Alyssa Lear, PharmD,
Critical Care Pharmacist
Carolinas Medical Center
Charlotte, North Carolina
Disclosure information not submitted.
Carolyn Pfeifer, PharmD, BCCCP
Pharmacist
Medical University of South Carolina, United States
Disclosure information not submitted.
Melanie Condeni, BCCCP, BCPS, PharmD
Pharmacist
MUSC Health of Medical University of South Carolina
Charleston, SC, United States
Disclosure information not submitted.
Title: Fixed vs Variable Dose Four Factor Prothrombin Complex Concentrate for Emergent Warfarin Reversal
INTRODUCTION/HYPOTHESIS: Four-factor prothrombin complex concentrate (4F-PCC) is FDA approved for emergent warfarin reversal with a dose based on patient weight and international normalized ratio (INR), however, the optimal approach to dosing is uncertain. The aim of this study was to compare clinical outcomes and evaluate the cost savings of a fixed dose (FD) 4F-PCC protocol compared to the FDA approved weight based (WB) dosing strategy for warfarin reversal.
Methods: This was a retrospective cohort study of adult patients on warfarin who received 4F-PCC during hospitalization. Patients included from 2014 to 2018 received the WB dose of 4F-PCC and those from 2019 to 2021 received a FD protocol (1500 units for intracranial hemorrhage, 1000 units for other major bleeding, with additional 500 units for INR ≥ 7 or weight ≥100 kg). The primary outcome was post-reversal INR. Secondary outcomes included achievement of hemostasis, development of new thromboembolic events during admission, and 4F-PCC cost.
Results: One hundred sixty-one patients met inclusion criteria with 137 patients in the WB group and 24 in the FD group. Baseline characteristics were similar, and intracranial hemorrhage was the most common indication for reversal between the two groups (42.6% WB and 50% FD). The median (IQR) INR prior to 4F-PCC administration was 2.70 (2.14-4.41) WB vs 2.55 (2.12-4.37) FD, p=0.827. The median (IQR) post-administration INR was no different between groups, WB 1.31 (1.18-1.55) vs FD 1.43 (1.26-1.73), p=0.813. More patients in the FD group achieved excellent hemostasis by Sarode criteria (41.6% vs 66.7%, p=0.057). There was no difference in rate of thrombotic events between groups (5.1% WB vs 16.6% FD). The median (IQR) dose of 4F-PCC in the WB group was 2280 IU (2000-2630) and 1500 IU (1091-1617.25) in the FD group (p=0.833). The median (IQR) cost of 4F-PCC per patient was less in the FD group $3071.28 ($2181.22-3204.50) compared to the WB group $4270.76 ($3820.00-5286.88) (p = 0.035).
Conclusions: The FD 4F-PCC protocol resulted in no difference in the post-reversal INR and similar clinical outcomes compared to the WB dosing strategy. A FD of 4F-PCC for warfarin reversal strategy may be an opportunity for cost savings with equal clinical efficacy and safety.