Dose and response in haemophilia – optimization of factor replacement therapy

Abstract

The mainstay of the management of haemophilia is the replacement of clotting factors, using clotting factor concentrates (CFC) in a way that prevents bleeding and its complications. Beginning with small doses, as whole blood and plasma over 50 years ago, highly purified CFCs are now administered frequently in large doses to effectively treat this condition so that even people with severe haemophilia can lead near normal lives. However, with such regimens, compliance and expense have both become significant issues. The question therefore is whether the current models of clotting factor replacement are optimal. This article reviews the literature on the dose-response relationship in haemophilia, with particular reference to management of musculoskeletal bleeding and surgical haemostasis. Current practices are based on uncontrolled observational data. Less intensive protocols could achieve similar outcomes. Large multi-centre prospective studies are needed to provide comparative data on unresolved issues so that factor replacement therapy can be optimized, based on evidence.