Factor VIII-Related Activities in therapeutic concentrates

Abstract

Levels of Factor VIII clotting activity (VIII:C), VIII clotting antigen (VIII: CAg), VIII related antigen (VIII R:Ag) and ristocetin co-factor (RCF) have been compared in several batches of the various concentrates used therapeutically in the U.K. The mean ratio of VIII R:Ag to VIII:C ranged from 2 to 4, but a major problem in VIII R:Ag assays of concentrates against a plasma standard was non-parallelism of the dose-response curves. This reflects the abnormality of the antigen in the concentrates, as shown by its more rapid mobility on crossed immunoelectrophoresis. Ratios of VIII: CAg to VIII:C ranged from less than 1 to about 2; the higher ratios indicate denaturation of the clotting part of the molecule during purification. All concentrates had RCF levels at least equivalent to their clotting activity, but lower than their VIII R:Ag levels. At high dilutions, most concentrates gave an acceptable parallel line bioassay against a plasma standard, but as the concentration of ristocetin co-factor was increased, non-parallelism was observed, due to a failure of the plasma response to increase with increasing dose. In treatment of patients with haemophilia and von Willebrand’s disease, it should be recognised that concentrates which are equivalent in VIII:C potency may nevertheless display a wide spectrum of other Factor VIII-related activities.