Clopidogrel platelet response

Serebruany VL, Steinhubl SR, Berger PB, Malinin Al, Bhatt DL, Topol EJ, Variability in platelet responsiveness to clopidogrel among 544 individuals. J Am Coll Cardiol 2005 45 246-251. 

Laboratory evaluation of platelet response to clopidogrel treatment... 

Suboptimal platelet response to clopidogrel may be due to an increased number of platelet P2Y 2 receptors or polymorphism of platelet receptors. Genetic polymorphisms of platelet GPIIb/llla, GPIa/lla, or P2Y 2 receptors have been reported to affect platelet function and may influence dopidogrel response variability (103-105). Recently, it was reported that an increased percentage of patients with peripheral arterial disease have the P2Y 2 receptor H2 haplotype (104). However, in another study, the relation of this haplotype to clopidogrel responsiveness could not be demonstrated (105). Since the relation... 

Tsantes AE, Dconomidis I, Papadakis I, Bonovas S, Gialeraki A, Kottaridi C, et al. Impact of the proton pump inhibitors and CYP2C19 2 polymorphism on platelet response to clopidogrel as assessed by four platelet function assays. Thromb Res 2013 132(2) el05-11. 

P2Y12 receptor is required for complete aggregation response to ADR Nevertheless, both (Fig. 6) receptors interact to lead the full response. ADP potentiates platelet secretion and irreversible aggregation, Enzymatic conversion of released ADP to inactive AMP by endothelial ecto-ADPase limits platelet activation by ADR Thienopyridines (ticlopidine, clopidogrel, prasugrel, cangrelor) are used for inhibiting ADP-induced platelet function in the prevention of acute coronary events,... 

Cilostazol is a PDE3 inhibitor and also is a drug with multiple mechanisms of action (23,24), some of which are directly platelet-related, and others of which exert their effects indirectly via endothelial cells (Figs, 4 and 5), As a PDE inhibitor, it increases the concentration of cyclic nucleotides within platelets and inhibits platelet aggregation in response to shear forces (via ADP) and a variety of agonists. Like other inhibitors of platelet activation, it blocks the expression and release of P-selectin, a key adhesion molecule on the membrane of platelet alpha granules that externalizes with activation, and plays an important role in the interactions between platelets, endothelial cells, and leukocytes, The effect of cilostazol on P-selectin expression appears to be additive to those of aspirin and clopidogrel (25). 

The mechanisms responsible for clopidogrel response variability are incompletely defined. Pharmacokinetic and pharmacodynamic differences in clopidogrel metabolism have been proposed to explain variable platelet inhibition. 

Sankyo Co. Ltd. Tokyo, Japan) is a new thienopyridine derivative that produces more potent platelet inhibition, and a rapid onset of action. The latter properties may provide a superior alternative to clopidogrel, with less response variability and a decreased prevalence of nonresponsiveness (I I I). 

Reports of high incidences of aspirin resistance may be due to laboratory measurements based on nonspecific methods that do not isolate the response of platelet COX-1 to aspirin or due to an inadequate dose required to fully inhibit the COX-1 in selected patients. Clopidogrel nonresponsiveness is a consistent phenomenon observed in research studies conducted at multiple medical centers around the world. Data from small studies support that patients with high ex vivo platelet reactivity to ADP during and after percutaneous intervention may be at greatest risk for subsequent ischemic events. 

Gurbel PA, Bliden KR Hiatt BL, O Connor CM. Clopidogrel for coronary stenting response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation 2003 107 2908-2913. 

Samara WM, Bliden KR Tantry US, Gurbel PA, The difference between clopidogrel responsiveness and posttreatment platelet reactivity. Thromb Res 2005 I I 5 89-94,... 

I 10 Tantry US, Bliden KR Gurbel PA. What is the best measure of thrombotic risks—pretreatment platelet aggregation, clopidogrel responsiveness, or posttreatment platelet aggregation Catheter Cardiovasc Interv 2005 66 597. 

Bouman HJ, Parlak E, Van Werkum JWV, Breet NJ, Ten Cate H, Hackeng CM, Ten Berg JM, Taubert D (2009) Which platelet function test is suitable to monitor clopidogrel responsiveness A pharmacokinetic analysis on the active metabolite of clopidogrel. J Thromb Haemost 8 482—488... 

Gurbel PA, Bliden KP, Etherington A, Tantry US. Assessment of clopidogrel responsiveness measurements of maximum platelet aggregation, final platelet aggregation and their correlation with vasodilator-stimulated phosphoprotein in resistant patients. Thromb Res 2007 121 107—15. 

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