Potential Thrombogenic Complications With the Use of Recombinant Activated Factor VII in Combat Trauma

Abstract

by many medical experts for expanded usage in the management of medical, surgical, and traumaassociated bleeding in hospitalized patients. There is no question that NovoSeven administration has been associated with numerous miraculous saves; however, there also is a dearth of well-controlled clinical trials that could provide insight into what criteria should be applied to maximize its safe use in the context of its known potential thrombogenicity. More recently the Israeli and US armies have used NovoSeven for the control of bleeding occurring with battlefield and combat trauma. The US Army has developed and posted guidelines for the use of recombinant FVIIa in military hospitals. Although this use of NovoSeven is off-label and nonstandardized, the Army is to be commended for exploring its use in the management of bleeding in battlefield conditions where the conventional methods have not always been effective. A recent article, “Dangerous Remedy. Military doctors in Iraq say that factor VIIa saves wounded soldiers, but other doctors and medical research suggest that it can cause fatal clots” (Baltimore Sun, November 19, 2006) authored by Robert Little, a Sun reporter, has provided a comprehensive review of the adverse thrombogenic complications associated with the use of NovoSeven. This article reported that the US Amy has injected more than 1000 trauma-inflicted soldiers with NovoSeven. The Baltimore Sun article is based on the extensive battlefield observations and research conducted by the reporter. Moreover, the reporter also interviewed several experts in the field of hemostasis and Recombinant activated factor VII (FVIIa; NovoSeven, Novo Nordisk, Copenhagen) was approved by the United States (US) Food and Drug Administration (FDA) in March 1999 for the alternate hemostatic management of hemophilia patients who develop antibodies to FVIII. Although medically useful, there have been reports of adverse thrombogenic complications associated with its use. In an article published in the Journal of the American Medical Association in December 2005, the FDA cautioned that the administration of NovoSeven for heretofore unlicensed indications to healthy, nonhemophilic individuals could result in complications such as stroke and myocardial infarction, possibly leading to death. Almost all of these clotting complications were detected in older individuals administered NovoSeven to reverse bleeding not related to hemophilia. Clotting complications rarely have occurred in the much younger individuals with hemophilia-related antibodies who have received NovoSeven to treat or prevent active bleeding. Because anecdotal reports have provided the impression that life-threatening and overwhelming bleeding complications in desperate situations could be treated successfully and rapidly with NovoSeven administration, the use of this genetically Editorial