Longterm Prophylactic Treatment with Recombinant Factor VIIa (NovoSeven) in Severe Congenital Factor VII Deficient Patients

Background: Treatment of congenital FVII deficiency consists of replacement therapy with plasmic FVII concentrates or recombinant FVIIa (rFVIIa). Relatively small amounts of rFVIIa are required for replacement therapy in FVII deficient patients. Because of its short half-life of approximately 3 hours rFVIIa has not been regarded as a routine prophylactic treatment option for FVII deficiency.

Case Reports: We report on our experience of prophylactic treatment with rFVIIa in two FVII deficient patients. Patient one is 43-year-old male with severe FVII deficiency (<1% activity) associated with compound heterozygous Gly78Asp and heterozygous Cys194Tyr mutations. After birth, he experienced severe tissue bleeding complications and later on various joint bleedings with consecutive hemophilic arthropathy. He is now on treatment with rFVII (1.2 mg 3 times per week) since 28 months. Patient two is a 36-year-old male with FVII deficiency of <1% FVII activity. He experienced recurrent mucosal bleeding episodes and large skin hematomas. His genetic defect consists in a homozygous missense mutation (1061 C>T, Ala354Val), a heterozygous missense mutation (218 T>A, Leu73Gln), and a heterozygous frameshift mutation (1391delC, Pro464HisfsX32). The patient is on prophylactic treatment with rFVII (1.2 mg 3 times per week) since 22 months. Since substitution with rFVII, no spontaneous bleeding episodes occurred and no side effects were observed in both patients. In conclusion, prophylactic treatment with rFVIIa in FVII deficient patients appears to be an effective and safe therapeutic option. The mechanisms by which rFVIIa prevents bleeding episodes despite a short half-life of 3 hours remains to be elucidated.