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.

Plasma tissue factor pathway inhibitor levels in coronavirus disease 2019 patients: a systematic review and meta-analysis

“…Tissue factor pathway inhibitor (TFPI) is one of the major anticoagulant factors, which is typically found on the endothelial surface and plays a critical regulatory role in controlling inappropriate excess of clotting by modulation of tissue factor-induced coagulation [1–3]. It is a multivalent Kunitz-type protease inhibitor that forms a quaternary complex with factor VII active (FVIIa), tissue factor (TF), and FXa [2,3].…”

“…Tissue factor pathway inhibitor (TFPI) is one of the major anticoagulant factors, which is typically found on the endothelial surface and plays a critical regulatory role in controlling inappropriate excess of clotting by modulation of tissue factor-induced coagulation [1–3]. It is a multivalent Kunitz-type protease inhibitor that forms a quaternary complex with factor VII active (FVIIa), tissue factor (TF), and FXa [2,3]. Studies have shown that removing TFPI by immunodepletion causes a sharp reduction in the threshold of initiation of coagulation by tissue factor and raises the predisposition to the development of disseminated intravascular coagulation (DIC) [4].…”

“…In normal hemostasis, there is equilibrium between pro-thrombogenic systems and antithrombogenic mechanisms, which ensure adequate hemostasis and prevent from occurrence of unsuitable excess of clotting or bleeding. A disequilibrium between pro-coagulant and anticoagulant factors can initiate thrombus formation or bleeding [3]. Thrombosis is a life-threatening complication in patients with COVID-19, which is not due to as simple as a single factor imbalance to the other factors and a combination of changes are involved.…”

“…Thrombosis is a life-threatening complication in patients with COVID-19, which is not due to as simple as a single factor imbalance to the other factors and a combination of changes are involved. Endotheliopathy and up-regulation of pro-coagulants in combination with impaired anticoagulant mechanisms are involved in the occurrence of coagulopathic events in COVID-19 [3,17–20]. Following the outbreak of COVID-19, some studies investigating the hemostatic status of COVID-19 patients evaluated the TFPI levels [3].…”

“…Endotheliopathy and up-regulation of pro-coagulants in combination with impaired anticoagulant mechanisms are involved in the occurrence of coagulopathic events in COVID-19 [3,17–20]. Following the outbreak of COVID-19, some studies investigating the hemostatic status of COVID-19 patients evaluated the TFPI levels [3]. No previous reviews or meta-analyses have examined the effect of SARS-CoV-2 infection on the level of TFPI.…”