tetano
Editor, Senior Moderator
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[SUP] 1 [/SUP], Gerard F Curley[SUP] 2 [/SUP], Michelle Lavin[SUP] 1 [/SUP], Helen Fogarty[SUP] 1 [/SUP], Ellie Karampini[SUP] 1 [/SUP], Natalie L McEvoy[SUP] 2 [/SUP], Jennifer Clarke[SUP] 2 [/SUP], Maria Boylan[SUP] 2 [/SUP], Razi Alalqam[SUP] 2 [/SUP], Amy P Worrall[SUP] 3 [/SUP], Claire Kelly[SUP] 4 [/SUP], Eoghan de Barra[SUP] 3 5 [/SUP], Siobhan Glavey[SUP] 4 [/SUP], Cliona Ni Cheallaigh[SUP] 6 [/SUP], Colm Bergin[SUP] 6 [/SUP], Ignacio Martin-Loeches[SUP] 1 6 [/SUP], Liam Townsend[SUP] 6 [/SUP], Patrick W Mallon[SUP] 7 8 [/SUP], Jamie M O'Sullivan[SUP] 1 [/SUP], James S O'Donnell[SUP] 1 9 10 [/SUP], 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.
. 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[SUP] 1 [/SUP], Gerard F Curley[SUP] 2 [/SUP], Michelle Lavin[SUP] 1 [/SUP], Helen Fogarty[SUP] 1 [/SUP], Ellie Karampini[SUP] 1 [/SUP], Natalie L McEvoy[SUP] 2 [/SUP], Jennifer Clarke[SUP] 2 [/SUP], Maria Boylan[SUP] 2 [/SUP], Razi Alalqam[SUP] 2 [/SUP], Amy P Worrall[SUP] 3 [/SUP], Claire Kelly[SUP] 4 [/SUP], Eoghan de Barra[SUP] 3 5 [/SUP], Siobhan Glavey[SUP] 4 [/SUP], Cliona Ni Cheallaigh[SUP] 6 [/SUP], Colm Bergin[SUP] 6 [/SUP], Ignacio Martin-Loeches[SUP] 1 6 [/SUP], Liam Townsend[SUP] 6 [/SUP], Patrick W Mallon[SUP] 7 8 [/SUP], Jamie M O'Sullivan[SUP] 1 [/SUP], James S O'Donnell[SUP] 1 9 10 [/SUP], Irish COVID-19 Vasculopathy Study (ICVS) Investigators
Collaborators, Affiliations
- PMID: 33326604
- DOI: 10.1111/bjh.17273
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.