Fig. 1

Activation of coagulation in the perivascular space and inhibition of coagulation in the intravascular space. Tissue factor (TF)-bearing fibroblasts, which reside in the perivascular space but not in the intravascular space under physiologic conditions, play an important role in the initiation of hemostasis. An injury to the vessel wall allows plasma coagulation factor VII (FVII) to come into contact with TF-bearing fibroblasts. The FVIIa/TF complex then activates FX and FIX. This results in the generation of a small amount of thrombin, which activates FV, FVIII, FXI, and platelets. This pathway serves as a propagation of coagulation, leading to the generation of large amounts of thrombin and fibrin. Fibrin polymers are then stabilized by FXIIIa, which introduces fibrin–fibrin and fibrin–α2-antiplasmin (α2AP) cross-links. Endothelial cells display heparan sulphate proteoglycans, a component of glycocalyx, which bind and potentiate plasma anticoagulant proteins, including tissue factor pathway inhibitor (TFPI) and antithrombin (AT). Endothelial cells also display thrombomodulin (TM), which promotes thrombin-mediated activation of protein C (PC). Endothelial protein C receptor (EPCR) augments this reaction. Activated protein C (APC) then limits the amplification of coagulation by inactivating FVa and FVIIIa with support from cofactor protein S (PS). Endothelial cells synthesize and release tissue-type plasminogen activator (tPA), which promotes the conversion of plasminogen (Plg) to plasmin (Pln) on the surface of fibrin, leading to the generation of fibrin degradation products (FDPs)