Fig. 3
From: Endotheliopathy in septic conditions: mechanistic insight into intravascular coagulation
Mechanisms of intravascular coagulation in septic conditions. In septic conditions, anticoagulant potential in the intravascular environment can be compromised because of disruption of endothelial glycocalyx, downregulation of endothelial thrombomodulin, and decline of plasma anticoagulant proteins such as tissue factor pathway inhibitor (TFPI) and antithrombin. In addition, activated leukocytes and endothelial cells provide tissue factor within the blood vessel, leading to intravascular activation of coagulation. Neutrophil extracellular traps (NETs) also provide a scaffold for intravascular coagulation by activating the intrinsic coagulation pathway, facilitating FXa-mediated thrombin generation, and inactivating anticoagulant TFPI. Fibrinolysis inhibitors, such as plasminogen activator inhibitor-1 (PAI-1) and thrombin-activatable fibrinolysis inhibitor (TAFI), are upregulated in septic conditions and exacerbate microvascular thrombosis by preventing fibrin removal. Recombinant thrombomodulin (rTM) and antithrombin gamma (rAT) are potential therapeutic agents that may restore anticoagulant potential within the septic microcirculation. Similar to endogenous thrombomodulin, rTM binds to thrombin to generate activated protein C (APC), which can limit the amplification of coagulation. rAT is an alternative to plasma-derived antithrombin, which traps activated coagulation factors, including thrombin and FXa