13 - The Crosstalk of Inflammation and Coagulation in Infectious Disease and Their Roles in Disseminated Intravascular Coagulation

Abstract

Abstract Systemic infection sepsis is almost invariably associated with some degree of activation of coagulation. There is ample evidence that demonstrates a wide-ranging crosstalk between hemostasis and inflammation, which is probably implicated in the pathogenesis of organ dysfunction in patients with sepsis. Inflammation not only leads to initiation and propagation of coagulation activity, but coagulation also markedly influences inflammation. Molecular mechanisms that play a role in inflammation-induced effects on coagulation have been recognized in much detail. Proinflammatory cells and cytokines and chemokines can activate the coagulation system and downregulate crucial physiologic anticoagulant mechanisms. Initiation of coagulation activation and consequent thrombin generation is caused by expression of tissue factor on activated monocytes and endothelial cells and is ineffectually offset by tissue factor pathway inhibitor. At the same time, endothelial-associated anticoagulant pathways, in particular the protein C system, is impaired by proinflammatory cytokines. In addition, fibrin removal is severely obstructed by inactivation of the endogenous fibrinolytic system, mainly as a result of upregulation of its principal inhibitor, plasminogen activator inhibitor type 1 (PAI-1). Increased fibrin generation and impaired breakdown lead to deposition of (micro)vascular clots, which may contribute to tissue ischemia and ensuing organ dysfunction. The foundation of the management of coagulation in sepsis is the explicit and thorough treatment of the underlying disorder by antibiotic treatment and source control measures. Adjunctive strategies focused at the impairment of coagulation, including anticoagulants and restoration of physiologic anticoagulant mechanisms, may supposedly be indicated and have been found advantageous in experimental and initial clinical trials.