title: Use of recombinant factor VIIa for the prevention and treatment of bleeding in patients without hemophilia: a systematic review and meta-analysis.
abstract: BACKGROUND
  The benefits and risks of off-label use of recombinant factor VIIa in patients without hemophilia are contested. We performed a systematic review to assess the effectiveness and safety of such use.
  
  
  METHODS
  We searched electronic databases including MEDLINE, EMBASE and CENTRAL for randomized controlled trials comparing recombinant factor VIIa with placebo in any patient population except those with hemophilia up to January 2010. Eligible articles were assessed for inclusion, data were extracted, and study quality was evaluated. Outcomes included mortality, blood loss, requirements for red blood cell transfusion, number of patients transfused and thromboembolic events.
  
  
  RESULTS
  We identified 26 trials: 14 on off-label prophylactic use of recombinant factor VIIa (n = 1137) and 12 on off-label therapeutic use (n = 2538). In the studies on prophylactic use, we found no significant difference in mortality or thromboembolic events between the treatment and placebo groups. We found modest benefits favouring recombinant factor VIIa in blood loss (weighted mean difference -276 mL, 95% confidence interval [CI] -411 to -141 mL), red blood cell transfusion (weighted mean difference -281 mL, 95% CI -433 to -129 mL) and number of patients transfused (relative risk 0.71, 95% CI 0.50 to 0.99). In the therapeutic trials, we found a nonsignificant decrease in mortality and a nonsignificant increase in thromboembolic events but no difference in control of bleeding or red blood cell transfusion.
  
  
  CONCLUSIONS
  Clinically significant benefits of recombinant factor VIIa as a general hemostatic agent in patients without hemophilia remain unproven. Given its potential risks, such use cannot be recommended, and in most cases, it should be restricted to clinical trials.
authors.affiliation: Department of Clinical Pathology, Sunnybrook Health Sciences Centre, Toronto, Toronto, Ont, Canada. yulia.lin@sunnybrook.ca
authors.forename: Yulia
authors.initials: Y
authors.lastname: Lin
authors.forename: Simon
authors.initials: S
authors.lastname: Stanworth
authors.forename: Janet
authors.initials: J
authors.lastname: Birchall
authors.forename: Carolyn
authors.initials: C
authors.lastname: Doree
authors.forename: Christopher
authors.initials: C
authors.lastname: Hyde
mesh_terms: D015942:Factor VIIa / Q000627:therapeutic use*; D006467:Hemophilia A; D006470:Hemorrhage / Q000517:prevention & control*; D006801:Humans; D056687:Off-Label Use; D011994:Recombinant Proteins / Q000627:therapeutic use; D018570:Risk Assessment
chemical_list: D011994:Recombinant Proteins; C103587:recombinant FVIIa; D015942:Factor VIIa