Endothelial cell dysfunction and coagulation

a) To review endothelial properties and to establish how these unperturbed properties contribute to the maintenance of endothelium anticoagulant activity; b) to better understand the relative contributions of endothelial cells and monocytes in sepsis-induced altered coagulation.

A summary of published literature from MEDLINE search files and other original articles and reviews published on endothelial cell and monocyte functions and modifications owing to sepsis.

Unperturbed endothelial cells provide anticoagulant properties; exposure to inflammatory and/or septic stimuli can rapidly lead to procoagulant behavior. Sepsis alters endothelial cell surface and induces tissue factor synthesis at the endothelial and subendothelial levels. During endotoxemia, endothelial cells generate adhesion molecules that bind leukocytes and monocytes, increasing local procoagulant reactions. Tissue factor expression is also increased at the level of the monocyte; the relative importance of endothelial injury and monocyte activation in coagulation disorders was recently assessed. Endothelium protection before induction of septic shock was not associated with any reduction in monocyte tissue factor expression, suggesting that altered coagulation was present despite normal endothelial cell function. On the other hand, decreased monocyte tissue factor expression was associated with a marked reduction in endothelial injury, increased endothelium-derived relaxation, and improved survival rate in treated animals.

This review suggests that monocyte activation and tissue factor expression may be of paramount importance in sepsis-associated injuries and that coagulation activation may contribute to the endothelial cell injury observed during sepsis. Endothelial injury, in turn, exacerbates sepsis-induced coagulation abnormalities.