title: The effects of recombinant activated factor VII dose on the incidence of thromboembolic events in patients with coagulopathic bleeding.
abstract: BACKGROUND
  Previous studies have suggested the used of off-label recombinant factor VII (rFVIIa) increases the risk of thromboembolic events, but the effect of the dose of rFVIIa is not well described in the literature.
  
  
  METHODS
  All adult patients that received off-label rFVIIa from 2005-2012 were included in this single-center, retrospective cohort study. The primary endpoint was the incidence of a thromboembolic event in the low dose (<50 mcg/kg) compared to the high dose (≥50 mcg/kg) cohort. Secondary endpoints compared time to thromboembolic event, incidence of arterial compared to venous events, and mortality.
  
  
  RESULTS
  There were 152 patients that received rFVIIa during the study period with 66 in the low dose cohort and 86 in the high dose cohort. Mean total dose of rFVIIa was 30.2 mcg/kg (SD ± 9.5 mcg/kg) in the low dose and 99.8 mcg/kg (SD ± 64.7 mcg/kg) in the high dose cohort (p=0.0001). The overall incidence of thromboembolic events was 12.5%. There were 12 (14%) events in the low dose cohort and seven (10.6%) in the high dose cohort, RR=0.76 (95% CI 0.31-1.82). There were no differences in any of the secondary outcomes. A higher incidence of thromboembolic events in cardiothoracic surgery (20.8%) and penetrating trauma patients (21.4%) was seen compared to the remaining cohort (6.7%).
  
  
  CONCLUSIONS
  No significant difference in the incidence of thromboembolic events was seen between low dose versus high dose rFVIIa over a seven year period at our institution. However, due to the relatively low overall incidence and a small sample size, type II error may be present.
authors.affiliation: University of Tennessee Medical Center, Department of Pharmacy, 1924 Alcoa Hwy, Knoxville, TN 37920. Electronic address: mbucklin@mc.utmck.edu.
authors.forename: Mason H
authors.initials: MH
authors.lastname: Bucklin
authors.affiliation: Department of Pharmacy, University of Rochester Medical Center; Department of Emergency Medicine, University of Rochester Medical Center.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Acquisto
authors.affiliation: Department of Surgery, University of Rochester Medical Center.
authors.forename: Catherine
authors.initials: C
authors.lastname: Nelson
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D015942:Factor VIIa / Q000008:administration & dosage*; D005260:Female; D006470:Hemorrhage / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage; D012189:Retrospective Studies; D013923:Thromboembolism / Q000453:epidemiology*
chemical_list: D011994:Recombinant Proteins; C103587:recombinant FVIIa; D015942:Factor VIIa
keywords: coagulopathy; recombinant activated factor VII; stroke; thromboembolism; trauma