Bidirectional relation between inflammation and coagulation.

Inflammation and coagulation play pivotal roles in the pathogenesis of vascular disease. Increasing evidence points to extensive cross-talk between these two systems, whereby inflammation leads not only to activation of coagulation, but coagulation also considerably affects inflammatory activity. Activation of coagulation and fibrin deposition as a consequence of inflammation is well known and can be viewed as an essential part of the host defense of the body against, for example, infectious agents or nonidentical cells, in an effort to contain the invading entity and the consequent inflammatory response to a limited area. An exaggerated or insufficiently controlled response may, however, lead to a situation in which coagulation and thrombosis contribute to disease, as illustrated by the fact that thrombus formation on a ruptured atherosclerotic plaque, containing abundant inflammatory cells, is the pathological basis of acute arterial thrombotic events such as myocardial infarction or unstable angina.1 Expression of procoagulant material by inflammatory cells in the unstable plaque (in particular tissue factor) may initiate activation of coagulation, and the thrombin generated will both activate platelets and result in the formation of a platelet-fibrin thrombus (Figure 1). Another example is the occurrence of systemic coagulation activation in combination with microvascular failure that results from the systemic inflammatory response to severe infection or sepsis and that contributes to multiple organ dysfunction.2 However, rather than this being a 1-way process with inflammation leading to coagulation, both systems closely interact, whereby coagulation can also substantially modulate inflammatory activity. Coagulation factors (such as thrombin) or anticoagulant proteins (such as activated protein C) may activate specific cell receptors on mononuclear cells or endothelial cells, which may affect, for example, cytokine production or inflammatory cell apoptosis.