Tissue factor pathway inhibitors as a novel approach to antithrombotic therapy

Tissue factor is the initiator of the extrinsic pathway of the coagulation cascade. It is expressed by endothelial cells when stimulated by cytokines and other mediators. The effect of tissue factor is physiologically balanced by tissue factor pathway inhibitor. Atherosclerotic plaques are rich in tissue factor. It stimulates thrombus formation when plaques rupture. The emerging role of tissue factor in cellular signaling and in the pathogenesis of atherosclerosis has directed attention to inhibitors of tissue factor as a new antithrombotic approach. In comparison to currently used anticoagulants, tissue factor pathway inhibitors have the potential advantage of inhibiting the coagulation cascade at its earliest stage. These agents also act locally at the site of endothelial injury with minimal disturbance of systemic hemostasis. In addition, their inhibitory effect on neointimal formation and restenosis after vascular intervention are appealing features in the management of the complications of atherosclerosis.