title: Comparison of a low, fixed dose and a high, weight-based dose of recombinant factor VIIa in the treatment of warfarin-associated intracranial hemorrhage.
abstract: BACKGROUND
  Recombinant activated Factor VII (rFVIIa) can be used for rapid INR normalization in patients with warfarin-associated intracranial hemorrhage (WA-ICH); however, the optimal dose to normalize INR has not been established.
  
  
  METHODS
  This is a retrospective review comparing two rFVIIa hospital protocols for WA-ICH [weight-based dose (80 mcg/kg) or fixed dose (2 mg)]. Primary endpoint was the percentage of patients with INR reversal (INR <1.3) at the next INR draw and the need for further doses of rFVIIa. Secondary endpoints included time to documented INR reversal and sustained INR normalization, morbidity, mortality, change in hematoma size, cost, and adverse drug reactions.
  
  
  RESULTS
  Twenty-nine patients were included in each group. The weight-based group received a mean dose of 78.9 ± 21 mcg/kg versus 26.6 ± 8 mcg/kg in the fixed dose group. More patients in the fixed dose protocol achieved documented INR reversal than those in the weight-based group (92.6 vs 72.4 %, p = 0.19). The weight-based group achieved INR normalization in 229.5 [102, 331] minutes versus 165 [83, 447] minutes in the fixed dose group (p=0.02). Time to sustained INR normalization was similar in both groups. Four patients in the fixed dose group received an additional dose of 1 mg per hospital protocol. With the exception of medication acquisition cost savings of about $4,300 per patient who received fixed dose protocol, all other endpoints were similar between groups.
  
  
  CONCLUSIONS
  A low, fixed dose of rFVIIa appears to be as effective as a high, weight-based dose in achieving INR normalization in patients with WA-ICH.
authors.affiliation: Department of Pharmacy, Wake Forest University Baptist Medical Center, Medical Center Blvd, Winston Salem, NC, 27157, USA, adele.robbins@gmail.com.
authors.forename: Adele
authors.initials: A
authors.lastname: Robbins
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Fong
authors.forename: Wiley
authors.initials: W
authors.lastname: Hall
authors.forename: Kristen
authors.initials: K
authors.lastname: Ditch
authors.forename: Stephen
authors.initials: S
authors.lastname: Rolfe
authors.forename: Melissa
authors.initials: M
authors.lastname: Miller
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D015942:Factor VIIa / Q000008:administration & dosage*; D005260:Female; D006490:Hemostatics / Q000008:administration & dosage; D006801:Humans; D019934:International Normalized Ratio; D020300:Intracranial Hemorrhages / Q000139:chemically induced* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage; D012189:Retrospective Studies; D014859:Warfarin / Q000009:adverse effects*
chemical_list: D000925:Anticoagulants; D006490:Hemostatics; D011994:Recombinant Proteins; D014859:Warfarin; C103587:recombinant FVIIa; D015942:Factor VIIa