In critically ill patients, the activation of blood coagulation occurs in parallel with the release of inflammatory mediators, which characterizes systemic inflammatory response syndrome and sepsis and sepsis-related conditions such as severe sepsis and septic shock. As a consequence, the overall hemostatic balance is shifted toward the activation of the coagulation, due to either the activation of the clotting system or the downregulation of the anticoagulant pathways. Systemic inflammation during sepsis leads to the generation of proinflammatory cytokines that, among other things, orchestrate coagulation and fibrinolytic activation. Abundant intravascular fibrin formation leads to microvascular thrombosis, which causes widespread ischemic organ damage up to organ necrosis and clinically impresses as widespread skin necrosis and multiple organ dysfunction syndrome. On the basis of the pathophysiologic concepts and the striking anticoagulant and anti-inflammatory properties of coagulation inhibitors in models for severe sepsis, administration of these inhibitors has been considered an attractive therapeutic approach for human sepsis.
