(463) Clinical Efficacy of Fixed-Dose Prothrombin Complex Concentrate for Anticoagulant Reversal

Introduction: Four-factor prothrombin complex concentrate (4F-PCC) contains vitamin K-dependent clotting factors and is approved for urgent reversal of warfarin-induced factor deficiency. However, it is often used off-label for life-threatening hemorrhages associated with factor Xa inhibitors apixaban and rivaroxaban. Manufacturer and guideline recommended dosing strategies vary between 25 - 50 units/kg (maximum of 2500 - 5000 units, respectively). However, high drug costs and thrombotic risk have resulted in newer studies evaluating the efficacy of lower doses.

Methods: This is a retrospective analysis of patients who received 4F-PCC between August 1, 2020 and August 1, 2022 for an active hemorrhage while on apixaban, rivaroxaban, or warfarin. In 2021, our institution implemented a protocol limiting the dose to 2,000 units; thus, this study aims to assess clinical outcomes between the antecedent weight-based protocol and the newer fixed dose protocol. The primary outcome was the number of patients who required a repeat dose within 12 hours due to inadequate hemostasis. Secondary outcomes included expansion of intracerebral hemorrhage (ICH) and in-hospital mortality.

Results: Twenty six of 57 patients received weight-based 4F-PCC and the remaining 31 patients received fixed doses, most commonly for ICH. Of the 26 patients in the weight-based group, 2 received a repeat dose for ongoing bleeding (7.7%). Two of the 31 patients (6.5%) in the fixed dose group also received a second dose (p=1.00). There was no significant difference between groups in hemorrhagic expansion or in-hospital mortality. Patients in the fixed dose group received an average of 2,114 units (25.4 units/kg) of 4F-PCC as compared to 2,794 units (32.9 units/kg) in the weight-based group (p < 0.0001). Using wholesale costs, this is an estimated cost difference of $2,000 per patient.

Conclusions: Administration of fixed dose 4F-PCC did not increase the need for repeat doses nor increase mortality. To minimize cost and reduce the potential for thrombosis while maintaining efficacy, fixed dose 4F-PCC should be considered in the reversal of apixaban, rivaroxaban, and warfarin for clinically significant bleeding.