Evaluation of a Fixed-Dose Regimen of 4-Factor Prothrombin Complex Concentrate for Warfarin Reversal

Background: Fixed-dose (FD) regimens of 4-factor prothrombin complex concentrate (4F-PCC) may be effective for the emergent reversal of warfarin; however, the optimal dosing is unknown. Our institution transitioned to a FD regimen of 1000 or 2000 units of 4F-PCC based on indication. Objective: The purpose of this study is to report our experience with FD 4F-PCC compared with a historical weight-based dosing cohort for warfarin reversal. Methods: A retrospective analysis was conducted for 3 groups: central nervous system (CNS) bleeds regardless of international normalized ratio (INR), non-CNS bleeds with an initial INR <= 6, and non-CNS bleeds with an initial INR >= 6.1. The primary outcome of the study was achievement of the target INR. Results: There were 54 patients with a CNS bleed, 153 with a non-CNS bleed and INR <= 6, and 19 with a non-CNS bleed and INR >= 6.1. In the CNS bleeding group, weight-based and FD achieved target INR 79.4% and 70% (P = 0.52). In the INR >= 6.1 non-CNS bleeding group, weight-based and FD achieved target INR 100% and 70% (P = 0.21). In the INR <= 6 non-CNS bleeding group, weight-based and FD achieved target INR 86.4% and 57.5% (P = 0.0002). Conclusion and Relevance: An FD strategy of 2000 units for warfarin reversal for CNS bleeds or INR >= 6.1 was comparable to weight-based dosing. The FD strategy of 1000 units for INR <= 6 achieved target INR less often than weight-based dosing. Application of findings suggest that higher doses may be needed to achieve target INR.