Clotting factor concentrates and immune function in haemophilic patients

Abstract

Patients with haemophilia often exhibit a variety of disturbances in immune function. Although infections with HIV, hepatitis and other viruses no doubt contribute to these abnormalities, chronic exposure to extraneous proteins in clotting factor concentrates (CFCs) may also play a role. Numerous in vitro and ex vivo studies show that protein contaminants--such as immunoglobulins, fibrinogen and fibronectin--can depress various immune function indicators. Generally, such studies show that intermediate-purity CFCs are more inhibitory than very high-purity (e.g. monoclonal-purified) CFCs. In many, but not all, studies, the degree of immunosuppression correlates with the amount of intermediate-purity CFC administered over time. Among various indicators of immune function, CD4+ lymphocyte number is a marker for the progression of HIV infection, and maintenance of CD4+ number is associated with delayed progression. A number of studies suggest that, compared with intermediate-purity CFCs, use of very high-purity CFCs is associated with longer preservation of this class of lymphocytes. However, it remains to be seen whether this translates to improved long-term clinical outcomes. Further research is needed on the impact of CFCs on the immune system. For the time being, however, evidence to date favours the use of very high-purity products because they appear to preserve immune function and reduce the risk of infection with hepatitis and other viruses.