INCIDENCE OF FACTOR-VIII INHIBITOR DEVELOPMENT IN HEMOPHILIA-A PATIENTS TREATED WITH LESS PURE PLASMA-DERIVED CONCENTRATES

Very-high-purity Factor VIII concentrates produced by monoclonal or re combinant technology have been postulated to be more antigenic resulti ng in an increased risk of inhibitor development in hemophilia A patie nts. However, previous reports, mainly based on prevalence figures, ma y have understimated the ''true'' risk of this complication in patient s treated with less pure Factor VIII concentrates. The present study, started in 1975, has been designed to calculate the risk of inhibitor development in patients with severe or moderate hemophilia A, followed since their first exposure to intermediate or high-purity Factor VIII concentrates, produced by conventional technologies. Sixty-four hemop hiliacs fulfilled the enrollment criteria. Inhibitors developed in 20. 3% (13/64) of all patients and in 23% (11/48) of those with severe Fac tor VIII deficiency. Eleven patients manifested a strong anamnestic re sponse after exposure to Factor VIII (high responders) and 2 had low i nhibitor concentrations despite repeated Factor VIII infusions (low re sponders). The incidence of inhibitor development was 24.6 per 1000 pa tient-years of observation. The cumulative risk of inhibitor formation was 19.9% at age of 6 years, and 20.3% at 5 years after the first exp osure. The risk was 19.3% at 70 days of exposure to Factor VIII concen trates, and 17.2% after a total of 50,000 units of Factor VIII given. Further studies are needed to confirm the above risk of acquiring an i nhibitor, which indicates an under-estimation by previous studies. In addition, more data is needed to demonstrate whether very-high-purity Factor VIII concentrates may be more antigenic than conventional prepa rations.