Recombinant FVIIa in the management of uncontrolled hemorrhage.

BACKGROUND: Recombinant FVIIa (rFVIIa/NovoSeven) is a novel hemostatic agent originally developed to treat patients with hemophilia who had developed inhibitors. Several case reports have suggested that rFVIIa may be effective in treating patients without a pre-existing bleeding disorder who have uncontrolled bleeding. STUDY DESIGN AND METHODS: Data on the efficacy and safety of rFVIIa in the treatment of massive hemorrhage were obtained retrospectively from the NovoSeven extended-use data collection system. RESULTS: A total of 40 patients received rFVIIa for uncontrolled bleeding, and in these patients, bleeding stopped or decreased in 32 (80%). Blood product usage was significantly decreased after rFVIIa administration. Thromboembolic events occurred in three patients with additional risk factors for thrombosis. Of 40 patients, 23 (57.5%) died. Bleeding was the direct cause of death in seven cases (all within 24 hr of administration of rFVIIa). The remaining 16 deaths were the result of sepsis, multi-organ failure, or the underlying disease. CONCLUSIONS: In this retrospective study of data voluntarily submitted to a web-based drug surveillance program, we present preliminary results on the use of rFVIIa in nonhemophilia patients with bleeding. Although some efficacy is suggested, there was a high mortality rate from nonhemorrhagic causes. Randomized controlled trials are needed to properly assess the role of rFVIIa in the management of hemorrhage.

Analysis and results of the recombinant factor VIIa extended-use registry.

This paper describes the analysis of recombinant factor VIIa (rFVIIa; NovoSeven; Novo Nordisk, Bagsvaerd, Denmark) use in 40 patients with intractable bleeding in the UK. All cases were reported on the 'rFVIIa extended use database' (Traumanet) between its launch in February 1999 and 12 March 2002. Twenty-one other cases reporting rFVIIa use in different circumstances were excluded from the analysis. Recombinant FVIIa was effective in stopping or markedly reducing blood loss in 80% of patients; 20% of patients did not respond to treatment. Non-responders tended to have more deranged coagulation and lower platelet counts compared with responders. Despite a wide range of underlying illnesses, including malignancy and sepsis, few patients suffered adverse events. Thrombotic events occurred in three of 40 (7.5%) patients and these patients were considered as already at risk of thrombosis from other causes. The data suggest that rFVIIa is safe and effective therapy in patients with uncontrollable haemorrhage.