plasminogen Activator Inhibitor 1; Polymorphism, Genetic; Pulmonary Embolism; Rivaroxaban; Thrombophilia

Direct oral anticoagulants have been shown safe and effective in the treatment of pulmonary emboli and deep vein thrombi. Their role in the treatment of patients with hypercoagulability is uncertain. We designed a retrospective exploratory analysis of all patients with definite heparin induced thrombocytopenia (HIT) and antiphospholipid syndrome (APS) that were treated with either apixaban or rivaroxaban from September 2011 through November 2015. Patients were reviewed for several clinico-pathologic features, including efficacy and safety. 23 patients were identified (12 patients with HIT and 11 patients with APS). Sixteen patients (70 %) were treated with apixaban and seven patients (30 %) were treated with rivaroxaban over a median follow up of 7 months (range 2-39). Zero patients developed recurrent thrombi. Two patients being treated for HIT developed major bleeding leading to discontinuation of all anticoagulation. Therefore, apixaban and rivaroxaban appear safe and effective for treatment of patients with HIT and APS in this small retrospective cohort and should be considered on an individual basis for patients who refuse, fail or are intolerant of warfarin. There were no sources of funding.

Topics: Adult; Aged; Anticoagulants; Antiphospholipid Syndrome; Female; Hemorrhage; Heparin; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Recurrence; Retrospective Studies; Rivaroxaban; Thrombophilia; Thrombosis

: Activated protein C resistance (APC-R) is assessed as part of thrombophilia screening, preferably in patients not taking oral anticoagulants. Rivaroxaban is known to alter some APC-R assays. To our knowledge, there have been no reports on the effect of rivaroxaban on the Russell viper venom time (RVVT)-based APC-R assay in real-life patients. In 168 consecutive outpatients suspected of having venous thromboembolism because of thrombophilia, APC-R was determined using the RVVT-based ProC Ac R assay (Siemens, Marburg, Germany). Patients receiving rivaroxaban or vitamin K antagonists were eligible. We measured rivaroxaban concentrations using the anti-Xa Biophen DiXal assay (Hyphen Biomed, Neuville-Sur-Oise, France) and factor V Leiden using the real-time PCR. APC-R was detected in 23 (28%) patients on rivaroxaban (n = 81) administrated 2-48 h since the blood draw, 15 (28%) patients on vitamin K antagonists (n = 54), and in four (12%) patients off anticoagulation (n = 33). Compared with nonanticoagulated patients, APC-R ratios were similar in patients on rivaroxaban, without any correlation with rivaroxaban concentrations (from 0 to 303 μg/l). None of the patients on rivaroxaban were found to have false-negative or false-positive APC-R ratios. Rivaroxaban concentrations up to 300 μg/l do not affect results of the ProC Ac R RVVT-based assay, which could be recommended in patients referred to a clinic for thrombophilia screening in whom the time since the last dose of rivaroxaban is uncertain.

Topics: Activated Protein C Resistance; Adult; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Prothrombin Time; Rivaroxaban; Thrombophilia; Venous Thromboembolism; Vitamin K

: The aim of the study was to investigate whether treatment with non-vitamin K antagonist oral anticoagulants (NOACs) is effective and well tolerated in real-life patients following venous thromboembolism (VTE) associated with severe inherited thrombophilia. We evaluated 33 consecutive patients with severe inherited thrombophilia, defined as the presence of deficiencies in protein C, protein S, or anti-thrombin, homozygous factor V Leiden and prothrombin G20210A mutations, or combined defects. The patients were recruited from March 2010 to December 2015 and followed till July 2016. Rivaroxaban was used in 23 patients (70%), whereas dabigatran and apixaban were used in 4 patients each. During a median 21 (range 8-34) months' follow-up, three recurrent VTE episodes (9%) were observed. Deep vein thrombosis recurred after 6 months on rivaroxaban in a protein S-deficient 32-year-old woman who had heavy menstrual bleeding resulting in interruptions of therapy. A long journey preceded deep vein thrombosis recurrence after 12 months of rivaroxaban use in a 59-year-old obese man homozygous for prothrombin 20210A mutation. The third recurrent VTE following anticoagulation withdrawal prior to surgery and during hospitalization was observed in a 56-year-old woman with protein S deficiency and heterozygous factor V Leiden. The three patients continued use of NOACs, apixaban, dabigatran, and rivaroxaban, respectively. This largest real-life series of patients with severe thrombophilia receiving NOACs indicates that such patients could be safely and effectively treated with NOACs. Lower efficacy was observed in protein S deficiency. Recurrent VTE was mostly related with nonadherence, which highlights an important role of regular intake of NOACs in high-risk patients.

