The effect of clotting factor concentrates on the immune system in HIV-negative haemophilics C. BALKAN,* K. KAVAKLI,* N. KUTUKCULER,  G. AKSU,  D. YILMAZ* and Y. AYDINOK* *Department of Pediatric Hematology; and  Department of Immunology, Ege University School of Medicine, Izmir, Turkey Summary. Immune abnormalities have been repor- ted in patients with haemophilia. Although infections with HIV and hepatitis viruses contribute to these abnormalities, chronic exposure to extraneous pro- teins 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 admin- istered over time. The purpose of this study was to investigate whether there were cellular and humoral immunological abnormalities in haemophilics receiv- ing intensive factor replacement therapy with inter- mediate 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 ¼ 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 haemo- philic patients receiving intermediate purity CFC. Keywords: factor concentrates, haemophilia, immune parameters Introduction It is known that extensive blood product usage affects the immune system of the recipient. Prophy- lactic therapy for haemophilia has been practiced in the world for many years especially after the current viral inactivation methods. Aim of prophylaxis is to prevent haemorrhage and arthropathy, to maintain joint function and to integrate haemophilic children into society. However, there is a need to use intensive amount of clotting factor concentrates (CFC) for prophylaxis. Abnormalities of various immune parameters have been reported not only in HIV-positive but also in HIV-negative haemophilics [1,2]. Previous studies have shown some immune abnormalities in haemo- philics receiving CFC. These include decreased CD4+/CD8+ T-cell ratio, decreased IL-2 secretion, cutaneous anergy and monocyte function defects [3]. It has been reported that these abnormalities are due to prolonged massive exposure to blood proteins such as fibrinogen, fibronectin, IgG, IgM, albumin, alloantigens transfused with the factor concentrates, viral infections and chronic liver diseases [1,4]. While some studies have revealed a few immune parameter abnormalities in haemophilic patients exposed to low and intermediate purity CFC [3,5], other studies did not show any abnormality in these patients [6,7]. An increased susceptibility to infection in patients with haemophilia receiving CFC has also been reported [8,9]. The cause of abnormal immune Correspondence: Can Balkan MD, Specialist, Department of Pediatric Hematology, Ege University School of Medicine, 35100 Bornova, Izmir, Turkey. Tel.: +90 532 627 5964; fax: +90 232 388 9900; e-mail: cbalkan@med.ege.edu.tr Accepted after revision 26 May 2005 Haemophilia (2005), 11, 366–370 DOI: 10.1111/j.1365-2516.2005.01110.x 366 Ó 2005 Blackwell Publishing Ltd