Current Drug Targets (CDT) special issue on Covid-19 and Coagulopathy Fibrinolysis in COVID-19: impact on clot lysis and modulation of inflammation

Curr Drug Targets. 2022 Oct 11. doi: 10.2174/1389450123666221011102250. Online ahead of print.ABSTRACTCOVID-19 is a multisystem disease caused by SARS-CoV-2 and is associated with an imbalance between the coagulation and fibrinolytic systems. Systemically, hypercoagulation, hypofibrinolysis and fibrin-clot resistance to fibrinolysis predispose patients to thrombotic and thromboembolic events. In the lungs, the virus triggers alveolar and interstitial fibrin deposition, endothelial dysfunction, and pulmonary intravascular coagulation, all events intrinsically associated with activation of inflammation and organ injury. Adding to the pathogenesis of COVID-19, there is a positive feedback loop by which local fibrin deposition in the lungs can fuel inflammation and consequently dysregulates coagulation, a process known as immunothrombosis. Therefore, fibrinolysis plays a central role in maintaining hemostasis and tissue homeostasis during COVID-19 by cleaning fibrin clots and controlling feed-forward products of coagulation. In addition, components of the fibrinolytic system have important immunomodulatory roles, as evidenced by studies showing the contribution of Plasminogen/Plasmin (Plg/Pla) to the resolution of inflammation. Herein, we review clinical evidence for the dysregulation of the fibrinolytic system and discuss its contribution to thrombosis risk and exacerbated inflammation in severe COVID-19. We also discuss the current concept of an interplay between fibrinolysis a...
Source: Current Drug Targets - Category: Drugs & Pharmacology Authors: Source Type: research