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

Immune abnormalities have been reported in patients with haemophilia. Although infections with HIV and hepatitis viruses contribute to these abnormalities, chronic exposure to extraneous proteins in clotting factor concentrates (CFC) may also play a role. A number of studies suggest that the degree of immunological abnormalities correlates with the amount of intermediate purity CFC administered over time. The purpose of this study was to investigate whether there were cellular and humoral immunological abnormalities in haemophilics receiving intensive factor replacement therapy with intermediate purity CFC. For this purpose 48 severe haemophilics and 33 healthy controls were enrolled in this study. T and B lymphocytes, CD4+ and CD8+ cell counts, CD4/CD8 ratio, natural killer cells, active T cells were studied in prophylaxis group, on-demand therapy group and healthy controls. In the percentages and absolute counts of lymphocyte subgroups, no significant difference was found between three groups. We also investigated serum antitetanus IgG levels in these 48 haemophilics and the controls to evaluate the specific antibody response. Antitetanus IgG levels were significantly lower in haemophilics compared to healthy controls (P < 0.001). Additionally we evaluated the response to tuberculin skin test in 45 of 48 haemophilics vaccinated with BCG. The response to PPD test was significantly lower in haemophilics compared to the controls (P = 0.037). There was no response to tuberculin test, which is the best marker of delayed type hypersensitivity (DTH) reactions in 24% of haemophilics. In conclusion, although there was no significant change in the ratio of CD4/CD8 and lymphocyte subgroups, specific antibody responses and DTH tests were partially impaired in haemophilic patients receiving intermediate purity CFC.