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Anticoagulation reversal — ABIM Board MCQ

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HardHematology/OncologyAnticoagulation reversalABIM Board

A 78-year-old man taking apixaban 5 mg twice daily for atrial fibrillation presents with an acute neurologic deficit 3 hours after his last dose. CT of the head shows a large intracerebral hemorrhage with early hematoma expansion. His estimated glomerular filtration rate is 48 mL/min/1.73 m², and the prothrombin time and activated partial thromboplastin time are normal. Apixaban is discontinued, blood pressure is being controlled, and neurosurgery is involved. Andexanet alfa is not available. Which immediate hemostatic intervention is most appropriate?

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Correct answer: E — Administer intravenous four-factor prothrombin complex concentrate

The correct answer is E. This patient has life-threatening apixaban-associated intracerebral hemorrhage shortly after his last dose, requiring immediate anticoagulant reversal. Normal PT and aPTT do not exclude clinically important apixaban activity. When andexanet alfa is unavailable, four-factor prothrombin complex concentrate is the appropriate hemostatic therapy under AHA/ASA guidance. This is also consistent with current US practice after commercial sales of andexanet alfa ended in December 2025. Vitamin K reverses vitamin K antagonists, not apixaban; protamine reverses unfractionated heparin and only partially reverses low-molecular-weight heparin. Fresh frozen plasma does not provide targeted or reliable reversal of factor Xa inhibitors. Activated charcoal may reduce absorption after a very recent ingestion in an airway-protected patient, but it is not adequate as sole treatment for an expanding intracerebral hemorrhage.

Reference: US Food and Drug Administration. Update on the Safety of Andexxa by AstraZeneca: FDA Safety Communication, December 2025, https://www.fda.gov/safety/medical-product-safety-information/update-safety-andexxa-astrazeneca-fda-safety-communication; Greenberg SM et al. 2022 AHA/ASA Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage, anticoagulant-related hemorrhage section, https://www.heart.org/en/-/media/CPR2-Files/Private/2022-Guideline-for-the-Management-of-Patients-With-Spontaneous-Intracerebral-Hemorrhage-1.pdf