Journal
THROMBOSIS RESEARCH
Volume 201, Issue -, Pages 100-112Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.thromres.2021.02.012
Keywords
COVID-19; SARS-COV-2; von Willebrand factor; ADAMTS13; Thrombosis; Endothelium; Inflammation; rADAMTS13
Categories
Funding
- NIHR Bristol Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristo
Ask authors/readers for more resources
Thrombosis is common in severe COVID-19 patients, with an imbalance of VWF/ADAMTS13 implicated in its pathogenesis. Correction of this imbalance through rADAMTS13 may help restore hemostatic balance and potentially serve as a therapeutic approach in severe COVID-19 cases.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available