Abstract
The pathogenesis of arterial thrombosis is complex and dynamic. Unlike venous thrombi, arterial thrombi typically form under conditions of high blood flow and are mainly composed of platelet aggregates, giving them the appearance of 'white clots'. Strong evidence suggests that arterial thrombi originate as a consequence of an injured atherosclerotic plaque, and that their formation involves the release of prothrombotic material (such as tissue factor), platelet aggregation, and platelet adhesion to the vascular wall. The initially labile platelet plaque is then stabilized by insoluble fibrin produced upon activation of the coagulation cascade. Inherited genetic factors (gene polymorphisms) and acquired predisposing conditions (such as the concentration and activity of clotting factors) can influence both the composition and the size of an arterial thrombus. Further research is needed to elucidate the functions of blood coagulation proteins and cellular elements that are critical to the pathogenesis of arterial thrombosis. This Review explains mechanisms of pathological arterial thrombus formation and discusses genetic and acquired risk factors of atherothrombosis.
Key Points
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Arterial thrombus formation is a complex and dynamic pathological process that is initiated at an injured atherosclerotic plaque
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Several factors are involved in arterial thrombus formation, including the platelet glycoprotein VI, glycoprotein receptor Ia/IIa, collagenous plaque components, and blood coagulation protein
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Coronary artery disease (CAD) in young individuals often has a genetic basis, but whether genetic variants or disorders predispose to an increased risk of CAD in adults remains unclear
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Reliable associations have been demonstrated between CAD and acquired risk factors such as antiphospholipid antibodies, hyperhomocysteinemia, and elevated levels of fibrinogen, C-reactive protein, and lipoprotein(a)
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Future research should aim to further elucidate the functions of blood coagulation proteins and cellular elements that are critical to thrombus formation
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A better knowledge of the pathophysiological mechanisms of arterial thrombosis might open up new therapeutic options in the treatment of atherothrombosis
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Lippi, G., Franchini, M. & Targher, G. Arterial thrombus formation in cardiovascular disease. Nat Rev Cardiol 8, 502–512 (2011). https://doi.org/10.1038/nrcardio.2011.91
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