Inflammation and haemostasis

Abstract

Inflammation and haemostasis are interrelated pathophysiologic processes that considerably affect each other. In this bidirectional relationship, inflammation leads to activation of the haemostatic system that in turn also considerably influences inflammatory activity. Such, the haemostatic system acts in concert with the inflammatory cascade creating an inflammation-haemostasis cycle in which each activated process promotes the other and the two systems function in a positive feedback loop. The extensive crosstalk between immune and haemostatic systems occurs at level of all components of the haemostatic system including vascular endothelial cells, platelets, plasma coagulation cascade, physiologic anticoagulants and fibrinolytic activity. During inflammatory response, inflammatory mediators, in particular proinflammatory cytokines, play a central role in the effects on haemostatic system by triggering its disturbance in a number of mechanisms including endothelial cell dysfunction, increased platelet reactivity, activation of the plasma coagulation cascade, impaired function of physiologic anticoagulants and suppressed fibrinolytic activity. The two examples of pathophysiologic processes in which the tight interdependent relationship between inflammation and haemostasis considerably contribute to the pathogenesis and/or progression of disease are systemic inflammatory response to infection or sepsis and acute arterial thrombosis as a consequence of ruptured atherosclerotic plaque. Close links between inflammation and haemostasis help explain the prothrombotic tendency in these two clinical conditions in which inflammation shifts the haemostatic activity towards procoagulant state by the ability of proinflammatory mediators to activate coagulation system and to inhibit anticoagulant and fibrinolytic activities. This review summarizes the current knowledge of the complex interactions in the bidirectional relationship between inflammation and haemostasis.

Figure 1.

Mechanisms of inflammation-induced disturbance of the haemostatic system.

Figure 2.

Endothelial cell dysfunction induced by inflammation. EC - endothelial cell; TXA2 – thromboxane A2; PAF – platelet-activating factor; vWF – von Willebrand factor; PAI-1 – plasminogen activator inhibitor-1; VCAM-1 – vascular cell adhesion molecule-1; ICAM-1 – intercellular adhesion molecule-1; TF – tissue factor; EPCR – endothelial protein C receptor; TM – thrombomodulin; tPA – tissue plasminogen activator; PGI2 – prostacyclin.

Figure 3.

Platelet activation induced by inflammation. EC – endothelial cell; TXA2 – thromboxane A2; vWF – von Willebrand factor; PGI2 – prostacyclin; PAF – platelet activating factor; GPIIb/IIIa – glycoprotein complex IIb/IIIa; PDGF – platelet derived growth factor; TGF-β - transforming growth factor-beta; EGF – epidermal growth factor; IL-1β - interleukin 1beta; PF-4 – platelet factor 4; RANTES – CCL5 chemokine; PAI-1 – plasminogen activator inhibitor 1; TF – tissue factor.

Figure 4.

Tissue factor-mediated activation of coagulation induced by inflammation. TF – tissue factor; ECs – endothelial cells; PL – phospholipids.

Figure 5.

The three major physiological anticoagulant mechanisms: antithrombin, protein C system and tissue factor pathway inhibitor.

Figure 6.

Mechanisms of suppressed fibrinolytic activity induced by inflammation. uPA – urokinase plasminogen activator; tPA – tissue plasminogen activator; PAI-1 – plasminogen activator inhibitor-1; FDP – fibrin degradation products.