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.
E. coli sepsis - endotoxemia - protein C network - endothelium - nonovert DIC
