Thrombosis is integral to the development and progression and clinical sequelae of atherosclerosis. Acute thrombosis can occur spontaneously, leading to catastrophic arterial occlusion and resulting in myocardial infarction, unstable angina, stroke, and sudden death (1, 2). Acute thrombosis also occurs as a complication of arterial bypass surgery, balloon angioplasty, atherectomy, or coronary artery stenting (3-5). Non-occlusive thrombus is an important component of the atherosclerotic plaque. Thrombus is comprised principally of platelets and fibrin. White blood cells and circulating proteins are also trapped within the platelet-fibrin thrombus. Activated platelets release a variety of growth factors and cytokines that have been implicated in vessel inflammation and in vascular smooth muscle cell (SMC) proliferation and migration (6, 7). Thrombin (8) and factor XlXa (9, 10) also have direct effects on SMC and may play a role in the development of intimal hyperplasia. In addition, products secreted by leukocytes trapped within the thrombus may have direct effects on the vessel wall.

Tissue factor (TF) is a membrane-bound glycoprotein that initiates coagulation (11, 12). Human TF consists of three domains: a short cytoplasmic domain of 19 residues, a single transmembrane domain of 23 residues, and a large extracel-lular domain of 219 residues. In addition, there is a 32 resi-due amino-terminal leader sequence which is cleaved to produce the mature molecule. TF binds to factor VIIA/IIa, and the resulting complex acts as a catalyst for the conversion of factors IX and X to IXa and Xa respectively, triggering the clotting cascade. This ultimately leads to the generation of thrombin, which in turn cleaves fibrinogen to fibrin, the ma-jor ingredient of the thrombus. Recent studies suggest that the accumulation of TF in atherosclerotic plaques plays a major role in determining plaque thrombogenicity. TF is also rapidly induced in the vessel wall as a consequence of acute arterial injury. Both phenomena may be important in the thrombotic complications of atherosclerotic heart disease.