Spontaneous Pleural, Pericardial, and Intracranial Hemorrhages in a Patient with End-Stage Kidney Disease Receiving Apixaban: A Case Report

BACKGROUND Apixaban, the direct oral anticoagulant (DOAC) with the lowest renal clearance (~27%), is often preferred for stroke prevention in non-valvular atrial fibrillation (NVAF) among patients with kidney impairment. According to U.S. prescribing information, a dose of 5 mg twice daily is permitted in patients with severe kidney disease, unless they are aged ≥80 years or weigh ≤60 kg. However, in severe chronic kidney disease (CKD) or end-stage kidney disease (ESKD), even limited renal excretion can result in elevated drug levels and bleeding. Apixaban-related bleeding most commonly occurs in the gastrointestinal tract, but rare events such as pleural or pericardial effusions can also develop and may precede intracranial hemorrhage. CASE REPORT We describe a 73-year-old man with NVAF and stage 3b CKD who presented with progressive dyspnea and chest pain. Renal function had declined significantly from baseline. Imaging revealed large bilateral hemorrhagic pleural effusions and a concurrent pericardial effusion; both improved following apixaban discontinuation and therapeutic thoracentesis. During hospitalization, he was diagnosed with ESKD (CKD G5D), defined by a glomerular filtration rate <15 mL/min/1.73 m² and the initiation of dialysis. Despite this, apixaban was restarted in a nursing facility, after which he developed an intracranial hemorrhage. His condition deteriorated despite aggressive management, and he subsequently died. CONCLUSIONS This report emphasizes vigilant monitoring for rare but serious hemorrhagic complications of apixaban. Such bleeding may involve uncommon sites like the pleura, pericardium, or intracranial space, especially in patients with severe kidney disease, despite guideline-based dosing.