Reversing the anticoagulation effects of dabigatran.
The standard of care for oral anticoagulation therapy has primarily been warfarin, which is limited by its indirect mechanism-of-action, variable kinetics, tolerability, and routine monitoring concerns. The direct-acting oral anticoagulants (DOACs) have predictable pharmacokinetics and pharmacodynamics, and improved safety and efficacy compared to warfarin for the prevention of stroke in patients with nonvalvular atrial fibrillation and prevention or management of venous thromboembolism. Consequential bleeding is a concern with all anticoagulants. Vitamin K is not a rapid reversal agent for warfarin; rather it facilitates synthesis of new vitamin K-dependent clotting factors, which can take longer than 24 h. Other nonspecific agents, including recombinant activated factor VII, three- and four-factor prothrombin complex concentrates (PCC), and activated PCC or Factor Eight Inhibitor Bypassing Activity (FEIBA®), are options based on clinical need. Specific agents to quickly reverse the effects of DOACs have been under development, and idarucizumab, a monoclonal antibody fragment that rapidly binds dabigatran, has been approved for clinical use in cases of dabigatran-related life-threatening bleeding, or if a dabigatran-treated patient needs emergency surgery or an invasive procedure. Idarucizumab specifically and rapidly reverses dabigatran-induced anticoagulation as measured by established coagulation assays. However, this does not guarantee complete hemostasis, especially if a patient has underlying comorbidities such as renal or liver disease, or has experienced recent trauma that requires urgent surgery. In these cases, concomitant supportive therapy and/or administration of concentrated clotting factors may be considered. Emerging data from ongoing trials and clinical experience will further inform providers regarding optimal approaches for anticoagulation reversal.
a Department of Pharmaceutical Services , University of California, Davis Medical Center , Sacramento , CA , US.
William E
WE
Dager
b Department of Clinical Sciences , Touro University California, College of Pharmacy , Vallejo , CA , US.
Linda
L
Banares
D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000925:Anticoagulants / Q000009:adverse effects*; D000991:Antithrombins / Q000009:adverse effects*; D001777:Blood Coagulation / Q000187:drug effects*; D001779:Blood Coagulation Factors / Q000494:pharmacology / Q000627:therapeutic use; D001780:Blood Coagulation Tests / Q000379:methods / Q000592:standards; D000069604:Dabigatran / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D006470:Hemorrhage / Q000139:chemically induced / Q000188:drug therapy; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D006435:Renal Dialysis / Q000379:methods; D057832:Watchful Waiting
D061067:Antibodies, Monoclonal, Humanized; D000925:Anticoagulants; D000991:Antithrombins; D001779:Blood Coagulation Factors; C000594745:idarucizumab; D000069604:Dabigatran
Apixaban; dabigatran; edoxaban; idarucizumab; prothrombin complex concentrates (PCC); rivaroxaban