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

Thromb Haemost. 2020 Feb;120(2):207-215. doi: 10.1055/s-0039-3400958. Epub 2019 Dec 14.


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.

Publication types

  • Comparative Study
  • Multicenter Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anticoagulants / adverse effects
  • Blood Coagulation Factors / administration & dosage*
  • Electronic Health Records
  • Emergency Service, Hospital
  • Female
  • Hemorrhage / chemically induced*
  • Hemorrhage / drug therapy*
  • Humans
  • Intensive Care Units
  • International Normalized Ratio
  • Length of Stay
  • Male
  • Middle Aged
  • Retrospective Studies
  • Thrombosis / drug therapy
  • Thrombosis / prevention & control
  • Warfarin / adverse effects*


  • Anticoagulants
  • Blood Coagulation Factors
  • prothrombin complex concentrates
  • Warfarin