| Summary: | Intermediate purity factor VIII concentrates have greatly improved care for haemophilia sufferers but have been implicated in contributing to subclinical immunodeficiency observed <i>in vivo</i>. During the course of factor VIII replacement therapy haemophilia patients are reepatedly exposed to an enormous number of allogeneic protein contaminants and this substantial protein load may be responsible for establishing immunological abnormalities. Indeed, it has been proposed that intermediate purity factor VIII concentrates could accelerate the rate of disease progresssion in those haemophiliacs infected with the human immunodeficiency virus. Highly purified factor VIII preparations are now available commercially, but are extremely expensive compared to conventional intermediate purity concentrates and their use must therefore be justified in terms of patient benefit. I have set out to investigate whether intermediate purity factor VIII concentrates could contribute significantly to immune abnormalities observed in haemophilia patients <i>in vivo</i>. I have approached this problem by investigating the effects of various factor VIII preparations on immune stimulation <i>in vitro</i>. My results demonstrate that intermediate purity factor VIII concentrates can modulate lymphocyte proliferation <i>in vitro</i>. In contrast, highly purified factor VIII preparations have no effect on immune stimulation in this system. Although I have failed to identify the factor(s) responsible for the observed immune modulation <i>in vitro</i> I have excluded a number of potential candidates. The inhibitory effects of factor VIII preparations on lymphocyte proliferation previously demonstrated <i>in vitro</i> are probably not related directly to observed abnormalities in haemophilia patients <i>in vivo</i>. Immune alterations <i>in vivo</i> may be related to stimulation, rather than suppression of the immune system. My findings have a bearing on these stimulatory effects and suggest that the use of highly purified factor VIII preparations in the treatment of haemophilia is justified.
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