von Willebrand's disease: laboratory investigation using an improved functional assay for von Willebrand factor

This report details extensive studies investigating an improved screening procedure for the laboratory confirmation of clinically suspected von Willebrand's disease (vWD). Over the past two years, over 400 plasma samples, comprising samples derived from both normal individuals (n = 112) and from patients undergoing investigation on clinical grounds, underwent analysis in this screening procedure, comprising three distinct assays: a standard ELISA assay for von Willebrand Factor (vWF) antigen levels (vWF:Ag), a standard ristocetin cofactor (R Cof) assay, and a functional collagen based ELISA assay for vWF ('CBA'). Normal individual plasma samples yielded normal reference values (mean +/- 2SD) approximating 50-200% (vWF:Ag, R Cof) or 50-250% (CBA). In order to permit comparative analysis, and based upon derived assay values, and subsequent multimer analysis, patient samples were either deemed to derive from persons unlikely to suffer vWD ('non-vWD' patient group) or those potentially suffering vWD. The latter group was further separated into subgroups based upon the likelihood, and probable subtype of vWD. In conjunction with the vWF:Ag assay, the CBA provides the basis by which an effective predictor system (likelihood and probable subtype of vWD) can be offered on the basis of preliminary screening procedures. To date, there has been no overlap in vWF:Ag to CBA ratios (vWF:CBA) between patients yielding Type II vWD like multimer patterns and those yielding Type I vWD, or normal, multimer patterns. Thus, high vWF:CBA (i.e. > or = 3.0) would suggest a Type II, or pseudo, -vWD like defect, whereas low vWF:CBA (< or = 2.5) would likely derive from either normal individuals, or persons suffering from Type I vWD.(ABSTRACT TRUNCATED AT 250 WORDS)