Continuous infusion of factor VIII for surgery and major bleeding

In a clinical trial, 24 patients with haemophilia A who needed surgery or had suffered severe bleeding were treated by continuous infusion of Monoclate P, a factor VIII concentrate that is immunopurified by monoclonal antibodies. Continuous infusion of Monoclate P began with a dose of 2 U/kg per h that was adjusted according to the results of factor VIII assays to achieve a factor VIII target level of 100IU/dl for 2 days and then 80IU/dl for 5 days. The safety, efficacy, and economics of this approach were assessed. No haemorrhagic episodes were observed. The continuous infusion was convenient and had the advantage of producing steady-state levels of factor VIII. With a single-compartment model, we found median factor VIII clearance values of 3.11 (range 1.79-7.78) x 10(3) litres/kg per h, elimination rates of 5.0-19.4 x 10(-2)/h and a median half-life of 9.9 h (range 4.8-20.0 h). Clearance and the elimination rate appeared to decline over the infusion period, as judged by the decreasing infusion rate required to maintain the target concentration of factor VIII. An economic comparison with bolus therapy, using theoretically derived bolus dosages, indicated that the potential saving was related inversely to the factor VIII half-life. Potential savings of 75% were predicted on the first postoperative day, averaging 35% over the full course of therapy.