Yee Donald L, Sun Carol W, Bergeron Angela L, Dong Jing-Fei, Bray Paul F
Thrombosis Research Section, Baylor College of Medicine, One Baylor Plaza, BCM 286, N1319, Houston, TX 77030.
Blood. 2005 Oct 15;106(8):2723-9. doi: 10.1182/blood-2005-03-1290. Epub 2005 Jun 21.
Aggregometry is widely used to assess platelet function, but its use in identifying platelet hyperreactivity is poorly defined. We studied platelet aggregation in 359 healthy individuals using the agonists adenosine diphosphate (ADP), epinephrine, collagen, collagen-related peptide, and ristocetin. We also assessed the reproducibility of these assays in 27 subjects by studying them repeatedly on at least 4 separate occasions. Healthy subjects exhibited considerable interindividual variability in aggregation response to agonists, especially at concentrations lower than those typically used in clinical laboratories. For each agonist tested at these submaximal concentrations, a small proportion of individuals demonstrated an unusually robust aggregation response. Subjects who exhibited such in vitro hyperreactivity to one agonist tended to demonstrate a similar response to others, suggesting that hyperreactivity is a global characteristic of platelets. Epinephrine and collagen-related peptide were especially reliable and efficient in detecting hyperreactivity. For epinephrine, excellent reproducibility persisted for up to 3 years, and hyperreactivity was associated with female sex and higher fibrinogen levels (P < .02). We recommend these assays as appropriate candidates for future studies requiring accurate assessment of increased platelet reactivity. These include clinical studies to improve risk assessment for arterial thrombosis, as well as genetic studies to establish determinants of the hyperreactive platelet phenotype.
血小板聚集测定法被广泛用于评估血小板功能,但其在识别血小板高反应性方面的应用尚缺乏明确界定。我们使用二磷酸腺苷(ADP)、肾上腺素、胶原、胶原相关肽和瑞斯托菌素等激动剂,对359名健康个体的血小板聚集情况进行了研究。我们还通过在至少4个不同时间点对27名受试者进行重复研究,评估了这些检测方法的可重复性。健康受试者对激动剂的聚集反应存在相当大的个体间差异,尤其是在低于临床实验室通常使用浓度的情况下。对于在这些次最大浓度下测试的每种激动剂,一小部分个体表现出异常强烈的聚集反应。对一种激动剂表现出体外高反应性的受试者,对其他激动剂往往也有类似反应,这表明高反应性是血小板的一个整体特征。肾上腺素和胶原相关肽在检测高反应性方面尤其可靠和有效。对于肾上腺素,良好的可重复性可持续长达3年,且高反应性与女性性别及较高的纤维蛋白原水平相关(P <.02)。我们推荐这些检测方法作为未来需要准确评估血小板反应性增加的研究的合适候选方法。这些研究包括旨在改善动脉血栓形成风险评估的临床研究,以及旨在确定高反应性血小板表型决定因素的遗传学研究。