The inflammatory-coagulant axis in the host response to gram-negative sepsis: regulatory roles of proteins and inhibitors of tissue factor.
Reciprocal interactions between elements of the acute inflammatory response and the coagulation system play important roles in host defense homeostasis during Gram-negative bacterial sepsis. However, derangements in the regulation of the inflammatory-coagulant axis in this setting may result in progressive tissue damage and disseminated intravascular coagulation. In this article, the integrated responses in the baboon model of Escherichia coli sepsis are analyzed as a basis of understanding these response interactions in the critically ill. In particular, three topics will be reviewed. First, the role of tissue factor in mediating the coagulant response to inflammation and the role of tumor necrosis factor (TNF) in initiating and amplifying this coagulant response into a full-blown consumptive coagulopathy are defined. A second and parallel topic concerns the role played by tissue factor pathway inhibitor and other anticoagulant systems in not only regulating this coagulant response, but also in attenuating the initial inflammatory response. The third topic concerns the use of assays of enzyme inhibitor complexes composed of components of these regulatory anticoagulant systems to help define the hypercoagulable state and possibly to make an early, specific diagnosis of sepsis prior to overt failure of the hemostatic system.
Taylor
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Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City 73104.
D000818:Animals; D001777:Blood Coagulation / Q000502:physiology*; D001779:Blood Coagulation Factors / Q000502:physiology*; D004211:Disseminated Intravascular Coagulation / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000502:physiology; D004927:Escherichia coli Infections / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D005337:Fibrin / Q000502:physiology; D007249:Inflammation / Q000503:physiopathology; D008074:Lipoproteins / Q000502:physiology*; D010215:Papio; D018805:Sepsis / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D013925:Thromboplastin / Q000037:antagonists & inhibitors* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D001779:Blood Coagulation Factors; D008074:Lipoproteins; D014409:Tumor Necrosis Factor-alpha; C051928:lipoprotein-associated coagulation inhibitor; D005337:Fibrin; D013925:Thromboplastin