PURITY OF FACTOR Vlll CONCENTRATES AND IMMUNE FUNCTION IN HEMOPHILIACS

The report by de Biasi et all is an important contribution to the debate regarding the possible role of product purity in modulating immune function in hemophiliacs. However, some aspects of the study bear comment. Patients treated with an intermediate-purity concentrate showed a deterioration in immune function compared with those treated with a high-purity product. The two products, however, did not differ simply in the degree of purity. Indeed, it is curious that the investigators state that “both the concentrates have been previously established to be efficacious and safe in the treatment of hemophilia A patients.”’ Their supporting reference shows that the intermediate purity concentrate, Kryobulin TIM 3, has been implicated in the transmission of hepatitis B.2 As is remarked in this latter study, this may also have masked transaminase elevations from hepatitis C infection. Recent findings suggest that hepatitis C infection is more closely associated with certain immunologic abnormalities in both human immundeficiency virus (H1V)-positive and HIV-negative hemophiliacs than the amount or type of concentrate i n f ~ s e d . ~ Previously unexposed hemophiliacs treated over 5 years with an intermediate-purity, severely heat-treated concentrate have shown no evidence of infection by HIV, hepatitis B virus, and hepatitis C virus, and immune function was unaffected! Although this patient group was HIV-negative (due to life-long treatment with a severely heated product), as opposed to the patients studied by de Biasi et al,’ it seems that infection with agents other than HIV may play a role in immune modulation. This may be difficult to distinguish from any effects due to chronic protein infusion unless fully accredited methods, such as severe dry heating or solvent detergent treatment, are used to sterilize the intermediate-purity concentrates being compared with the high-purity products. Until such studies are made in both HIV-positive and HIV-negative hemophiliacs, it is difficult to fully endorse de Biasi et al’s conclusion that “the results of this study clearly support the use of very high purity concentrates for the replacement therapy of HIV-infected hemophiliacs.”’