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BACKGROUND: Recombinant factor VIIa (rFVIIa) is licensed for use in patients with haemophilia and inhibitory allo-antibodies. It is also increasingly being used for off-license indications to prevent bleeding in operations where blood loss is likely to be high, and/or to stop bleeding that is proving difficult to control by other means. OBJECTIVES: To assess the effectiveness of rFVIIa when used therapeutically to control active bleeding, or prophylactically to prevent (excessive) bleeding in patients without haemophilia. SEARCH STRATEGY: We searched the Cochrane Injuries Group Specialised Register, CENTRAL, MEDLINE, EMBASE and other specialised databases up to 25 February 2009. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing rFVIIa with placebo, or one dose of rFVIIa with another, in any patient population (except haemophilia). Outcomes were mortality, blood loss or control of bleeding, red cell transfusion requirements, number of patients transfused and thromboembolic adverse events. DATA COLLECTION AND ANALYSIS: Two authors independently assessed potentially relevant studies for inclusion, extracted data and examined risk of bias. We considered prophylactic and therapeutic rFVIIa studies separately. MAIN RESULTS: Twenty-five RCTs were included: 24 were placebo-controlled double-blind RCTs and one compared different doses of rFVIIa.Fourteen trials involving 1137 participants examined the prophylactic use of rFVIIa; 713 received rFVIIa. There was no evidence of mortality benefit (RR 1.06; 95% CI 0.50 to 2.24). There was decreased blood loss (WMD -272 mL; 95% CI -399 to -146) and decreased red cell transfusion requirements (WMD -243 mL; 95% CI -393 to -92) with rFVIIa treatment; however these values were likely overestimated due to the inability to incorporate data from trials showing no difference of rFVIIa treatment compared to placebo. There was a trend in favour of rFVIIa in the number of participants transfused (RR 0.91; 95% CI 0.82 to 1.02). But there was a trend against rFVIIa with respect to thromboembolic adverse events (RR 1.32; 95% CI 0.84 to 2.06).Eleven trials involving 2366 participants examined the therapeutic use of rFVIIa; 1507 received rFVIIa. There were no outcomes where any observed advantage, or disadvantage, of rFVIIa over placebo could not have been observed by chance alone. There was a trend in favour of rFVIIa for reducing mortality (RR 0.89; 95% CI 0.77 to 1.03). However, there was a trend against rFVIIa for increased thromboembolic adverse events (RR 1.21; 95% CI 0.93 to 1.58). AUTHORS' CONCLUSIONS: The effectiveness of rFVIIa as a more general haemostatic drug, either prophylactically or therapeutically, remains unproven. The use of rFVIIa outside its current licensed indications should be restricted to clinical trials.

Original publication




Journal article


Cochrane Database Syst Rev

Publication Date



Blood Loss, Surgical, Factor VIIa, Hemorrhage, Hemostatics, Humans, Randomized Controlled Trials as Topic, Recombinant Proteins