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Clinically relevant differences between assays for von Willebrand factor activity
Author(s) -
Boender J.,
Eikenboom J.,
Bom J. G.,
Meijer K.,
Meris J.,
Fijnvandraat K.,
Cnossen M. H.,
Larosvan Gorkom B. A. P.,
Heerde W. L.,
MauserBunschoten E. P.,
Maat M. P. M.,
Leebeek F. W. G.
Publication year - 2018
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.14319
Subject(s) - von willebrand factor , ristocetin , von willebrand disease , platelet , platelet membrane glycoprotein , platelet glycoprotein gpib ix complex , glycoprotein ib , immunology , population , medicine , environmental health
Essentials It is unclear whether there are differences between von Willebrand factor (VWF) activity assays. We compared the four most used VWF activity assays in 661 von Willebrand disease (VWD) patients. All assays correlated excellently, but a discrepant classification was seen in 20% of patients. Differences between VWF activity assays have a large impact on the classification of VWD.Summary Background Measuring the ability of von Willebrand factor ( VWF ) to bind to platelets is crucial for the diagnosis and classification of von Willebrand disease ( VWD ). Several assays that measure this VWF activity using different principles are available, but the clinical relevance of different assay principles is unclear. Objective To compare the four most widely used VWF activity assays in a large VWD patient population. Methods We measured VWF : RC o (ristocetin to activate VWF + whole platelets), VWF : GPI bR (ristocetin + platelet glycoprotein Ib receptor [ GPI b] fragments), VWF : GPI bM (gain‐of‐function GPI b fragments that bind VWF spontaneously without ristocetin) and VWF :Ab (monoclonal antibody directed against the GPI b binding epitope of VWF to mimic platelets) in 661 VWD patients from the nationwide ‘Willebrand in the Netherlands’ (WiN) Study. Results All assays correlated excellently (Pearson r > 0.9), but discrepant results led to a different classification for up to one‐fifth of VWD patients. VWF : RC o was not sensitive enough to classify 18% of patients and misclassified half of genotypic 2B VWD patients, especially those with p.Arg1306Trp. VWF : GPI bR was more sensitive, accurately classified the vast majority of patients, and was unaffected by the p.Asp1472His variant that causes artificially low VWF : RC o. VWF : GPI bM was the most precise assay but misclassified over a quarter of genotypic 2A, 2B and 3 patients. VWF :Ab, often not considered an actual VWF activity assay, performed at least equally to the other assays with regard to accurate VWD classification. Conclusion Although the different VWF activity assays are often considered similar, differences between assays have a large impact on the classification of VWD .