Reversal of Warfarin-Associated Major Hemorrhage: Activated Prothrombin Complex Concentrate versus 4-Factor Prothrombin Complex Concentrate

Abstract

Background Warfarin-associated major hemorrhage is frequently treated with prothrombin complex concentrates to correct international normalized ratio (INR).

Objective This article aims to investigate the efficacy of activated prothrombin complex concentrate (aPCC) versus 4-factor prothrombin complex concentrate (4PCC) for vitamin K antagonist reversal in patients with warfarin-associated major hemorrhage.

Materials and Methods This was a multicenter, retrospective cohort study. Patients included were age ≥ 18 years with pretreatment INR of > 1.5. Exclusion criteria were patients treated for urgent procedures without hemorrhage, treated but not taking warfarin, unavailable INR values, and pregnant patients. Patients were stratified into two groups: aPCC or 4PCC. The primary outcome was achievement of INR ≤ 1.5 at the posttreatment INR sampling. Secondary outcomes focused on thrombotic events and mortality.

Results Of 342 patients, 237 patients received aPCC and 105 patients received 4PCC. After 1:1 propensity score matching, 86 patients remained in each group. In the matched cohort, the proportion of patients who achieved target INR ≤ 1.5 was greater with 4PCC (aPCC = 61 [70.9%] vs. 4PCC = 76 [88.4%]; 95% confidence interval [CI] –29.2% to –5.7%) and groups had comparable in-hospital thrombotic events and mortality. In the unmatched cohort, achievement of target INR ≤ 1.5 was greater with 4PCC (aPCC = 151 [63.7%] vs. 4PCC = 92 [87.6%]; 95% CI –32.7% to –15.1%).

Conclusion In the treatment of warfarin-associated major hemorrhage, 4PCC compared with aPCC was associated with greater achievement of INR ≤ 1.5 with comparable thrombotic events and mortality. Further controlled studies are needed to confirm these findings and determine the optimal dosing strategy that maximizes efficacy and safety.

Keywords

anticoagulants - hemorrhage - prothrombin complex concentrates - warfarin - vitamin K antagonist

Authors' Contributions

G.D.P. and R.K.M. conceived the study idea with input from B.M., N.G.P., and R.T.S. G.D.P., R.K.M., and M.A.R. contributed to the final study design and were responsible for conduct at their respective study sites. J.M.D. and G.D.P. were responsible for data analysis. G.D.P. and R.K.M. drafted the majority of the manuscript with all authors contributing significantly to its revision. G.D.P. takes responsibility for the manuscript as a whole.

Note

This study was presented at the 47th Annual Congress of the Society of Critical Care Medicine, San Antonio, Texas, February 2018. The study was conducted at the following sites:

 1. Rush University Medical Center, Chicago, Illinois, United States (primary site).

 2. Advocate Christ Medical Center and Advocate Children's Hospital, Oak Lawn, Illinois, United States.

 3. Loyola University Medical Center, Maywood, Illinois, United States.

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