MECHANISMS OF THROMBOEMBOLISM AT ARTERIAL PLAQUES

Thrombus formation at a ruptured arterial plaque forming a stenotic lu minal outgrowth may trigger acute vascular occlusion. The pathobiology of the complex mechanisms and their interrelationships during this ev ent is not fully understood. However, it is generally believed that co mponents of the subendothelial plaque and the disturbed blood flow con ditions caused by the stenosis are of pivotal importance for the throm bus formation. The shape and the severity of the occluding stenosis ha ve profound impacts on the physical aspects of the blood flow. The wal l shear rate at the apex may reach extremely high values (> 40 000 s-1 ). Zones of recirculation proximal and distal to the stenosis as well as turbulent blood flow further downstream from the lesion may occur. The significance of these rheological factors for the mural thrombus f ormation at various locations at the stenosis is not well established. The extracellular matrix and the cellular components of the subendoth elial plaque exposed to the blood stream following plaque rupture are potent inducers of thrombus formation. Matrix components such as colla gen fibrils, fibronectin and von Willebrand factor interact specifical ly with platelet membrane glycoprotein receptors, Ia-IIa, Ib-IX, and I Ib-IIa, enabling platelet-subendothelium adhesion, particularly at hig h wall shear rates. The coagulation cascade is concomitantly activated by the binding of FVII from plasma to tissue factor expressed on the membranes of macrophages and smooth muscle cells. Thrombin, which is s ubsequently generated at the rupture, enhances the platelet recruitmen t, and thus the thrombus growth. The thrombin formation simultaneously enhances the deposition of fibrin in and around the platelet masses. Further augmentation of these processes is mediated by the formation o f prothrombinase complexes on the phospholipid-rich surfaces of the ac tivated platelets, which increases the local concentration of thrombin at the evolving thrombus. Thrombus fragmentation may represent a seri ous event, since these fragments may embolize and occlude smaller vess els, producing ischaemia. It is apparent that acute arterial thromboti c occlusion triggered by a ruptured stenotic plaque involves both phys ical and chemical mechanisms. The inter-relationship and the significa nce of these complex mechanisms are not well understood. Efficient mod alities for therapeutic intervention in thromboembolism at such lesion s may not be available before the physical and chemical events are bet ter identified and characterized.