Review article
Two-Way Interactions Between Inflammation and Coagulation

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Activation of inflammatory and coagulation pathways is important in the pathogenesis of vascular disease. There is ample evidence that extensive cross-talk between these two systems exists, whereby inflammation not only leads to activation of coagulation, but coagulation also markedly affects inflammatory activity. The main interfaces linking coagulation and inflammation are the tissue factor pathway, thrombin, the protein C system and the fibrinolytic (or plasminogen–plasmin) system. Proinflammatory cytokines and chemokines can affect all these coagulation mechanisms, and vice versa, activated coagulation proteases and physiological anticoagulants or components of the plasminogen–plasmin system can modulate inflammation by specific cell receptors. The intricate relationship between inflammation and coagulation may not only be relevant for vascular thrombotic disease but also has major consequences in the pathogenesis of microvascular failure and subsequent multiple organ failure in the setting of severe infection. This review focuses on the present understanding of the bidirectional relationship between inflammation and coagulation.

Section snippets

How Inflammation Causes Activation of Coagulation

Activation of coagulation and deposition of fibrin as a consequence of inflammation can be considered instrumental in containing inflammatory activity to the site of injury or infection, rendering this relationship physiologically efficient. However, inflammation-induced coagulation may also importantly contribute to disease, as illustrated by the coagulopathy that is associated with severe infection, such as sepsis, and also by the fact that thrombus formation on a ruptured atherosclerotic

How Coagulation Modulates Activation of Inflammation

Rather than being a one-way direction of inflammation leading to coagulation, both systems interact intensely, whereby coagulation can also importantly modulate inflammatory activity (Figure 1). Binding of coagulation proteases (such as thrombin or tissue factor) or anticoagulant proteins (such as activated protein C) to specific cell receptors on mononuclear cells or endothelial cells may affect cytokine production or inflammatory cell apoptosis. This cross-talk between the two systems is

Conclusions

Systemic inflammation will invariably lead to activation of the coagulation system, but vice versa, components of the coagulation system may markedly modulate the inflammatory response. Increasing evidence points to extensive cross-talk between the two systems at various points, with pivotal roles of tissue factor, thrombin, components of the protein C pathway, and fibrinolytic activators and inhibitors. Increased insight into the molecular mechanisms that play a role in the close relationship

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