Reversal agents for direct oral anticoagulants: considerations for hospital physicians and intensivists

Abstract

Direct oral anticoagulants (DOACs) include dabigatran etexilate, a direct thrombin inhibitor, and specific inhibitors of activated coagulation factor X (FXa; e.g. apixaban, betrixaban, edoxaban, rivaroxaban). DOACs are associated with lower rates of major and fatal bleeding events compared with warfarin. Clinicians may need to achieve rapid reversal of anticoagulation effects of the DOACs in an emergency setting. Idarucizumab and andexanet alfa, which reverse the anticoagulant effects of dabigatran and FXa inhibitors, respectively, are DOAC reversal agents available in the US. Other reversal agents (e.g. ciraparantag for heparins, DOACs) are in development. Alternative nonspecific agents (e.g. fresh frozen plasma, prothrombin complex concentrate) are available. Nonspecific prohemostatic agents can counteract the anticoagulant action of DOACs in emergency situations, when specific reversal agents are unavailable. However, specific reversal agents are efficacious and safe and should be preferred when available. In this review, we discuss practical issues in the initiation of DOAC therapy, situations where reversal may be needed, coagulation assays, reversal agents, and post-reversal complications in the context of published evidence and guidelines.

Healthcare Resource Utilization for Oral Anticoagulant Reversal Therapies in Non-Valvular Atrial Fibrillation/Venous Thromboembolism Patients

“…Between late-2013 and mid-2019, the ratio was reversed with 77% receiving NOACs and 23% receiving warfarin [ 30 ]. In light of the increased uptake of NOAC use, to the best of our knowledge, there appears to be no literature that has examined HCRU and associated costs in non-specific anticoagulant reversal strategies for warfarin versus dabigatran-reversal by IDA [ 31 , 32 ]. This study presents a unique real-world evidence perspective towards understanding the HCRU and costs in those patients using a geographically diverse, all-payer database.…”

Anticoagulation in COVID-19: current concepts and controversies

“…While idarucizumab and andexanet alfa are two such drugs approved for use in the USA as well as EU, other reversal agents are under development. 14 Fondaparinux was approved for use in the USA in 2001 as an indirect inhibitor of factor Xa, which achieves anticoagulation by binding to and activating antithrombin. 15…”

Pathogenesis and Management in Cerebrovenous Outflow Disorders

“…Anticoagulant therapy functions by halting the growth of existing thrombi, promoting recanalization, and preventing deep vein thrombosis and pulmonary embolism. The new anticoagulants offer the advantages of requiring infrequent blood testing and conferring low risks of thrombus recurrence and bleeding, while their main drawback has historically been the unavailability of antagonists; this has recently changed, however, with the advent of the reversal agents idarucizumab and andexanet alfa [88][89][90][91].…”