rivaroxaban and Blood-Coagulation-Disorders

Dabigatranetexilate and rivaroxaban were approved for prevention of thromboembolic events after orthopedic surgery in 2008. Dabigatran is a direct inhibitor of thrombin and rivaroxaban of factor Xa. Inhibition is reversible and the duration of action is predictable. Both drugs considerably influence the global tests of coagulation thus making postoperative coagulation monitoring more difficult. In order to keep the interaction as low as possible blood samples for assessment of the thromboplastin time (PT) and the partial thromboplastin time (PTT) should be taken immediately before the next drug administration. Blood sampling about 2-4 h after drug administration can be performed to check the efficacy of drug action. Non-urgent operations should be started earliest 24 h after the previous drug application. In cases of emergency interventions due to life-threatening bleeding, administration of prothrombin complex concentrate might be a successful treatment option. Specific antidotes are not available.

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; Blood Coagulation Disorders; Dabigatran; Factor Xa Inhibitors; Humans; International Normalized Ratio; Intraoperative Complications; Morpholines; Partial Thromboplastin Time; Pyridines; Rivaroxaban; Thiophenes; Thrombin; Thromboembolism

The use of direct factor Xa inhibitors rivaroxaban and apixaban (XABANs) has rapidly increased; however, there is no validated test available to monitor the effect on hemostasis. This study aims to assess how hemostatic management based on the Rapid Thromboelastography (R-TEG) variable activated clotting time (ACT) of XABAN patients with ongoing bleedings or in need for acute surgical intervention, affected patient outcome. A total of 343 XABAN patients were included in the main analysis together with 50 healthy volunteers to validate the reference value for ACT. An ACT >120 s (s) was defined as having XABAN-induced coagulopathy. Sixty-five percent of the XABAN patients presented with R-TEG ACT within the normal reference. Patients with XABAN-induced coagulopathy had a significantly increased risk of severe bleeding. Significantly more patients with extra-cerebral bleeding (ECB) and ACT above 120 s were transfused with five red blood cell (RBC) units or more compared to patients with ACT at 120 s or below (17% vs. 3%,

Topics: Blood Coagulation Disorders; Factor Xa Inhibitors; Hemorrhage; Humans; Rivaroxaban; Thrombelastography

We describe a patient with tertiary hyperparathyroidism with history of three episodes of deep vein thrombosis and on rivaroxaban. The patient underwent a subtotal parathyroidectomy, developing cervical hematoma with airway compression. Therefore, emergency surgical decompression was necessary. Later, on the ninth postoperative day, the serum ionized calcium levels were low. Medical team knowledge about preexisting diseases and their implication in the coagulation state are essential conditions to reduce morbidity and mortality of surgeries. However, no reports were found in literature about the association of hypocalcemia with the use of the new class of anticoagulants, which act as factor X inhibitors (Stuart-Prower factor), predisposing to increased bleeding in the immediate postoperative period.

Topics: Blood Coagulation Disorders; Calcium; Factor Xa Inhibitors; Humans; Hyperparathyroidism; Hypocalcemia; Male; Middle Aged; Parathyroidectomy; Renal Insufficiency, Chronic; Risk Factors; Rivaroxaban

Screening for primary hypercoagulable states (PHSs) in venous thromboembolism (VTE) patients was not mandated in the EINSTEIN trials; and therefore, few patients with a known PHS were available for analysis. We sought to assess the effectiveness and safety of rivaroxaban versus warfarin for treatment of VTE in patients with a known PHS.. Using MarketScan claims data from 1/2012-9/2015, we identified adults with a primary diagnosis of VTE during a hospitalization/emergency department visit (the index event), with ≥180-days of continuous insurance coverage prior to the index event, a documented diagnosis for a PHS and newly-initiated as an outpatient on rivaroxaban or warfarin within 30-days of the index VTE. Rivaroxaban and warfarin users were 1:1 propensity-score matched. Balance between cohorts was evaluated by inspecting standardized differences for baseline covariates (<0.1 considered well-balanced). Patients were followed up to 12-months from the index event or until occurrence of an endpoint, switch/discontinuation of index oral anticoagulation or insurance disenrollment. Rates of recurrent VTE and major bleeding were compared using Cox regression and reported as hazard ratios (HRs) with 95% confidence intervals (CIs).. We matched 403 rivaroxaban and 403 warfarin patients with VTE and a known PHS. All baseline covariates had a standardized difference < 0.1. Rivaroxaban use was associated with a non-significant reduction in recurrent VTE (HR = 0.70, 95%CI = 0.33-1.49) and major bleeding (HR = 0.55, 95%CI = 0.16-1.86) versus warfarin.. In routine practice, the effectiveness and safety of rivaroxaban versus warfarin in VTE patients with a known PHS appears to be similar to that observed in the EINSTEIN trial program.

Topics: Anticoagulants; Blood Coagulation Disorders; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Outpatients; Retrospective Studies; Rivaroxaban; Venous Thromboembolism; Warfarin

Slow-flow vascular malformations (VM) can be associated with localized intravascular coagulopathy (LIC) that is characterized by elevated D-Dimer levels and low fibrinogen and platelets. This can lead to bleeding and clotting tendencies, which can give rise to functional limitations such as pain and swelling and even progress to disseminated intravascular coagulopathy.. We conducted a chart review of four patients with evidence of LIC who were started on rivaroxaban. We found an improvement of D-Dimer and/or fibrinogen levels in all four patients. They also had an improvement of pain and functionality.. We report on four patients in whom anticoagulation with a direct oral anticoagulant, rivaroxaban, was effective in controlling signs and symptoms of consumptive coagulopathy with no evidence of bleeding from the use of rivaroxaban.

