S1.1. Actin-binding compounds as potential therapeutic agents in cystic fibrosis

Abstract

Background: Initial clinical experience with recombinant factor VIIa (rVIIa) for treatment of haemophilia patients with inhibitors against factor VIII or IX has been obtained by administration of rVIIa by repeated intravenous bolus injections. However, continuous infusion of rVIIa may be a more appropriate administration method if prolonged treatment is indicated.Methods: We have surveyed and analysed the initial experience with continuous infusion of rVIIa in the Netherlands and Belgium.Results: Five hospitals treated 7 haemophilia patients with inhibitors on 9 different occasions (4 bleedings, 5 surgical interventions) by continuous infusion of rVIIa over a total of 59 days. Haemostatic coverage was considered effective in 8 out of 9 cases and partially effective in 1 case. Continuous infusion of rVIIa was aimed at rVIIa target plasma levels of 10 U/ml and a decrease in prothrombin time (PT) of 3 s compared to control levels. This was obtained by an initial bolus injection of 90 μg/kg prior to continuous infusion of rVIIa at doses between 30–6 μg/kg/h (mean 17.5 μg/kg/h). A conventional one-stage factor VII coagulation assay, often used in combination with a PT, was satisfactory in monitoring rVIIa treatment. The additional clinical value of anti-fibrinolytic and anti-thrombophlebitic treatment was unclear.Conclusion: In our experience, rVIIa appeared to be efficacious and safe when administered by continuous infusion. Continuous infusion of rVIIa is more convenient than bolus injections of rVIIa, easy to monitor and provides a cost reduction of >50%. These advantages make continuous infusion an attractive administration method for prolonged treatment with rVIIa.