Off-label use of recombinant factor VIIa in patients following bone marrow transplantation

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Abstract
Recombinant factor VIIa (rFVIIa, NovoSeven) is FDA-approved for the treatment of bleeding in patients with hemophilia A/B with inhibitors. A growing literature suggests that there may be expanded indications for the use of NovoSeven in patients with significant bleeding who do not have a known factor deficiency. Severe bleeding refractory to standard hematologic or hemostatic support is common in patients undergoing bone marrow transplantation (BMT). We review our experience with rFVIIa in three patients (8 years 8 months to 19 years, median 13 years) treated for pulmonary hemorrhage (n = 1), hemorrhagic cystitis (n = 3), and gastrointestinal bleeding (n = 2). Boluses of 90-270 microg/kg rVIIa with subsequent doses of 90 microg/kg every 4-24 h for 3-14 days were given, concurrent with maintaining platelet counts >50,000/mm(3). Transient clinical responses in gross hematuria (two patients) and in pulmonary hemorrhage were noted within several days of starting rFVIIa, but bleeding in a new site in two patients and renewed bleeding of the initial site in the third resulted in discontinuation of the drug. No toxicity or adverse events were observed while the patients were on rFVIIa treatment. Because of the substantial cost of this product, the lack of adequate monitoring methodology, and the variability of current dose and dosing intervals, large randomized studies are needed before definitive off-label use in the setting of BMT can be recommended.