rivaroxaban and Hemophilia-A

The phase III non-vitamin K dependent oral anticoagulants (NOAC) studies and recently published real world data on the use of dabigatran and rivaroxaban have shown that the bleeding profile in particular of intracranial and other life-threatening bleeding of NOAC is more favourable than that of warfarin. In case of a bleeding complication in a patient treated with a NOAC the recently updated EHRA practical guide offers management strategies. Idarucizumab, the specific antidot for dabigatran is approved to reverse the anticoagulant effect of dabigatran-treated patients who have serious bleeding and require an urgent procedure. Andexanet alfa, a specific antidot for direct and indirect factor Xa-inhibitors will be available in the future. The frequency of thrombocytopenia in ICU patients is high whereas the heparin induced thrombocytopenia (HIT) only counts for a small minority of patients with thrombocytopenia. To avoid an overdiagnosis of HIT a reliable and complete clinical and laboratory workup has to be performed. New immunoassays have been developed to provide results within a short period of time. These tests appear to have improved diagnostic accuracy compared with ELISAs in patients with suspected HIT and may reduce misdiagnosis and overtreatment. Acquired haemophilia (AH) is a rare and often life threatening bleeding disorder caused by autoantibodies against factor VIII. Susoctocog alfa is a B-domain deleted recombinant factor VIII porcine sequence that has recently been approved to treat severe bleeding in patients with AH. Susoctocog alfa offers the ability to effectively titrate and monitor dosing based on factor VIII activity levels.

Topics: Anticoagulants; Dabigatran; Hemophilia A; Hemorrhage; Heparin; Humans; Intensive Care Units; Rivaroxaban; Thrombocytopenia; Thrombosis; Warfarin

What is the correct use of established clotting factors, prothrombin complex concentrates (PCCs), and activated factor VII in bleeding complications of trauma, surgery, and old and new oral anticoagulants? How will new clotting factors, specifically the long-acting factors, change the hemostatic management of coagulation deficiency disorders? From bench to bedside, comparative coagulation studies and clinical trials of modified clotting factors are providing insights to help guide hemostatic management of congenital and acquired bleeding disorders. Comparative thrombin-generation studies and preclinical and clinical trials suggest that PCCs and fresh-frozen plasma are effective in reversing the anticoagulant effects of warfarin, yet there are few data to guide reversal of the new oral anticoagulants dabigatran and rivaroxaban. Although coagulation studies support the use of PCCs to reverse new oral anticoagulants, correlation with clinical response is variable and clinical trials in bleeding patients are needed. For congenital bleeding disorders, exciting new technologies are emerging from the bench. Data from clinical trials of molecularly modified coagulation factors with extended half-lives suggest the possibility of fewer infusions, reduced bleeds, and better quality of life in persons with hemophilia. Preclinical studies of other novel prohemostatic approaches for hemophilia and other congenital coagulation disorders include RNA interference silencing of antithrombin, monoclonal anti-tissue factor pathway inhibitor (anti-antibody, anti-tissue factor pathway inhibitor) aptamer, bispecific anti-IXa/X antibody, and fucoidans. Understanding the comparative coagulation studies of established prohemostatic agents, the pharmacokinetics of new long-acting clotting factors, and their correlation with bleeding outcomes will provide opportunities to optimize the hemostatic management of both congenital and acquired hemostatic disorders.

Topics: Antibodies; Anticoagulants; Benzimidazoles; beta-Alanine; Blood Coagulation Factors; Clinical Trials as Topic; Dabigatran; Factor VIIa; Female; Half-Life; Hemophilia A; Hemorrhage; Hemostatics; Humans; Male; Morpholines; Rivaroxaban; RNA Interference; Thiophenes

In this article, we have selected four topics that particularly caught our attention during the year 2022, and which are related to anticoagulation, its bleeding complications, and hemophilia. Thus, we discuss the issue of the treatment with rivaroxaban of atrial fibrillation associated with rheumatic valvulopathy, which has been studied in a randomized trial, the intensity of thromboprophylaxis in COVID outpatients and inpatients, and the bleeding risk of anticoagulation in patients with cerebral tumors. Finally, recent data on gene therapy in severe hemophilia A, an upcoming treatment, are discussed.. Dans cet article, nous avons sélectionné 4 sujets qui ont particulièrement retenu notre attention durant l’année 2022, en lien avec l’anticoagulation, ses complications hémorragiques et l’hémophilie. Ainsi, nous abordons le traitement par rivaroxaban de la fibrillation atriale associée à une valvulopathie rhumatismale qui a fait l’objet d’une étude randomisée, l’intensité de la thromboprophylaxie chez les patients hospitalisés ou traités en ambulatoire avec un Covid dont les données se sont bien étoffées, le risque associé à l’anticoagulation chez les patients avec une néoplasie cérébrale et, finalement, la thérapie génique dans l’hémophilie A sévère qui devrait apparaître sur le marché très prochainement.

Topics: Anticoagulants; Atrial Fibrillation; Cardiology; COVID-19; Hemophilia A; Hemostasis; Humans; Rivaroxaban; Stroke; Venous Thromboembolism

Topics: Antibodies, Monoclonal, Humanized; Anticoagulants; Arthroscopy; Blood Loss, Surgical; Dabigatran; Factor VIII; Hemophilia A; Humans; Randomized Controlled Trials as Topic; Rivaroxaban; Single-Domain Antibodies; Venous Thromboembolism

Direct oral anticoagulants (DOACs) were recently introduced and are being increasingly prescribed. Most DOACs alter the values of traditional coagulation tests, such as the international normalized ratio (INR) or the activated partial thromboplastin time (aPTT). Although vitamin K antagonists raise the INR value to an extent that mirrors their anticoagulant effect, DOACs do not, in general, alter standard clotting values in any consistent way. Thus, there is a risk that abnormal INR and aPTT values can be misinterpreted.. A woman taking rivaroxaban, a DOAC, presented with ileus and was scheduled for urgent surgery. A prolonged aPTT was, at first, wrongly attributed to rivaroxaban, delaying the correct diagnosis of autoantibody-associated acquired hemophilia (a rare condition with incidence, 1.34-1.48 cases per million people per year). The patient had a history of unusually intense bleeding in the skin and mucous membranes during anticoagulant treatment. Her aPTT had been prolonged even before any anticoagulants were taken.. The operation was delayed to await the elimination of rivaroxaban. The aPTT was still prolonged 24 hours later. The diagnosis of autoantibody-associated acquired hemophilia was suspected and then confirmed by the measurement of a factor VIII residual activity of 1% and the demonstration of factor VIII inhibition at an intensity of 9.2 Bethesda units per mL.. The causes of abnormal clotting test results must be clarified before beginning anticoagulant therapy. Unusually intense bleeding during oral anticoagulation should arouse suspicion of a previously undiagnosed acquired coagulopathy, e.g., antibody-associated acquired hemophilia.

Topics: Administration, Oral; Aged; Anticoagulants; Blood Coagulation Tests; Diagnosis, Differential; Diagnostic Errors; Emergency Medical Services; Female; Hemophilia A; Humans; Morpholines; Rivaroxaban; Thiophenes; Treatment Outcome