Resistance to aspirin in vitro is associated with increased platelet sensitivity to adenosine diphosphate

Macchi, Laurent; Christiaens, Luc; Brabant, Séverine; Sorel, Nathalie; Allal, J; Mauco, Gérard; Brizard, A.

doi:10.1016/s0049-3848(02)00210-4

Cited by 155 publications

(103 citation statements)

References 21 publications

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“…38 Aspirin-resistant patients appear to have platelets that are more sensitive to ADP, which may partially explain the high prevalence of dualantiplatelet resistance in this population. 39 Furthermore, arachidonic acid appears to be able to incompletely activate platelets through an ADP-dependent and COX-independent pathway in COX-inhibited cells, suggesting some overlap in these pathways. 6 …”

Section: Mechanisms Of Aspirin Resistancementioning

confidence: 99%

Aspirin Resistance: Current Status and Role of Tailored Therapy

Grinstein

Cannon

2012

Clinical Cardiology

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Aspirin is integral in the primary and secondary prevention of coronary artery disease and acute coronary syndrome. Given the high clinical importance of aspirin in the management of coronary artery disease, much attention has been directed towards the concept of “aspirin resistance.” Unfortunately, the term aspirin resistance is ill‐defined in the literature, leading to a large variance in the reported prevalence of this phenomenon. In this review, the current understanding of aspirin resistance is discussed. Commonly used functional and diagnostic tests of platelet function, including their strengths and weakness, are reviewed. We next discuss several proposed mechanisms of aspirin resistance and special high‐risk groups at risk for aspirin treatment failure. We then discuss optimal dosing and diagnostic strategies for those populations at risk for aspirin resistance with a focus on tailored aspirin therapy for high‐risk groups. Finally, future topics of interest in the field of aspirin resistance are considered. Clin. Cardiol. 2012 doi: 10.1002/clc.22031Jonathan Grinstein has no funding, financial relationships, or conflicts of interest to disclose. Christopher P. Cannon receives research grants/support from the following companies: Accumetrics, AstraZeneca, Essentialis, GlaxoSmithKline, Merck, Regeneron, Sanofi, and Takeda. He is also on the advisory board (but funds donated to charity) for Alnylam, Bristol‐Myers Squibb, and Pfizer. He is a Clinical Advisor, equity in Automedics Medical Systems.

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Section: Mechanisms Of Aspirin Resistancementioning

confidence: 99%

Aspirin Resistance: Current Status and Role of Tailored Therapy

Grinstein

Cannon

2012

Clinical Cardiology

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“…The mechanisms responsible for insufficient platelet function inhibition during aspirin therapy should be looked for among the several aforementioned variables that affect the platelet function tests that have been used: increased sensitivity to ADP-induced GPIIb/IIIa activation, 71 increased responsiveness to collagen, 47 high plasma levels of VWF, 61 GPIIb/IIIa polymorphisms, 72 among others. In addition, the role of a nonenzymatic, oxidation-dependent pathway for the synthesis of the arachidonic acid derivatives isoprostanes, which exhibit potent proaggergatory activity, should also be considered.…”

Section: Unproven Aspirin Resistancementioning

confidence: 99%

Aspirin and Clopidogrel

Cattaneo

2004

ATVB

370

133

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Abstract-Aspirin and the thienopyridines ticlopidine and clopidogrel are antiplatelet agents that display good antithrombotic activity. In the past few years, the concept of aspirin resistance has been largely emphasized in the medical literature, although its definition is still uncertain. I suggest that "aspirin-resistant" should be considered as a description for those individuals in whom aspirin fails to inhibit thromboxane A 2 production, irrespective of the results of unspecific tests of platelet function, such as the bleeding time, platelet aggregation, or the PFA-100 system. Less well known than aspirin resistance, but certainly better characterized, is the issue of "clopidogrel resistance," which is probably mostly caused by inefficient metabolism of the prodrug clopidogrel to its active metabolite. At present, aspirin and clopidogrel resistance should not be looked for in the clinical setting, because there is no definite demonstration of an association with clinical events conditioning cost-effective changes in patient management. Key Words: aspirin resistance Ⅲ clopidogrel resistance Ⅲ antiplatelet agents Ⅲ cardiovascular diseases Ⅲ cerebrovascular diseases A spirin and the thienopyridines ticlopidine and clopidogrel are inhibitors of platelet aggregation that display good antithrombotic activity. They are used in the prophylaxis of patients undergoing vascular grafting or percutaneous angioplasty, in the medical management of acute coronary syndromes, and in long-term prevention of cardiovascular and cerebrovascular events.Both aspirin and the thienopyridines selectively inhibit a single pathway of platelet activation: aspirin affects the arachidonate-thromboxane A 2 (TxA 2 ) pathway by irreversibly inhibiting cyclo-oxygenase-1 (COX-1) (Figure 1). 1 The thienopyridines affect the adenosine diphosphate (ADP) pathway, by irreversibly blocking the ADP receptor P2Y 12 ( Figure 1). 2 Despite their selective mechanism of action, which does not counteract the many alternative pathways for platelet activation, aspirin and thienopyridines display a good antithrombotic activity. This is explained by the fact that both the arachidonate-TxA 2 pathway and the ADP pathway contribute to the amplification of platelet activation and are essential for the full aggregation and secretion response of platelets to agonists. 2

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“…These include insufficient dosing (Helgason et al 1994), polymorphism of glycoprotein IIIa (Undas et al 1999;Macchi et al 2003), production of prostaglandin H 2 in moncyte and endothelial cells by COX-2 pathway (Cipololone et al 1997), increased levels of COX-2 as a result of increased platelet degradation (Weber et al 1999), and increased sensitivity of platelets to ADP (Macchi et al 2002).…”

Section: Discussionmentioning

confidence: 99%