title: Endothelial-dependent procoagulant and anticoagulant mechanisms. Recent advances in understanding.
abstract: Modulation of endothelial cell coagulant function is one of a group of changes common to many cytokine-mediated events. Changes that 1) cause migration of leukocytes, 2) increase vascular permeability, and 3) increase the thrombotic potential occur at atherosclerotic arterial branch points, in tumor vasculature, and at sites of inflammation. Regulation of procoagulant activity on the luminal surface of the vessel is crucial and is achieved by presentation of a predominantly anticoagulant surface on the endothelium. Inflammatory mediators can cause a decrease in the expression of the anticoagulant mechanisms and up-regulation of the procoagulant tissue factor. However, under these conditions very little tissue factor is exposed to the blood; instead it is sequestered under the endothelium and presumably becomes exposed only when significant vascular damage is present. Inhibition of intravascular coagulation by factor IXai without impairment of extravascular hemostasis suggests that when tissue factor concentrations are low, the continued generation of factor Xa is dependent on the presence of factor IXa. The demonstration that the blockade of factor IXa is selective for prevention of intravascular thrombus formation suggests a new means for managing intravascular thrombosis without altering the normal hemostatic mechanisms.
authors.affiliation: Department of Internal Medicine, University of Texas Medical School, Houston 77030.
authors.forename: C R
authors.initials: CR
authors.lastname: Benedict
authors.forename: R
authors.initials: R
authors.lastname: Pakala
authors.forename: J T
authors.initials: JT
authors.lastname: Willerson
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D013925:Thromboplastin / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D014409:Tumor Necrosis Factor-alpha; D013925:Thromboplastin