Topics: Adult; Anticoagulants; Dabigatran; Female; Humans; Male; Medication Adherence; Middle Aged; Pyrazoles; Pyridones; Recurrence; Rivaroxaban; Thrombophilia; Venous Thromboembolism; Young Adult

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Drug Utilization; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thrombophilia; Urban Health Services

We report the case of a 65--year-old woman admitted for inferior ST-segment elevation myocardial infarction complicated by complete atrioventricular block. The patient was under treatment with a novel oral anticoagulant (NOAC, rivaroxaban) because of a history of recurrent idiopathic pulmonary embolism. Emergency angiography showed complete acute thrombotic occlusion of the right coronary artery. After manual thrombectomy, there was no angiographic evidence of underlying atherosclerosis, therefore no further percutaneous coronary intervention was performed. Subsequent clinical course was uneventful. Laboratory tests demonstrated the presence of a heterozygous mutation of the factor II gene (G20210A), confirming the clinical evidence of a thrombophilic state. As rivaroxaban seemed to be ineffective in preventing spontaneous coronary thrombosis in this patient, antithrombotic therapy was shifted to warfarin plus low-dose aspirin. No further ischemic events occurred during the 1-year follow-up. It can be hypothesized that factor Xa inhibition by NOACs, such as rivaroxaban, could be insufficient in case of a thrombophilic state due to thrombin mutation. A brief review of the current literature on use of NOACs in acute coronary syndromes is also reported.

Topics: Aged; Anticoagulants; Female; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Rivaroxaban; ST Elevation Myocardial Infarction; Thrombophilia; Treatment Outcome

The introduction of direct oral anticoagulants (DOA) in the early stage of cerebral infarction after thrombolysis may reduce the recurrence rate but raises safety concern. We sought to study the feasibility and safety of the introduction of rivaroxaban or dabigatran in this context. Thirty-four consecutive patients admitted for ischemic stroke related to non-valvular atrial fibrillation in whom DOA were given within the first two weeks following intravenous rt-PA were studied. A clinical and radiological monitoring protocol was established to ensure the safety of the prescription. None of the patients experienced symptomatic hemorrhagic transformation or a symptomatic recurrent ischemic event after early rivaroxaban or dabigatran introduction.

Topics: Aged; Aged, 80 and over; Antithrombins; Atrial Fibrillation; Brain Ischemia; Dabigatran; Drug Administration Schedule; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Humans; Intracranial Hemorrhages; Length of Stay; Male; Pilot Projects; Radiography; Recombinant Proteins; Recurrence; Retrospective Studies; Rivaroxaban; Severity of Illness Index; Thrombolytic Therapy; Thrombophilia; Tissue Plasminogen Activator

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Contraindications; Dabigatran; Drug Interactions; Drug Monitoring; Drug Substitution; Female; Hemorrhage; Humans; Kidney Diseases; Kidney Function Tests; Male; Morpholines; Pyrazoles; Pyridines; Pyridones; Risk Factors; Rivaroxaban; Stroke; Thiazoles; Thiophenes; Thrombophilia

Topics: Adult; Aged; Anticoagulants; Atrial Fibrillation; Electric Countershock; Embolism; Factor Xa Inhibitors; Heart Diseases; Hemorrhage; Humans; International Normalized Ratio; Middle Aged; Morpholines; Multicenter Studies as Topic; Myocardial Infarction; Prospective Studies; Randomized Controlled Trials as Topic; Research Design; Risk; Rivaroxaban; Stroke; Thiophenes; Thrombophilia; Time Factors; Treatment Outcome; Vitamin K; Warfarin

