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Thromb Res. 2004;114(5-6):321-7.

The impact of the inflammatory response on coagulation.

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  • 1Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, OK, USA. Charles-Esmon@omrf.ouhsc.edu

Abstract

Inflammation contributions to the thrombotic response involve both cellular and humoral modulation. Inflammation impacts the initiation, propagation and the inhibitory phases of blood coagulation. Inflammatory mediators like endotoxin and tumor necrosis factor alpha (TNF alpha) elicit the expression of tissue factor on blood cells. Under normal circumstance, negatively charged membrane surfaces are limiting so that, even if some activated coagulation factors are generated, propagation of the coagulant stimulus is minimal. Complement activation, however, or exposure of collagen in combination with thrombin, provides a potent stimulus eliciting the exposure of negatively charged phospholipid membrane surfaces. Natural anticoagulant mechanisms limit the thrombotic response, but these pathways are depressed by inflammatory mediators. The protein C pathway is one of the major targets. Thrombomodulin and the endothelial cell protein C receptor are both required for optimal protein C activation, but both are down regulated by inflammatory mediators. Furthermore, free protein S levels often decrease resulting in impaired anticoagulant function of the activated protein C that is generated. In addition, anti-phospholipid antibodies severely impair the protein C pathway further inhibiting this pathway in inflammatory states associated with auto-immunity. In addition to shifting the hemostatic system in favor of clot formation, inflammation elevates the levels of plasminogen activator inhibitor thereby decreasing fibrinolytic activity. The procoagulant impact of inflammation can also be seen at the cellular level. Inflammatory mediators like interleukin 6 can increase both platelet count and their responsiveness to agonists like thrombin. All of these events tend to shift the hemostatic balance in favor of clot formation.

PMID:
15507261
[PubMed - indexed for MEDLINE]
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