Validation of the European Practice Guidelines for the Use of Recombinant Activated Factor VII In Patients with Massive Bleeding

Recombinant activated factor VII (rfVIIa) is approved for the treatment of bleeding in patients with hemophilia A or B with inhibitors, congenital factor VII deficiency and Glanzman's thrombasthenia. Since its approval there has been an increase in off-label use of rfVIIa in patients with massive bleeding. In 2006, a European consensus guideline was developed for the use of rfVIIa as an adjunctive therapy for massive bleeding¹. The European guidelines recommend using rFVIIa in patients with massive bleeding from blunt trauma, post-partum hemorrhage and uncontrolled post surgical bleeding including cardiac surgery. The guidelines do not recommend use of rfVIIa for penetrating trauma, elective or liver surgery prophylaxis and bleeding in patients with cirrhosis. It is recommended that the efficacy of rfVIIa should be assessed visually and based on transfusion requirements. We conducted a retrospective study in 60 consecutive patient admissions to the Hahnemann University Hospital who were given rfVIIa over the past 2.5 years. The data was analyzed to assess the efficacy according to the clinical indications to validate the European practice guidelines. Details of the results are shown in the table below.

In our analysis, use of rfVIIa in patients with inhibitors and uncontrolled post-surgical bleeding including cardiac surgery was effective in achieving hemostasis in an average of 6.4 hours. Conversely in blunt trauma we did not find significant hemostasis. We suspect that this was attributable to the presumed cirrhosis and active anticoagulation therapy in four of the eleven patients. Our study supports the consensus that rfVIIa therapy is not effective in bleeding patients with cirrhosis and penetrating trauma in achieving hemostasis. The average utilization of PRBC/Platelets/FFP in patients with penetrating trauma and cirrhosis were 4.3/0.9/4.2 in comparison with 1.1/0.3/1.0 in patients with inhibitors and uncontrolled peri-operative bleeding including cardiac surgery. The dosing and frequency of rfVIIa was inconsistent, ranging from 60–120 mcg/kg every 2–12 hours and over 1 to 45 days. We observed only one adverse event of venous-thromboembolism at a median follow up of 11 days in the entire group. We conclude that our study validates the efficacy of rfVIIa as an adjunctive therapy for massive bleeding in selected patient populations as recommended in the European guidelines. In addition, there is wide variation in the off-label usage of this product emphasizing the need for a clinical practice guideline for the use of recombinant activated factor VII in the USA.

*Diffuse alveolar hemorrhage, Hemorrhage on anticoagulation, AML/MDS with thrombocytopenia, Congenital Hemophilia A, and Type I vWD.

1. Vincent JL, Rossaint R, Riou B, Ozier Y, Zideman D, Spahn DR: Recommendations on the use of recombinant activated factor VII as an adjunctive treatment for massive bleeding – a European perspective, Crit Care 2006, 10:R120.

Off Label Use: Recombinant activated factor VIIa (rfVIIa) is approved for the treatment of bleeding in patients with hemophilia A or B with inhibitors, congenital factor VII deficiency and Glanzman's thrombasthenia.