Pharmacy and Wellness Review
Abstract
The coagulation cascade comprises intrinsic, extrinsic, and common pathways that converge when thrombin converts fibrinogen (factor I) into fibrin, leading to fibrin mesh formation, stabilization of the platelet plug, and ultimately thrombus formation. Inhibition of the coagulation cascade can be achieved with a variety of anticoagulant medications, including direct oral anticoagulants (DOACs). The mechanism of action of DOACs is to inhibit either factor Xa or thrombin. Reversal of anticoagulation remains an important clinical consideration when managing patients on DOACs who experience serious bleeding events. Andexanet alfa is a recombinant, modified human factor Xa protein previously indicated for patients receiving rivaroxaban or apixaban who required reversal of anticoagulation for life-threatening or uncontrolled bleeding. Andexanet alfa was approved in May 2018 but was withdrawn from the market in December 2025 due to an increased risk of thrombosis. Therefore, management of factor Xa inhibitor-related bleeding increasingly depends on four-factor prothrombin complex concentrates (4F-PCCs) and supportive therapies tailored to patient-specific deficiencies. While andexanet alfa demonstrated slightly higher hemostatic efficacy, 4F-PCCs remain widely used, with comparable outcomes and a lower thrombotic risk.
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