Response of anticoagulant pathways in disseminated intravascular coagulation.
This article describes the microvascular endothelium as both a target and a regulator of events after hemostatic and inflammatory stress. The first section describes the four-quadrant hemostatic system as consisting of the two coagulant and anticoagulant domains that control clot formation and the two fibrinolytic and antifibrinolytic domains that control clot removal. This section concentrates on the anticoagulant domain that operates from the microvascular endothelium and protects it from the effects of hemostatic and inflammatory stress. The next two sections present examples of pure hemostatic and inflammatory stress and illustrate how the four functional domains of the hemostatic systems respond as a unit to these stresses. The following section correlates the response of molecular markers that reflect the activity of the hemostatic system with markers of microvascular endothelial injury to increasing sublethal concentrations of Escherichia coli in the baboon model of E. coli sepsis. The final section correlates the response of these same markers to endotoxin in the human model of endotoxemia. Both sections emphasize that the hemostatic and inflammatory stress and injury to the microvascular endothelium occur at surprisingly low concentrations of E. coli and endotoxin, long before there is evidence of fibrinogen consumption and before the other standard criteria for disseminated intravascular coagulation (DIC) are met. We conclude that this represents a compensated response to stress that can be measured and can be designated as nonovert DIC. We further conclude that as bedside assays of these molecular markers become available they should be helpful in diagnosing and staging early nonovert DIC.
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Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA. Marie-Brewer@omrf.ouhsc.edu
D000818:Animals; D001777:Blood Coagulation; D004730:Endothelium, Vascular / Q000503:physiopathology; D004927:Escherichia coli Infections / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D006801:Humans; D008833:Microcirculation / Q000503:physiopathology; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood* / Q000150:complications / Q000503:physiopathology