LABORATORY ASSESSMENT OF VON-WILLEBRAND-FACTOR - ALTERED INTERPRETATION OF LABORATORY DATA, AND ALTERED DIAGNOSIS OF VON WILLEBRANDS DISEASE

Three laboratory assays for von Willebrand Factor (vWF), namely, (i) a standard ''antigen'' [antisera-enzyme-linked immunosorbent assay (ELI SA)-based] (vWF:Ag), (ii) a standard ristocetin-dependent platelet agg lutination procedure (vWF:RCof), and (iii) a newly developed ELISA-bas ed functional vWF collagen binding assay (vWF:CBA), were coevaluated. We (a) assessed their ability to detect VWF under different assay cond itions and Cb) reevaluated normal vWF reference ranges using citrated plasma from >200 normal individuals, The following effective normal re ference ranges were derived: vWF-Ag (40-200%), vWF:CBA (50-400%), and vWF:RCof (45-200%). Based on other laboratory data, caution is indicat ed in the interpretation of ''borderline'' or ''equivocal'' test resul ts (e.g., 35-55%), since these may derive from normal individuals or f rom vWD patients. Ln addition, our study shows that selection of diffe rent assay conditions, different test plasma dilutions, or different t est sample processing methods can also lead to differences in the ''ap parent'' levels of detected vWF. For example, using plasma from 100 no rmal individuals processed as ''test samples,'' we determined that hig her sample dilutions tended to provide lower (dilution factor adjusted ) assay results in the case of the vWF:Ag and vWF:CBA, and higher assa y results in the case of the vWF:RCof, with greater differences noted in test samples containing higher levels of vWF. The explanation for t hese findings relate to the assay design. Thus, in the diagnostic labo ratory, the standard vWF:Ag, vWF:CBA, and vWF:RCof assays procedures a re designed to provide calibration curves that are ''upward linear'' i n the (vWD) clinically important region of 0-50% of normal, with a pla teau tending at higher VWF levels. Using these standard methodologies, and standard plasma dilutions, high-vWF level test samples will tend to fall on or near the plateau, and results will be unreliable, with a tendency to be exaggerated the higher the vWF. These findings have pa rticular relevance to research studies measuring VWF in patients suffe ring various clinical conditions (e.g., thrombotic thrombocytopenic pu rpura, diabetes, renal failure) where higher than normal levels of VWF may be anticipated. In these cases, laboratory-derived vWF levels cou ld be ''misrepresented'' if the study design did not take into account the need to revise the vWF testing procedure.