Apixaban-Associated Intracranial Hemorrhage in a Patient With Elevated International Normalized Ratio

Area of Science:

• Pharmacology
• Neurology
• Cardiology

Background:

• Apixaban, an oral anticoagulant, can elevate the international normalized ratio (INR), but the clinical significance of these elevations is not well-defined.
• Elevations in INR are common due to assay interactions and do not always indicate a need for concern, though closer monitoring may be necessary in high-risk patients.

Observation:

• An 82-year-old woman with atrial fibrillation and prior strokes was treated with apixaban post-mechanical thrombectomy for a left M1 occlusion.
• She developed elevated INR, a significant increase in apixaban peak levels, and new intracranial hemorrhage despite vitamin K administration.
• The patient experienced neurological decline and ultimately expired following apixaban reversal with andexanet alfa.

Findings:

• This case demonstrates a fatal intracranial hemorrhage in a patient receiving apixaban, associated with supratherapeutic drug levels.
• The prothrombin time assay interaction with apixaban can lead to common INR elevations, complicating therapeutic drug monitoring.
• The lack of readily available therapeutic drug monitoring for oral anti-factor Xa inhibitors poses a challenge in managing high-risk medications.

Implications:

• Highlights the critical need for effective therapeutic drug monitoring strategies for oral anti-factor Xa inhibitors.
• Underscores the potential risks associated with apixaban in patients with specific risk factors, necessitating vigilant management.
• Emphasizes the challenges in balancing anticoagulation efficacy with bleeding risk, particularly in complex neurological cases.