Vascular biology—the role of tissue factor

Abstract 

It is well established that tissue factor (TF) is abundantly present in various extravascular tissues, in the adventitia of blood vessels, and in atheroma. Thus, in the event of plaque rupture or damage to the blood vessel wall, TF is readily exposed to flowing blood, allowing it to form a complex with circulating factor VIIa (FVIIa) in order to activate factor X (FX) both directly, and indirectly via factor IX (FIX). Platelets quickly adhere to the injured site, facilitating localized thrombin formation and subsequent fibrin production. With each new layer of platelets and fibrin that adheres to the injured surface, the exposed TF on the vessel wall, along with the localized circulating factors IX (FIXa) and X (FXa) that it generates, becomes increasingly isolated from the events near the surface of the growing thrombus. The physical blanketing of an injured surface by platelets and fibrin in addition to the release of platelet tissue factor pathway inhibitor (TFPI), prevents FIXa and FXa from diffusing more than a few tens of microns away from the vessel wall, far short of the 3 mm thickness needed for occlusive thrombosis. Thus an alternative FXa-generating mechanism must be involved that allows for the formation of prothrombinase activity far away from the vessel wall near the front of a growing thrombus.