Factor VII

Factor VII has been controversial in the use of trauma.  The FDA approved this medication for the treatment of bleeding in patients with coagulation disorders such as hemophilia, but here was no FDA indication for trauma.  People started using this off label because it theoretically makes sense; if people are bleeding to death and you give them a medication that can stop bleeding, they might live more often.  Although the exact mechanism is unknown, most believe it reacts with tissue factor that is exposed on damaged endothelium.  This triggers the formation of fibrin polymers to stop bleeding.  Around 2005 the FDA told everyone that there might be an increased risk of thromboembolic events associated with Factor VII, and since that time, many people have been trying to prove its efficacy and safety profile.

I could only find two prospective, randomized, placebo-controlled trials that would be worth mentioning in the review.  Please check these out if you get a chance to see the differences in their study design, which makes a big difference, but there is too much detail to describe here.   The Boffard article came out in 2005 and the CONTROL trial was published in 2010.  Note:  The CONTROL trial was “supported” by the manufacturer of the drug.  Take that for what it’s worth.  NEITHER STUDY FOUND A DIFFERENCE IN MORTALITY AT 30 DAYS!  Several previous smaller prospective studies found an increased in arterial thromboembolism in patients receiving factor VII compared to those receiving placebo, although there was no difference in the rates of venous thromboembolism.  The Boffard and CONTROL studies both reported no difference in thromboembolic rates.  MI was included in the arterial thromboembolic group as a complication.   The CONTROL study found a decreased rate of ARDS in the factor VII group (remember there was no change in mortality), and the Boffard trial claimed a decrease in the amount of massive transfusion necessary in patients receiving factor VII.  The latter claim, however, was not a primary aim and was found with post-hoc analysis.

Bottom line:  We still need a lot more data before we can officially make a stance on this issue, but for now, it’s probably better to stay away from a medication with no mortality benefit and a possibly bad side effect profile.  The CONTROL trial seemed to be happy to say there was no increased risk of thromboembolism, but completely skipped over the fact that they found no improvement in mortality.  This is just my take on the issue.  Please read the articles and make up your own mind!

Boffard, et al. Recombinant factor VIIa as adjunctive therapy for bleeding in severely injured trauma patients:  two parallel randomized, placebo-controlled, double-blind clinical trials.  J Trauma.  Jul, 2005.  59(1): 8-15.

Dutton R, Parr M, et al. Recombinant Activated Factor VII in Safety in Trauma Patients:  Results from the CONTROL Trial.  The Journal of Trauma.  July 2011. 71(1):  12-19.