Malinin Alex I, Atar Dan, Callahan Kevin P, McKenzie Marcus E, Serebruany Victor L
Center for Thrombosis Research, Sinai Hospital of Baltimore, Johns Hopkins University, 2401 West Belvedere Avenue, Schapiro Research Building R 202, Baltimore, MD 21215, USA.
Eur J Pharmacol. 2003 Feb 21;462(1-3):139-43. doi: 10.1016/s0014-2999(02)02956-4.
We sought to assess how one tablet of non-enteric coated aspirin (325 mg) affects human platelets in subjects with risk factors for coronary artery disease. Data from 63 individuals with multiple cardiac risk factors were analyzed. Platelets were assessed twice at baseline (pre-aspirin), and after 3-4 h (post-aspirin). We employed 5 microM epinephrine-induced conventional aggregometry, closure time with epinephrine/collagen cartridge by PFA-100(R) (Dade-Behring), and aspirin response units (ARU) stimulated by propyl gallat with Ultegra (Accumetrics, San Diego, CA, USA) for measuring platelet function. In addition, the expression of platelet receptors was determined by using the following monoclonal antibodies: anti-CD31, CD41, CD42b, CD51/CD61, CD62p, CD63, CD107a, and CD151. Platelet-leukocyte formation was detected utilizing dual antibodies for a pan-platelet marker CD151, and CD14, a monocyte/macrophage marker. PAC-1 was used to measure fibrinogen-platelet binding. One pill of aspirin significantly decreased platelet-rich plasma (PRP) aggregation (74.18+/-16.75% vs. 24.92+/-8.64%; p<0.0001) and resulted in reduction of the aspirin response units (ARU) (662.24+/-65.65 vs. 451.05+/-69.31; p<0.0001). There was also prolongation of the closure time (194.4+/-25.3 vs. 258.63+/-55.61 s; p<0.0001). High correlation (r(2)=0.73-0.86) between platelet analyzer readings and aggregation was observed. One tablet of aspirin moderately inhibited expression of most surface platelet receptors measured, and such inhibition reached significance (p<0.05) for PAC-1, CD31, CD41, CD42, CD62p, and CD151. We conclude that a single dose of aspirin affects major platelet receptors, presumably directly or indirectly through the inhibition of prostanoids via platelet cyclooxygenase-1 blockade. The Ultegra Analyzer with a novel cartridge seems to be reliable in reflecting aspirins' effects on platelets and could be used in the future in clinical practice for monitoring aspirin therapy.
我们试图评估一片非肠溶阿司匹林（325毫克）对有冠状动脉疾病风险因素的受试者体内人类血小板的影响。分析了63名具有多种心脏风险因素的个体的数据。在基线时（服用阿司匹林前）以及3 - 4小时后（服用阿司匹林后）对血小板进行了两次评估。我们采用5微摩尔肾上腺素诱导的传统凝集测定法、通过PFA - 100（达德 - 拜林公司）的肾上腺素/胶原蛋白检测盒测定的闭合时间，以及用没食子酸丙酯与Ultegra（美国加利福尼亚州圣地亚哥的Accumetrics公司）刺激的阿司匹林反应单位（ARU）来测量血小板功能。此外，使用以下单克隆抗体测定血小板受体的表达：抗CD31、CD41、CD42b、CD51/CD61、CD62p、CD63、CD107a和CD151。利用针对全血小板标志物CD151和单核细胞/巨噬细胞标志物CD14的双抗体检测血小板 - 白细胞形成。使用PAC - 1测量纤维蛋白原 - 血小板结合。一片阿司匹林显著降低富含血小板血浆（PRP）的聚集（74.18±16.75%对24.92±8.64%；p<0.0001），并导致阿司匹林反应单位（ARU）降低（662.24±65.65对451.05±69.31；p<0.0001）。闭合时间也延长了（194.4±25.3对258.63±55.61秒；p<0.0001）。观察到血小板分析仪读数与聚集之间具有高度相关性（r² = 0.73 - 0.86）。一片阿司匹林适度抑制了所测量的大多数表面血小板受体的表达，并且这种抑制对于PAC - 1、CD31、CD41、CD42、CD62p和CD151具有统计学意义（p<0.05）。我们得出结论，单剂量阿司匹林会影响主要的血小板受体，可能是直接或间接通过血小板环氧化酶 - 1阻断抑制前列腺素。带有新型检测盒的Ultegra分析仪在反映阿司匹林对血小板的作用方面似乎是可靠的，并且未来可用于临床实践中监测阿司匹林治疗。
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