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Investigating von Willebrand Factor Pathophysiology Using a Flow Chamber Model of von Willebrand Factor-platelet String Formation
Published on: August 14, 2017
Von Willebrand Factor Biomarkers in Prosthetic Valve Dysfunction: An Adjunct to Imaging and Hemodynamic Assessment
Sameed Arshad1, Sabir Khan2, Muhammad Zahid1
1From the Department of Internal Medicine, Saint Agnes Medical Center, Fresno, CA.
Abstract:
Imaging remains the foundation of prosthetic valve surveillance because it identifies valve morphology, lesion mechanism, and hemodynamic severity. However, acoustic shadowing, eccentric or multiple regurgitant jets, loading conditions, and reader variability can complicate assessment, particularly for paravalvular regurgitation after transcatheter aortic valve replacement. High shear stress unfolds von Willebrand factor (VWF), promotes proteolysis of its high-molecular-weight multimers, and produces a measurable defect in primary hemostasis. Multimer analysis, closure time with adenosine diphosphate (CT-ADP), and the VWF activity-to-antigen ratio therefore provide a biologic signal of abnormal flow rather than an anatomic image. Prospective studies show that VWF abnormalities track residual paravalvular regurgitation during transcatheter aortic valve replacement, occur with dysfunctional prostheses, change after mitral paravalvular-leak repair, and are associated with bleeding. The evidence nevertheless remains observational; most diagnostic cohorts are small and single-center, thresholds lack independent validation, assays are vulnerable to hematologic and preanalytic confounding, and no completed randomized trial has shown that VWF-guided management improves outcomes. VWF testing is best viewed as an investigational adjunct when imaging and the clinical picture are discordant or when prosthetic dysfunction coexists with otherwise unexplained bleeding. It should not replace guideline-directed echocardiography or be used for routine surveillance outside research protocols.
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