Atherosclerosis Thrombus

The aggregation of platelets contributes to the development of atherosclerosis and to the formation of acute thrombus. The activated platelets that adhere to the vascular endothelium generate lipid peroxides and oxygen free radicals, inhibiting the endothelial formation of prostacyclin and nitric oxide. 

Ischemic strokes account for 88% of all strokes and are due either to local thrombus formation or to emboli that occlude a cerebral artery. Cerebral atherosclerosis is a causative factor in most cases of ischemic stroke, although 30% are of unknown etiology. Emboli can arise either from intra- or extracranial arteries. Twenty percent of embolic strokes arise from the heart. 

In carotid atherosclerosis, plaques may rupture, resulting in collagen exposure, platelet aggregation, and thrombus formation. The clot may cause local occlusion or may dislodge and travel distally, eventually occluding a cerebral vessel. 

Arterial thrombi (white thrombi) are formed initially from both platelets and fibrin in medium-sized arteries on the basis of atherosclerosis. These thrombi can lead to symptoms of, among others, myocardial ischemia and myocardial infarction. The treatment is primarily aimed at prevention of thrombus formation with platelet aggregation inhibitors. For the treatment of myocardial infarction thrombolytic agents are used and for secondary prevention both oral anticoagulants and anti-platelet drugs are employed. 

The atherosclerotic lesions develop in a complex, chronic process. The first detectable lesion is the so-called fatty streak, an aggregation of lipid-laden macrophage foam cells. The next stage of development is the formation of plaques consisting of a core of lipid and necrotic cell debris covered by a layer of connective tissue and smooth muscle cells. These plaques hinder arterial blood flow and may precipitate clinical events by plaque rupture and thrombus formation. Platelets from the thrombi, activated macrophages, and smooth muscle cells release growth factors and cytokines resulting in an inflammatory-fibroproliferative response that leads to the advanced lesions of atherosclerosis. 

Atherosclerosis mainly affects large- and mediumsized arteries. Extracranial manifestations at the carotid bifurcation statistically dominate the intracranial arteries. Besides typical manifestations at the carotid siphon or the vertebrobasilar junction, atherosclerosis is occasionally also found in peripheral intracranial vessel segments. Typical sequelae of atherosclerosis are stenosing plaque formations, ulcerations, dilatations or the evolution of fusiform aneurysms, which can be accompanied by extensive formation of thrombus. 

Patients with atherosclerosis present with stenoses and irregularities of vessel walls and elongated and ectatic arteries. Extreme dilative atherosclerotic pseudoaneurysms can typically occur with wall adherent thrombus. The differentiation of flow and thrombus signal can be difficult, although its age... 

Thrombus versus embolus A clot that adheres to a vessel wall is called a thrombus, whereas an intravascular clot that floats within the blood is termed an embolus. Thus, a detached thrombus becomes an embolus. Both thrombi and emboli are dangerous, because they may occlude blood vessels and deprive tissues of oxygen and nutrients. Arterial thrombosis most often involves medium-sized vessels rendered thrombogenic by surface lesions of endothelial cells caused by atherosclerosis. In contrast, venous thrombosis is triggered by blood stasis or inappropriate activation of the coagulation cascade, often as a result of a defect in the normal defense hemostatic mechanisms. 

Cardiovascular diseases are the leading cause of death in the Western world. Basically, atherosclerosis manifests itself in three major organs and thereby leads to severe secondary diseases. Coronary disease results from atherosclerosis of the coronary arteries and culminates in myocardial infarction when vessels are occluded by a thrombus. In the brain, atherosclerosis gives rise to arterial thrombi or ruptures that result in a stroke. Atherosclerosis in the kidney leads to renal failure. Since these diseases significantly lower life expectancy, early recognition and elimination of risk factors (hypertension, diabetes mellitus, hyperlipidemia, and smoking) that promote atherosclerosis are essential. 

Q1 A stroke involves significant reduction in blood flow to a part of the brain. It can be caused either (i) by an embolus or by intravascular clotting, which blocks blood flow to an area (approximately 85% of strokes), or (ii) by haemorrhage from a ruptured blood vessel, which compresses the brain tissue (approximately 15% of strokes). Patients with extensive atherosclerosis are at risk of intravascular coagulation and blockage of cerebral blood flow, but a vessel can be blocked by a thrombus originating in another part of the circulation. This cause of stroke is common in elderly patients >60 years of age. Aneurysms which rupture suddenly are a more common cause of stroke in younger patients. 

Atherosclerosis is a major cause of death in most industrial societies. The characteristic lesion of this disease, the atherosclerotic plaque, is found in the intima of large- and medium-sized arteries. An additional problem with advanced plaques is that thrombus formation is likely to occur in regions of plaque rupture. The combination of the two events can lead to partial or even total occlusion of major arteries. If this occurs in one or more of the coronary arteries, a serious or even fatal MI may result. A discussion of arteriosclerosis and exogenous agents that can modulate this condition is presented below. 

Atherosclerosis (athero = fatty and sclerosis = scarring or hardening) of the coronary and peripheral vasculature is the leading cause of morbidity and mortality worldwide. Lesions (called plaque) are initiated by an injury to endothelium and thicken the intima of arteries, occlude the lumen, and compromise delivery of nutrients and oxygen to tissue (ischemia). Atherosclerotic lesions primarily occur in large and medium-sized elastic and muscular arteries and progress over decades of life. These lesions cause ischemia, which can result in infarction of the heart (myocardial infarction) or brain (stroke), as well as abnormalities of extremities. The proximate cause of occlusion in these pathological conditions is thrombus formation. 

Aberrant thrombus formation and deposition on blood vessel walls imderlies the pathogenesis of acute cardiovascular disease states which remain the principal cause of morbidity and mortality in the industrialized world [1,2,3]. Plasma proteins, proteases and specific cellular receptors that participate in hemostasis have emerged as important risk considerations in thrombosis and thromboembolic disorders. The clinical manifestations of the above disease states include acute coronary artery and cerebrovascular syndromes, peripheral arterial occlusion, deep vein thrombosis and pulmonary/renal embolism [3]. The most dilabilitating acute events precipitated by these disorders are myocardial infarction and stroke. In addition, the interplay between hemostatic factors and hypertension (4) or atherosclerosis (5) dramatically enhances the manifestation of these pathologic states. 

Even though apparently sudden, a heart attack is the end result of a buildup of causes over years, particularly atherosclerosis in the coronary arteries. The immediate cause is a blood clot (thrombus) that, once having formed, blocks the narrowed lumen of a coronary artery. This denies the affected part of the myocardium blood and therefore oxygen. Technically, this may be referred to as a coronary thrombosis or myocardial infarction (Ml). Angina pectoris, which should also be mentioned, is characterized by severe pain and oppression above the heart, radiating to the shoulder and down the left arm. 

Inflammation in the plaque wall has been postulated to influence thrombus formation in myocardial infarction (Ml) as well as stroke. Recent studies have focused on the possibility that infection in the plaque contributes to thrombus formation and subsequent stroke or Ml. Chlamydia pneumoniae particles have been recently discovered in carotid and coronary plaques [15]. Although several studies have shown an association between elevated serum antibody titers for Chlamydia pneumoniae and cerebrovascular and cardiovascular events, there remains no clear evidence of stroke risk reduction associated with antibiotic therapy [6, 16]. Another condition that can produce progressive carotid narrowing not due to atherosclerosis is intimal hyperplasia, which can occur after radiation treatment to the neck or prior carotid endarterectomy. 

---