Blais Normand, Pharand Chantal, Lordkipanidzé Marie, Sia Ying K, Merhi Yahye, Diodati Jean G
CHUM - Hôpital Notre-Dame, 6ième étage, Pavillon Deschamps, Montréal, Canada.
Thromb Haemost. 2009 Aug;102(2):404-11. doi: 10.1160/TH09-02-0126.
Variable biological effect of aspirin is suggested to be related to pharmacological resistance. The incidence of this so-called "resistant" state varies with the study population and the assay used. We determined performance features of five assays used to assess aspirin effects in non-smoking healthy volunteers not taking any drug known to interfere with platelet function. Blood and urine samples were obtained immediately before and after 8-10 days of aspirin 80 mg intake. Forty-five participants 19-59 years old were enrolled. The sensitivity (SE), specificity (SP), and optimal cut-off (CO) value to detect the effect of aspirin were: light transmission aggregometry (LTA) with 1.6 mM arachidonic acid (AA) - SE 100%, SP 95.9%, CO 20%; LTA with adenosine diphosphate (ADP) 10 microM - SE 84.4%, SP 77.8%, CO 70%; VerifyNow Aspirin - SE 100%, SP 95.6%, CO 550 ARU; platelet count drop - SE 82.2%, SP 86,7%, CO 55%; TEG((R)) - SE 82,9%, SP 75,8%, CO 90%; and urinary 11-dehydrothromboxane B(2) levels (11-dHTB(2)) - SE 62.2%, SP 82.2%, CO 60 pg/ml. AA-induced LTA and the VerifyNow assay reliably detected aspirin intake in all subjects; there was wide overlap in pre- and post- aspirin results with ADP-induced LTA, platelet count drop, TEG((R)) and urinary 11-dHTB(2) assays. These results suggest that some of the variability in the reported incidence of "aspirin resistance" is unrelated to aspirin intake but related to inherent limitations of some assays to detect aspirin mediated effects or to underlying platelet reactivity variability independent of aspirin-mediated cyclooxygenase-1 inhibition.
阿司匹林的生物学效应存在差异,这被认为与药理抗性有关。这种所谓“抗性”状态的发生率因研究人群和所采用的检测方法而异。我们测定了用于评估阿司匹林对不吸烟且未服用任何已知会干扰血小板功能药物的健康志愿者作用的五种检测方法的性能特征。在摄入80毫克阿司匹林8 - 10天前后,即刻采集血液和尿液样本。招募了45名年龄在19 - 59岁的参与者。检测阿司匹林效应的灵敏度(SE)、特异性(SP)和最佳临界值(CO)分别为:采用1.6毫摩尔花生四烯酸(AA)的透光聚集法(LTA) - SE 100%,SP 99.5%,CO 20%;采用10微摩尔二磷酸腺苷(ADP)的LTA - SE 84.4%,SP 77.8%,CO 70%;VerifyNow阿司匹林检测 - SE 100%,SP 95.6%,CO 550 ARU;血小板计数下降 - SE 82.2%,SP 86.7%,CO 55%;血栓弹力图(TEG) - SE 82.9%,SP 75.8%,CO 90%;以及尿11 - 脱氢血栓素B2水平(11 - dHTB2) - SE 62.2%,SP 82.2%,CO 60皮克/毫升。AA诱导的LTA和VerifyNow检测能可靠地检测出所有受试者是否摄入了阿司匹林;ADP诱导的LTA、血小板计数下降、TEG和尿11 - dHTB2检测在阿司匹林服用前后的结果存在广泛重叠。这些结果表明,报告的“阿司匹林抵抗”发生率的一些变异性与阿司匹林摄入无关,而是与某些检测方法检测阿司匹林介导效应的固有局限性或与独立于阿司匹林介导的环氧化酶 - 1抑制作用的潜在血小板反应性变异性有关。