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Proposed Mechanisms of Aspirin Resistance12
Extrinsic Mechanisms
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Accentuation of platelet thrombosis by exogenous substances (e.g., cigarette smoke) |
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Drugs, such as NSAIDs, that may interact with the acetylation of cyclooxygenase (COX-1) by aspirin |
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Increased platelet turnover overcoming once-daily aspirin dosing |
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Inadequate aspirin dosing |
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Intrinsic Mechanisms
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Inducible COX-2 that is not adequately inhibited by low-dose ASA, thereby allowing for platelet thromboxane A2 production, despite inhibition of COX-1 |
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Polymorphisms in the COX-1 gene that alter the structure of the active site and prevent acetylation by aspirin |
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Regenerated, uninhibited COX-1 in nucleated cells, such as macrophages, and vascular endothelial cells producing prostaglandin H2 that is shunted into platelets, thereby bypassing platelet COX-1 |
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Polymorphisms in the GPIIb/IIIa receptor complex that confers varying degrees of platelet responsiveness to aspirin |
Whatever the reason, it is clear that the risk of thrombosis increases in patients with cardiovascular disease when their platelets are inadequately inhibited.14-16 There is general consensus among cardiologists that the intent of aspirin therapy, in part, is to directly inhibit the function of platelets to reduce their involvement in promoting cardiovascular disease. However, if patient's platelets are not affected by aspirin, that is, they are “insensitive to aspirin,” it becomes important to ask:
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What is the platelet function status of the patient taking aspirin? |
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Is the aspirin dose sufficient? |
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Is the patient noncompliant? |
To learn how to answer these questions, click here.
To learn more about the new standard for assessing how aspirin affects platelet function, click here.
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