Tumor necrosis factor (TNF), also known as cachectin, is a mediator of the septic state that affects coagulation throughout the vasculature. This study shows that TNF modulates endothelial cell hemostatic properties, which are crucial in coagulation. Incubation of cultured endothelial cells with TNF resulted in a time- and dose-dependent increase in tissue factor, a key procoagulant protein normally not expressed on endothelial cells. This increase was accompanied by a suppression of the protein C pathway, an anticoagulant mechanism on the endothelial cell surface. TNF also reduced thrombin-mediated protein C activation and the formation of the functional activated protein C-protein S complex, which is essential for anticoagulation. These effects were dose- and time-dependent, with half-maximal effects observed at around 50 pM TNF and 4 hours of incubation. The results indicate that TNF induces endothelial cells to synthesize and express tissue factor, promoting clot formation. This shift in endothelial cell hemostatic properties from an anticoagulant to a procoagulant state may contribute to the pathogenesis of thrombotic disorders associated with inflammation and malignancy. The study also suggests that TNF can lead to coagulopathy by altering endothelial cell coagulant properties, potentially interrupting blood flow to tumors and causing necrosis. These findings highlight the role of TNF in modulating endothelial cell hemostatic properties, which can influence the development of thrombotic states in response to inflammatory and neoplastic stimuli.Tumor necrosis factor (TNF), also known as cachectin, is a mediator of the septic state that affects coagulation throughout the vasculature. This study shows that TNF modulates endothelial cell hemostatic properties, which are crucial in coagulation. Incubation of cultured endothelial cells with TNF resulted in a time- and dose-dependent increase in tissue factor, a key procoagulant protein normally not expressed on endothelial cells. This increase was accompanied by a suppression of the protein C pathway, an anticoagulant mechanism on the endothelial cell surface. TNF also reduced thrombin-mediated protein C activation and the formation of the functional activated protein C-protein S complex, which is essential for anticoagulation. These effects were dose- and time-dependent, with half-maximal effects observed at around 50 pM TNF and 4 hours of incubation. The results indicate that TNF induces endothelial cells to synthesize and express tissue factor, promoting clot formation. This shift in endothelial cell hemostatic properties from an anticoagulant to a procoagulant state may contribute to the pathogenesis of thrombotic disorders associated with inflammation and malignancy. The study also suggests that TNF can lead to coagulopathy by altering endothelial cell coagulant properties, potentially interrupting blood flow to tumors and causing necrosis. These findings highlight the role of TNF in modulating endothelial cell hemostatic properties, which can influence the development of thrombotic states in response to inflammatory and neoplastic stimuli.