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. 2024 Jan;30(1):161-168.
doi: 10.1111/hae.14901. Epub 2023 Nov 27.

Von Willebrand Factor (VWF) multiplex activity assay differentiation of type 1 von Willebrand Disease (VWD) and variant VWD

Jonathan C Roberts  1   2 , Pamela A Christopherson  3 , Michael D Tarantino  1   2 , Sarah E Gonzales  1 , Patti A Morateck  3 , Crystal L Perry  3 , Veronica H Flood  3   4 , Thomas C Abshire  3   4 , Robert R Montgomery  3   4 ; Zimmerman Program Investigators
Affiliations

Von Willebrand Factor (VWF) multiplex activity assay differentiation of type 1 von Willebrand Disease (VWD) and variant VWD

Jonathan C Roberts et al. Haemophilia. 2024 Jan.

Abstract

Introduction: VWD diagnosis is challenging requiring multiple VWF activity tests using many individual assays. We have developed an ELISA-based VWF Multiplex Activity Assay (VWF-MAA) to address this concern; however, the ability of the VWF-MAA to discriminate between type 1 VWD, variant VWD, and normal subjects has not been evaluated.

Aim: To evaluate the VWF-MAA and its ability to differentiate between type 1 VWD, variant VWD and normal subjects in individuals undergoing an initial laboratory evaluation for bleeding.

Methods: A total of 177 plasma samples from the Zimmerman Program: Comparative Effectiveness in the Diagnosis of VWD were evaluated from 11 centres across the US and Canada. The VWF-MAA was compared to Versiti Blood Research Institute (VBRI) and Local Center (LC) assigned VWD diagnosis.

Results: Overall, 129/177 (72.9%) were correctly assigned as normal (non-VWD), type 1, or variant VWD compared to the VBRI assigned diagnosis. VWF-MAA assigned non-VWD accurately in 29/57 (50.9%) samples, and type 1 VWD accurately in 93/110 (84.6%) samples. Considering LC diagnosis where there was agreement with VWF-MAA and not VBRI diagnosis, type 1 VWD was accurate in 105/110 (95.5%) samples. Bland-Altman analysis demonstrated good correlation between laboratory methods. VWD, types 2A, 2B, 1C VWD were also assigned by the VWF-MAA.

Conclusions: We demonstrate that the VWF-MAA has utility in differentiating type 1 VWD, variant VWD and normal subjects in individuals undergoing an initial laboratory evaluation for bleeding.

Keywords: haemostasis; laboratory diagnosis; laboratory testing; von Willebrand Disease; von Willebrand Factor.

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Conflict of interest statement

Conflict of Interest

R.R.M. holds a patent assigned to the Versiti Blood Center of Wisconsin for a VWF platelet binding assay. The remaining authors report no conflicts of interest related to this study.

Figures

Figure 1:
Figure 1:. Agreement between Versiti Blood Research Institute, Local Center Laboratory, and VWF-MAA Measurements
A. Analysis of agreement of non-VWD between Versiti Blood Research Institute (VBRI) VWF:Ag and the von Willebrand Factor multiplex activity assay (VWF-MAA) showed mean difference (MD) 69.7, lower limit of agreement (LoA) 17.8, upper LoA 121.5, and a standard deviation (SD) 26.4 B. Analysis of agreement of non-VWD between Local Center (LC) VWF:Ag and the VWF-MAA demonstrated MD 69.3, lower LoA 16.2, upper LoA 122.4, and SD 27.1. C. Analysis of agreement of type 1 VWD between VBRI VWF:Ag and the VWF-MAA showed MD 49, lower LoA 13.9, upper LoA 84.1, and SD 17.9. D. Analysis of agreement of type 1 VWD between LC VWF:Ag and the VWF-MAA demonstrated MD 47.7, lower LoA 17.1, upper LoA 78.3, and SD 15.6.
Figure 1:
Figure 1:. Agreement between Versiti Blood Research Institute, Local Center Laboratory, and VWF-MAA Measurements
A. Analysis of agreement of non-VWD between Versiti Blood Research Institute (VBRI) VWF:Ag and the von Willebrand Factor multiplex activity assay (VWF-MAA) showed mean difference (MD) 69.7, lower limit of agreement (LoA) 17.8, upper LoA 121.5, and a standard deviation (SD) 26.4 B. Analysis of agreement of non-VWD between Local Center (LC) VWF:Ag and the VWF-MAA demonstrated MD 69.3, lower LoA 16.2, upper LoA 122.4, and SD 27.1. C. Analysis of agreement of type 1 VWD between VBRI VWF:Ag and the VWF-MAA showed MD 49, lower LoA 13.9, upper LoA 84.1, and SD 17.9. D. Analysis of agreement of type 1 VWD between LC VWF:Ag and the VWF-MAA demonstrated MD 47.7, lower LoA 17.1, upper LoA 78.3, and SD 15.6.
Figure 1:
Figure 1:. Agreement between Versiti Blood Research Institute, Local Center Laboratory, and VWF-MAA Measurements
A. Analysis of agreement of non-VWD between Versiti Blood Research Institute (VBRI) VWF:Ag and the von Willebrand Factor multiplex activity assay (VWF-MAA) showed mean difference (MD) 69.7, lower limit of agreement (LoA) 17.8, upper LoA 121.5, and a standard deviation (SD) 26.4 B. Analysis of agreement of non-VWD between Local Center (LC) VWF:Ag and the VWF-MAA demonstrated MD 69.3, lower LoA 16.2, upper LoA 122.4, and SD 27.1. C. Analysis of agreement of type 1 VWD between VBRI VWF:Ag and the VWF-MAA showed MD 49, lower LoA 13.9, upper LoA 84.1, and SD 17.9. D. Analysis of agreement of type 1 VWD between LC VWF:Ag and the VWF-MAA demonstrated MD 47.7, lower LoA 17.1, upper LoA 78.3, and SD 15.6.
Figure 1:
Figure 1:. Agreement between Versiti Blood Research Institute, Local Center Laboratory, and VWF-MAA Measurements
A. Analysis of agreement of non-VWD between Versiti Blood Research Institute (VBRI) VWF:Ag and the von Willebrand Factor multiplex activity assay (VWF-MAA) showed mean difference (MD) 69.7, lower limit of agreement (LoA) 17.8, upper LoA 121.5, and a standard deviation (SD) 26.4 B. Analysis of agreement of non-VWD between Local Center (LC) VWF:Ag and the VWF-MAA demonstrated MD 69.3, lower LoA 16.2, upper LoA 122.4, and SD 27.1. C. Analysis of agreement of type 1 VWD between VBRI VWF:Ag and the VWF-MAA showed MD 49, lower LoA 13.9, upper LoA 84.1, and SD 17.9. D. Analysis of agreement of type 1 VWD between LC VWF:Ag and the VWF-MAA demonstrated MD 47.7, lower LoA 17.1, upper LoA 78.3, and SD 15.6.
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