The safety and effectiveness of non-vitamin K antagonist (VKA) oral anticoagulants, dabigatran or rivaroxaban, were compared with VKA in anticoagulant-naive patients with nonvalvular atrial fibrillation during the early phase of anticoagulant therapy.. With the use of the French medico-administrative databases (SNIIRAM and PMSI), this nationwide cohort study included patients with nonvalvular atrial fibrillation who initiated dabigatran or rivaroxaban between July and November 2012 or VKA between July and November 2011. Patients presenting a contraindication to oral anticoagulants were excluded. Dabigatran and rivaroxaban new users were matched to VKA new users by the use of 1:2 matching on the propensity score. Patients were followed for up to 90 days until outcome, death, loss to follow-up, or December 31 of the inclusion year. Hazard ratios of hospitalizations for bleeding and arterial thromboembolic events were estimated in an intent-to-treat analysis using Cox regression models. The population was composed of 19 713 VKA, 8443 dabigatran, and 4651 rivaroxaban new users. All dabigatran- and rivaroxaban-treated patients were matched to 16 014 and 9301 VKA-treated patients, respectively. Among dabigatran-, rivaroxaban-, and their VKA-matched-treated patients, 55 and 122 and 31 and 68 bleeding events and 33 and 58 and 12 and 28 arterial thromboembolic events were observed during follow-up, respectively. After matching, no statistically significant difference in bleeding (hazard ratio, 0.88; 95% confidence interval, 0.64-1.21) or thromboembolic (hazard ratio, 1.10; 95% confidence interval, 0.72-1.69) risk was observed between dabigatran and VKA new users. Bleeding (hazard ratio, 0.98; 95% confidence interval, 0.64-1.51) and ischemic (hazard ratio, 0.93; 95% confidence interval, 0.47-1.85) risks were comparable between rivaroxaban and VKA new users.. In this propensity-matched cohort study, our findings suggest that physicians should exercise caution when initiating either non-VKA oral anticoagulants or VKA in patients with nonvalvular atrial fibrillation.

Topics: Adolescent; Adult; Aged; Anticoagulants; Antithrombins; Arterial Occlusive Diseases; Atrial Fibrillation; Dabigatran; Databases, Factual; Factor Xa Inhibitors; Follow-Up Studies; Hemorrhage; Hospitalization; Humans; Middle Aged; Risk; Rivaroxaban; Thromboembolism; Thrombophilia; Vitamin K; Warfarin; Young Adult

Increased hypercoagulability has been reported with low doses of direct thrombin inhibitors but not with direct factor Xa inhibitors.. To compare the effects of rivaroxaban with those of melagatran and dabigatran on thrombin generation (TG) and tissue factor-induced hypercoagulability and to explore the possible involvement of the thrombin-thrombomodulin/activated protein C system.. In normal human plasma and in protein C-deficient plasma, TG was investigated in vitro in the presence and absence of recombinant human soluble thrombomodulin (rhs-TM). TG was determined by calibrated automated thrombography and an ELISA for prothrombin fragments 1+2 (F1+2 ). In an in vivo rat model, hypercoagulability was induced by tissue factor; levels of thrombin-antithrombin (TAT) and fibrinogen and the platelet count were determined.. Rivaroxaban inhibited TG in a concentration-dependent manner. In the absence of rhs-TM, melagatran and dabigatran also inhibited TG concentration dependently. However, in the presence of rhs-TM, lower concentrations of melagatran (119-474 nmol L(-1) ) and dabigatran (68-545 nmol L(-1) ) enhanced endogenous thrombin potential, peak TG, and F1+2 formation in normal plasma but not in protein C-deficient plasma. In vivo, rivaroxaban dose-dependently inhibited TAT generation, whereas melagatran showed a paradoxical effect, with an increase in TAT and a small decrease in fibrinogen and platelet count at lower doses.. Low concentrations of the direct thrombin inhibitors melagatran and dabigatran enhanced TG and hypercoagulability, possibly via inhibition of the protein C system. In contrast, rivaroxaban reduced TG and hypercoagulability under all conditions studied, suggesting that it does not suppress this negative-feedback system.

