TISSUE FACTOR EXPRESSION BY ENDOTHELIAL-CELLS IN SICKLE-CELL-ANEMIA

The role of the vascular endothelium in activation of the coagulation system, a fundamental homeostatic mechanism of mammalian biology, is u ncertain because there is little evidence indicating that endothelial cells in vivo express tissue factor (TF), the system's triggering mech anism. As a surrogate for vessel wall endothelium, we examined circula ting endothelial cells (CEC) from normals and patients with sickle cel l anemia, a disease associated with activation of coagulation. We find that sickle CEC abnormally express TF antigen (expressed as percent C EC that are TF-positive), with 66+/-13% positive in sickle patients in steady-state, 83+/-19% positive in sickle patients presenting with ac ute vasoocclusive episodes, and only 10+/-13% positive in normal contr ols. Repeated samplings confirmed this impression that TF expression i s greater when sickle patients develop acute vasoocclusive episodes. S ickle CEC are also positive for TF mRNA, with excellent concurrence be tween antigen and mRNA expression. The TF expressed on the antigen-pos itive CEC is functional, as demonstrated by a binding assay for Factor VIIa and a chromogenic assay sensitive to generation of Factor Xa. By establishing that endothelial cells in vivo can express TF, these dat a imply that the vast endothelial surface area does provide an importa nt pathophysiologic trigger for coagulation activation.