Immature platelet fraction (IPF) determined with an automated method predicts clopidogrel hyporesponsiveness

Immature platelet fraction (IPF) determined with an automated method predicts clopidogrel hyporesponsiveness
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DOI:
10.1007/s11239-011-0665-7
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发表时间:
2012-02-01
影响因子:
4
通讯作者:
Kleiman, Neal S.
Kleiman, Neal S.
中科院分区:
医学4区
文献类型:
--
作者:
Ibrahim, Homam;Nadipalli, Srinivas;Kleiman, Neal S.

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氯吡格雷抗血小板作用变异性的机制尚未完全阐明。未成熟(网织)血小板可能调节氯吡格雷的抗血小板作用,但必须使用流式细胞术进行测量。新的自动检测技术是否会产生类似的结果尚不清楚。本研究的目的是通过自动化方法评估未成熟血小板在氯吡格雷抗血小板作用中的作用。29名健康志愿者在每日75 mg氯吡格雷给药前和给药后1周进行血小板研究。使用自动颗粒计数器测定未成熟血小板分数(IPF)。根据IPF将受试者分层为三分位数。血小板研究包括光透射聚集测定法(LTA)和通过血小板反应性指数(PRI)测定的血管扩张剂刺激的磷蛋白磷酸化(VASP-P)。基线血小板对2、5和20 μ M ADP的聚集反应在所有三个三分位数中相似,但是在氯吡格雷对5 μ M ADP的反应中,未成熟血小板的上三分位数大于下三分位数(54% vs. 23%,P = 0.02),其他两个浓度的趋势一致。氯吡格雷治疗后,上三分位数的PRI也更高(71.2% vs. 57.8%,P = 0.04)。氯吡格雷低反应性(对5 μ M ADP的反应聚集> 50%)的频率在上三分位数中也高于下三分位数,分别为60%和10%(P = 0.0001)。使用自动化方法测量的未成熟血小板与氯吡格雷抗血小板作用的应答受损相关。
The mechanisms for the variability in antiplatelet effects of clopidogrel are not elucidated entirely. Immature (reticulated) platelets may modulate the antiplatelet effects of clopidogrel but must be measured using flow cytometry. Whether new automated detection techniques yield similar results is not known. The objectives of the study to evaluate the role of immature platelets assessed by an automated method in response to the antiplatelet effects of clopidogrel. Twenty-nine healthy volunteers had platelet studies performed before and 1 week after 75 mg daily dosing of clopidogrel. Immature platelet fraction (IPF) was determined using an automated particle counter. Subjects were stratified into tertiles based on the IPF. Platelet studies included light transmission aggregometry (LTA), and vasodilator stimulated phosphoprotein phosphorylation (VASP-P) determined by platelet reactivity index (PRI). Baseline platelet aggregation responses to 2, 5 and 20 mu M ADP, were similar in all three tertiles, however they were greater in the upper than in the lower tertile of immature platelets after clopidogrel in response to 5 mu M ADP (54% vs. 23%, P = 0.02), with concordant trends for the other two concentrations. PRI was also greater in the upper tertile after clopidogrel (71.2% vs. 57.8%, P = 0.04). The frequency of clopidogrel hyporesponsiveness (aggregation > 50% in response to 5 mu M of ADP) was also higher in the upper tertile when compared to lower tertile, (60%) versus (10%) respectively (P = 0.0001). Immature platelets measured using an automated method, are associated with impaired response to antiplatelet effects of clopidogrel.