Roles of Four-Factor Prothrombin Complex Concentrate in the Management of Critical Bleeding

Four-factor prothrombin complex concentrate (4F-PCC) is the term used to describe a pathogen-reduced, lyophilized concentrate that contains therapeutic amounts of at least 4 coagulation factors: Factor II (FII), Factor VII (FVII), Factor IX (FIX), and Factor X (FX). 4F-PCC has proven to be an effective hemostatic agent compared to plasma transfusion in several prospective randomized trials in acute warfarin reversal. In recent years, 4F-PCC has been used in various acquired coagulopathies including post-cardiopulmonary bypass bleeding, trauma-induced coagulopathy, coagulopathy in liver failure, and major bleeding due to anti-FXa (anti-Xa) inhibitors (eg, rivaroxaban and apixaban). As transfusion of frozen plasma (FP) has not been found efficacious in the above critical bleeding scenarios, there is increasing interest in expanding the use of 4F-PCC. However, efficacy, safety, and clinical implications of expanded use of 4F-PCC have not been fully elucidated. Prothrombin time and international normalized ratio are commonly used to assess dose effects of 4F-PCC. Prothrombin time/international normalized ratio are standardly use for warfarin titration, but they are not suited for real-time monitoring of complex coagulopathies. Optimal dosing of 4F-PCC outside of the current approved use for vitamin K antagonist reversal is yet to be determined. In this review, we will discuss the use of 4F-PCC in four critical bleeding settings: cardiac surgery, major trauma, end-stage liver disease, and oral anti-Xa reversal. We will discuss recent studies in each area to explore the dosing, efficacy, and safety of 4F-PCC.