Evaluation of fixed-dose versus variable-dose prothrombin complex concentrate for warfarin reversal

Abstract

Introduction: The purpose was to compare hemostatic efficacy rates for fixed- and variable-dose four-factor prothrombin complex concentrate (4F-PCC) for warfarin reversal.

Material and methods: Retrospective study of patients with non-intracranial major bleeding or undergoing emergent surgery/procedure who received 4F-PCC for warfarin reversal from September 2013 through August 2020. Hemostatic efficacy at 48 h following fixed- or variable-dose 4F-PCC was evaluated using modified International Society on Thrombosis and Hemostasis (ISTH) criteria for major bleeding. Secondary outcomes included occurrence of post-4F-PCC INR ≤ 1.5, in-hospital mortality, time to 4F-PCC administration, and 4F-PCC cost. Univariate analyses were completed and logistic regression used to identify patient-specific factors associated with hemostatic efficacy.

Results: A total of 265 patients, 90 (34%) fixed- and 175 (66%) variable-dose 4F-PCC, were included. Hemostatic efficacy was achieved in 34 (37.8%) and 38 (21.7%) in fixed- and variable-dose groups, respectively, p = 0.005. Achievement of INR ≤ 1.5 occurred in 55 (62.5%) in the fixed- and 120 (69.4%) in the variable-dose groups, p = 0.26, and there was no in-hospital mortality difference. Time to administration was a mean 20 min faster and cost was reduced by a mean $1881/dose in the fixed-dose group. The unadjusted odds of achieving hemostatic efficacy was 2.27 among those receiving fixed-dose compared to variable-dose 4F-PCC (95% CI 1.30, 3.98); this was not confounded by initial INR or patient weight.

Conclusion: Fixed-dose 4F-PCC is associated with a higher likelihood of achieving hemostatic efficacy, quicker time to administration, and reduced cost compared to variable-dose 4F-PCC for warfarin reversal.

Keywords: Blood coagulation factors; Factor IX; Hemostasis; Prothrombin complex concentrates; Warfarin.