ORIGINAL CONTRIBUTIONS HIGH-PURITY FACTOR VIII CONCENTRATES PRODUCED WITHOUT USING MONOCLONAL ANTIBODIES PIER MANNUCCIOMANNUCCI,ALESSANDRO GRINGERI, MARCO CATTANEO Centro Emofilia e Trombosi Angelo Bianchi Bonomi ed Istituto di Medicina lnterna, Universita degli Studied Ospedale Maggiore, Milano In the last decade, commercial and noncommercial manufacturers of clot- ting factor concentrates have increased the purity of their plasma-derived fac- tor VIII (FVIII) concentrates. Taking specific activity (expressed in interna- tional units of FVIII coagulant activity, FVIII:C, per mg of total protein con- tained in the concentrate) as an indicator for purity, all products available until very recently (the so-called intermediate-purity concentrates) had values of less than 5 U/rag a6. This meant that, of the total proteins contained in these products, FVIII:C (the only protein needed by the hemophiliac) accounted for only about 0.05%. However, these products have been successfully used for about 20 years to treat hemophiliacs. The advent of the acquired immunode- ficiency syndrome (AIDS) epidemic was the main factor that stimulated the development of purer concentrates. On the basis of preliminary data indicat- ing that protein load induced by multiple infusions of intermediate-purity con- centrates might adversely influence the immune status of hemophiliacs ~z,24, it was postulated that purer concentrates (with a lower alloantigenic burden) might stabilize the immunological derangement in hemophiliacs and perhaps delay the progression of asymptomatic human immunodeficiency virus (HIV) infections towards AIDS 3. While still remaining unproven, this hypothesis undoubtedly stimulated most manufacturers of concentrates to increase the purity of their products. The general strategy followed to achieve this goal was that of adding to the regular fractionation process a further purification step. Highly purified FVIII concentrates were first prepared by immunoaffmity chromatography using murine monoctonal antibodies to FVIII or to von Willebrand factor y,23. More recently, other protein purification methods have been employed, such as ion- exchange chromatography, gel filtration (molecular sieving) and affinity chro- matography using Iigands of non-antibody origin. These methods appear to give a better yield of FVIII than those based on monoclonal antibodies, al- Key-words: Factor VIII; Factor VIII concentrates; Hemophilia; Viruddal methods; yon Willebrand disease. Accepted for publication on August 27, t990. Res. Clin. Lab. 20, 227-237, 1990. 227