Successful Antithrombin Administration in Andexanet Alfa-Associated Heparin Resistance

ANDEXANET ALFA (Ondexxya, Portola Pharmaceuticals, San Francisco, CA) is a modified recombinant inactivated human factor Xa. Although it currently only is approved to reverse the effects of direct factor Xa (FXa) inhibitors, andexanet alfa initially was developed as a reversal agent for direct and indirect FXa inhibitors. The agent acts as a decoy FXa molecule that reversibly binds FXa inhibitors and consequently temporarily inhibits the anticoagulant effects. In vitro studies showed a binding affinity for heparin-bound antithrombin and suggested an inhibitory effect against heparin-induced coagulopathy. Andexanet alfa was approved for use by authorities in the United States and Europe to reverse the effects of rivaroxaban and apixaban in individuals with life-threatening or uncontrolled bleeding after a fast-track approval procedure. Consequently, there is limited clinical experience, especially for cardiovascular surgery, with the concomitant use of cardiopulmonary bypass (CPB). During routine CPB, high-dose unfractionated heparin (UFH) prevents consumptive coagulopathy and the formation of thrombi within the CPB circuit and the patient’s circulation. Prior treatment with andexanet alfa can pose difficulties in achieving adequate anticoagulation during CPB with UFH. The administration of antithrombin, in combination with UFH, may overcome these difficulties.