About: Severity-stratified and longitudinal analysis of VWF/ADAMTS13 imbalance, altered fibrin crosslinking and inhibition of fibrinolysis as contributors to COVID-19 coagulopathy

Facets (new session)
Description
Metadata
Settings
- owl:sameAs
- Inference Rule:

About: Severity-stratified and longitudinal analysis of VWF/ADAMTS13 imbalance, altered fibrin crosslinking and inhibition of fibrinolysis as contributors to COVID-19 coagulopathy Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Severity-stratified and longitudinal analysis of VWF/ADAMTS13 imbalance, altered fibrin crosslinking and inhibition of fibrinolysis as contributors to COVID-19 coagulopathy
Creator	Hussell, Tracy Felton, Timothy Smith, Craig Ustianowski, Andrew Morris, Mann, Elizabeth Grainger, John Stuart, Prof Dark, Prof Diar Bakerly, Nawar Horsley, Alexander Knight, Sean Konkel, Joanne Menon, Madhvi Mres, Lucy Roberts, Lucy Simpson, Angela South, Kieron
Source	MedRxiv
abstract	Background: Early clinical reports have suggested that the prevalence of thrombotic complications in the pathogenesis of COVID-19 may be as high as 30% in intensive care unit (ICU)-admitted patients and could be a major factor contributing to mortality. However, mechanisms underlying COVID-19-associated thrombo-coagulopathy, and its impact on patient morbidity and mortality, are still poorly understood. Methods: We performed a comprehensive analysis of coagulation and thromboinflammatory factors in plasma from COVID-19 patients with varying degrees of disease severity. Furthermore, we assessed the functional impact of these factors on clot formation and clot lysis. Results: Across all COVID-19 disease severities (mild, moderate and severe) we observed a significant increase (6-fold) in the concentration of ultra-large von Willebrand factor (UL-VWF) multimers compared to healthy controls. This is likely the result of an interleukin (IL)-6 driven imbalance of VWF and the regulatory protease ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13). Upregulation of this key pro-coagulant pathway may also be influenced by the observed increase (~6-fold) in plasma -defensins, a consequence of increased numbers of neutrophils and neutrophil activation. Markers of endothelial, platelet and leukocyte activation were accompanied by increased plasma concentrations of Factor XIII (FXIII) and plasminogen activator inhibitor (PAI)-1. In patients with high FXIII we observed alteration of the fibrin network structure in in vitro assays of clot formation, which coupled with increased PAI-1, prolonged the time to clot lysis by the t-PA/plasmin fibrinolytic pathway by 52% across all COVID-19 patients (n=23). Conclusions: We show that an imbalance in the VWF/ADAMTS13 axis causing increased VWF reactivity may contribute to the formation of platelet-rich thrombi in the pulmonary vasculature of COVID-19 patients. Through immune and inflammatory responses, COVID-19 also alters the balance of factors involved in fibrin generation and fibrinolysis which accounts for the persistent fibrin deposition previously observed in post-mortem lung tissue.
has issue date	2020-08-21(xsd:dateTime)
bibo:doi	10.1101/2020.08.18.20159608
has license	medrxiv
sha1sum (hex)	83bd8e088444ae1e01e8b5cb2e012ba2e4ca205c
schema:url	https://doi.org/10.1101/2020.08.18.20159608
resource representing a document's title	Severity-stratified and longitudinal analysis of VWF/ADAMTS13 imbalance, altered fibrin crosslinking and inhibition of fibrinolysis as contributors to COVID-19 coagulopathy
resource representing a document's body	covid:83bd8e088444ae1e01e8b5cb2e012ba2e4ca205c#body_text
is schema:about of	named entity 'ADAMTS13' named entity 'longitudinal analysis' named entity 'VWF' named entity 'fibrin' named entity 'crosslinking' named entity 'D-dimer' named entity 'COVID' named entity 'ADAMTS13' named entity 'VWF' named entity 'fibrinolysis' named entity 'antigen' named entity 'flow cytometer' named entity 'alveolar spaces' named entity 'IL-17A' named entity 'post-mortem' named entity 'plasma' named entity 'ADAMTS13' named entity 'fibrin' named entity 'obese' named entity 'anti-coagulant' named entity 'coagulopathy' named entity 'coagulopathy' named entity 'endothelial activation' named entity 'peer review' named entity 'P-selectin' named entity 'thrombotic events' named entity 'risk factors' named entity 'COVID' named entity 'fibrinolysis' named entity 'ischaemic heart disease' named entity 'COVID' named entity 'platelet count' named entity 'plasma' named entity '10.9' named entity 'confidence intervals' named entity 'VWF' named entity 'peer review' named entity 'VWF' named entity 'low volume' named entity 'Plasminogen' named entity 'fibrin' named entity 'pro-coagulant' named entity 'tissue factor' named entity 'plasminogen' named entity 'neutrophil' named entity 'medRxiv' named entity 'deep vein thrombosis' named entity 'normal range' named entity 'Hoffmann La Roche' named entity 'α-defensins' named entity 'coagulation' named entity 'VWF' named entity 'neutrophil' named entity 'COVID-19' named entity 'IL-1β' named entity 'fluorescence' named entity 'α-defensins' named entity 'COVID-19' named entity 'TAFI' named entity 'stroke' named entity 'COVID' named entity 'COVID-19' named entity 'fibrinolysis' named entity 'correlation' named entity 'coagulation factors' named entity 'thrombotic' named entity 'Bio-Rad' named entity 'anti-coagulants'

Faceted Search & Find service v1.13.91 as of Mar 24 2020

Alternative Linked Data Documents: Sponger | ODE Content Formats:

RDF

ODATA

Microdata

About

OpenLink Virtuoso version 07.20.3229 as of Jul 10 2020, on Linux (x86_64-pc-linux-gnu), Single-Server Edition (94 GB total memory)
Data on this page belongs to its respective rights holders.
Virtuoso Faceted Browser Copyright © 2009-2024 OpenLink Software