The Prothrombotic State Associated with SARS-CoV-2 Infection: Pathophysiological Aspects.

Abstract

Severe coronavirus disease-2019 (COVID-19) is frequently associated with microvascular thrombosis, especially in the lung, or macrovascular thrombosis, mainly venous thromboembolism, which significantly contributes to the disease mortality burden. COVID-19 patients also exhibit distinctive laboratory abnormalities that are compatible with a prothrombotic state. The key event underlying COVID-19-associated thrombotic complications is an excessive host inflammatory response to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection generating multiple inflammatory mediators, mainly cytokines and complement activation products. The latter, along with the virus itself, the increased levels of angiotensin II and hypoxia, drive the major cellular changes promoting thrombosis, which include: (1) aberrant expression of tissue factor by activated alveolar epithelial cells, monocytes-macrophages and neutrophils, and production of other prothrombotic factors by activated endothelial cells (ECs) and platelets; (2) reduced expression of physiological anticoagulants by dysfunctional ECs, and (3) suppression of fibrinolysis by the endothelial overproduction of plasminogen activator inhibitor-1 and, likely, by heightened thrombin-mediated activation of thrombin-activatable fibrinolysis inhibitor. Moreover, upon activation or death, neutrophils and other cells release nuclear materials that are endowed with potent prothrombotic properties. The ensuing thrombosis significantly contributes to lung injury and, in most severe COVID-19 patients, to multiple organ dysfunction. Insights into the pathogenesis of COVID-19-associated thrombosis may have implications for the development of new diagnostic and therapeutic tools.

• Authors: Nicola Semeraro, Mario Colucci
• Journal: Mediterranean journal of hematology and infectious diseases (Mediterr J Hematol Infect Dis) Vol. 13 Issue 1 Pg. e2021045 ( 2021) ISSN: 2035-3006 [Print] Italy
• PMID: 34276914 (Publication Type: Journal Article, Review)