Hidden behind thromboinflammation: revealing the roles of von Willebrand factor in sickle cell disease pathophysiology

• Type of Material: Article
• Authors: Eudorah F Vital, Emory University; Wilbur Lam, Emory University
• Language: English
• Date: 2023-05-01
• Publisher: LIPPINCOTT WILLIAMS & WILKINS
• Publication Version: Final Published Version
• Copyright Statement: © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1097/MOH.0000000000000755
• Title of Journal or Parent Work: CURRENT OPINION IN HEMATOLOGY
• Volume: 30
• Issue: 3
• Start Page: 86
• End Page: 92
• Grant/Funding Information: Financial support for the work was provided by the National Institutes of Health by the following grants 5F31HL158223 (to E.F.V), R01HL140589 (to W.A.L.) and R35HL145000 (to W.A.L.)
• Keywords: VONWILLEBRAND-FACTOR; von Willebrand factor; pathophysiology; MARKERS; Science & Technology; Life Sciences & Biomedicine; Hematology; THROMBOTIC THROMBOCYTOPENIC PURPURA; RECOMBINANT ADAMTS13; sickle cell disease; ADAMTS13; vaso-occlusion; ADHESION; thrombosis
• Research Categories: Engineering, Biomedical

Abstract

Purpose of review: This review provides an update on the pathophysiology of sickle cell disease (SCD) with a particular focus on the dysregulation of the von Willebrand factor (VWF) - ADAMTS13 axis that contributes to its pathogenesis. In discussing recent developments, we hope to encourage new and ongoing discussions surrounding therapeutic targets for SCD. Recent findings Within the last 5 years, the role of VWF in the pathophysiology of SCD has been further elucidated and is now a target of study in ongoing clinical trials. Summary The pathophysiology of SCD is multifaceted, as it involves systemwide vascular activation, altered blood rheology, and the activation of immune responses and coagulative pathways. The presence of VWF in excess in SCD, particularly in its largest multimeric form, greatly contributes to its pathogenesis. Understanding the molecular mechanisms that underly the presence of large VWF multimers in SCD will provide further insight into the pathogenesis of SCD and provide specific targets for therapy.