Thrombin plays a pivotal role in vascular re-occlusion after PTCA and coronary thrombolysis

Acute coronary syndromes are the clinical presentations of complex biochemical events which in most cases culminate in intracoronary thrombosis. A central role in the process of intravascular thrombosis is played by thrombin, a glycosylated trypsin-like serine protease with multiple action in vascular biology [l]. In patients with acute coronary syndromes thrombin is generated by the exposure of tissue factor after fissuring or rupture of a coronary plaque. Tissue factor leads to thrombin generation through the activation of the coagulation factors VII and IX and the prothrombinase complex. Once generated, thrombin initiates a positive feed-back autocatalytic loop by directly activating factors V and VIII, thus amplifying its generation by about lOOO-fold. At substrate level, other than activating factors V and VIII, thrombin cleaves fibrinogen to fibrin and activates factor XIII which results in formation of stable, cross-linked fibrin clot. Thrombin binds to a specific receptor on the platelet surface initiating a number of intracellular processes, including ADP and thromboxane A, release and expression of GP IIb/IIIa receptors, which result in platelet aggregation. Thrombin receptors have been cloned from human platelets and vascular smooth muscle cells [2,3]. The activation of thrombin receptor on vascular smooth muscle cells is followed by most of the multiple cellular effects of thrombin, mainly by smooth muscle cell mitogenesis and migration. High concentrations of thrombin are present at the time and the site of mechanical injury or PTCA and persist throughout the period of vascular formation. The restenosis process appears to be triggered by the formation of a “neointima”