Current State of Knowledge on Oral Anticoagulant Reversal Using Procoagulant Factors

Abstract

To discuss current trends and challenges in the use of procoagulants for treating bleeding caused by use of oral anticoagulants. Literature searches of PubMed (MEDLINE), Google, and Medscape were conducted in February 2013. There were no date limitations. Search terms included anticoagulation agents, anticoagulation reversal, anticoagulation reversal agents, apixaban, clinical studies, dabigatran, 3-factor PCCs, 4-factor PCCs, FEIBA, fresh frozen plasma, human studies, pharmacology, prescribing information, rFVIIa, rivaroxaban, vitamin K, and warfarin. Warfarin has been the mainstay for the treatment and prevention of primary and secondary thrombosis in patients with cardiovascular dis orders such as atrial fibrillation, deep vein thrombosis, pulmonary embolism, and stroke. Three oral anticoagulants have recently become available in the US: a direct thrombin inhibitor, dabigatran etexilate, and 2 direct factor Xa inhibitors, rivaroxaban and apixaban. Reversal strategies for anticoagulant-associated bleeding are well established for warfarin; however, strategies to stop bleeding in a patient who has taken one of the newer anticoagulants are less clear. In the US, agents available for oral anticoagulant reversal include activated prothrombin complex concentrate (APCC), 3-factor PCCs, and recombinant activated factor VII (rFVIIa). Few studies have evaluated the 3-factor PCCs, and current evidence for APCC and rFVIIa as reversal agents for dabigatran and rivaroxaban is based primarily on laboratory or animal studies, or on small studies in healthy humans and case reports. Patients contemplating using the new oral anticoagulants should be informed about specific clinical situations that could pose a bleeding risk such as the need for emergency surgery because no reliable antidote is available to stop the bleeding, which could prove fatal.