Status of major hemostatic components in the setting of COVID-19: the effect on endothelium, platelets, coagulation factors, fibrinolytic system, and complement

Abstract

The coagulation, fibrinolytic, anticoagulation, and complement systems are in delicate balance with the vessel wall endothelium ensuring appropriate hemostasis. Coagulopathy in coronavirus disease 2019 (COVID-19) is not a simple disorder of one hemostatic component but a complicated process affecting most of the hemostasis system. COVID-19 disturbs the balance between the procoagulant systems and the regulatory mechanisms. Here, we investigate the effect of COVID-19 on key hemostatic components, including platelets, endothelial cells, coagulation factors, fibrinolytic system, anticoagulant protein system, and complement system, to improve our understanding of the pathophysiological processes underlying COVID-19 coagulopathy based on evidence.

Keywords: Blood platelets; COVID-19; Endothelium; Fibrinolysis; Hemostasis; Thrombosis.

Fig. 1

Overview of hypercoagulability in COVID-19. COVID-19 can upregulate prothrombogenic state and downregulate anti-thrombogenic state which predispose patients to fibrin clot formation and platelet aggregation. The complement system and coagulation are functionally dependent, and complement activation is among the main drivers of COVID-19-associated coagulopathy. Neutrophils contribute to this process through the release of NETs, which activate platelets and the extrinsic and intrinsic coagulation pathways and inactivate natural anticoagulants. Monocytes activate the extrinsic pathway of coagulation by expressing and releasing of activated TFs. AT, antithrombin; EPCR, endothelial protein C receptor; PC, protein C; PS, protein S; TF, tissue factor; TFPI, tissue factor pathway inhibitor; TM, thrombomodulin; t-PA, tissue plasminogen activator, is profibrinolytic and serve to activate plasminogen; PAI-1, plasminogen activator inhibitor 1, inhibits t-PA and is antifibrinolytic; TAFI, thrombin-activatable fibrinolysis inhibitor; vWF, von Willebrand factor, helping platelets to attach to each other and to the surface of the vessel; NO, nitric oxide; CD39, a membrane-associated ectoADPase; NETs, neutrophil extracellular traps; MDMs, monocyte-derived microvesicles