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Gain-of-function GPIb ELISA assay for VWF activity in the Zimmerman Program for the Molecular and Clinical Biology of VWD. Blood 2011 Feb 10;117(6):e67-74



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Pubmed Central ID




Scopus ID

2-s2.0-79951469339   73 Citations


von Willebrand disease (VWD) is a common bleeding disorder, but diagnosis is sometimes challenging because of issues with the current von Willebrand factor (VWF) assays, VWF antigen (VWF:Ag) and VWF ristocetin cofactor activity (VWF:RCo), used for diagnosis. We evaluated 113 healthy controls and 164 VWD subjects enrolled in the T.S. Zimmerman Program for the Molecular and Clinical Biology of VWD for VWF:Ag, VWF:RCo, and a new enzyme-linked immunosorbent assay (ELISA)-based assay of VWF-glycoprotein Ib (GPIb) interactions using a gain-of-function GPIb construct (tGPIbα(235Y;239V)) as a receptor to bind its ligand VWF in an assay independent of ristocetin (VWF:IbCo ELISA). Healthy controls, type 1, 2A, 2M, and 2N subjects had VWF:RCo/VWF:Ag ratios similar to the ratio obtained with VWF:IbCo ELISA/VWF:Ag. Type 2B VWD subjects, however, had elevated VWF:IbCo ELISA/VWF:Ag ratios. Type 3 VWD subjects had undetectable (< 1.6 U/dL) VWF:IbCo ELISA values. As previously reported, VWF:RCo/VWF:Ag ratio was decreased with a common A1 domain polymorphism, D1472H, as was direct binding to ristocetin for a 1472H A1 loop construct. The VWF:IbCo ELISA, however, was not affected by D1472H. The VWF:IbCo ELISA may be useful in testing VWF binding to GPIb, discrimination of type 2 variants, and in the diagnosis of VWD as it avoids some of the pitfalls of VWF:RCo assays.

Author List

Flood VH, Gill JC, Morateck PA, Christopherson PA, Friedman KD, Haberichter SL, Hoffmann RG, Montgomery RR


Veronica H. Flood MD Professor in the Pediatrics department at Medical College of Wisconsin
Kenneth D. Friedman MD Professor in the Medicine department at Medical College of Wisconsin
Robert R. Montgomery MD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amino Acid Substitution
Blood Chemical Analysis
Case-Control Studies
Enzyme-Linked Immunosorbent Assay
In Vitro Techniques
Membrane Glycoproteins
Mutant Proteins
Platelet Glycoprotein GPIb-IX Complex
Platelet Membrane Glycoproteins
Polymorphism, Genetic
Protein Binding
Protein Multimerization
Recombinant Proteins
von Willebrand Disease, Type 1
von Willebrand Disease, Type 2
von Willebrand Disease, Type 3
von Willebrand Diseases
von Willebrand Factor