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.

The natural history of chronic hepatitis C in a cohort of HIV-negative Italian patients with hereditary bleeding disorders

“…Furthermore, we must consider the immunosuppressive effect of the clotting factor concentrates that could have favored the HCV progression. 45 Patients with severe hemophilia were likely to have been treated more frequently with blood products than patients with mild hemophilia.…”

Effect of factor VIII concentrate on leucocyte cytokine receptor expression in vitro: relevance to inhibitor formation and tolerance induction

“…The effects were pdFVIII batch dependent, with one batch of pdFVIII being more inhibitory than two other batches. This is an important finding and may explain the variable incidence of FVIII inhibitors in recipients of different FVIII concentrates [10], although published data suggest that there may be no difference between inhibitor development in recipients of either pdFVIII and rFVIII products [11]. One could speculate that use of very inhibitory batches of pdFVIII, as shown in Fig.…”

The effect of clotting factor concentrates on the immune system in HIV‐negative haemophilics

“…However, these abnormalities may develop in haemophilics without any infection. Immunological changes such as decreased CD4+ lymphocyte number and CD4/CD8 ratio, reduced IL‐2 secretion, monocyte function defects and inhibition of delayed hypersensitivity reactions against intradermal antigens are observed more in haemophilics treated with low and intermediate purity CFC [13]. Whether the observed changes in the immune system are of clinical importance remains unclear.…”

“…Decreased CD4+ lymphocyte number is accepted as an indicator of poor prognosis in AIDS [3,5]. Treatment with very high purity CFC, when compared with lower purity products, slows the decline in CD4+ lymphocyte number [13]. Therefore in clinical practice, very highpurity CFCs are recommended in HIV positive haemophilics.…”