Reversal Agents for the Direct Factor Xa Inhibitors: Biochemical Mechanisms of Current and Newly Emerging Therapies

Schreuder, M.; Reitsma, P.H.; Bos, M.H.A. (2020)

Article / Letter to editor

The direct oral anticoagulants targeting coagulation factor Xa or thrombin are widely
used as alternatives to vitamin K antagonists in the management of venous thromboembolism
and nonvalvular atrial fibrillation. In case of bleeding or emergency surgery,
reversal agents are helpful to counteract the anticoagulant therapy and restore
hemostasis. While idarucizumab has been established as an antidote for the direct
thrombin inhibitor dabigatran, reversal strategies for the direct factor Xa inhibitors
have been a focal point in clinical care over the past years. In the absence of specific
reversal agents, the off-label use of (activated) prothrombin complex concentrate and
recombinant factor VIIa have been suggested as effective treatment options during
inhibitor-induced bleeding complications. Meanwhile, several specific reversal agents
have been developed. In this review, an overview of the current state of nonspecific and
specific reversal agents for the direct factor Xa inhibitors is provided, focusing on the
biochemistry and mechanism of action and the preclinical assessment of newly
emerging therapies.

• factor Xa inhibitors
• hemorrhage
• anticoagulants
• antidotes

• All authors: Schreuder, M.; Reitsma, P.H.; Bos, M.H.A.
• Date: 2020-11-01
• Journal: Seminars in Thrombosis and Hemostasis
• Volume: 46
• Issue: 08
• Pages: 986 - 998
• DOI: doi:10.1055/s-0040-1709134