Reversal of novel oral anticoagulants in patients with major bleeding.

Novel oral anticoagulants (NOACs) that directly inhibit thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban, edoxaban) are effective therapies for the prevention and treatment of thromboembolism with reduced bleeding complications compared with warfarin for some indications. However, specific antidotes to reverse the anticoagulant activity of NOACs in the event of major bleeding are not available. Evidence supporting non-specific prohemostatic therapies (prothrombin complex concentrate [PCC], activated prothrombin complex concentrate [aPCC], recombinant factor VIIa) in this setting is limited to healthy human volunteers, animal models, and in vitro studies. Clinical outcome data are lacking. Administration of PCC or aPCC may be considered in addition to supportive measures for patients with severe or life-threatening bleeding. Clinical studies are needed to establish the efficacy and safety of these treatments. Target-specific antidotes are in development and hold promise for NOAC reversal, but require further investigation.