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Von Willebrand factor propeptide in severe coronavirus disease 2019 (COVID-19): evidence of acute and sustained endothelial cell activation.
Ward, Soracha E; Curley, Gerard F; Lavin, Michelle; Fogarty, Helen; Karampini, Ellie; McEvoy, Natalie L; Clarke, Jennifer; Boylan, Maria; Alalqam, Razi; Worrall, Amy P; Kelly, Claire; de Barra, Eoghan; Glavey, Siobhan; Ni Cheallaigh, Cliona; Bergin, Colm; Martin-Loeches, Ignacio; Townsend, Liam; Mallon, Patrick W; O'Sullivan, Jamie M; O'Donnell, James S.
  • Ward SE; Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland.
  • Curley GF; Department of Anaesthesia and Critical Care, RCSI, Dublin, Ireland.
  • Lavin M; Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland.
  • Fogarty H; Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland.
  • Karampini E; Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland.
  • McEvoy NL; Department of Anaesthesia and Critical Care, RCSI, Dublin, Ireland.
  • Clarke J; Department of Anaesthesia and Critical Care, RCSI, Dublin, Ireland.
  • Boylan M; Department of Anaesthesia and Critical Care, RCSI, Dublin, Ireland.
  • Alalqam R; Department of Anaesthesia and Critical Care, RCSI, Dublin, Ireland.
  • Worrall AP; Department of Infectious Diseases, Beaumont Hospital, Dublin, Ireland.
  • Kelly C; Department of Haematology, Beaumont Hospital, Dublin, Ireland.
  • de Barra E; Department of Infectious Diseases, Beaumont Hospital, Dublin, Ireland.
  • Glavey S; Department of Tropical Medicine and International Health, RCSI, Dublin, Ireland.
  • Ni Cheallaigh C; Department of Haematology, Beaumont Hospital, Dublin, Ireland.
  • Bergin C; St James's Hospital, Trinity College Dublin, Dublin, Ireland.
  • Martin-Loeches I; St James's Hospital, Trinity College Dublin, Dublin, Ireland.
  • Townsend L; Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland.
  • Mallon PW; St James's Hospital, Trinity College Dublin, Dublin, Ireland.
  • O'Sullivan JM; St James's Hospital, Trinity College Dublin, Dublin, Ireland.
  • O'Donnell JS; Centre for Experimental Pathogen Host Research, University College Dublin, Dublin, Ireland.
Br J Haematol ; 192(4): 714-719, 2021 02.
Article in English | MEDLINE | ID: covidwho-978695
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 (VWFAg) 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 VWFAg [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/VWFAg ratio was reduced, demonstrating that decreased VWF clearance contributes to the elevated plasma VWFAg 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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Protein Precursors / Von Willebrand Factor / Endothelial Cells / SARS-CoV-2 / COVID-19 Type of study: Prognostic study Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: Br J Haematol Year: 2021 Document Type: Article Affiliation country: Bjh.17273

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Protein Precursors / Von Willebrand Factor / Endothelial Cells / SARS-CoV-2 / COVID-19 Type of study: Prognostic study Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: Br J Haematol Year: 2021 Document Type: Article Affiliation country: Bjh.17273