The endothelium plays an active role in the regulation of the coagulation mech anism. Multiple anticoagulant properties are operative on the cell surface in homeostasis. In the protein C/protein S pathway, for example, endothelium provides cofactors promoting activation of protein C, assembly of the activated protein C/protein S complex, and synthe sizes protein S. In contrast, following exposure to cytokines and other pathologic stimuli, endothelial cell activation occurs. This activated state includes upregulation of procoagulant properties, such as tissue factor, with concomitant downregulation of anticoagulant cofac tors, such as thrombomodulin. Modulation of endothelial cell coagulant properties by cyto kines provides a mechanism linking activation of the clotting mechanism to the cellular response to environmental stimuli.

Until quite recently endothelium was considered to be a passive barrier preventing contact of fluid and cellular elements of the blood with interstitial matrix, thus preserv ing its fluidity. In the presence of a contin uous layer of intact endothelium, blood re mains fluid: thus, disruption of endothelial cell continuity was considered the initial event leading to clot formation which indeed occurs effectively after vessel injury in which the integrity of the endothelium is clearly compromised. Furthermore, the adherence of platelets to the collagenous subendothelial basement membrane and the ability of inter stitial cells, such as fibroblasts, to promotecoagulation leant credence to this view. Re