Four-factor prothrombin complex concentrate dose response relationship with INR for warfarin reversal

Introduction: For reversal of warfarin-induced coagulopathy, FDA labeling of four-factor prothrombin complex concentrate (4F-PCC) endorses a dosing strategy based on body weight and baseline INR. Recent literature suggests lower, fixed doses of 4F-PCC may be equally efficacious. The present evaluation aims to characterize the relationship between 4F-PCC dose and degree of reduction in INR. Methods: This is a retrospective, single-center review of 4F-PCC administrations for warfarin reversal between May 2014 and August 2017. The primary endpoint evaluates the relationship between doses of 4F-PCC and INR measurement after reversal, represented as a linear regression. Exploratory endpoints characterize the relationships of both body weight and baseline INR, the components determining initial 4F-PCC dose, with INR after reversal. Additionally, for records presenting with an INR of 23.9, mean INR after reversal was characterized as a function of two 4F-PCC dose cohorts (< 30 and >= 30 IU fIX/kg). Results: A significant linear relationship between 4F-PCC dose and INR after reversal (INR after 4F-PCC = 1.3651-0.00004(4F-PCC Dose), p = 0.0071, R-2 = 0.0630) was observed. Body weight and baseline INR were not correlated with INR after reversal. The subgroup analysis of records with presenting INR of 23.9 demonstrated no difference in mean INR after reversal with 4F-PCC for those receiving <30 IU fIX/kg and those receiving >= 30 IU fIX/kg. Conclusion: This evaluation found no clinically relevant relationship with 4F-PCC doses and degree of INR reversal. Further prospective study is required to determine optimal dosing schemes of 4F-PCC for warfarin reversal. (C) 2019 Elsevier Inc. All rights resented.