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本文引用的文献

1
Clopidogrel response: head-to-head comparison of different platelet assays to identify clopidogrel non responder patients after coronary stenting.氯吡格雷反应:不同血小板检测方法的头对头比较,以确定冠状动脉支架置入术后氯吡格雷无应答患者。
Arch Cardiovasc Dis. 2010 Jan;103(1):39-45. doi: 10.1016/j.acvd.2009.11.004. Epub 2010 Jan 25.
2
Prevalence of aspirin and clopidogrel resistance among patients with and without drug-eluting stent thrombosis.有和无药物洗脱支架血栓形成的患者中阿司匹林和氯吡格雷抵抗的患病率。
Am J Cardiol. 2009 Aug 15;104(4):525-30. doi: 10.1016/j.amjcard.2009.04.015. Epub 2009 Jun 24.
3
Assessment, mechanisms, and clinical implication of variability in platelet response to aspirin and clopidogrel therapy.血小板对阿司匹林和氯吡格雷治疗反应变异性的评估、机制及临床意义
Am J Cardiol. 2009 Jul 15;104(2):227-33. doi: 10.1016/j.amjcard.2009.03.022. Epub 2009 May 13.
4
The P2Y12 antagonists, 2-methylthioadenosine 5'-monophosphate triethylammonium salt and cangrelor (ARC69931MX), can inhibit human platelet aggregation through a Gi-independent increase in cAMP levels.P2Y12拮抗剂2-甲硫基腺苷5'-单磷酸三乙铵盐和坎格雷洛(ARC69931MX)可通过不依赖Gi的方式提高环磷酸腺苷(cAMP)水平来抑制人血小板聚集。
J Biol Chem. 2009 Jun 12;284(24):16108-16117. doi: 10.1074/jbc.M809780200. Epub 2009 Apr 3.
5
Platelet cyclooxygenase inhibition by low-dose aspirin is not reflected consistently by platelet function assays: implications for aspirin "resistance".低剂量阿司匹林对血小板环氧化酶的抑制作用在血小板功能检测中并未始终得到体现:对阿司匹林“抵抗”的启示。
J Am Coll Cardiol. 2009 Feb 24;53(8):667-77. doi: 10.1016/j.jacc.2008.10.047.
6
Platelet adhesion under flow.流动状态下的血小板黏附
Microcirculation. 2009 Jan;16(1):58-83. doi: 10.1080/10739680802651477.
7
Thrombotic events in high risk patients are predicted by evaluating different pathways of platelet function.通过评估血小板功能的不同途径来预测高危患者的血栓形成事件。
Thromb Haemost. 2008 Dec;100(6):1136-45. doi: 10.1160/th08-06-0374.
8
Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study.心肌梗死后接受氯吡格雷治疗的年轻患者的细胞色素P450 2C19基因多态性:一项队列研究。
Lancet. 2009 Jan 24;373(9660):309-17. doi: 10.1016/S0140-6736(08)61845-0. Epub 2008 Dec 26.
9
Cytochrome p-450 polymorphisms and response to clopidogrel.细胞色素P-450基因多态性与氯吡格雷的反应
N Engl J Med. 2009 Jan 22;360(4):354-62. doi: 10.1056/NEJMoa0809171. Epub 2008 Dec 22.
10
Genetic determinants of response to clopidogrel and cardiovascular events.氯吡格雷反应及心血管事件的遗传决定因素。
N Engl J Med. 2009 Jan 22;360(4):363-75. doi: 10.1056/NEJMoa0808227. Epub 2008 Dec 22.

在血流中,P2Y12 抑制对血小板血栓体积的影响存在差异。

Variable effect of P2Y12 inhibition on platelet thrombus volume in flowing blood.

机构信息

Thrombosis Center, IRCCS Istituto Clinico Humanitas, Rozzano, Milan, Italy.

出版信息

J Thromb Haemost. 2011 Feb;9(2):373-82. doi: 10.1111/j.1538-7836.2010.04144.x.

DOI:10.1111/j.1538-7836.2010.04144.x
PMID:21083646
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3030676/
Abstract

BACKGROUND AND OBJECTIVES

Patients treated with percutaneous coronary intervention receive aspirin and P2Y12 ADP receptor inhibitors to reduce thrombotic complications. The choice of methodology for monitoring the effects of treatment and assessing its efficacy is still a topic of debate. We evaluated how decreased P2Y12 function influences platelet aggregate (thrombus) size measured ex vivo.

METHODS AND RESULTS

We used confocal videomicroscopy to measure in real time the volume of platelet thrombi forming upon blood perfusion over fibrillar collagen type I at a wall shear rate of 1500 s(-1). The average volume was significantly smaller in 31 patients receiving aspirin and clopidogrel (19) or ticlopidine (12) than in 21 controls, but individual values were above the lower limit of the normal distribution, albeit mostly within the lower quartile, in 61.3% of cases. Disaggregation of platelet thrombi at later perfusion times occurred frequently in the patients. Vasodilator-stimulated phosphoprotein phosphorylation, reflecting P2Y12 inhibition, was also decreased in the patient group, and only 22.6% of individual values were above the lower normal limit. We found no correlation between volume of thrombus formed on collagen fibrils and level of P2Y12 inhibition, suggesting that additional and individually variable factors can influence the inhibitory effect of treatment on platelet function.

CONCLUSIONS

Measurements of platelet thrombus formation in flowing blood reflects the consequences of antiplatelet therapy in a manner that is not proportional to P2Y12 inhibition. Combining the results of the two assays may improve the assessment of thrombotic risk.

摘要

背景和目的

接受经皮冠状动脉介入治疗的患者接受阿司匹林和 P2Y12 ADP 受体抑制剂治疗,以减少血栓并发症。监测治疗效果和评估其疗效的方法选择仍然是一个争论的话题。我们评估了 P2Y12 功能降低如何影响体外测量的血小板聚集(血栓)大小。

方法和结果

我们使用共焦视频显微镜实时测量在 1500 s(-1)壁剪切率下血液灌注在纤维状 I 型胶原蛋白上形成的血小板血栓的体积。在接受阿司匹林和氯吡格雷(19 例)或噻氯匹定(12 例)治疗的 31 例患者中,平均体积明显小于 21 例对照者,但个体值虽然大多在四分位数范围内,但在 61.3%的情况下仍高于正常分布的下限。在患者中,血小板血栓的解聚在后期灌注时间经常发生。反映 P2Y12 抑制的血管扩张刺激磷酸蛋白磷酸化在患者组中也降低,并且只有 22.6%的个体值高于正常下限。我们发现胶原纤维上形成的血栓体积与 P2Y12 抑制程度之间没有相关性,这表明其他单独的可变因素可以影响治疗对血小板功能的抑制作用。

结论

在流动血液中测量血小板血栓形成以与 P2Y12 抑制不成比例的方式反映抗血小板治疗的后果。将两种检测结果结合起来可能会改善血栓形成风险的评估。