title: Low-dose recombinant factor VIIa for trauma patients with coagulopathy.
abstract: BACKGROUND
  Coagulopathy in injured patients is common and is generally treated with fresh frozen plasma (FFP). Response can be variable, thus complete correction may take hours and require large volumes of fluids. High-dose recombinant factor VIIa (FVIIa, Novoseven, Novo Nordisk, Bagsvaerd, Denmark) has been used off-label to treat severe coagulopathy following trauma. Expense has limited use. Recently, we began administering low dose FVIIa (1.2mg) to patients with mild to moderate coagulopathy after trauma, hypothetising that it would be effective and safe.
  
  
  METHODS
  We retrospectively reviewed consecutive patients who received a low dose of 1.2mg of FVIIa over a 2-year period. Factor VIIa is administered after approval by a gatekeeper at the discretion of the treating physician. Demographics, injury and laboratory data were abstracted as were indications for use, source of coagulopathy, effectiveness, and complications. A two-tailed paired t-test was used to determine significant changes in coagulation parameters and blood product utilisation.
  
  
  RESULTS
  Eighty-one patients received 84 low doses of FVIIa. The mean age of the patients was 51 (+/-22) with a mean ISS of 29 (+/-11). Seventy-three per cent were male and 67% had a traumatic brain injury (TBI) as their primary injury. The aetiology of the coagulopathy in the study population included; TBI (40%), warfarin use (22%), and cirrhosis (13%). Mean prothrombin time (PT) fell from 17.0 s (+/-3.2) to 10.6s (+/-1.4) (p<0.0001). All patients had a good clinical response with no bleeding complications. Utilisation of packed red blood cells and fresh frozen plasma were significantly less in the 24h after FVIIa administration as compared to the 24h prior. Subsequent thromboembolic events were observed in 12 of the 81 patients (15%) and included; cerebrovascular accident (CVA) (6), mesenteric thrombosis (2), myocardial infarction (MI) (1), pulmonary embolism/deep venous thrombosis (PE/DVT) (2), and atrial thrombus (1). Only four of these events were thought to be related to the FVIIa administration, with two of the four contributing to a lethal outcome.
  
  
  CONCLUSIONS
  Low dose FVIIa rapidly and effectively treats mild to moderate coagulopathy following injury. This low dose (1.2mg) FVIIa is the smallest available unit dose. It costs approximately the same as 8 units of plasma and may be cost-effective in patients who require high volume factor administration. Low dose FVIIa may be effective in coagulopathic trauma patients who are not in shock but require rapid normalisation of clotting function.
authors.affiliation: R Adams Cowley Shock Trauma Centress, Program in Trauma, University of Maryland School of Medicine, Baltimore, MD 21201, USA. dstein@umm.edu
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Stein
authors.forename: Richard P
authors.initials: RP
authors.lastname: Dutton
authors.forename: John R
authors.initials: JR
authors.lastname: Hess
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Scalea
mesh_terms: D000328:Adult; D000368:Aged; D001778:Blood Coagulation Disorders / Q000188:drug therapy* / Q000209:etiology; D015331:Cohort Studies; D015942:Factor VIIa / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012189:Retrospective Studies; D014947:Wounds and Injuries / Q000188:drug therapy*
chemical_list: D011994:Recombinant Proteins; C103587:recombinant FVIIa; D015942:Factor VIIa