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Br J Haematol . Von Willebrand factor propeptide in severe coronavirus disease 2019 (COVID-19): evidence of acute and sustained endothelial cell activation

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  • Br J Haematol . Von Willebrand factor propeptide in severe coronavirus disease 2019 (COVID-19): evidence of acute and sustained endothelial cell activation


    Br J Haematol


    . 2020 Dec 16.
    doi: 10.1111/bjh.17273. Online ahead of print.
    Von Willebrand factor propeptide in severe coronavirus disease 2019 (COVID-19): evidence of acute and sustained endothelial cell activation


    Soracha E Ward 1 , Gerard F Curley 2 , Michelle Lavin 1 , Helen Fogarty 1 , Ellie Karampini 1 , Natalie L McEvoy 2 , Jennifer Clarke 2 , Maria Boylan 2 , Razi Alalqam 2 , Amy P Worrall 3 , Claire Kelly 4 , Eoghan de Barra 3 5 , Siobhan Glavey 4 , Cliona Ni Cheallaigh 6 , Colm Bergin 6 , Ignacio Martin-Loeches 1 6 , Liam Townsend 6 , Patrick W Mallon 7 8 , Jamie M O'Sullivan 1 , James S O'Donnell 1 9 10 , Irish COVID-19 Vasculopathy Study (ICVS) Investigators



    Collaborators, Affiliations

    Abstract

    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.

    Keywords: COVID-19; SARS-CoV-2; VWF propeptide; coagulopathy; endothelium.

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