Comparing Branded 4-Factor Prothrombin Complex Concentrates for Reversal in Intracranial Bleeding

Introduction: In 2023 the FDA approved Balfaxar® (4FPCC-lans; Octaplex® in Europe since 2003) as a second US 4FPCC product to Kcentra® (4FPCC). The products are similar but vary in factor composition and heparin dose. The only published comparative data comes from the FDA approval trial that studied surgical bleeding; hemostatic efficacy for intracranial bleeding was not assessed, and reversal was limited to vitamin K antagonists. Our study aims to compare the hemostatic efficacy and clinical outcomes of two different 4FPCC products in intracranial bleeding.


Methods: This single-center retrospective cohort included patients who received a 4FPCC product from June 2023 to May 2025 for intracranial bleeding. Patients were grouped into cohorts based on product received: 4FPCC or 4FPCC-lans. The primary outcome was hemostatic efficacy as defined by hematoma expansion (HE) on follow-up imaging within 24 hours. Secondary outcomes included rate of thrombotic events (TE) and changes in modified Rankin Scale (mRS) score from baseline to discharge. Descriptive statistics with median and IQR or count and percentages were used. Categorical variables were analyzed with Fisher’s exact or Chi-square test as appropriate, and continuous variables were analyzed with Mann-Whitney U. Alpha was set at 0.05.


Results: A total of 87 patients were included, with 35 and 52 patients given 4FPCC and 4FPCC-lans, respectively. Patients were mostly males aged 74-76 years with a baseline mRS of 0-1. Median initial NIHSS scores were 3.5 (IQR 1-14) in the 4FPCC group vs 10 (IQR 4-22) in the 4FPCC-lans group (p=0.02). Apixaban was the most reversed agent, and the most common site of bleeding was intracerebral hemorrhage. HE was experienced in 26% of 4FPCC vs 8% of 4FPCC-lans patients (p=0.03). TE occurred in 14% of 4FPCC and 21% of 4FPCC-lans patients (p=0.47). For those with a documented baseline mRS and discharge mRS, the change from baseline was 2 (IQR 1-4) vs 3 (IQR 2-5) in the 4FPCC and 4FPCC-lans groups respectively (p=0.21).


Conclusions: 4FPCC-lans resulted in improved hemostatic efficacy as evidenced by lower rates of HE with no differences in TE or change in mRS scores when compared to 4FPCC in intracranial bleeding. Larger prospective trials are needed to confirm these results.