Currently, recombinant activated factor VII (rFVIIa) is approved in Australia and New Zealand for the control of bleeding and prophylaxis for surgery in patients with inhibitors to coagulation factors FVIII or FIX, congenital factor VII deficiency and Glanzmann’s thrombasthenia (with glycoproteinIIb-IIIa, and/or antibodies to human leukocyte antigen plus refractoriness to platelet infusion). Any use outside of these indications is considered ‘off-licence’.

Although the literature review for this question identified nine systematic reviews, only one trial met the inclusion criteria (i.e. critical bleeding requiring massive transfusion).⁶ This study reported no statistically significant differences in 48-hour or 30-day mortality between patients receiving rFVIIa and those receiving placebo, in either the blunt or penetrating trauma patient groups. In the patients with blunt trauma, there was a significant reduction in the volume of RBC transfusion and the incidence of massive transfusion and ARDS. The number of thromboembolic events was too small to determine any significant difference between the treatment and placebo groups.

A further international placebo-controlled double-blind RCT — CONTROL — was intended to assess the efficacy and safety of rFVIIa in exsanguinating trauma patients.⁹³ The trial began active recruitment in October 2005, but was halted on 11 June 2008 because the observed mortality in the 576 enrolled patients was so far below expectations that, with the planned number of subjects, the study would have lacked the statistical power to demonstrate a benefit. As of April 2010, the effect of rFVIIa on the study outcomes has not been published.

Much of the current use of rFVIIa is for patients with critical bleeding unresponsive to conventional measures of surgical haemostasis and adequate component therapy. This use remains controversial, particularly because of concerns about the risk of potential thrombotic complications.

When rFVIIa is used in off-licence situations, the dose of rFVIIa is also under debate. Doses of 100–200 μg/kg in critical bleeding due to trauma have been reported.⁶ Due to logistics and ethical considerations, studies to determine efficacy and dose are unlikely to be performed; therefore, cumulative registry data may assist in providing guidance. The Haemostasis Registry was established to provide a database of off-licence use in hospitals throughout Australia and New Zealand. Registry data published in 2007 reported a median dose of rFVIIa of approximately 90 μg/kg.⁹⁴ Up to mid-2009, more than 2800 cases had been entered.

Evidence statement

In trauma patients with critical bleeding requiring massive transfusion, administration of rFVIIa has no effect on 48-hour or 30-day mortality.6 (See evidence matrix 7 in Appendix E.) NA In patients with critical bleeding requiring massive transfusion, there is insufficient evidence to determine any association between rFVIIa and thromboembolism.6 (See evidence matrix 8 in Appendix E.) NA In patients with blunt trauma and critical bleeding requiring massive transfusion, administration of rFVIIa is associated with reduced RBC transfusion requirements and incidence of ARDS.6 In patients with penetrating trauma and critical bleeding requiring massive transfusion, administration of rFVIIa has no effect on morbidity.6 (See evidence matrix 9 in Appendix E.) NA = A = B = C = D NA = not applicable (one study only) (See table 2.2)

Practice points