Factor Viii Related Activities in Concentrates

Abstract

Factor VIII related activities were investigated in 3 low purity concentrates (fraction 1‐0 and freeze‐dried cryoprecipitates), 2 intermediate concentrates, and 8 high purity concentrates. The parameters studied were VIII:C by one‐stage assay and chromogenic assay, VIII clotting antigen (VIII:CAg), VIII related antigen (VIIIR:Ag) by electroimmunoassay, immunoradiometric assay (IRMA), crossed immuno‐electrophoresis (CIE) and SDS agarose gel electrophoresis followed by staining with radioactive antibody, ristocetin cofactor activity (R:RCF) and fibrinogen. The VIII:C values from the chromogenic assay method agreed well with those obtained by the one‐stage assay. The specific activity varied considerably between the different concentrates and even between different batches. DDAVP Octonativ and Factorate had the highest specific activity. With the exception of Factorate, all preparations had higher concentrations of VIII:CAg than of VIII:C — probably indicating inactivation of the biological activity of VIII:C during the manufacturing process. Studies of the Factor VIII/von Willebrand factor showed that all the concentrates contain considerable amounts of VIIIR:Ag as measured by electroimmunoassay. The intermediate and the high purity concentrates had much lower concentration of VIIIR:Ag as determined by IRMA than by electroimmunoassay, and the dose response curves were non‐parallel. On CIE they showed an abnormal migration. Multimeric sizing demonstrated that all the intermediate and high purity concentrates were lacking in the high molecular weight multimers. Fraction 1‐0 and the cryoprecipitates, the only preparations capable of correcting the bleeding defect in patients with von Willebrand's disease, showed about the same concentration of VIIIR:Ag as determined by electroimmunoassay and IRMA, normal migration in CIE, and the same multimeric pattern as normal plasma. The VIIIR:RCF values were much lower than those for VIIIR:Ag, as determined by electroimmunoassay. Thus, considerable differences were found of the in vitro properties of Factor VIII related activities between low, intermediate and high purity Factor VIII concentrates. The action of proteases and the techniques used in purification probably have a crucial effect on the properties.

von Willebrand's disease

“…Fresh frozen plasma can only be used in those cases where more intensive substitution therapy is not required. Most commercial factor VIII concentrates of intermediate or high purity used in the treatment of hemophilia A generally fail to correct the bleeding defect in vWD because such preparations lack the large multimers of vWF and are unable to provide platelet adhesion to subendothelium (115,(118)(119)(120). The concentrates used in hemophilia A are, of course, effective in increasing the factor VIII concentrations, and can be used in cases of hemophilia-like lesions in patients with type 111 vWD, though it should be stressed that they cannot be used in such situations where it is necessary to correct the defective primary hemostasis and the prolonged bleeding time.…”

The use of blood components in the treatment of congenital coagulation disorders

“…Several commercial concentrates prepared from American plasma are available such as Hemofil-Travenol, Factorate-Armour, Profilate-Alpha, and Kryobulin-Immuno. Since 1980, Sweden has had its own high-purity concentrate manufactured from Swedish plasma, Octonativ-Kabi [8,9]. All these preparations are now heat-treated in different ways.…”

Biochemical and in vivo properties of commercial virus‐inactivated factor VIII concentrates

“…Since factor VIII concentrates are necessary for the treatment not only of patients with hemophilia A but also for those with severe von Willebrand's disease, it is important to know all the factor VIII-related activities contained in the various concentrates available. In an earlier series of studies, we examined the in vitro and in vivo properties of different factor VIII concentrates (1)(2)(3). The in vitro properties of factor VIII-related activities were found to differ considerably between low, intermediate and high purity concentrates.…”