Schematic representation of the systemic activation of coagulation during a severe inflammatory response. Pro-inflammatory cytokines activate mononuclear cells and endothelial cells (which thereupon can also produce cytokines). Mononuclear cells and endothelial cells express tissue factor, the main initiator of coagulation. Simultaneously, impairment of the physiological anticoagulant mechanism and endogenous fibrinolysis, due to down-regulation of endothelial-bound proteins and endothelial cell perturbation, cause an insufficient counterbalance towards intravascular fibrin formation, which may contribute to organ failure. Simultaneously, consumption of platelets and clotting factors may cause serious bleeding.