Recombinant ADAMTS13 reduces abnormally up-regulated von Willebrand factor in plasma from patients with severe COVID-19
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Thrombosis affecting the pulmonary and systemic vasculature is common during severe COVID-19 and causes adverse outcomes. Although thrombosis likely results from inflammatory activation of vascular cells, the mediators of thrombosis remain unconfirmed. In a cross-sectional cohort of 36 severe COVID-19 patients, we show that markedly increased plasma von Willebrand factor (VWF) levels were accompanied by a partial reduction in the VWF regulatory protease ADAMTS13. In all patients we find this VWF/ADAMTS13 imbalance to be associated with persistence of ultra-high-molecular-weight (UHMW) VWF multimers that are highly thrombogenic in some disease settings. Incubation of plasma samples from patients with severe COVID-19 with recombinant ADAMTS13 (rADAMTS13) substantially reduced the abnormally high VWF activity, reduced overall multimer size and depleted UHMW VWF multimers in a time and concentration dependent manner. Our data implicate disruption of normal VWF/ADAMTS13 homeostasis in the pathogenesis of severe COVID-19 and indicate that this can be reversed ex vivo by correction of low plasma ADAMTS13 levels. These findings suggest a potential therapeutic role for rADAMTS13 in helping restore haemostatic balance in COVID-19 patients.
Date Issued
2021-02-18
Date Acceptance
2021-02-08
Citation
Thrombosis Research: vascular obstruction, hemorrhage and hemostasis, 2021, 201, pp.100-112
ISSN
0049-3848
Publisher
Elsevier
Start Page
100
End Page
112
Journal / Book Title
Thrombosis Research: vascular obstruction, hemorrhage and hemostasis
Volume
201
Copyright Statement
© 2021 The Authors
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/33662796
PII: S0049-3848(21)00060-8
Subjects
ADAMTS13
COVID-19
Endothelium
Inflammation
SARS-COV-2
Thrombosis
rADAMTS13
von Willebrand factor
Publication Status
Published online
Coverage Spatial
United States
Date Publish Online
2021-02-18