THROMBIN IN ARTERIAL THROMBOSIS

Thrombin plays a pivotal role in the pathogenesis of arterial thrombos is. Platelet-rich thrombosis after arterial injury is dependent on the depth and extent of injury, local rheological conditions and the pers istence of residual mural thrombus. The unique effects of specific thr ombin inhibitors, including thrombin action on platelets and blood coa gulation, demonstrated in experimental and preliminary clinical trials , suggest that specific thrombin inhibitors may be the next major adva nce in antithrombotic therapy of acute coronary syndromes. The importa nce of thrombin lies not just in acute thrombus formation following ar terial injury but thrombin also contributes to smooth muscle cell prol iferation by stimulating platelet secretion of growth factors (especia lly platelet derived growth factor, PDGF) and directly acting on smoot h muscle cells. Thus, thrombin has direct effects on cell proliferatio n and influences the cellular synthetic mechanisms responsible for mat rix protein and collagen production. The role for thrombin as a possib le mitogen for vascular cells has gained support by the identification of a cellular thrombin receptor and by the recent detection of m-RNA for this receptor in human atherosclerotic plaques. Therefore, specifi c thrombin inhibition may also have a potential impact on the relative proliferative response of endothelial and smooth muscle cells after a rterial injury such as PTCA by preventing restenosis.