Functional and immunological assays of FVIII in 133 haemophiliacs--characterization of a subgroup of patients with mild haemophilia A and discrepancy in 1- and 2-stage assays.

A systematic study of the levels of FVIII antigen and activity was done in 133 haemophiliacs. No measurable antigen was demonstrated in the 60 severe haemophiliacs, with the exception of 3 patients with levels ranging between 1.5 and 4.5 U/dl, which corresponded to a dramatic FVIII deficiency. The situation was more complex with the 73 moderate and mild haemophiliacs: 39 of them (53.4%) had a partial, concordant deficiency of both the antigen and the procoagulant activity (1- and 2-stage methods), likely corresponding to a decrease in the synthesis of normal FVIII. The conclusion for the other 34 patients, was a qualitative abnormality of FVIII, the levels of antigen in comparison with the procoagulant activity (1-stage method) appearing to be either very reduced (n = 6) or even nil (n = 8), or on the contrary very much higher (n = 20) or normal. For 11 patients in this last category, we found a clear discrepancy between the procoagulant activity levels obtained with the 2 different techniques, the 1-stage levels being higher than the 2-stage levels. This discrepancy which was stable with restudy on multiple occasions and found in different members of the same families was remedied when vWF was absent in one-stage assay. This suggests that we have identified a variant of haemophilia A with an inherited abnormality of FVIII characterized by an in vitro vWF-dependent expression of procoagulant activity.