title: Reversal of elevated international normalized ratios and bleeding with low-dose recombinant activated factor VII in patients receiving warfarin.
abstract: OBJECTIVE
  To assess the effectiveness of using low-dose recombinant activated factor VII (rFVIIa) to reverse the effects of warfarin in critically ill patients with major bleeding events.
  
  
  METHODS
  Prospective observational study.
  
  
  METHODS
  Intensive care unit of a 500-bed university-affiliated hospital.
  
  
  METHODS
  Sixteen nonhemophiliac patients who had been receiving warfarin and had an acute major bleeding event.
  
  
  METHODS
  Patients received rFVIIa 1.2 mg for reversal of anticoagulation.
  
  
  RESULTS
  Patients were identified from clinical pharmacology consult service electronic tracking records, and their data were cross-checked with the pharmacy information system. Information collected for each patient included extent of bleeding and magnitude of elevation in international normalized ratio (INR). A mean +/- SD dose of rFVIIa 16.3 +/- 4.1 microg/kg (range 11-25 microg/kg) reduced the mean INR from 2.8 +/- 1.6 (range 1.44-6.34) to 1.07 +/- 0.27 (range 0.86-1.92, p<0.001). A rapid onset of response for achieving a desirable hemostatic effect was observed in 14 of the 16 patients.
  
  
  CONCLUSIONS
  Low-dose rFVIIa appears to be an effective, rapid reversal modality for major bleeding events in the presence of warfarin and an elevated INR. The agent's response is quicker than that expected with fresh frozen plasma combined with vitamin K. In emergency situations, rFVIIa 1.2 mg can be used to reverse the anticoagulant effect of warfarin and other vitamin K antagonists without inducing a hypercoagulable state; the product, however, is expensive.
authors.affiliation: Department of Pharmaceutical Services, University of California, Davis Medical Center, Sacramento, California 95817-2201, USA. william.dager@ucdmc.ucdavis.edu
authors.forename: William E
authors.initials: WE
authors.lastname: Dager
authors.forename: Jeff H
authors.initials: JH
authors.lastname: King
authors.forename: Ron C
authors.initials: RC
authors.lastname: Regalia
authors.forename: Dean
authors.initials: D
authors.lastname: Williamson
authors.forename: Robert C
authors.initials: RC
authors.lastname: Gosselin
authors.forename: Richard H
authors.initials: RH
authors.lastname: White
authors.forename: R Steven
authors.initials: RS
authors.lastname: Tharratt
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Albertson
mesh_terms: D000293:Adolescent; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects*; D001777:Blood Coagulation / Q000187:drug effects; D003029:Coagulants / Q000008:administration & dosage*; D003422:Critical Care; D005167:Factor VII / Q000008:administration & dosage*; D015942:Factor VIIa; D005260:Female; D006470:Hemorrhage / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage; D014859:Warfarin / Q000009:adverse effects*
chemical_list: D000925:Anticoagulants; D003029:Coagulants; D011994:Recombinant Proteins; D014859:Warfarin; D005167:Factor VII; C103587:recombinant FVIIa; D015942:Factor VIIa