4-Factor Prothrombin Complex Concentrate Dosing Strategies: A Retrospective Evaluation

Abstract

Objectives Determine indication specific 4-Factor prothrombin complex concentrate (4FPCC) dosing strategies within a hospital system and subsequent effectiveness. Background: 4FPCC is FDA approved for reversal of vitamin K antagonists (VKA) for acute major bleeding or need for urgent surgery/invasive procedure. Since its approval, off label use has expanded to include direct oral anticoagulant reversal and perioperative hemostasis. Optimal dosing strategies remain controversial, and recent studies have evaluated fixed-dose regimens with lower doses than those recommended in product labeling. Methods/Materials: Retrospective cohort with manual chart review for patients who received 4FPCC spanning 2 years. Primary outcome was to characterize dosing. Secondary outcomes were INR normalization, hemostatic efficacy, in-hospital mortality, and renal function change. Results: Of the 300 patients evaluated, 80% received 4FPCC for anticoagulant reversal, with 66% of those for VKA and 34% for DOAC. The remaining 20% received 4FPCC for a non-reversal indication. Of the patients requiring anticoagulation reversal, 25% received doses lower than recommended and 6% received higher. 71% of patients received 4FPCC for life-threatening bleed, and 45% of them had intracranial hemorrhage. Higher mortality with higher than recommended doses was the only statistically significant secondary outcome ( P = .018). Conclusion: We found that lower doses than recommended were used in a significant number of patients. The higher than recommended doses group constituted a small proportion of patients and the higher mortality was attributed to patient acuity on presentation. Additional studies evaluating dosing approach are required to determine lowest effective dosing for various indications.