The development of inhibitory antibodies to human factor VIII in a significant minority

of patients with haemophilia A treated with concentrates derived from human plasma was already well recognized by the early 1970s. The treatment options at the time were limited to either infusions of high doses of human factor VIII or primitive prothrombin complex concentrates (PCCs) like Autoplex and Proplex. Neither of these options could guarantee control of haemostasis and the use of PCCs was also known to be associated with a risk of venous and arterial thromboembolism. A highly purified preparation of porcine Ixazomib chemical structure factor VIII was developed in the early 1980s using polyelectrolyte chromatographic fractionation. This product was specifically developed to provide another treatment option for patients who had developed inhibitory antibodies to human factor VIII. The rationale was that porcine factor VIII was sufficiently similar to human factor VIII to work just like the natural product, but it was also sufficiently different in structure to render it less susceptible to inactivation by circulating inhibitory antibodies. The very early work was undertaken by Speywood Laboratories

in Nottingham (which later became part of the Ipsen group) in conjunction with researchers in Oxford. An attractive offer from the Welsh Development Agency persuaded Speywood to 3-Methyladenine nmr Thymidine kinase set up its production facility for Hyate:C in Wrexham, where a fractionation plant was built to handle porcine plasma obtained from abattoirs in England [Figs 2–4]. The first published report of the clinical use of Hyate:C appeared in 1984 and described the successful use of the product in eight patients over an 18-month period [6]. A total of 297 infusions were given for the treatment of 45 distinct bleeding episodes. A clear advantage over other products was that measureable levels of factor VIII were obtained after infusion, which could be used to monitor treatment. In most cases,

the inhibitory antibodies against human factor VIII showed little or no cross-reactivity with porcine factor VIII. Where no baseline antibody against porcine factor VIII was detectable, the mean postinfusion rise in plasma factor VIII was 1.29 U dL−1 per unit infused kg−1. Furthermore, there was usually little or no anamnestic rise in antibody titre after treatment with Hyate:C, by contrast with the steep rise frequently reported after treatment with human factor VIII or activated prothrombin complex concentrates. Multiple and prolonged courses of therapy were used in this series without evidence of loss of clinical or laboratory efficacy. Apparently allergic reactions, including fever, were observed after approximately 10% of the infusions.