Serial studies in von Willebrand's disease: variability versus "variants"

The variability of laboratory findings in von Willebrand's disease (vWd) was evaluated by performing serial studies of bleeding time (BT), factor VIII coagulant activity (VIII:C), factor-VIII-related antigen (VIIIR:Ag) and ristocetin cofactor (VIIIR:Rcof) in 50 individuals from 25 families with this disorder. The types of results were characterized from 1 to 16 based on the possible combinations of findings using these four tests. The only patients observed to have consistently abnormal results of all four tests were three individuals with homozygous vWd. Individuals with autosomal dominant vWd were found to have a variety of results and all 16 possible types were observed. Although a consistent pattern was present within some families, others with equivalent history of bleeding demonstrated widely variable types of results. The results within some families, others with equivalent history of bleeding demonstrated widely variable types of results. The results of serial studies of the same tests in 10 normal individuals indicated relative stability, with nearly all values within the usual range of normal, but some independent variation of factor-VIII-related activities was observed. These studies indicate that: (1) the results of BT, VIII:C, VIIIR:Ag, and VIIIR:Rcof vary considerably from time to time in many individuals with vWd, (2) a classification of “variants” of vWd based solely on such studies may be inappropriate, particularly if the tests are not repeated, and (3) repeated testing may be required to establish the diagnosis of vWd in some individuals.