Fig. 3

Pathophysiology of sepsis-associated coagulation disorder. Monocytes, neutrophils, and platelets express various receptors such as Toll-like receptors (TLRs), Fcγ receptor (FcγR), and protease-activated receptor (PAR)-1, and induce inflammatory and procoagulant responses in these cells. Activated monocytes express tissue factor (TF) and phosphatidylserine (PS) on the surface, which initiate coagulation cascades. At the same time, monocytes release proinflammatory cytokines and stimulate neutrophils. Activated neutrophils release damage-associated molecular patterns (DAMPs) after cell death, and expel extracellular traps (NETs) that facilitate inflammation through binding to TLRs. Platelets release procoagulant microvesicles and prothrombotic substances such as von Willebrand factor (VWF) and platelet factor 4 (PF4). VWF helps platelet aggregation, and PF4 neutralizes heparan sulfate of the glycocalyx. Vascular endothelial cells lose anti-thrombogenicity by decreasing the production of nitric oxide (NO) and prostaglandin I₂ (PG I₂), and by increasing the production of plasminogen activator inhibitor 1 (PAI-1). Thrombomodulin which converts protein C (PC) to its activated form activated protein C (APC) is released from endothelial cells, and antithrombin is extravasated with increased vascular permeability. LPS lipopolysaccharide, Ig G immunoglobulin G, GP glycoprotein