Von Willebrand factor propeptide in severe coronavirus disease 2019 (COVID-19): evidence of acute and sustained endothelial cell activation.
COVID-19
SARS-CoV-2
VWF propeptide
coagulopathy
endothelium
Journal
British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
29
10
2020
accepted:
22
11
2020
pubmed:
17
12
2020
medline:
2
3
2021
entrez:
16
12
2020
Statut:
ppublish
Résumé
Endothelial cell (EC) activation plays a key role in the pathogenesis of pulmonary microvascular occlusion, which is a hallmark of severe coronavirus disease 2019 (COVID-19). Consistent with EC activation, increased plasma von Willebrand factor antigen (VWF:Ag) levels have been reported in COVID-19. Importantly however, studies in other microangiopathies have shown that plasma VWF propeptide (VWFpp) is a more sensitive and specific measure of acute EC activation. In the present study, we further investigated the nature of EC activation in severe COVID-19. Markedly increased plasma VWF:Ag [median (interquatile range, IQR) 608·8 (531-830)iu/dl] and pro-coagulant factor VIII (FVIII) levels [median (IQR) 261·9 (170-315) iu/dl] were seen in patients with severe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Sequential testing showed that these elevated VWF-FVIII complex levels remained high for up to 3 weeks. Similarly, plasma VWFpp levels were also markedly elevated [median (IQR) 324·6 (267-524) iu/dl]. Interestingly however, the VWFpp/VWF:Ag ratio was reduced, demonstrating that decreased VWF clearance contributes to the elevated plasma VWF:Ag levels in severe COVID-19. Importantly, plasma VWFpp levels also correlated with clinical severity indices including the Sequential Organ Failure Assessment (SOFA) score, Sepsis-Induced Coagulopathy (SIC) score and the ratio of arterial oxygen partial pressure to fractional inspired oxygen (P/F ratio). Collectively, these findings support the hypothesis that sustained fulminant EC activation is occurring in severe COVID-19, and further suggest that VWFpp may have a role as a biomarker in this setting.
Substances chimiques
Biomarkers
0
Protein Precursors
0
von Willebrand Factor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
714-719Subventions
Organisme : 3M Foundation
Organisme : Health Research Board COVID-19 Rapid Response award
ID : COV19-2020-086
Organisme : Health Service Executive, National Doctors Training and Planning
Organisme : Health and Social Care, Research and Development Division, Northern Ireland
Organisme : National Children's Research Centre Project Award
ID : C/18/1
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Health Research Board
ID : 203930/B/16/Z
Pays : Ireland
Investigateurs
Niamh O'Connell
(N)
Kevin Ryan
(K)
Mary Byrne
(M)
Roger Preston
(R)
Dermot Kenny
(D)
Informations de copyright
© 2020 British Society for Haematology and John Wiley & Sons Ltd.
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