(460) Fixed-Dose Four-Factor Prothrombin Complex Concentrate in Warfarin and Factor Xa Inhibitor Reversal

Introduction: Controversy exists regarding variable and fixed-dose (FD) of 4F-PCC in the reversal of warfarin and factor Xa (fXa) inhibitors. The 2020 American College of Cardiology (ACC) Expert Consensus recommends either variable or fixed dosing with warfarin reversal yet provides no guidance on preferred dose calculations or target INRs. With fXa inhibitor reversal, ACC recommends andexanet alfa, but due to cost limitations, FD of 4F-PCC 2,000 units is provided as an alternative. Despite this, studies have yielded conflicting results. To address current knowledge gaps, this study aimed to evaluate the efficacy and safety of current institutional FD 4F-PCC dosing protocols with warfarin and evaluate the possibility of switching from variable to FD for fXa inhibitor reversal.

Methods: This retrospective observational study identified patients from three hospitals who were administered 4F-PCC from January 2021 to December 2021. Electronic health records were used to collect baseline demographics, achievement of effective hemostasis as defined by the International Society on Thrombosis and Hemostasis (ISTH), thrombotic complications, and all-cause mortality. Data on efficacy and safety outcomes for warfarin and fXa inhibitor reversal were analyzed using descriptive statistics.

Results: Of 133 patients screened, 96 patients were eligible for inclusion, of which 41 were in the warfarin reversal cohort and 55 in the fXa inhibitor reversal cohort. The most prevalent indication for 4F-PCC was gastrointestinal bleeds. The median dose of 4F-PCC administered was 2,000 units for warfarin and 3,500 units for fXa inhibitors. Hemostatic efficacy was achieved by 59% in the warfarin group. 63% reached an INR goal < 1.5, increasing to 83% with a target INR < 2.0. With fXa inhibitor reversal, 58% achieved effective hemostasis. Adverse outcomes consisted of a single thrombotic event and 15 total mortalities.

Conclusions: The majority of patients had good clinical outcomes after 4F-PCC administration despite lower than anticipated rates of hemostatic efficacy. Utilizing FD 4F-PCC in warfarin reversal achieved predicted rates of INR goal achievement. For fXa inhibitor reversal, the hospital system concluded that further studies were needed before a switch to fixed dosing could be supported.