Seminars in immunopathology
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The parallel expression of activation products of the coagulation, fibrinolysis, and complement systems has long been observed in both clinical and experimental settings. Several interconnections between the individual components of these cascades have also been described, and the list of shared regulators is expanding. ⋯ However, dysregulation of the cascade activities or functions of inhibitors in one or both systems can result in clinical manifestations of disease, such as sepsis, systemic lupus erythematosus, or ischemia-reperfusion injury, with critical thrombotic and/or inflammatory complications. An appreciation of the precise relationship between complement activation and thrombosis may facilitate the development of novel therapeutics, as well as improve the clinical management of patients with thrombotic conditions that are characterized by complement-associated inflammatory responses.
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In the pathogenesis of sepsis, inflammation and coagulation play a pivotal role. Increasing evidence points to an extensive cross-talk between these two systems, whereby inflammation not only leads to activation of coagulation but coagulation also considerably affects inflammatory activity. The intricate relationship between inflammation and coagulation may not only be relevant for vascular atherothrombotic disease in general but has in certain clinical settings considerable consequences, for example in the pathogenesis of microvascular failure and subsequent multiple organ failure, as a result of severe infection and the associated systemic inflammatory response. ⋯ Pro-inflammatory cytokines and other mediators are capable of activating the coagulation system and downregulating important physiological anticoagulant pathways. Activation of the coagulation system and ensuing thrombin generation is dependent on an interleukin-6-induced expression of tissue factor on activated mononuclear cells and endothelial cells and is insufficiently counteracted by physiological anticoagulant mechanisms and endogenous fibrinolysis. Interestingly, apart from the overall systemic responses, a differential local response in various vascular beds related to specific organs may occur.
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The integrity of our bodies is under constant threat by external forces. Blood coagulation and inflammatory pathways are important, highly efficient defence systems that support health and well-being in both normal and challenged conditions. Being potentially dangerous for the own organism, they are kept under strict control by anticoagulant and anti-inflammatory mechanisms. ⋯ Efficient anticoagulant systems not only keep coagulation reactions under strict control but also exert control on inflammatory reactions. During inflammation, these anticoagulant/anti-inflammatory systems are repressed allowing full activation of coagulation and inflammation. Dysregulation of the delicate balance between these systems contributes to the pathogenesis of many diseases.