Fresh frozen plasma and cryoprecipitates were traditionally the principal treatments for patients with inherited clotting factor deficiencies. The revolutionary development of plasma-derived clotting factor concentrates (pdCFCs), via the fractionation of plasma [66], provided benefits for both haemophilia treaters and patients and enabled the widespread adoption of home treatment [67]. Large blood donor pools of up to 30 000 donations were used as a source of plasma to manufacture pdCFCs

and at the time there were no virucidal procedures or specific tests for infectious agents [68]. This led to an epidemic in the 1970s and early 1980s, with large numbers NVP-AUY922 of people with bleeding disorders becoming infected with blood-borne viruses such as hepatitis C virus (HCV) and HIV ERK inhibitor [66]. High infection rates were seen among haemophilia patients, particularly in those with severe haemophilia. Approximately 60% of patients were reported to have been infected with HIV [69] and almost 100% of patients treated with CFCs derived from pooled blood products developed non-A non-B hepatitis (today known as hepatitis C) [70]. Some countries with a national plasma supply had better

control of plasma and donors, and therefore were able to limit these epidemics. During this time, patients were also exposed to hepatitis B virus (HBV) infection, although symptomatic infection remains uncommon in haemophilia patients [71]. The high rates of infection observed within the haemophilia population had a significant impact on mortality rates. In the UK, prior to 1984, annual mortality for patients with haemophilia was Thymidine kinase 0.9% for severe disease and 0.4% for mild/moderate haemophilia. Post-1984 this remained relatively constant for patients without HIV, but increased progressively in patients infected with HIV to a maximum

of 12.7% for severe patients in 1994 and 13.1% for mild/moderate patients in 1996 (Fig. 4). The decrease in annual mortality rates after this period was due in part to the introduction of highly active antiretroviral therapy [72], and also to the introduction of screening procedures for HIV infection, starting from 1986. HCV complications also affected mortality rates. For example, in a UK cohort study, the mortality rates due to liver disease and liver cancer were found to be 16.7-times and 5.6-times higher, respectively, for haemophilia patients than in the general population [73]. Overall, the infection of haemophilia patients with HIV and HCV has placed severe health, economic and emotional burdens on affected patients and families, as well as on the wider bleeding disorders community [74]. The viral epidemic associated with pdCFCs acted as a trigger within the patient community and industry to drive the improvement of the processes involved in their manufacture.