Ohmori T, Yatomi Y, Nonaka T, Kobayashi Y, Madoiwa S, Mimuro J, Ozaki Y, Sakata Y
Research Division of Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical School, Minamikawachi, Tochigi, Japan.
J Thromb Haemost. 2006 Jun;4(6):1271-8. doi: 10.1111/j.1538-7836.2006.01958.x.
Although the concept of aspirin resistance is extensively reported in medical literature, its precise mechanisms and clinical outcomes are largely unknown. In this study, we examined individual thromboxane biosynthesis and platelet aggregation in aspirin-treated patients, and whether the results of a platelet aggregation test influenced clinical outcomes.
Subjects taking 81 mg of aspirin (n = 50) and controls (n = 38) were evaluated for platelet aggregation and platelet cyclooxygenase-1 (COX-1) activity by measuring collagen-induced thromboxane B2 production. For aggregometry, both light transmission (LT) and laser-light scattering methods were employed to quantitatively evaluate aggregate sizes and numbers. Aspirin treatment resulted in the inhibition of collagen-induced platelet aggregation, particularly the transition from small to large platelet aggregates. Although platelet COX-1 activity seemed to be uniformly inhibited in all patients, platelet aggregation studies showed great inter-individual differences; variation in platelet COX-1 activity only accounted for 6-20% of the individual aggregations. Factor analysis revealed the existence of a common factor (other than platelet COX-1) that explained 48.4% of the variations in platelet aggregation induced by collagen, adenosine diphosphate (ADP), and collagen-related peptide. We then prospectively enrolled 136 aspirin-treated patients in our study, and we found that being in the upper quartile level of LT, or with large aggregate formation induced by collagen, was an independent risk factor for developing cardiovascular events within 12 months [hazard ratio (HR) = 7.98, P = 0.008 for LT; HR = 7.76, P = 0.007 for large aggregates]. On the other hand, the existence of diabetes mellitus was an independent risk factor for overall outcomes (HR 1.30-11.9, P = 0.015-0.033).
Aspirin resistance expressed as unsuppressed platelet COX-1 activity is a rare condition in an out-patient population. Other factor(s) affecting collagen-induced platelet aggregation may influence early outcomes in aspirin-treated patients.
尽管阿司匹林抵抗的概念在医学文献中已有广泛报道，但其确切机制和临床结局在很大程度上仍不清楚。在本研究中，我们检测了服用阿司匹林患者的个体血栓素生物合成及血小板聚集情况，以及血小板聚集试验结果是否会影响临床结局。
通过测量胶原诱导的血栓素B2生成情况，对服用81 mg阿司匹林的受试者（n = 50）和对照组（n = 38）进行血小板聚集及血小板环氧化酶-1（COX-1）活性评估。对于血小板聚集测定，采用光透射（LT）和激光散射两种方法定量评估聚集体大小和数量。阿司匹林治疗可抑制胶原诱导的血小板聚集，尤其是从小血小板聚集体向大血小板聚集体的转变。尽管所有患者的血小板COX-1活性似乎均受到一致抑制，但血小板聚集研究显示个体间存在很大差异；血小板COX-1活性的变化仅占个体聚集差异的6 - 20%。因子分析显示存在一个共同因子（血小板COX-1除外），该因子可解释胶原、二磷酸腺苷（ADP）和胶原相关肽诱导的血小板聚集变化的48.4%。然后，我们前瞻性纳入了136例服用阿司匹林的患者进行研究，发现处于LT上四分位数水平或出现胶原诱导的大聚集体形成是12个月内发生心血管事件的独立危险因素[LT的风险比（HR）= 7.98，P = 0.008；大聚集体的HR = 7.76，P = 0.007]。另一方面，糖尿病的存在是总体结局的独立危险因素（HR 1.30 - 11.9，P = 0.015 - 0.033）。
以未受抑制的血小板COX-1活性表示的阿司匹林抵抗在门诊患者中是一种罕见情况。影响胶原诱导的血小板聚集的其他因素可能会影响服用阿司匹林患者的早期结局。
