Plasma tissue plasminogen activator and plasminogen activator inhibitor-1 in hospitalized COVID-19 patients

Abstract Patients with coronavirus disease-19 (COVID-19) are at high risk for thrombotic arterial and venous occlusions. However, bleeding complications have also been observed in some patients. Understanding the balance between coagulation and fibrinolysis will help inform optimal approaches to thr...

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Autores principales:	Yu Zuo, Mark Warnock, Alyssa Harbaugh, Srilakshmi Yalavarthi, Kelsey Gockman, Melanie Zuo, Jacqueline A. Madison, Jason S. Knight, Yogendra Kanthi, Daniel A. Lawrence
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/15613acf473e49538de79328cd7add3a
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spelling	oai:doaj.org-article:15613acf473e49538de79328cd7add3a2021-12-02T15:23:01ZPlasma tissue plasminogen activator and plasminogen activator inhibitor-1 in hospitalized COVID-19 patients10.1038/s41598-020-80010-z2045-2322https://doaj.org/article/15613acf473e49538de79328cd7add3a2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80010-zhttps://doaj.org/toc/2045-2322Abstract Patients with coronavirus disease-19 (COVID-19) are at high risk for thrombotic arterial and venous occlusions. However, bleeding complications have also been observed in some patients. Understanding the balance between coagulation and fibrinolysis will help inform optimal approaches to thrombosis prophylaxis and potential utility of fibrinolytic-targeted therapies. 118 hospitalized COVID-19 patients and 30 healthy controls were included in the study. We measured plasma antigen levels of tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) and performed spontaneous clot-lysis assays. We found markedly elevated tPA and PAI-1 levels in patients hospitalized with COVID-19. Both factors demonstrated strong correlations with neutrophil counts and markers of neutrophil activation. High levels of tPA and PAI-1 were associated with worse respiratory status. High levels of tPA, in particular, were strongly correlated with mortality and a significant enhancement in spontaneous ex vivo clot-lysis. While both tPA and PAI-1 are elevated among COVID-19 patients, extremely high levels of tPA enhance spontaneous fibrinolysis and are significantly associated with mortality in some patients. These data indicate that fibrinolytic homeostasis in COVID-19 is complex with a subset of patients expressing a balance of factors that may favor fibrinolysis. Further study of tPA as a biomarker is warranted.Yu ZuoMark WarnockAlyssa HarbaughSrilakshmi YalavarthiKelsey GockmanMelanie ZuoJacqueline A. MadisonJason S. KnightYogendra KanthiDaniel A. LawrenceNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yu Zuo Mark Warnock Alyssa Harbaugh Srilakshmi Yalavarthi Kelsey Gockman Melanie Zuo Jacqueline A. Madison Jason S. Knight Yogendra Kanthi Daniel A. Lawrence Plasma tissue plasminogen activator and plasminogen activator inhibitor-1 in hospitalized COVID-19 patients
description	Abstract Patients with coronavirus disease-19 (COVID-19) are at high risk for thrombotic arterial and venous occlusions. However, bleeding complications have also been observed in some patients. Understanding the balance between coagulation and fibrinolysis will help inform optimal approaches to thrombosis prophylaxis and potential utility of fibrinolytic-targeted therapies. 118 hospitalized COVID-19 patients and 30 healthy controls were included in the study. We measured plasma antigen levels of tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) and performed spontaneous clot-lysis assays. We found markedly elevated tPA and PAI-1 levels in patients hospitalized with COVID-19. Both factors demonstrated strong correlations with neutrophil counts and markers of neutrophil activation. High levels of tPA and PAI-1 were associated with worse respiratory status. High levels of tPA, in particular, were strongly correlated with mortality and a significant enhancement in spontaneous ex vivo clot-lysis. While both tPA and PAI-1 are elevated among COVID-19 patients, extremely high levels of tPA enhance spontaneous fibrinolysis and are significantly associated with mortality in some patients. These data indicate that fibrinolytic homeostasis in COVID-19 is complex with a subset of patients expressing a balance of factors that may favor fibrinolysis. Further study of tPA as a biomarker is warranted.
format	article
author	Yu Zuo Mark Warnock Alyssa Harbaugh Srilakshmi Yalavarthi Kelsey Gockman Melanie Zuo Jacqueline A. Madison Jason S. Knight Yogendra Kanthi Daniel A. Lawrence
author_facet	Yu Zuo Mark Warnock Alyssa Harbaugh Srilakshmi Yalavarthi Kelsey Gockman Melanie Zuo Jacqueline A. Madison Jason S. Knight Yogendra Kanthi Daniel A. Lawrence
author_sort	Yu Zuo
title	Plasma tissue plasminogen activator and plasminogen activator inhibitor-1 in hospitalized COVID-19 patients
title_short	Plasma tissue plasminogen activator and plasminogen activator inhibitor-1 in hospitalized COVID-19 patients
title_full	Plasma tissue plasminogen activator and plasminogen activator inhibitor-1 in hospitalized COVID-19 patients
title_fullStr	Plasma tissue plasminogen activator and plasminogen activator inhibitor-1 in hospitalized COVID-19 patients
title_full_unstemmed	Plasma tissue plasminogen activator and plasminogen activator inhibitor-1 in hospitalized COVID-19 patients
title_sort	plasma tissue plasminogen activator and plasminogen activator inhibitor-1 in hospitalized covid-19 patients
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/15613acf473e49538de79328cd7add3a
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_version_	1718387310216609792

Plasma tissue plasminogen activator and plasminogen activator inhibitor-1 in hospitalized COVID-19 patients

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