The central role of fibrinolytic response in covid‐19— a hematologist’s perspective

Hau C. Kwaan*, Paul F. Lindholm

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

27 Scopus citations


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‐angio-tensin‐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 hypercoagu-lable 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.

Original languageEnglish (US)
Article number1283
Pages (from-to)1-16
Number of pages16
JournalInternational journal of molecular sciences
Issue number3
StatePublished - Feb 1 2021


  • COVID‐19
  • Fibrinolysis
  • Plasminogen activator inhibitor 1 (PAI‐1)
  • Renin‐aldosterone‐angiotensin‐system (RAAS)

ASJC Scopus subject areas

  • Molecular Biology
  • Spectroscopy
  • Catalysis
  • Inorganic Chemistry
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry


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