Fig. 2

Mechanism of glycocalyx degradation in LPS or septic conditions. Mechanisms of intravascular coagulation in LPS or septic conditions. In LPS or septic conditions, anticoagulant and coagulant balance in the intravascular environment can be disrupted by the disruption of endothelial glycocalyx, down-regulation of endothelial thrombomodulin, and decline of plasma anticoagulant proteins such as tissue factor pathway inhibitor (TFPI) and antithrombin. Additionally, activated endothelial cells (ECs) and leukocytes release tissue factor (TF) into the bloodstream, triggering intravascular coagulation. Neutrophil extracellular traps (NETs) also contribute a plethora of proteins that participate in coagulation. In conditions induced by lipopolysaccharide (LPS) or sepsis, fibrinolysis inhibitors such as plasminogen activator inhibitor-1 (PAI-1) and thrombin-activatable fibrinolysis inhibitor (TAFI) are up-regulated, further hindering the fibrinolytic process and potentially leading to disseminated intravascular coagulation (DIC). Recombinant thrombomodulin (rTM) and antithrombin gamma (rAT) represent potential therapeutic agents that could rebalance anticoagulant and coagulant activity in LPS or septic conditions. Moreover, the upregulation of adhesion factors promotes ECs to secrete von Willebrand factor (vWf), which in turn recruits platelets to aid in the repair of damaged ECs. However, shedding of endothelial protein C receptor (EPCR) from ECs results in impaired conversion of protein C to activated protein C (APC), further complicating the coagulation imbalance in these conditions