Problems in the standardization of Factor VIII assays.

An international system of unitage, based on the World Health Organization International Standard, exists for the measurement of factor VIII clotting activity (VIII: C). In recent years, systematic discrepancies between assay results in different laboratories have brought to light two major problems in VIII: C standardization. Firstly, large discrepancies can arise between laboratories even when the same assay method is used. These are due mainly to differences in reagents. Secondly, when assaying plasmas against concentrates, there is, on average, a 20% discrepancy between one-stage and two-stage potency estimates. At least half this discrepancy appears to be attributable to the step of aluminium hydroxide adsorption, which is routine in the two-stage assay, but not used in the one-stage assay. The combined implication of these discrepancies, namely that the result of an VIII: C assay depends both on assay method and on reagents, reveals certain limitations in the present system of standardization.