Tissue factor, coagulation proteases, and protease-activated receptors in endotoxemia and sepsis

Sepsis represents a systemichost response to infection byGram-negative bacteria andother pathogenic microorgan-isms. This syndrome is associated with activation of inflammation and coagula-tion, and it can lead to multiple organ failure and death in many patients (1, 2). In sepsis caused by Gram-negative infec-tions, bacterial lipopolysaccharide in-duces the expression of tissue factor (TF) within the vasculature (3). The subse-quent formation of a TF–factor VIIa com-plex activates factors IX and X, which leads to thrombin generation and fibrin deposition (Fig. 1). The disseminated in-travascular coagulation that occurs in en-dotoxemia and sepsis is likely to impai