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Elevated Angiopoiet...
Elevated Angiopoietin-2 inhibits thrombomodulin-mediated anticoagulation in critically ill COVID-19 patients
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- Hultström, Michael, 1978- (author)
- Uppsala universitet,Anestesiologi och intensivvård,Institutionen för medicinsk cellbiologi
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- Fromell, Karin (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Larsson, Anders (author)
- Uppsala universitet,Klinisk kemi
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Quaggin, Susan E (author)
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- Betsholtz, Christer (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Frithiof, Robert (author)
- Uppsala universitet,Anestesiologi och intensivvård
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- Lipcsey, Miklós (author)
- Uppsala universitet,Hedenstiernalaboratoriet
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- Jeansson, Marie (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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(creator_code:org_t)
- Cold Spring Harbor Laboratory Press (CSHL), 2021
- 2021
- English.
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In: medRxiv. - : Cold Spring Harbor Laboratory Press (CSHL). ; , s. 1-27
- Related links:
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https://www.mdpi.com...
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https://www.medrxiv....
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Several studies suggest that hypercoagulation and endothelial dysfunction play central roles in severe forms of COVID-19 infections. We hypothesized that the high levels of the inflammatory cytokine Angiopoietin-2 (ANGPT2) reported in hospitalized COVID-19 patients might promote hypercoagulation through ANGPT2 binding to thrombomodulin with resulting inhibition of thrombin/thrombomodulin-mediated physiological anticoagulation. Plasma was collected from critically ill COVID-19 patients treated in the intensive care unit (ICU) at Uppsala University Hospital and ANGPT2 was measured at admission (61 patients) and after ten days (40 patients). ANGPT2 levels were compared with biochemical parameters, clinical outcome, and survival. We found that ANGPT2 levels were increased in COVID-19 patients in correlation with disease severity, hypercoagulation, and mortality. To test causality, we administered ANGPT2 to wildtype mice and found that it shortened bleeding time in a tail injury model. In further support of a role for ANGPT2 in physiological coagulation, bleeding time was increased in endothelial-specific Angpt2 knockout mice. Using in vitro assays, we found that ANGPT2 inhibited thrombomodulin-mediated anticoagulation and protein C activation in human donor plasma. Our data reveal a novel mechanism for ANGPT2 in hypercoagulation and suggest that Angiopoietin-2 inhibition may be tested in the treatment of hypercoagulation in severe COVID-19 infection.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Anestesi och intensivvård (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Anesthesiology and Intensive Care (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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