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Systemic infection leads to activation of the coagulation system. The presence of endotoxins results in exposure of tissue factor. Tissue factor-mediated initiation of coagulation results in the generation of thrombin for fibrin formation. Thrombin formation continues after fibrin formation via feedback activation of factor XI, thereby propagating the intrinsic pathway of coagulation. The extra thrombin that is formed can lead to additional fibrin formation and protection of the fibrin clot from fibrinolysis. The activation of the coagulation system, with at the same time not fully working control mechanisms, induces a severe procoagulant state in sepsis. [ABSTRACT FROM AUTHOR]

The expression of surface tissue factor by cells of the monocyte/macrophage lineage is a major contributor to the development and progression of local and systemic inflammatory reactions. A wide variety of extracellular stimuli act to upregulate tissue factor (TF), the principal inducer of the coagulation cascade in vivo. Since both the coagulation cascade and TF have multiple roles, the expression of TF has consequences both for the inflammatory milieu and for the monocyte. TF expression is controlled primarily at the transcriptional level, particularly by activation of AP-1 and NF-κB transcription factors. Control is mediated both at the level of NF-κB and AP-1 nuclear translocation and DNA binding and by altering their transactivation potential; however, recent data suggests that while these factors are necessary, they are not sufficient for TF expression. Similarly, a number of intracellular signaling cascades have been studied and may affect TF upregulation both at the transcriptional and post-transcriptional level. In particular, the roles of protein tyrosine kinases, protein kinase C and the downstream Mitogen Activated Protein Kinases (MAPK) suggest that signal integration occurs at many stages. In this review, the roles of monocyte TF are briefly overviewed and the signaling pathways regulating TF gene expression and functional activity are examined in detail. [ABSTRACT FROM AUTHOR]

Sepsis can be associated with profound alterations in the hemostatic mechanism. In this article we discuss recent insights into which mediators are involved in the activation of the coagulation system. We focus on studies performed in healthy humans intravenously injected with a low dose of endotoxin, and investigations in nonhuman primates infused with either endotoxin or live gram-negative bacteria. Special emphasis is given to the role of cytokines, in particular tumor necrosis factor-α, interleukin (IL)-1, IL-6, IL-10 and IL-12. Moreover, the roles of tissue factor, activated protein C, and the fibrinolytic system are briefly addressed. Disseminated intravascular coagulation likely is the result of complex interactions between several host mediator systems. [ABSTRACT FROM AUTHOR]