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Recombinant ADAMTS13 reduces abnormally up-regulated von Willebrand factor in plasma from patients with severe COVID-19.
Turecek, Peter L; Peck, Rachel C; Rangarajan, Savita; Reilly-Stitt, Christopher; Laffan, Michael A; Kazmi, Rashid; James, Izabela; Dushianthan, Ahilanandan; Schrenk, Gerald; Gritsch, Herbert; Ewenstein, Bruce M; Mellgard, Bjorn; Erdlenbruch, Wolfhard; Jain, Nisha; Binder, Nikolaus B; Mumford, Andrew D.
  • Turecek PL; Baxalta Innovations GmbH, a Takeda company, Vienna, Austria.
  • Peck RC; School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom.
  • Rangarajan S; University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom; K J Somaiya Superspecialty Hospital and Research Centre, Mumbai, India.
  • Reilly-Stitt C; University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom.
  • Laffan MA; Imperial College London, Hammersmith Hospital, London, United Kingdom.
  • Kazmi R; University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
  • James I; University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
  • Dushianthan A; University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
  • Schrenk G; Baxalta Innovations GmbH, a Takeda company, Vienna, Austria.
  • Gritsch H; Baxalta Innovations GmbH, a Takeda company, Vienna, Austria.
  • Ewenstein BM; Baxalta US Inc., a Takeda company, Cambridge, MA, USA.
  • Mellgard B; Baxalta US Inc., a Takeda company, Cambridge, MA, USA.
  • Erdlenbruch W; Baxalta GmbH, a Takeda company, Zurich, Switzerland.
  • Jain N; Baxalta US Inc., a Takeda company, Cambridge, MA, USA.
  • Binder NB; Technoclone Herstellung von Diagnostika und Arzneimitteln GmbH, Vienna, Austria.
  • Mumford AD; School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom; University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom. Electronic address: a.mumford@bristol.ac.uk.
Thromb Res ; 201: 100-112, 2021 05.
Article in English | MEDLINE | ID: covidwho-1087279
ABSTRACT
Thrombosis affecting the pulmonary and systemic vasculature is common during severe COVID-19 and causes adverse outcomes. Although thrombosis likely results from inflammatory activation of vascular cells, the mediators of thrombosis remain unconfirmed. In a cross-sectional cohort of 36 severe COVID-19 patients, we show that markedly increased plasma von Willebrand factor (VWF) levels were accompanied by a partial reduction in the VWF regulatory protease ADAMTS13. In all patients we find this VWF/ADAMTS13 imbalance to be associated with persistence of ultra-high-molecular-weight (UHMW) VWF multimers that are highly thrombogenic in some disease settings. Incubation of plasma samples from patients with severe COVID-19 with recombinant ADAMTS13 (rADAMTS13) substantially reduced the abnormally high VWF activity, reduced overall multimer size and depleted UHMW VWF multimers in a time and concentration dependent manner. Our data implicate disruption of normal VWF/ADAMTS13 homeostasis in the pathogenesis of severe COVID-19 and indicate that this can be reversed ex vivo by correction of low plasma ADAMTS13 levels. These findings suggest a potential therapeutic role for rADAMTS13 in helping restore haemostatic balance in COVID-19 patients.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Thrombosis / Recombinant Proteins / COVID-19 Type of study: Cohort study / Observational study / Prognostic study / Randomized controlled trials Limits: Humans Language: English Journal: Thromb Res Year: 2021 Document Type: Article Affiliation country: J.thromres.2021.02.012

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Thrombosis / Recombinant Proteins / COVID-19 Type of study: Cohort study / Observational study / Prognostic study / Randomized controlled trials Limits: Humans Language: English Journal: Thromb Res Year: 2021 Document Type: Article Affiliation country: J.thromres.2021.02.012