High Versus Low 4F-PCC Dosing in Factor Xa Inhibitor-Associated Intracerebral Hemorrhage

Introduction: Four-factor prothrombin complex concentrate (4F-PCC) is used off-label for factor Xa inhibitor (FXaI)-associated life-threatening hemorrhages. The American Stroke Association Intracerebral Hemorrhage (ICH) 2022 Guidelines consider 4F-PCC use in FXaI-associated ICH but do not specify a dose. Several studies have demonstrated similar efficacy and cost savings with low-dose 4F-PCC (25 units/kg) compared to high-dose 4F-PCC (50 units/kg), regardless of bleed location. The purpose of this study was to determine if there was a difference in hemostatic effectiveness between 25 units/kg versus 50 units/kg of 4F-PCC in FXaI reversal in ICH.


Methods: This was a single-center, retrospective cohort study of adult patients who received 4F-PCC in the emergency department for reversal of FXaI-related ICH from February 1, 2020, to January 10, 2025. The primary outcome evaluated the hemostatic effectiveness within 24 hours of 4F-PCC administration, determined by improvement or worsening of hematoma size based on radiologist impression of computed tomography imaging. Secondary outcomes included the cumulative incidence of thromboembolic events (e.g., deep vein thrombosis, ischemic stroke) occurring 30 days after 4F-PCC, hospital mortality, hospital length of stay, average blood pressure within goal (defined as a systolic less than 140 mmHg, 24 hours-post 4F-PCC), and cost of dose.


Results: A total of 120 adult patients who received 4F-PCC for FXaI-associated ICH were included in the analysis. Hemostasis was evaluated in 113 patients with 24-hour post-4PCC imaging available. Hemostatic efficacy at 24 hours (92% vs. 86%; p=0.50) and 30-day thromboembolic events (5.4% vs. 7.2%; p=0.64) were similar between low- and high-dose groups. There was a higher incidence of in-hospital mortality among the high-dose group compared to the low-dose group (8.1% vs. 24.1%, p=0.04). However, patients in the high-dose group were noted to have more severe injuries upon presentation. The cost per dose was notably higher in the high-dose group ($4,842.41 vs. $8,156.02).


Conclusions: The findings of this study add to existing literature supporting a 25 units/kg dose as an effective alternative to 50 units/kg 4F-PCC dosing and provides cost savings for the reversal of FXaI in ICH.