Thromboembolic Risk of 4-Factor Prothrombin Complex Concentrate versus Fresh Frozen Plasma for Urgent Warfarin Reversal in the Emergency Department

West J Emerg Med. 2019 Jul;20(4):619-625. doi: 10.5811/westjem.2019.4.41649. Epub 2019 Jun 11.


Introduction: Warfarin is a potent anticoagulant used for the prevention and treatment of venous and arterial thrombosis. Occasionally, patients require emergent warfarin reversal due to active bleeding, supratherapeutic international normalized ratio, or emergent diagnostic or therapeutic interventions. Various agents can be used for emergent warfarin reversal, including fresh frozen plasma (FFP) and 4-factor prothrombin complex concentrate (4F-PCC). Both FFP and 4F-PCC are generally considered safe; however, both agents contain coagulation factors and have the potential to provoke a thromboembolic event. Although clinical trials have compared the efficacy and safety of FFP and 4F-PCC, data are limited comparing the risk of thromboembolism between the two agents.

Methods: A retrospective chart review was performed at a single, urban, academic medical center comparing the incidence of thromboembolism with FFP or 4F-PCC for warfarin reversal during a three-year period in the emergency department (ED) at Massachusetts General Hospital. Patients were included in the study if they were at least 18 years of age and were on warfarin per electronic health records. Patients were excluded if they had received both FFP and 4F-PCC during the same visit. The primary outcome was the frequency of thromboembolism within 30 days of 4F-PCC or FFP. Secondary outcomes included time to thromboembolic event and in-hospital mortality.

Results: Three hundred and thirty-six patients met the inclusion criteria. Thromboembolic events within 30 days of therapy occurred in seven patients (2.7%) in the FFP group and 14 patients (17.7%) in the 4F-PCC group (p=<0.001). Death occurred in 39 patients (15.2%) who received FFP and 18 patients (22.8%) who received 4F-PCC (p=0.115). Since the 4F-PCC group was treated disproportionately for central nervous system (CNS) bleeding, a subgroup analysis was performed including patients requiring reversal due to CNS bleeds that received vitamin K. The primary outcome remained statistically significant, occurring in four patients (4.1%) in the FFP group and nine patients (14.1%) in the 4F-PCC group (p=0.02).

Conclusion: Our study found a significantly higher risk of thromboembolic events in patients receiving 4F-PCC compared to FFP for urgent warfarin reversal. This difference remained statistically significant when controlled for CNS bleeds and administration of vitamin K.

MeSH terms

  • Aged
  • Anticoagulants / adverse effects
  • Blood Coagulation Factors / administration & dosage
  • Blood Coagulation Factors / adverse effects*
  • Emergency Service, Hospital
  • Female
  • Humans
  • Male
  • Plasma*
  • Retrospective Studies
  • Thromboembolism / chemically induced*
  • Thromboembolism / epidemiology
  • Warfarin / adverse effects


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