High-dose versus low-dose 4-factor prothrombin complex concentrate for factor Xa inhibitor reversal in intracranial hemorrhage.

Background & Purpose: 4-factor prothrombin complex concentrate (4FPCC) is used off-label for factor Xa (FXa) inhibitor-associated intracranial hemorrhage (ICH). Guideline recommendations provide various 4FPCC dosing regimens for FXa inhibitor reversal in this setting. We evaluated 4FPCC weight-based dosing and outcomes in FXa inhibitor-associated ICH.

Methods: We conducted a multi-center, retrospective, cohort study of ICH patients between July 2017 and February 2020. Patients were greater than 18 years of age, received 4FPCC, and were taking apixaban, rivaroxaban, or edoxaban. Patients were separated into high- (≥35 units/kg) or low-dose (<35 units/kg) 4FPCC groups. The primary outcome was hemostasis achievement. Secondary outcomes included in-hospital mortality, intensive care unit and hospital length of stay, discharge disposition, and thrombotic events. Outcomes were evaluated with binary logistic regression.

Results: Of 390 patients identified, 89 were included with 74 and 15 in the high- vs low-dose groups, respectively. Mean (SD) age was 76.6 (±10.8) years. Most were taking a FXa inhibitor for atrial fibrillation (76.4%) and apixaban was the most common FXa inhibitor (65.2%). Hemostasis achievement was greater in the high- vs low-dose group (89.2% vs 46.7%; OR 11.2; 95% CI 2.4-52.6, P = 0.002). Thrombotic events were 8.2% and 6.7% in the high vs low-dose groups, respectively (OR 0.8; 95% CI 0.08-8.2, P = 0.87). No statistically significant differences were found in secondary outcomes.

Conclusion: In patients with FXa inhibitor-associated ICH, high-dose 4FPCC was associated with increased odds of hemostasis achievement. There was no difference in thrombotic events.