A prospective study of recombinant activated factor VII administered by continuous infusion to inhibitor patients undergoing elective major orthopaedic surgery : a pharmacokinetic and efficacy evaluation

Summary. After surgery in haemophilia, haemostasis is difficult to maintain in the presence of an antifactor VIII antibody. This study assessed the pharmacokinetics of recombinant activated factor VII (rFVIIa) and its efficacy in securing post-operative haemostasis in haemophiliacs with inhibitors. Continuous infusion of rFVIIa was evaluated for elective major orthopaedic surgery in nine patients with neutralizing antibodies to FVIII and at high risk of bleeding. After an initial preoperative bolus of 90 µg/kg, rFVIIa was infused at a fixed rate of 50 µg/kg/h for a median of 20 d (range 7–20 d). The median plasma FVII coagulant activity (FVII:C) at 24 h, 72 h and 20 d after surgery was 38 IU/ml (range 22–169 IU/ml), 45 IU/ml (range 17–88 IU/ml) and 31 IU/ml (range 27–46 IU/ml) respectively. The median plasma FVIIa:C at the same time points was 51 (range 24–211), 63 (range 22–99) and 44 (range 28–76) IU/ml respectively. Median total rFVIIa clearance remained stable during the rFVIIa continuous infusion period and was 40 (range 9–70), 34 (range 17–86) and 48 (range 32–55)ml/kg/h at the end of 24 h, 72 h and 20 d infusion respectively. Post-operatively, there were bleeds in six patients, which settled readily after a single bolus of rFVIIa (60 µg/kg). There was a good clinical outcome for all patients. These data indicate that rFVIIa infusion at50 µg/kg/h achieves continuous plasma FVII procoagulant activity in excess of 30 IU/ml (12–15 nmol/l) and provides adequate haemostatic control for inhibitor patients during major orthopaedic surgery.