The Clinical Application of a Novel Ristocetin-Independent von Willebrand Factor Activity Assay Public
DiGiandomenico, Stefanie (Spring 2025)
Abstract
Background: Von Willebrand disease (VWD) and acquired von Willebrand syndrome (AVWS) are bleeding disorders that can result in significant morbidity and mortality. Initial screening includes measuring von Willebrand factor (VWF) activity. Current gold standard activity assays, ristocetin cofactor (VWF:RCo) and glycoprotein IbM (VWF:GPIbM), have limitations that can hinder accurate diagnosis. The novel glycoprotein Ib nanobody (GPIbNab) assay may mitigate these diagnostic challenges, but its clinical application remains unexplored.
Objective: To assess concordance of GPIbNab with gold standard activity assays in individuals with and without VWD or AVWS.
Methods: This was a cross-sectional study of subjects who were evaluated for a bleeding disorder or have a diagnosis of VWD or AVWS. Performance characteristics of the GPIbNab assay (GPIbNab:6C11 and GPIbNab:6D12) were assessed. All subjects presented with a historic diagnosis, or lack thereof, based on gold standard activity assays as determined by the local treating physician. Subjects were then assigned a diagnosis based on GPIbNab and VWF antigen (VWF:Ag). Criteria for diagnosis of VWD or AVWS was a GPIbNab or VWF:Ag level <50 IU/dL. A receiver operating characteristic curve determined the optimal cutpoint for GPIbNab activity to VWF:Ag ratio. Pearson correlation analysis measured concordance between assays.
Results: 91 samples from 82 individuals undergoing evaluation for VWD and 21 samples from 17 individuals undergoing evaluation for AVWS were collected from August 2021 to September 2023. VWD Cohort: There were 39 diagnoses of type 1 VWD, 12 of type 2 VWD, 4 of VWD of unclear type, and 2 historic diagnoses of VWD. Twenty-five patients did not have a diagnosis of VWD. There were statistically significant, positive correlations between GPIbNab:6D12 and VWF:GPIbM (r=0.80) and VWF:RCo (r=0.71), and between GPIbNab:6C11 and VWF:GPIbM (r=0.78) and VWF:RCo (r=0.51). AVWS Cohort: 10 of 17 subjects had a diagnosis of AVWS. There were statistically significant, positive correlations between VWF:GPIbM and GPIbNab:6D12 (r=0.88) and VWF:GPIbM and GPIbNab:6C11 (r=0.89). There were moderately positive correlations between both GPIbNab assays and VWF:RCo, though these results were not statistically significant.
Conclusion: The novel GPIbNab assay strongly correlates with VWF:GPIbM in the diagnosis of VWD and AVWS, supporting its potential as a valuable diagnostic tool.
Table of Contents
A. BACKGROUND……………………………………………………………………………………………1
B. METHODS………………………………………………………………………………………………....7
C. RESULTS…………………………………………………………………………………………………..12
D. DISCUSSION……………………………………………………………………………………………...17
E. REFERENCES…………………………………………………………………………………………..…22
F. TABLES/FIGURES…………………………………………………………………………………....….25
About this Master's Thesis
| School | |
|---|---|
| Department | |
| Degree | |
| Submission | |
| Language |
|
| Research Field | |
| Mot-clé | |
| Committee Chair / Thesis Advisor | |
| Committee Members |
Primary PDF
| Thumbnail | Title | Date Uploaded | Actions |
|---|---|---|---|
|
|
The Clinical Application of a Novel Ristocetin-Independent von Willebrand Factor Activity Assay () | 2025-04-23 10:49:03 -0400 |
|
Supplemental Files
| Thumbnail | Title | Date Uploaded | Actions |
|---|