Neurocritical Care

, Volume 25, Issue 3, pp 359–364 | Cite as

Safety and Efficacy of Warfarin Reversal with Four-Factor Prothrombin Complex Concentrate for Subtherapeutic INR in Intracerebral Hemorrhage

  • Ryan M. Rivosecchi
  • Joseph Durkin
  • David O. Okonkwo
  • Bradley J. Molyneaux
Original Article



The use of vitamin K antagonists is an independent risk factor for the development of intracerebral hemorrhage (ICH). Four-factor prothrombin complex concentrate (4F-PCC) is recommended for urgent reversal of anticoagulation in this setting. The safety and efficacy of 4F-PCC in ICH with subtherapeutic levels of anticoagulation is yet to be determined.


This was a retrospective, observational study of 4F-PCC administration data from September 2013 to July 2015. Patients with spontaneous or traumatic ICH with initial INR 1.4–1.9 were compared to those with INR 2–3.9. A Fisher’s exact test was used to compare the difference between the two groups in the effectiveness of 4F-PCC in reversing the INR to ≤1.3 and in the occurrence of thrombotic events within 7 days of administration.


A total of 131 patients with a presenting INR between 1.4 and 3.9 received 4F-PCC during the study period. Twenty-three of 29 patients (79 %) in the INR <2 group achieved an INR reduction to ≤1.3 after 4F-PCC administration compared to 47 of 92 patients (51 %) in the INR 2–4 group, p = 0.03. There was no difference in thrombotic complications within 7 days after administration (6.7 % in INR 1.4–1.9 group, 10 % in INR 2–3.9 group, p = 0.73).


The use of 4F-PCC in patients with INR between 1.4 and 1.9 results in an effective reduction in INR with similar thrombotic risks compared to patients presenting with an INR of 2–3.9.


Prothrombin complex concentrates Cerebral hemorrhage Vitamin K antagonist Anticoagulants 


Compliance with ethical standards

Conflicts of Interest

The authors declare that they have no conflict of interest.

Ethical approval

For this type of study formal consent is not required.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Ryan M. Rivosecchi
    • 1
  • Joseph Durkin
    • 1
  • David O. Okonkwo
    • 2
  • Bradley J. Molyneaux
    • 3
  1. 1.Department of PharmacyUPMC Presbyterian HospitalPittsburghUSA
  2. 2.Department of Neurologic SurgeryUniversity of PittsburghPittsburghUSA
  3. 3.Departments of Neurology and Critical Care MedicineUniversity of PittsburghPittsburghUSA

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