Rapid Warfarin reversal in the setting of intracranial hemorrhage: a comparison of plasma, recombinant activated factor VII, and prothrombin complex concentrate

World Neurosurg. 2014 Jan;81(1):110-5. doi: 10.1016/j.wneu.2012.12.002. Epub 2012 Dec 5.


Objective: To compare the safety and effectiveness of three methods of reversing coagulopathic effects of warfarin in patients with potentially life-threatening intracranial hemorrhage.

Methods: A retrospective electronic medical record review of 63 patients with warfarin-related intracranial hemorrhage between 2007 and 2010 in an integrated health care delivery system was conducted. The three methods of rapid warfarin reversal were fresh-frozen plasma (FFP), activated factor VII (FVIIa; NovoSevenRT [Novo Nordisk, Bagsværd, Denmark]), and prothrombin complex concentrate (PCC; BebulinVH [Baxter, Westlake Village, California, USA], ProfilnineSD [Grifols, North Carolina, USA]), each used adjunctively with vitamin K (Vit K, phytonadione). We determined times from reversal agent order to laboratory evidence of warfarin reversal (international normalized ratio [INR]) in the first 48 hours and compared INR rebound rates and complications in the first 48 hours.

Results: Reversal with FFP took more than twice as long compared with FVIIa or PCC. To reach an INR of 1.3, mean (±SD) reversal times were 1933 ± 905 minutes for FFP, 784 ± 926 minutes for FVIIa, and 980 ± 1021 minutes for PCC (P < 0.001; P < 0.01 between FFP and FVIIa, P < 0.05 between FFP and PCC). INR rebound occurred in 0 of 31 patients for FFP, 4 of 8 for FVIIa, and 0 of 7 for PCC (P = 0.001). Complications were uncommon. FVIIa was 15 and 3.5 times as expensive as FFP and PCC, respectively.

Conclusion: As an adjunct to Vit K for rapid warfarin reversal, FVIIa and PCC appear more effective than FFP. Either FVIIa or PCC are reasonable options for reversal, but FVIIa is considerably more expensive and may have greater risk of INR rebound.

Keywords: Intracranial hemorrhage; Plasma; Prothrombin complex concentrate; Recombinant activated factor vii; Reversal; Warfarin.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Anticoagulants / antagonists & inhibitors*
  • Blood Coagulation Disorders / chemically induced
  • Blood Coagulation Disorders / drug therapy
  • Blood Coagulation Factors / therapeutic use*
  • Electronic Health Records
  • Emergency Medical Services
  • Factor VII / therapeutic use*
  • Female
  • Humans
  • International Normalized Ratio
  • Intracranial Hemorrhages / drug therapy*
  • Male
  • Middle Aged
  • Neurosurgical Procedures / methods*
  • Plasma*
  • Recombinant Proteins / therapeutic use
  • Retrospective Studies
  • Vitamin K / therapeutic use
  • Warfarin / antagonists & inhibitors*


  • Anticoagulants
  • Blood Coagulation Factors
  • Recombinant Proteins
  • Vitamin K
  • prothrombin complex concentrates
  • Warfarin
  • Factor VII