Topics: Animals; Antithrombins; Azetidines; Benzylamines; Blood Coagulation; Blood Platelets; Enzyme-Linked Immunosorbent Assay; Factor Xa Inhibitors; Humans; Male; Morpholines; Plasma; Platelet Count; Protein C; Prothrombin; Rats; Rats, Wistar; Rivaroxaban; Thiophenes; Thrombelastography; Thrombin; Thrombomodulin; Thrombophilia; Thromboplastin

New oral anticoagulants (NOAC) are becoming available as alternatives to warfarin to prevent systemic embolism in patients with non-valvular atrial fibrillation and for the treatment and prevention of venous thromboembolism. An in-depth understanding of their pharmacology is invaluable for appropriate prescription and optimal management of patients receiving these drugs should unexpected complications (such as bleeding) occur, or the patient requires urgent surgery. The Australasian Society of Thrombosis and Haemostasis has set out to inform physicians on the use of the different NOAC based on current available evidence focusing on: (i) selection of the most suitable patient groups to receive NOAC, (ii) laboratory measurements of NOAC in appropriate circumstances and (iii) management of patients taking NOAC in the perioperative period, and strategies to manage bleeding complications or 'reverse' the anticoagulant effects for urgent invasive procedures.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Blood Coagulation Tests; Blood Loss, Surgical; Contraindications; Dabigatran; Drug Interactions; Drug Monitoring; Drug Substitution; Elective Surgical Procedures; Emergencies; Hematoma, Epidural, Spinal; Hemorrhage; Humans; Kidney Diseases; Liver Diseases; Morpholines; Patient Selection; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Thrombophilia

Topics: Adult; Aged; Anticoagulants; Female; Humans; Male; Mass Screening; Morpholines; Mutation; Prothrombin; Recurrence; Risk Factors; Rivaroxaban; Thiophenes; Thrombophilia; Treatment Outcome; Venous Thrombosis; Warfarin; Women's Health

Direct oral factor inhibitors (DOFIs) are an attractive alternative to vitamin K antagonists (VKA) for the treatment of patients with antiphospholipid syndrome (APS). In the absence of prospective, randomised trial data, reports of therapeutic failures in clinical practice alert clinicians to potential limitations of DOFI therapy for this indication. Data for all cases were collected from a centralised system that contains complete medical records of all patients treated and followed at Mayo Medical Center. We present here three consecutive APS patients who had had no thromboembolism recurrence on warfarin but were switched to DOFIs. The diagnosis of APS was established according to currently recommended criteria. The three cases were as follows: A woman with primary APS developed thrombotic endocarditis with symptomatic cerebral emboli after transition to dabigatran. A second woman with primary APS experienced ischemic arterial strokes and right transverse-sigmoid sinus thrombosis after conversion to rivaroxaban. A man with secondary APS suffered porto-mesenteric venous thrombosis after switching to rivaroxaban. None of these patients had failed warfarin prior to the transition to DOFIs. Based on these three cases, we advocate caution in using DOFIs for APS patients outside of a clinical trial setting, until further data becomes available.

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Benzimidazoles; beta-Alanine; Cerebral Infarction; Dabigatran; Drug Substitution; Female; Humans; International Normalized Ratio; Lupus Erythematosus, Systemic; Male; Mesenteric Veins; Middle Aged; Morpholines; Portal Vein; Recurrence; Retrospective Studies; Rivaroxaban; Splenic Vein; Stroke; Thiophenes; Thromboembolism; Thrombophilia; Treatment Failure; Venous Thrombosis; Warfarin

