{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:47:23Z","timestamp":1787028443602,"version":"build-2736575974"},"reference-count":138,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T00:00:00Z","timestamp":1611792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms22031283","type":"journal-article","created":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T05:23:05Z","timestamp":1611811385000},"page":"1283","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["The Central Role of Fibrinolytic Response in COVID-19\u2014A Hematologist\u2019s Perspective"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5733-6248","authenticated-orcid":false,"given":"Hau C.","family":"Kwaan","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul F.","family":"Lindholm","sequence":"additional","affiliation":[{"name":"Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1056\/NEJMoa2002032","article-title":"Clinical Characteristics of Coronavirus Disease 2019 in China","volume":"382","author":"Guan","year":"2020","journal-title":"N. 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