Andexanet Alfa-Induced Heparin Resistance During Percutaneous Coronary Intervention for ST elevation Myocardial Infarction: A Case Report

Structured Abstract Background Andexanet alfa is a recombinant modified factor Xa decoy protein used to reverse the anticoagulant effects of direct oral factor Xa inhibitors, including apixaban, rivaroxaban, and edoxaban. While effective in controlling life-threatening bleeding, it may induce heparin resistance, which complicates anticoagulation during procedures requiring urgent revascularization. Its potential to cause significant heparin resistance during percutaneous coronary intervention (PCI) has been reported only rarely and remains underrecognized. This phenomenon poses a major therapeutic dilemma when emergent PCI is required, especially in life-threatening settings. Case summary An 82-year-old man on edoxaban for atrial tachycardia presented with a left iliac bone fracture and expanding hematoma. Andexanet alfa was administered to reverse anticoagulation. Shortly thereafter, he developed acute anterior STEMI. Emergency PCI revealed a new occlusion in the proximal left anterior descending artery. Despite receiving 30,000 units of unfractionated heparin, the activated clotting time (ACT) reached only 249 seconds after a 36-minute delay, consistent with heparin resistance. Intra-aortic balloon pumping and veno-arterial extracorporeal membrane oxygenation were required to stabilize hemodynamics. Although revascularization was successfully completed, the patient ultimately died from pneumonia on postoperative day 21. Discussion Although ST-segment elevation myocardial infarction (STEMI) following andexanet alfa administration has been reported, this case underscores the additional challenge of profound heparin resistance compromising timely anticoagulation during emergent PCI. Rapid recognition of andexanet alfa-induced heparin resistance is crucial in urgent PCI settings to ensure effective anticoagulation and prevent procedural delays that may compromise outcomes.