Surgical experience with rFVIIa (NovoSeven) in congenital haemophilia A and B patients with inhibitors to factors VIII or IX.

Patients with congenital haemophilia with inhibitors are at risk of peri-operative bleeding complications, since replacement of the missing coagulation factor is ineffective, presenting a therapeutic challenge in elective or emergency surgery. Therefore, the management of peri-operative bleeding requires the use of bypassing agents, such as recombinant activated FVII (rFVIIa, NovoSeven(®) ). This article presents an updated evaluation of the safety and effectiveness of rFVIIa in the treatment of peri-operative bleeding in this patient population. Surgical and other medical procedures managed with rFVIIa from two randomized clinical trials, the Hemophilia Research Society/Hemophilia and Thrombosis Research Society (HRS/HTRS) registry databases and the medical literature were analysed. There were 395 rFVIIa-treated procedures (261 surgical, 89 dental and 45 other medical procedures) reported for 263 congenital haemophilia patients with inhibitors. In trials, initial rFVIIa dosing was 35-90 mcg kg(-1) bolus injection or 50 mcg kg(-1) h(-1) continuous infusion. Dosing in the registries and literature was more variable. Recombinant FVIIa effectiveness was comparable across data sources, with an overall rate of 84% (333/395). The incidence of thrombotic events was very low (0.4% of patients and 0.025% of procedures). Prior to the US approval of rFVIIa in 1999, surgical procedures in congenital haemophilia patients with inhibitors were often considered too risky. Recombinant FVIIa has consistently demonstrated effectiveness in treatment of bleeding in these patients during such procedures. Thrombotic events were rare. This analysis confirms the value of corroborating clinical trial results with post-marketing surveillance registries to assess small patient populations with clinically challenging management decisions.