title: The incidence of thromboembolism formation following the use of recombinant factor VIIa in patients suffering from blunt force trauma compared with penetrating trauma: a systematic review.
abstract: Rapid replacement of blood loss is critical in patients suffering from traumatic hemorrhage. When the availability of blood products is limited, certain interventions have shown promise in conserving blood supplies. Recombinant factor (rF) VIIa has been administered, as an off-label use, to assist in controlling hemorrhage in trauma patients. Although rFVIIa has a tendency to remain localized to areas of vascular insult, there may be an increase in thromboembolism formation when patients suffer multiple sites of injury as seen in blunt force trauma.
  
  
  
  This review aimed to synthesize the best available evidence regarding the incidence of thromboembolism formation after receiving rFVIIa as an adjunct to hemorrhage control measures (standard resuscitation efforts consisting of varying amounts of packed red blood cells [PRBCs], fresh frozen plasma [FFP], platelets and crystalloid solutions) in patients suffering from traumatic injuries (blunt force and penetrating trauma).
  
  
  
  Civilian and combat trauma patients who were 15 years and older suffering from blunt force and penetrating traumatic injuries.
  
  
  
  Use of rFVIIa as an adjunct to hemorrhage control measures (standard resuscitation efforts consisting of varying amounts of PRBCs, FFP, platelets and crystalloid solutions).
  
  
  
  This review considered both experimental and epidemiological study designs.
  
  
  
  Confirmed formation of thromboembolism (confirmation based on specific diagnostic tests such as ultrasound, ventilation-perfusion scan or angiography).
  
  
  
  The databases searched included CINAHL, Ovid MEDLINE, Web of Science, EMBASE and the Cochrane Control Register of Clinical Trials. Studies published after June 1986 were considered for inclusion in this review. Search for unpublished studies was performed.
  
  
  
  Studies selected for inclusion were critically appraised by two independent reviewers using standardized critical appraisal instruments from the Joanna Briggs Institute (JBI).
  
  
  
  Data was extracted from articles using standardized data extraction instruments from the JBI.
  
  
  
  Quantitative results were pooled in statistical meta-analysis using the Joanna Briggs software for meta-analysis.
  
  
  
  Two studies with a total of 831 participants were included. Both the studies were randomized, placebo-controlled, double-blind trials. No studies of combat trauma patients met the inclusion criteria for this review. A meta-analysis was performed. In blunt force trauma patients, the incidence of thromboembolism formation on administering rFVIIa revealed an overall relative risk of 1.17 with a 95% confidence interval (CI) from 0.77 to 1.79; results not statistically significant (P = 0.4594); large CI and imprecise estimate. In penetrating trauma patients, the incidence of thromboembolism formation on administering rFVIIa revealed an overall relative risk of 0.77 with a 95% CI from 0.27 to 2.20; results not statistically significant (P = 0.6242); very large CI and imprecise estimate.
  
  
  
  The estimates of the effects are imprecise, results are compatible with effects in opposite directions, increase or decrease of thromboembolism formation, and an increase of thromboembolism formation cannot be excluded.
  
  
  
  When rFVIIa is administered to trauma patients, there does not appear to be an increased risk of thromboembolism formation favoring one type of injury over the other (blunt force versus penetrating trauma). Owing to large CIs and imprecise estimates, the overall risk of thromboembolism cannot be excluded. The use of rFVIIa does appear to decrease the overall need for blood products in trauma patients with no statistically significant improvement in survival rates. With the high cost of rFVIIa, its use is limited to those facilities that can afford it. In situations wherein blood supply is limited, rFVIIa could conserve limited supplies of blood products with no difference in thromboembolism risk between blunt force versus penetrating trauma, but the high cost will ultimately limit its use to facilities that can afford it. The use of rFVIIa in blunt force and penetrating trauma patients has a JBI Grade B Recommendation (Appendix I).
  
  
  
  This review excluded patients receiving pharmacologic anticoagulation such as warfarin sodium or heparin. The actions of these drugs will most likely counteract the desired coagulation effect of rFVIIa. Many studies do not account for the effects of rFVIIa in trauma patients receiving pharmacologic anticoagulation and this could be a future area of research.
authors.affiliation: 1Louisiana Center for Evidence-based Nursing at LSUHSC School of Nursing: an Affiliate Center of the Joanna Briggs Institute.
authors.forename: Raymond
authors.initials: R
authors.lastname: Devlin
authors.forename: Laura
authors.initials: L
authors.lastname: Bonanno
authors.forename: Jennifer
authors.initials: J
authors.lastname: Badeaux
mesh_terms: D004311:Double-Blind Method; D015942:Factor VIIa / Q000627:therapeutic use*; D006801:Humans; D015994:Incidence; D011994:Recombinant Proteins / Q000627:therapeutic use; D013923:Thromboembolism / Q000209:etiology*; D014949:Wounds, Nonpenetrating; D014950:Wounds, Penetrating
chemical_list: D011994:Recombinant Proteins; C103587:recombinant FVIIa; D015942:Factor VIIa