Hypercoagulability, resulting in thromboembolic events, can be a life-threatening complication of nephrotic syndrome (NS). Conventional anticoagulants, such as warfarin, have been the standard of care for more than 50 years; however, the availability of target-specific oral anticoagulants (TSOACs) have provided additional options for the treatment and prevention of thromboembolic events. Documented use of the TSOACs in patients with NS and hypercoagulability is currently limited.. We present the case of an 18-year-old young woman with NS and renal vein thrombosis who was readmitted with bilateral pulmonary emboli on therapeutic doses of warfarin, with a goal international normalized ratio of 2.0 to 3.0. The decision was made to transition the patient from warfarin to rivaroxaban, an oral factor Xa inhibitor.. Rivaroxaban was the first of the emerging TSOACs to be FDA approved for both prevention and treatment of venous thromboembolism. With favorable safety and efficacy data compared with warfarin in addition to a predictable pharmacokinetic profile and the lack of requirement of routine monitoring, rivaroxaban provides a useful alternative in this patient population.. While on therapeutic anticoagulation, a patient previously diagnosed with NS and renal vein thrombosis experienced pulmonary emboli on a conventional anticoagulant and was switched to a target-specific oral anticoagulant with documented completion of 6 months of therapy without recurrent thromboembolism.

Topics: Administration, Oral; Adolescent; Anticoagulants; Factor Xa Inhibitors; Female; Humans; International Normalized Ratio; Morpholines; Nephrotic Syndrome; Pulmonary Embolism; Rivaroxaban; Thiophenes; Thrombophilia; Venous Thromboembolism; Warfarin

There is increasing recognition that thrombotic complications may occur in patients with cirrhosis, and literature on antithrombotic treatment in these patients is rapidly emerging. Due to extensive haemostatic changes in patients with cirrhosis, careful monitoring of anticoagulant therapy may be required. Recent data suggest that plasma levels of low molecular weight heparin (LMWH) are substantially underestimated by the anti-activated factor X (anti-Xa) assay in patients with cirrhosis. We studied the in vitro recovery of antithrombin (AT)-dependent and -independent anticoagulant drugs in plasma from 26 patients with cirrhosis and 30 healthy controls and found substantially reduced anti-Xa levels when AT-dependent anticoagulant drugs were added to the plasma of patients with cirrhosis. LMWH (0·2 U/ml) had the poorest recovery in plasma from patients with cirrhosis (0·13 ± 0·06 U/ml, compared to 0·23 ± 0·03 U/ml in controls, P < 0·0001), followed by unfractionated heparin and fondaparinux. In contrast, the recovery of rivaroxaban and dabigatran was identical between patients and controls. These data suggest that the anti-Xa assay cannot be used to monitor AT-dependent anticoagulant drugs in patients with cirrhosis, as it substantially underestimates drug levels. The direct factor Xa and IIa inhibitors, however, may be monitored through the respective anti-Xa and anti-IIa assays in patients with cirrhosis.

Topics: Anticoagulants; Antithrombins; Benzimidazoles; beta-Alanine; Blood Coagulation; Blood Coagulation Tests; Dabigatran; Diagnostic Tests, Routine; Drug Monitoring; Factor Xa Inhibitors; False Negative Reactions; Female; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Liver Cirrhosis; Male; Middle Aged; Morpholines; Polysaccharides; Prothrombin; Rivaroxaban; Sensitivity and Specificity; Thiophenes; Thrombophilia

