Reversal Agents for Oral Antiplatelet and Anticoagulant Treatment During Bleeding Events: Current Strategies

Abstract

There is an increasing prevalence of cardiovascular diseases that warrant antithrombotic therapy. Antithrombotic therapy includes antiplatelet agents and anticoagulation therapy with vitamin K antagonists (VKAs) or non-Vitamin K oral anticoagulants (NOACs). Antithrombotic therapy is associated with increased rates of bleeding. In this review we summarize the evidence and provide strategies for the management of severe bleeding in the setting of antithrombotic therapy. There is limited data on the management of bleeding in the setting of antiplatelet therapy. We recommend discontinuation of the antiplatelet, as well as administration of platelet transfusions and desmopressin only in the setting of life-threatening bleeding. For patients presenting with severe bleeding in the setting of VKAs, we recommend discontinuation of VKA and prompt administration of 10 mg intravenous vitamin K plus 50 units/kg 4-factor prothrombin complex concentrate (PCC). If 4-factor PCC is not available 3-factor PCC or fresh frozen plasma (FFP) can be used, but these are inferior to 4-factor PCC. For patients presenting with severe bleeding while on dabigatran, we recommend discontinuation of dabigatran and intravenous administration of 5g idarucizumab. There is currently no available reversal agent for factor Xa inhibitors. Andexanet alpha is a factor Xa-specific inhibitor that is currently undergoing FDA review. Until andexanet alpha becomes available we recommend discontinuation of the factor Xa inhibitor and administration of 50 units/kg 4- factor PCC. The decision to discontinue and/or reverse antithrombotic therapy should be made on a case-by-case basis and the competing risk from discontinuation and/or reversal of antithrombotic therapy should be taken into consideration.

Keywords: Antiplatelets; andexanet alfa; anticoagulants; antidotes; aripazine; idarucizumab; non-vitamin K oral anticoagulants; reversal; warfarin.