Skip to Main Content

Summary

This chapter discusses the pathophysiology of coronary thrombus formation (see accompanying Hurst’s Central Illustration), which constitutes the basis of acute coronary events. The luminal thrombus in up to three fourths of cases may be secondary to plaque rupture, and in the remaining cases it may result from plaque erosion; very infrequently calcific nodules may induce luminal thrombosis. Upon plaque rupture, components of deeper layers of the plaque are exposed to the circulating blood, which leads to marked platelet aggregation. The nature of the substrate exposed after plaque rupture likely determines whether a nonocclusive mural thrombus persists or whether the thrombus progresses to become occlusive. Indeed, the atheromatous core of a plaque is substantially more active than other substrates at triggering thrombosis and, therefore, ruptured plaques with large atheromatous core are at high risk of leading to acute coronary syndromes. The local geometry at the site of damage (degree of stenosis) and local hemodynamic conditions, as well as the presence of circulating systemic factors, also influence the mechanisms of thrombus formation.

eFig 33-01

Hurst’s Central Illustration: Coronary thrombus formation.

Coronary thrombus formation following rupture of an atherosclerotic plaque. When the endothelium is damaged and the deeper layers of the vessel walls are exposed to the circulating blood, ensuing biomolecular interactions result in activation and aggregation of platelets as well as the generation of thrombin. The consequential formation of a thrombus is influenced by various local and systemic factors.

INTRODUCTION

The formation of an acute thrombus on a ruptured coronary atherosclerotic lesion, obstructing coronary blood flow and reducing the oxygen supply to the myocardium, leads to the onset of acute coronary syndromes (ACS). These thrombotic episodes largely occur in response to atherosclerotic lesions that have progressed to a high-risk inflammatory or prothrombotic stage. Although they are distinct from one another, the atherosclerotic and thrombotic processes appear to be closely related, causing ACS through a complex, multifactorial process called atherothrombosis. ACS represents a spectrum of ischemic myocardial events that share similar pathophysiology; these include unstable angina/non–ST-segment elevation myocardial infarction (UA/NSTEMI), ST-segment elevation myocardial infarction (STEMI), and sudden cardiac death.

Atherosclerosis is a systemic disease involving the intima of large and medium-sized arteries, including the aorta, carotids, coronaries, and peripheral arteries, that is characterized by intimal thickening caused by the accumulation of cells and lipids (Fig. 33–1).1 Lipid accumulation results from an imbalance between the mechanisms responsible for the influx and efflux of lipids into the arterial wall.2 Secondary changes may occur in the underlying media and adventitia, particularly in advanced disease stages. The early atherosclerotic lesions might progress without compromising the lumen, because of compensatory vascular enlargement (Glagovian remodeling).3 Importantly, the culprit lesions leading to ACS are usually mildly stenotic and, therefore, barely detected by angiography.4 These high-risk, rupture-prone lesions usually have a large lipid core, a ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.