Topics: Administration, Oral; Adolescent; Adult; Anticoagulants; Blood Coagulation Disorders; Blood Flow Velocity; Factor Xa Inhibitors; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Humans; Male; Pain; Rivaroxaban; Treatment Outcome; Vascular Malformations; Young Adult

In patients receiving direct oral anticoagulants (DOACs), emergency treatment like thrombolysis for acute ischemic stroke is complicated by insufficient availability of DOAC-specific coagulation tests. Conflicting recommendations have been published concerning the use of global coagulation assays for ruling out relevant DOAC-induced anticoagulation.. Four hundred eighty-one samples from 96 DOAC-treated patients were tested using prothrombin time (PT), activated partial thromboplastin time (aPTT) and thrombin time (TT), DOAC-specific assays (anti-Xa activity, diluted TT), and liquid chromatography-tandem mass spectrometry. Sensitivity and specificity of test results to identify DOAC concentrations <30 ng/mL were calculated. Receiver operating characteristic analyses were used to define reagent-specific cutoff values.. Normal PT and aPTT provide insufficient specificity to safely identify DOAC concentrations <30 ng/mL (rivaroxaban/PT: specificity, 77%/sensitivity, 94%; apixaban/PT: specificity, 13%/sensitivity, 94%, dabigatran/aPTT: specificity, 49%/sensitivity, 91%). Normal TT was 100% specific for dabigatran, but sensitivity was 26%. In contrast, reagent-specific PT and aPTT cutoffs provided >95% specificity and a specific TT cutoff enhanced sensitivity for dabigatran to 84%. For apixaban, no cutoffs could be established.. Even if highly DOAC-reactive reagents are used, normal results of global coagulation tests are not suited to guide emergency treatment: whereas normal PT and aPTT lack specificity to rule out DOAC-induced anticoagulation, the low sensitivity of normal TT excludes the majority of eligible patients from treatment. However, reagent-specific cutoffs for global coagulation tests ensure high specificity and optimize sensitivity for safe emergency decision making in rivaroxaban- and dabigatran-treated patients.. URL: http://www.clinicaltrials.gov. Unique identifiers: NCT02371044 and NCT02371070.

Topics: Aged; Aged, 80 and over; Antithrombins; Blood Coagulation Disorders; Blood Coagulation Tests; Dabigatran; Emergencies; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Partial Thromboplastin Time; Point-of-Care Testing; Prothrombin Time; Pyrazoles; Pyridones; Rivaroxaban; Sensitivity and Specificity; Stroke; Thrombin Time; Thrombolytic Therapy

Topics: Anticoagulants; Benzimidazoles; beta-Alanine; Blood Coagulation Disorders; Dabigatran; Drug Approval; Fibrinolytic Agents; Humans; Morpholines; Rivaroxaban; Stroke; Thiophenes

Topics: Anticoagulants; Benzimidazoles; beta-Alanine; Blood Coagulation Disorders; Clinical Trials as Topic; Dabigatran; Humans; Morpholines; Postoperative Complications; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Warfarin

Topics: Acute Coronary Syndrome; Altitude; Blood Coagulation Disorders; Coffee; Factor Xa Inhibitors; Heparin; Humans; Lipoproteins; Lymphatic Diseases; Morpholines; Myocardial Infarction; Platelet Aggregation Inhibitors; Rivaroxaban; Thiophenes; Thrombocytopenia; Thrombosis; Troponin; Venous Thrombosis; von Willebrand Diseases

Interpatient variability in the safety and efficacy of oral anticoagulation with warfarin presents several challenges to clinicians, thus underscoring the emergent need for new orally available anticoagulants with predictable pharmacokinetic and pharmacodynamic profiles and ability to target circulating clotting factors. Seven compounds including rivaroxaban, apixaban, betrixaban, and eribaxaban are orally available direct inhibitors of activated factor X currently in development for the prevention and treatment of venous thromboembolism and for thromboprophylaxis in patients with atrial fibrillation or following an acute coronary syndrome. At doses used in phase 2 and 3 clinical trials, rivaroxaban and apixaban demonstrated a predictable onset of effect, maximal plasma concentration, and half-life that was unaffected by age, renal, or hepatic disease. In clinical trials for the treatment and prevention of venous thromboembolism, rivaroxaban and apixaban produced equivalent or superior reductions in the development or progression of venous thromboembolism compared with either low molecular weight heparin or warfarin. Trials comparing the efficacy of rivaroxaban or apixaban to standard therapy for stroke prophylaxis in patients with atrial fibrillation are in process. Rivaroxaban, the sentinel compound in this class, is already approved in the European Union and Canada. It is likely to be approved for use in the United States in 2010.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzamides; Blood Coagulation Disorders; Clinical Trials as Topic; Factor Xa Inhibitors; Heparin, Low-Molecular-Weight; Humans; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiophenes; Thromboembolism; Warfarin