Ej. Favaloro et J. Koutts, LABORATORY ASSAYS FOR VON-WILLEBRAND-FACTOR - RELATIVE CONTRIBUTION TO THE DIAGNOSIS OF VON-WILLEBRANDS-DISEASE, Pathology, 29(4), 1997, pp. 385-391
Appropriate investigation of a patient with suspected von Willebrand's
disease (VWD) involves a clinical assessment of the patient followed
by laboratory testing. A variety of laboratory assays may be performed
, not necessarily restricted to an assessment of von Willebrand factor
(VWF). Due to the limitations of each assay, and because of VWD heter
ogeneity, no single test procedure is sufficiently robust to permit de
tection of all VWD variants. Indeed, these factors often lead to consi
derable confusion in the process of laboratory interpretation regardin
g the likelihood of VWD, and the subtype of VWD. This paper attempts t
o clarify some of the issues that lead to this confusion. It analyses
the relative contribution of four separate assays for VWF [VWF:Multime
r analysis, VWF:Antigen (VWF:Ag), VWF:Ristocetin Cofactor (VWF:RCof),
and VWF:Collagen Binding Activity assay (VWF:CBA)] to the diagnosis an
d classification of VWD. Although each assay detects VWF, it is import
ant to recognise that each assay provides different information on the
VWF so detected. For example, while the VWF:Ag assay is a quantitativ
e assay and provides a very good measure of the overall level or VWF p
resent in a patient's plasma, it is not a functional assay and yields
no information concerning the quality of the VWF present. Thus, the VW
F:AS on its own will not permit detection of many qualitative defects
(consequently, use of this assay alone will lead to many Type 2 VWD pa
tients being missed by the laboratory). In contrast, the VWF:CBA is a
functional assay which provides very useful information on the quality
of VWF present. Although the VWF:CBA is also a quantitative assay, it
is less sensitive than the VWF:Ag assay in terms of its ability to me
asure the overall level of VWF (ie; the VWF:CBA detects only highly ad
hesive VWF, and therefore only a proportion of overall VWF). In essenc
e, the VWF:Ag and VWF:CBA assays are complementary assays and should b
e used in combination. The VWF:Multimer assay is a qualitative procedu
re, but at best is only semi-quantitative. The VWF:Multimer assay esse
ntially provides a snap-shot of the VWF present. Unfortunately conside
rable technical and interpretive problems limits its overall applicabi
lity and usefulness. The VWF:RCof assay is both a quantitative and qua
litative assay that provides information about the presence of VWF tha
t lies between that provided individually by the VWF:Ag and VWF:CBA as
says. unfortunately, the VWF:RCof suffers considerable technical probl
ems, including considerable assay variability, that also limits its ov
erall usefulness. Laboratories performing assays for VWF need to devel
op diagnostic strategies which include the use of appropriate multiple
test combinations so as to ensure that VWD is properly detected.