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OVERVIEW OF THROMBOSIS
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Thrombosis is defined as "hemostasis in the wrong place,"1 and it is a major cause of morbidity and mortality in a wide range of arterial and venous diseases and patient populations. In 2009 in the United States, an estimated 785,000 people had a new coronary thrombotic event, and about 470,000 had a recurrent ischemic episode. Each year, approximately 795,000 people have a new or recurrent stroke. Annually, more than 200,000 new cases of venous thromboembolism are found; 30% of these individuals die within 30 days, with one-fifth having sudden death due to pulmonary embolism.
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In the nondiseased state, physiologic hemostasis reflects a delicate interplay between factors that promote and inhibit blood clotting, favoring the former. This response is crucial as it prevents uncontrolled hemorrhage and exsanguination following injury. In specific settings, the same processes that regulate normal hemostasis can cause pathological thrombosis, leading to arterial or venous occlusion. Importantly, many commonly used therapeutic interventions may also alter the thrombotic–hemostatic balance adversely.
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Hemostasis and thrombosis primarily involve the interplay among three factors: the vessel wall, coagulation proteins, and platelets. Many prevalent acute vascular diseases are due to thrombus formation within a vessel, including myocardial infarction, thrombotic cerebrovascular events, and venous thrombosis. Although the end result is vessel occlusion and tissue ischemia, the pathophysiologic processes governing these pathologies have similarities as well as distinct differences. While many of the pathways regulating thrombus formation are similar to those that regulate hemostasis, the processes triggering thrombosis and, often, perpetuating the thrombus are distinct. In venous thrombosis, primary hypercoagulable states reflecting defects in the proteins governing coagulation and/or fibrinolysis or secondary hypercoagulable states involving abnormalities of blood vessels and blood flow lead to thrombosis. By contrast, arterial thrombosis is highly dependent on the state of the vessel wall, the platelet, and factors related to blood flow.
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OVERVIEW OF ARTERIAL THROMBOSIS
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In arterial thrombosis, the platelet and abnormalities of the vessel wall typically play a key role in vessel occlusion. Arterial thrombus forms via a series of sequential steps in which platelets adhere to the vessel wall, additional platelets are recruited, and thrombin is activated. The regulation of platelet adhesion, activation, aggregation, and recruitment will be described in detail later in the chapter. In addition, while the primary function of platelets is regulation of hemostasis, our understanding of their role in other processes, such as immunity and inflammation, continues to grow.
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ARTERIAL THROMBOSIS AND VASCULAR DISEASE
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Arterial thrombosis is a major cause of morbidity and mortality both in the United States and, increasingly, worldwide. Coronary heart disease is estimated to cause about one of every five deaths in the United States. In addition ...