title: Rapid Warfarin reversal in the setting of intracranial hemorrhage: a comparison of plasma, recombinant activated factor VII, and prothrombin complex concentrate.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacy, Kaiser Permanente Medical Center, San Francisco, California, USA. Electronic address: Carolyn.H.Woo@kp.org.
authors.forename: Carolyn H
authors.initials: CH
authors.lastname: Woo
authors.affiliation: Department of Neurosurgery/Neuroscience, Kaiser Permanente Medical Center, Redwood City, California, USA.
authors.forename: Nihar
authors.initials: N
authors.lastname: Patel
authors.affiliation: Division of Research, Kaiser Permanente Medical Center, Oakland, California, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Conell
authors.affiliation: Department of Neurosurgery/Neuroscience, Kaiser Permanente Medical Center, Redwood City, California, USA.
authors.forename: Vivek A
authors.initials: VA
authors.lastname: Rao
authors.affiliation: Department of Neurosurgery/Neuroscience, Kaiser Permanente Medical Center, Redwood City, California, USA.
authors.forename: Bonnie S
authors.initials: BS
authors.lastname: Faigeles
authors.affiliation: Department of Neurosurgery/Neuroscience, Kaiser Permanente Medical Center, Redwood City, California, USA.
authors.forename: Minal C
authors.initials: MC
authors.lastname: Patel
authors.affiliation: Department of Neurosurgery/Neuroscience, Kaiser Permanente Medical Center, Redwood City, California, USA.
authors.forename: Jasmeen
authors.initials: J
authors.lastname: Pombra
authors.affiliation: Department of Neurosurgery, Kaiser Permanente Medical Center, Sacramento, California, USA.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Akins
authors.affiliation: Department of Neurosurgery, Kaiser Permanente Medical Center, Sacramento, California, USA.
authors.forename: Yekaterina K
authors.initials: YK
authors.lastname: Axelrod
authors.affiliation: Department of Neurosurgery/Neuroscience, Kaiser Permanente Medical Center, Redwood City, California, USA.
authors.forename: Ivy Y
authors.initials: IY
authors.lastname: Ge
authors.affiliation: Department of Neurosurgery/Neuroscience, Kaiser Permanente Medical Center, Redwood City, California, USA.
authors.forename: William F
authors.initials: WF
authors.lastname: Sheridan
authors.affiliation: Department of Neurosurgery/Neuroscience, Kaiser Permanente Medical Center, Redwood City, California, USA.
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Flint
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000037:antagonists & inhibitors*; D001778:Blood Coagulation Disorders / Q000139:chemically induced / Q000188:drug therapy; D001779:Blood Coagulation Factors / Q000627:therapeutic use*; D057286:Electronic Health Records; D004632:Emergency Medical Services; D005167:Factor VII / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D020300:Intracranial Hemorrhages / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D019635:Neurosurgical Procedures / Q000379:methods*; D010949:Plasma; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D014812:Vitamin K / Q000627:therapeutic use; D014859:Warfarin / Q000037:antagonists & inhibitors*
chemical_list: D000925:Anticoagulants; D001779:Blood Coagulation Factors; D011994:Recombinant Proteins; D014812:Vitamin K; C025667:prothrombin complex concentrates; D014859:Warfarin; D005167:Factor VII