Derangements of coagulation and fibrinolysis in critically ill patients with sepsis and septic shock

In patients with sepsis and septic shock, both coagulation and fibrinolysis are activated frequently leading to the syndrome of diffuse intravascular coagulation (DIC). The different mechanisms leading to abnormalities in coa gulation and fibrinolysis are discussed in detail. The coagulation and fibr inolytic system appear to be influenced by the septic process largely indep endently, leading to a procoagulant imbalance between these systems. Coagul ation is initiated by mediator-induced expression of tissue factor and is a ssociated with consumption of the natural coagulation inhibitors antithromb in III, protein C, and protein S. As a result, high plasma levels of thromb in-antithrombin complex (TAT) can be found. The effects on fibrinolysis are dominated by (highly) increased levels of plasminogen activator inhibitor type 1 (PAI-1), leading to inadequate fibrinolysis. Although levels of plas minogen activator antigen are increased, its activity is almost completely inhibited by PAI-1. The resulting effects predispose to a procoagulant state, with widespread f ibrin deposition, which may be an important mechanism contributing to multi ple organ failure. A thorough understanding of the pathophysiological mecha nisms underlying the DIG-syndrome is a prerequisite for a rational approach and future therapy for this severe complication of sepsis.