Global coagulation assays display variable effects at different concentrations of rivaroxaban. The aim of this study is to quantify the ex vivo effects of low-dose rivaroxaban on thrombophilia screening assays and coagulation factor activities based on the administration time, and to show how to mask possible interferences. Plasma samples from 40 patients receiving rivaroxaban 10 mg daily were investigated to measure activities of clotting factor II, V, VII, VIII, IX, XI, XII and XIII; protein C- and protein S-levels; lupus anticoagulants; anticardiolipin IgG and IgM; D-dimer, heparin-platelet factor 4 (HPF4) antibodies and screening tests for von Willebrand disease (VWD). Two hours after rivaroxaban administration, the activities of clotting factors were significantly decreased to different extents, except for factor XIII. Dilution of plasma samples resulted in neutralisation of these interferences. The chromogenic protein C activity assay was not affected by rivaroxaban. Depending on the timing of tablet intake in relation to blood sampling protein S activity was measured falsely high when a clotting assay was used. False-positive results for lupus anticoagulants were observed depending on the assay system used and the administration time of rivaroxaban. ELISA-based assays such as anticardiolipin IgG and IgM, D-dimer, HPF4-antibodies and the turbidimetric assays for VWD were not affected by rivaroxaban. Specific haemostasis clotting tests should be performed directly prior to rivaroxaban intake. Assay optimisation in the presence of rivaroxaban can be achieved by plasma dilution. Immunologic assays are not influenced by rivaroxaban, while chromogenic assays can be used, when they do not depend on factor Xa.

Topics: Administration, Oral; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Biomarkers; Blood Coagulation; Blood Coagulation Factors; Blood Coagulation Tests; Chromatography, High Pressure Liquid; Chromogenic Compounds; Drug Administration Schedule; Enzyme-Linked Immunosorbent Assay; Factor Xa; Factor Xa Inhibitors; False Positive Reactions; Humans; Morpholines; Nephelometry and Turbidimetry; Predictive Value of Tests; Reproducibility of Results; Rivaroxaban; Tablets; Tandem Mass Spectrometry; Thiophenes; Thrombophilia; Thrombosis; Time Factors; Treatment Outcome

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Clinical Trials, Phase III as Topic; Dabigatran; Female; Humans; Male; Morpholines; Multicenter Studies as Topic; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Thrombophilia

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Clinical Trials, Phase III as Topic; Dabigatran; Female; Humans; Male; Morpholines; Multicenter Studies as Topic; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Thrombophilia

Guidelines concerning the prevention and treatment of pregnancy-associated venous thromboembolism (VTE) have been elaborated by the American College of Chest Physicians and published in Chest in 2008. In this review, they have been compared with European guidelines and discussed taking into account the papers published since 2008.Most recommendations are of low grade of evidence because randomized studies are lacking during pregnancy and many reflect guidelines proposed by experts. The decisions on the most appropriate prophylaxis, dose to be administered and moment of pregnancy for starting prophylaxis are often decided case by case after careful assessment of the risk of pregnancy-associated VTE, on one hand, and the risk for the mother, on the other.Risk factors (age >or= 35, obesity, history of VTE with or without sequellae, in vitro fertilization)or thrombophilia have to be taken into account. Scores have been proposed to improve standardisation and evaluation of the risk of VTE and they should be validated.

Topics: Abnormalities, Drug-Induced; Adult; Anticoagulants; Benzimidazoles; Blood Loss, Surgical; Cesarean Section; Contraindications; Dabigatran; Europe; Evidence-Based Medicine; Female; Fetus; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Infant, Newborn; Morpholines; Polysaccharides; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications, Hematologic; Puerperal Disorders; Pyridines; Rivaroxaban; Societies, Medical; Thiophenes; Thrombophilia; United States; Uterine Hemorrhage; Venous Thromboembolism; Warfarin

New oral anticoagulants, soon available in clinical practice, will deeply change the management of venous thromboembolism. The main advantage of these drugs is the route of administration. Moreover, among the new oral anticoagulants, rivaroxaban has a better efficacy than enoxaparin to prevent thromboembolic events after major orthopaedic surgery (THR and TKR). In phase III studies, safety profile seems adequate. A new era for prophylaxis of VTE is beginning with the new oral anticoagulants. However, improvement in the management of patients with renal failure, obese patients or elderly is needed considering that these patients have a high thrombotic and/or hemorrhagic risk.

Topics: Administration, Oral; Aged; Anticoagulants; Clinical Trials, Phase III as Topic; Comorbidity; Enoxaparin; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Humans; Kidney Failure, Chronic; Morpholines; Obesity; Postoperative Complications; Preanesthetic Medication; Rivaroxaban; Thiophenes; Thromboembolism; Thrombophilia; Venous Thrombosis