Abstract WP240: Andexanet Alfa versus 4F-PCC for Direct Anticoagulation Reversal in Intracranial Hemorrhage: A Quality Improvement Analysis

Introduction: Use of direct oral anticoagulants for atrial fibrillation and venous thromboembolism can cause intracranial bleeding. While guidelines recommend andexanet alfa for reversing factor Xa inhibitors, its high cost and thrombotic risk have led to off-label use of 4F-PCC, despite limited comparative data. This quality improvement study evaluates the effectiveness of andexanet alfa vs. 4F-PCC for bleeding control in clinical practice. Methods: We conducted a retrospective review (Oct 2020–Oct 2024) of patients who: (1) had a head CT showing acute intracranial hemorrhage, (2) were on a factor Xa inhibitor, and (3) received 4F-PCC or andexanet alfa. Demographics, clinical severity (NIH Stroke Scale [NIHSS], Glasgow Coma Scale [GCS]), hemorrhage features, treatment timing, and discharge outcomes were compared. Hemorrhage volumes were measured using Synapse imaging software. Primary outcomes were absolute and percent hemorrhage volume change, significant hemorrhage growth (>6 mL or >33%), and neurological deterioration (≥2-point GCS decrease or ≥4-point NIHSS increase). Data were analyzed using Wilcoxon Rank Sum and chi-squared tests; mortality was compared using Kaplan-Meier curves. Results: Among 134 eligible patients, 43 received andexanet alfa and 91 received 4F-PCC. Traumatic bleeds accounted for 64% of cases. Common diagnoses included traumatic subdural hemorrhage (n=31), spontaneous intracerebral hemorrhage (n=30), and traumatic multicompartmental hemorrhage (n=28). Mean age was 78 ± 12, baseline GCS was 13 ± 4, and average baseline hemorrhage volume was 43 mL (range: 0.1–284 mL). Age, gender, race, and door-to-needle times did not differ between groups. Andexanet alfa patients had higher NIHSS (20 vs. 13, p=0.004) and lower GCS (10 vs. 11, p=0.019) on admission. Mean absolute and percent hemorrhage volume changes were similar; however, more patients on andexanet alfa had significant hemorrhage growth (42% vs. 23%, p=0.029). Neurological deterioration rates were comparable. Ischemic or thromboembolic complications were similarly low for andexanet alfa (2%) and 4F-PCC (4%). Conclusions: In this real-world analysis, andexanet alfa was linked to a higher risk of significant intracranial hemorrhage growth than 4F-PCC, despite similar rates of neurological deterioration, thromboembolic events, functional disability, and mortality. 4F-PCC may serve as a clinically viable alternative for reversing FXa inhibitor anticoagulation in intracranial hemorrhage.