Thrombomodulin: A Bifunctional Modulator of Inflammation and Coagulation in Sepsis

Figure 1

Crosstalk between inflammation and coagulation. Proinflammatory stimulation induces TF expression in monocytes, macrophages, and endothelial cells. TF initiates a coagulation cascade and the FXa-FVa complex converts thrombin. Thrombin induces fibrin formation and activates platelets, monocytes, and endothelial cells through PARs. Thus, thrombin acts to form a positive feedback loop that augments coagulation and inflammation. In a negative feedback loop, the thrombin-TM complex activates protein C and downregulates coagulation and inflammation. APC, in tandem with its cofactor protein S, inactivates FVa and FVIIIa. In addition, the APC-EPCR complex induces anti-inflammatory effects through PARs. Therefore, thrombin, TM, and protein C-EPCR play pivotal roles in the crosstalk that occurs between inflammation and coagulation.