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The Central Role of Fibrinolytic Response in COVID-19—A Hematologist’s Perspective

The novel coronavirus disease (COVID-19) has many characteristics common to those in two other coronavirus acute respiratory diseases, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). They are all highly contagious and have severe pulmonary complications. Clinica...

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Detalles Bibliográficos
Autores principales: Kwaan, Hau C., Lindholm, Paul F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919196/
https://www.ncbi.nlm.nih.gov/pubmed/33525440
http://dx.doi.org/10.3390/ijms22031283
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author Kwaan, Hau C.
Lindholm, Paul F.
author_facet Kwaan, Hau C.
Lindholm, Paul F.
author_sort Kwaan, Hau C.
collection PubMed
description The novel coronavirus disease (COVID-19) has many characteristics common to those in two other coronavirus acute respiratory diseases, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). They are all highly contagious and have severe pulmonary complications. Clinically, patients with COVID-19 run a rapidly progressive course of an acute respiratory tract infection with fever, sore throat, cough, headache and fatigue, complicated by severe pneumonia often leading to acute respiratory distress syndrome (ARDS). The infection also involves other organs throughout the body. In all three viral illnesses, the fibrinolytic system plays an active role in each phase of the pathogenesis. During transmission, the renin-aldosterone-angiotensin-system (RAAS) is involved with the spike protein of SARS-CoV-2, attaching to its natural receptor angiotensin-converting enzyme 2 (ACE 2) in host cells. Both tissue plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1) are closely linked to the RAAS. In lesions in the lung, kidney and other organs, the two plasminogen activators urokinase-type plasminogen activator (uPA) and tissue plasminogen activator (tPA), along with their inhibitor, plasminogen activator 1 (PAI-1), are involved. The altered fibrinolytic balance enables the development of a hypercoagulable state. In this article, evidence for the central role of fibrinolysis is reviewed, and the possible drug targets at multiple sites in the fibrinolytic pathways are discussed.
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spelling pubmed-79191962021-03-02 The Central Role of Fibrinolytic Response in COVID-19—A Hematologist’s Perspective Kwaan, Hau C. Lindholm, Paul F. Int J Mol Sci Review The novel coronavirus disease (COVID-19) has many characteristics common to those in two other coronavirus acute respiratory diseases, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). They are all highly contagious and have severe pulmonary complications. Clinically, patients with COVID-19 run a rapidly progressive course of an acute respiratory tract infection with fever, sore throat, cough, headache and fatigue, complicated by severe pneumonia often leading to acute respiratory distress syndrome (ARDS). The infection also involves other organs throughout the body. In all three viral illnesses, the fibrinolytic system plays an active role in each phase of the pathogenesis. During transmission, the renin-aldosterone-angiotensin-system (RAAS) is involved with the spike protein of SARS-CoV-2, attaching to its natural receptor angiotensin-converting enzyme 2 (ACE 2) in host cells. Both tissue plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1) are closely linked to the RAAS. In lesions in the lung, kidney and other organs, the two plasminogen activators urokinase-type plasminogen activator (uPA) and tissue plasminogen activator (tPA), along with their inhibitor, plasminogen activator 1 (PAI-1), are involved. The altered fibrinolytic balance enables the development of a hypercoagulable state. In this article, evidence for the central role of fibrinolysis is reviewed, and the possible drug targets at multiple sites in the fibrinolytic pathways are discussed. MDPI 2021-01-28 /pmc/articles/PMC7919196/ /pubmed/33525440 http://dx.doi.org/10.3390/ijms22031283 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Kwaan, Hau C.
Lindholm, Paul F.
The Central Role of Fibrinolytic Response in COVID-19—A Hematologist’s Perspective
title The Central Role of Fibrinolytic Response in COVID-19—A Hematologist’s Perspective
title_full The Central Role of Fibrinolytic Response in COVID-19—A Hematologist’s Perspective
title_fullStr The Central Role of Fibrinolytic Response in COVID-19—A Hematologist’s Perspective
title_full_unstemmed The Central Role of Fibrinolytic Response in COVID-19—A Hematologist’s Perspective
title_short The Central Role of Fibrinolytic Response in COVID-19—A Hematologist’s Perspective
title_sort central role of fibrinolytic response in covid-19—a hematologist’s perspective
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919196/
https://www.ncbi.nlm.nih.gov/pubmed/33525440
http://dx.doi.org/10.3390/ijms22031283
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