Emergent Warfarin Reversal With Fixed-Dose 4-Factor Prothrombin Complex Concentrate

Background: Four-factor prothrombin complex concentrate (4FPCC) is used for emergent warfarin reversal, but dosing remains controversial. Following approval, further studies have evaluated a variety of fixed-dose regimens. The studies utilized lower doses as compared with package insert dosing and provided data in regard to efficacy, safety, and cost savings. Further data are needed, however, to determine which fixed-dose regimen provides optimal efficacy and safety for emergent warfarin reversal. Objectives: The purpose of this study is to evaluate the efficacy, safety, and cost-savings of a fixed-dose 4FPCC protocol. Methods: This multicentered, retrospective chart review of adult patients requiring 4FPCC for emergent warfarin reversal utilized a fixed-dose regimen of 1500 units. The 2 primary outcomes were the proportion of patients who achieved a post-4FPCC international normalized ratio (INR) of ≤1.5 and ≤2. Secondary outcomes included thrombotic events within 7 days of 4FPCC administration and survival to discharge. A cost analysis was also performed to identify potential cost savings. Results: Of the 64 patients included, 44 (68.8%) achieved a post-4FPCC INR ≤1.5, and 61 (95.3%) achieved a post-4FPCC INR ≤2.0. No thrombotic events were reported; 55 (85.9%) patients survived to hospital discharge. More than $1000 was saved per patient via utilization of the fixed-dose protocol. Conclusion and Relevance: A fixed-dose of 1500 units of 4FPCC successfully achieved a target INR of ≤1.5 in the majority of patients and resulted in no thrombotic events. This study adds to the data evaluating alternative 4FPCC dosing regimens in comparison to package insert recommended dosing.