Fixed-Dose Four-Factor Prothrombin Complex Concentrate for Reversal of Anticoagulation: Evaluation of Efficacy, Safety, and Cost Savings

Abstract

Background: Four-factor prothrombin complex concentrate (4F-PCC) is used for warfarin reversal and off-label management of bleeding in patients taking direct oral anticoagulants (DOACs). Dosing strategies that optimize hemostatic efficacy and cost, such as fixed dosing of 4F-PCC, are still under evaluation. The objective of this study was to retrospectively evaluate the efficacy, safety, and cost savings of fixed-dosing of 4F-PCC (1,500 IU for warfarin, 2,000 IU for DOACs).

Methods: Patients records from October 1, 2018, to April 30, 2021, at three hospitals within the Froedtert Health System were retrospectively reviewed for individuals who received fixed-dosing of 4F-PCC. Safety and efficacy were reflected in 30-day bleeding and thrombosis events, the need for repeat doses, and all-cause mortality. Cost savings were defined as the difference in the cost between the administration of fixed-dosing and the projected weight- and international normalized ratio (INR)-based dosing based on the package insert for warfarin reversal or 50 IU/kg in patients treated with DOACs.

Results: A total of 592 patients received fixed-dosing of 4F-PCC during the prespecified period, of whom 541 received it for warfarin reversal (n = 414) or DOACs (n = 127) management in emergency settings. INR below 2 was achieved in 89% of patients on warfarin. Less than 5% in either group required repeat doses of 4F-PCC. Within 30 days, both groups had similar bleeding (12%) and thrombotic (5%) events. All-cause 30-day mortality rates in patients treated with warfarin and DOACs were 24% and 30%, respectively. The median cost savings of fixed-dosing per patient on warfarin and DOACs were $1,567 and $3,936, respectively, with annualized median hospital cost savings of $176,239 and $146,733, respectively.

Conclusions: Fixed-dosing of 4F-PCC had significantly less cost than adjusted dose and is associated with similar rates of thrombosis and death compared to other studies.