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Invited Critique
March 1, 2008

Efficacy and Safety of Recombinant Activated Factor VII in Major Surgical Procedures: Systematic Review and Meta-analysis of Randomized Clinical Trials—Invited Critique

Arch Surg. 2008;143(3):304. doi:10.1001/archsurg.2007.67

In 1999, the US Food and Drug Administration approved the use of rFVIIa for the treatment of bleeding episodes in patients with the inherited coagulation disorder hemophilia A or B and inhibitors to factor VIII or IX. Increasingly, however, this product is being used by surgeons to treat patients with acquired coagulopathy, particularly during surgical procedures in which large blood loss is anticipated, such as cardiac, vascular, and liver transplantation surgery. As experience continues to accumulate and the literature documents its effectiveness, this drug is often administered prophylactically to limit transfusion requirements. However, as outlined in the meta-analysis by Ranucci et al, there is considerable variation across studies in the dose used and in the timing of administration. Because the effectiveness of rFVIIa in promoting clot formation may be affected by other factors, such as the platelet count, the fibrinogen level, and the pH at the time of administration, further research in this area is clearly in order. In addition, although most studies document a decrease in transfusion requirements in patients receiving rFVIIa, improvements in mortality rates are not well supported by the small and underpowered studies reviewed. The prohibitive cost of this drug must also be taken into consideration. Most important, there is the potential to do harm by administering a procoagulant in a patient who has other risk factors for thrombosis. In January 2006, O’Connell et al1 released a summary of the adverse events associated with the use of rFVIIa as reported to the Food and Drug Administration. One hundred eighty-five thrombotic events were reported, with most occurring when the drug was administered for an unlabeled use. The total number of patients receiving rFVIIa during that period is unknown, so the number 185 hangs out there as a numerator without a denominator. Mayer et al2 suggested that treatment with rFVIIa within 4 hours of the onset of intracerebral hemorrhage was effective in limiting the size of the hematoma, reduced the mortality rate, and improved functional outcomes at 3 months. However, serious thromboembolic events (including myocardial and cerebral infarction) occurred in 7% of patients treated with rFVIIa vs 2% of those treated with placebo.

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