Differential sensitivity of von Willebrand factor (VWF) 'activity' assays to large and small VWF molecular weight forms: a cross-laboratory study comparing ristocetin cofactor, collagen-binding and mAb-based assays
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Date
2012
Authors
Favaloro, E. J.
Bonar, R.
Chapman, K.
Meiring, M.
Funk, D.
Journal Title
Journal ISSN
Volume Title
Publisher
International Society on Thrombosis and Haemostasis
Abstract
Background: von Willebrand disease (VWD), the
most common inherited bleeding disorder, is caused by
deficiencies and/or defects in von Willebrand factor (VWF).
An effective diagnostic and VWD typing strategy requires
plasma testing for factor VIII, and VWF antigen plus one or
moreVWF'activity' assays. VWFactivity is classically assessed
by using VWF ristocetin cofactor activity (VWF:RCo),
although VWF collagen-binding (VWF:CB) and VWF mAbbased
(VWF activity [VWF:Act]) assays are used by some
laboratories. Objective: To perform a cross-laboratory study
to specifically evaluate these three VWF activity assays for
comparative sensitivity to loss of high molecular weight
(HMW) VWF, representing the form of VWF that is most
functionally active and that is absent in some types of VWD,
namely 2A and 2B. Methods: A set of eight samples, including
six selectively representing stepwise reduction in HMW VWF,
were tested by 51 different laboratories using a variety of
assays. Results: The combined data showed that the VWF:CB
and VWF:RCo assays had higher sensitivity to the loss of
HMW VWF than did the VWF:Act assay. Moreover, withinmethod
analysis identified better HMW VWF sensitivity of
some VWF:CB assays than of others, with all VWF:CB assays
still showing better sensitivity than the VWF:Act assay.
Differences were also identified between VWF:RCo methodologies
on the basis of either platelet aggregometry or as
performed on automated analyzers. Conclusions: We believe
that these results have significant clinical implications for the
diagnosis of VWD and monitoring of its therapy, as well as for
the future diagnosis and therapy monitoring of thrombotic
thrombocytopenic purpura.
Description
Keywords
Diagnosis, High molecular weight sensitivity, Laboratory testing, Von Willebrand disease, Von Willebrand factor, Diagnosis, Laboratory, Blood -- Diseases
Citation
Favaloro, E. J., Bonar, R., Chapman, K., & Meiring, M. (2012). Differential sensitivity of von Willebrand factor (VWF)‘activity’assays to large and small VWF molecular weight forms: a cross‐laboratory study comparing ristocetin cofactor, collagen‐binding and mAb‐based assays. Journal of Thrombosis and Haemostasis, 10(6), 1043-1054.