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Factors VIII and IX administration exposes haemophiliac patients to the risk of inhibitor development which reduces treatment efficacy. Methods and results of 17 studies (transversal and longitudinal) and of one clinical trial dealing with haemophilia A and of 3 studies dealing with haemophilia B were reviewed. Besides differences in study design, lack of method standardisation complicates comparison between studies. In patients with haemophilia A, prevalence of inhibitors ranges from 4 to 18% (5 studies), and incidence between 3 and 39/1,000 person-years (7 studies). Cumulative age incidence is above or equal to 20% after 6 years of age (4 studies). Cumulative incidence by exposure days is estimated at 22% at 100 exposure days in a retrospective cohort observed between 1975 and 1992, and above or equal to 36% at 25 exposure days in two prospective cohorts of patients receiving recombinant factor VIII products. The new European regulation dealing with stable blood products will make the evaluation of new products by clinical trials mandatory. With The National therapeutic Follow up of Haemophiliacs which begun in October 1994, following a decision by the French Minister of Health, the adverse effects in patients receiving factor VIII and IX which have been approved for sales will be evaluated.

We observed for a two years period 157 hemophiliacs (138 with hemophilia A whose 13 were severe and 19 with hemophilia B whose 13 were severe) and we studied the incidence of liver dysfunction and the role played by HB and non-A, non-B, viruses. Whereas 32 patients not related had no evidence of serological HB virus markers (by radioimmunoassay), 88 (70,4 %) among the 135 hemophiliacs with large or small exposure to blood products were "HB positive". 90,9 % were positive for anti-HBs and anti-HBc antibodies and only two patients had persistent antigenemia. These results appeared independent of the kind of treatment (factor VIII or factor IX concentrates). Six among 17 children born since 1974, when the antigen was detected by RIA, had the serological HB virus markers, showing that this method is not sufficient to completely eliminate the HB virus. However the amount of viruses injected is too small to induce an acute hepatitis and rather produces specific antibodies which protect hemophiliacs against reinfection. An elevated level of serum transaminases (SGPT) was observed in 9,4 % of non treated hemophiliacs, 15,1 % of treated hemophiliacs with no serological markers of HB virus and 27,7 % of treated hemophiliacs "HB positive". This shows that the use of concentrates and the occurring of HB virus in the patients are not the only factors producing liver dysfunction. The role of non-A, non-B viruses has been recognized in 7 patients out of 9 with transient elevation of serum transaminase levels, by Trepo with an immunodiffusion technique.

Blood T-lymphocyte subsets and serum immunoglobulin levels were studied in a group of 52 haemophiliacs (44 patients with haemophilia A and 8 patients with haemophilia B). None of the patients had AIDS or belonged to any AIDS high-risk group. Patients were exclusively treated with clotting fractions obtained from healthy volunteers in metropolitan France. As compared to a group of 52 normal donors, haemophiliacs had increased numbers of suppressor lymphocytes, which resulted in depressed helper/suppressor (H/S) ratios, and increased levels of serum IgG and IgA. 21 haemophiliacs (40,3%) had a H/S ratio less than 1.4. Among patients with haemophilia A a higher mean IgG level was found in patients presenting lymphadenopathy. Decreased mean H/S ratio and increased mean serum IgG level were found in patients receiving more than 50 000 U of factor VIII during the 2 years preceding the study. No striking difference in mean serum IgG, IgA and IgM levels was found in patients with haemophilia A when H/S ratios were higher and lower than 1.4 respectively. As AIDS and immunological abnormalities among haemophiliacs probably share a common viral origin, this study emphasize the need to discourage blood donation from donors who belong to any AIDS high-risk group, and to screen sera from the blood donor population for antibodies to LAV/HTLV III.