(980) Adverse Outcomes of Andexanet Alfa

Introduction: Andexanet alfa is a recombinant modified factor Xa designed for reversal of anticoagulation from factor Xa inhibitors in cases of life-threatening bleeding. The use of this has been associated with serious complications including ischemic events such as stroke and myocardial infarction. We report a case of multiple simultaneous ischemic events of myocardial infarction and stroke in a patient that received this medication.

Description: A 85-year-old female with a past medical history of atrial fibrillation on apixaban, and breast cancer was evaluated for suspected gastrointestinal bleed. She was found to have a drop in hemoglobin from 14 g/dL (three months ago) to 7 g/dL on admission, and occult blood stool was positive. A tagged red blood cell scan was suggestive of a rectosigmoid colonic bleed. Apixaban reversal was initiated in the intensive care unit using low dose andexanet alfa protocol. The following day, the patient appeared confused and complained of chest discomfort. On physical examination, she was noted to have complete left-sided hemineglect. On further workup Troponin-T trended up to 701 over next 24 hours (negative on admission) with new ST elevation in the inferior leads. Echocardiogram revealed a new finding of decreased ejection fraction of 55% with multiple areas of akinesis. No left ventricular thrombus was seen. MRI brain was remarkable for numerous bilateral acute embolic strokes in medial right temporal and occipital lobes. Patient was found to not be a candidate for intervention by cardiology, while neurology recommended resuming anticoagulation at the earliest as possible. Given the catastrophic events, the patient was made comfort care and passed away the next day.

Discussion: The risks of use of this medication are tremendous. A phase-3b/4 study evaluating this agent in patients with acute life-threatening bleed reported incidence of myocardial infarction and ischemic stroke as 1.9% and 3.9%, respectively. The median time to event in these patients was seven days. Our patient suffered two major events of myocardial infarction and ischemic stroke simultaneously within 24 hours of administration of andexanet alfa. Our case highlights the risks of using this novel medication and to balance these risks by restricting its use to only life-threatening bleeds only.