Non Factor Viii Related Constituents in Concentrates

Factor VIII preparations contain a variety of components unrelated to the Factor VIII complex which represents only a trace protein. Some of these “contaminants” are plasma proteins, mainly fibrinogen, fibronectin, IgG, IgM and albumin accounting for over 70 per cent of the total protein content. Biologically active proteins such as AT III, Factor XIII, proteolytic enzymes and prekallikrein activator are also present and may interfere with clinical tolerance of Factor VIII activity. However, immunoglobulins are the major source of side effects related to both the structure and the specificities of these molecules. Hemolysis caused by anti‐A or anti‐B allo‐agglutinins is a well characterized side effet. Various chemicals added during the purification process of the final product are found in the therapeutic concentrates. Viral infective agents originating from unscreened donors contaminate large plasma pools and concentrates. Viruses related to hepatitis (B hepatitis, non‐A, non‐B hepatitis, CMV, EBV) or not formally pathogenic (HTLV, LAV, Parvovirus) are transmitted by Factor VIII infusion and a high incidence of specific viral markers are found in hemophilia A patients. The iatrogenic role of these constituents in the short or long term should be thoroughly evaluated. Factor VIII related proteins are only a very small fraction among the numerous components present in the so called “Factor VIII concentrates”. Recipients are therefore submitted to various hazards related to: other human proteins which copurified with Factor VIII; infective agents, primarily viruses, whose large molecular weights tend to follow large molecular weight proteins like the Factor VIII complex; trace amounts of various chemicals used during the purification process. Since most hemophilia A patients are repeatedly treated with these complex mixtures, it is of primary importance to identify these components termed “contaminants” and to evaluate their potential side effects in immediate, short and long terms. This chapter will list these contaminants irrespective of their potential iatrogenic value and indicate briefly some of their harmful consequences.