Prospective Evaluation of a Fixed-Dose 4-Factor Prothrombin Complex Concentrate Protocol for Urgent Vitamin K Antagonist Reversal.

Background: Four-factor prothrombin complex concentrate (4F-PCC) is the standard of care for reversal of vitamin K antagonists (VKAs). Research has demonstrated noninferior efficacy with the use of lower, fixed-dose strategies for 4F-PCC dosing.

Objectives: We compared a fixed-dose 4F-PCC protocol to weight-based dosing at our institution.

Methods: This was a multicenter, noninferiority, interventional, quasiexperimental cohort study including subjects who were administered 4F-PCC for VKA reversal. The retrospective cohort consisted of subjects given a weight-based dose of 4F-PCC dependent on international normalized ratio (INR). The prospective cohort was managed with a fixed-dose protocol. The fixed dose was 1500 units of factor IX unless subjects weighed >100 kg or had a baseline INR >7.5, in which case the dose was 2000 units of factor IX. The primary endpoint was achievement of a postinfusion INR of <2. Secondary endpoints included achievement postinfusion INR <1.5, mean 24-h INR, 7-day mortality, and 7-day venous thromboembolic events.

Results: Twenty-four subjects were enrolled in the prospective cohort and 30 in the retrospective cohort. A postinfusion INR <2 was achieved in 96% of subjects in the retrospective cohort and 95% in the prospective cohort (p = 0.0035 for noninferiority). A postinfusion INR <1.5 occurred in 90% of subjects in the retrospective cohort and 75% in the prospective cohort (p > 0.4 for noninferiority). There were no significant differences in 24-h postinfusion INRs, mortality, or venous thromboembolic events.

Conclusion: The use of a fixed-dose 4F-PCC protocol is safe and effective for the rapid reversal of VKA-associated anticoagulation.