抗血小板治疗对老年人血小板功能的影响及其环氧化酶1和环氧化酶2基因多态性研究

Changes of Platelet Function after Antiplatelet Therapy and Single Nucleotide Polymorphism of COX-1 and COX-2 in Elderly Patients

目的检测行抗血小板治疗的老年患者的血小板功能及环氧化酶1(COX-1)、环氧化酶2(COX-2)基因多态性(SNP),为临床抗血小板治疗提供个体化干预指导。方法选取2011年1月—2012年12月在上海交通大学医学院附属新华医院住院的≥60岁且服用拜阿司匹林1年以上患者114例,其中具有血栓高危因素者55例(高危组),发生过动脉血栓事件者59例(血栓组);另选取同期在我院行体检健康且从未服用过拜阿司匹林者55例为对照组。检测3组受试者血小板计数(PLT)、血小板平均体积(MPV)、血栓最大坚固度(TEG-MA)、花生四烯酸诱导的血小板抑制率(TEG-AA)及COX-1基因-1676A>G位点、COX-2基因-765G>C位点SNP。结果 3组受试者PLT比较,差异无统计学意义(P>0.05);血栓组MPV、TEG-MA均大于高危组和对照组,高危组TEGMA大于对照组(P<0.05)。根据TEG-AA将所有受试者分为非阿司匹林敏感(NAS)组66例和阿司匹林敏感(AS)组103例,两组COX-1基因-1676A>G位点基因型和等位基因频率比较,差异均有统计学意义(P<0.05);两组COX-2基因-765G>C位点基因型和等位基因频率比较,差异均无统计学意义(P>0.05)。结论血小板活性增强是血栓形成的重要原因,具有血栓高危因素或发生过动脉血栓事件而进行抗血小板治疗的老年患者存在阿司匹林抵抗(AR)现象,需注意调整抗血小板治疗方案;COX-1基因-1676A>G位点SNP可能与AR有关,COX-2基因-765G>C位点SNP可能与AR无关。

Objective To investigate the impacts of antiplatelet therapy （APT） on platelet function and the single nucleotide polymorphism （SNP） of COX -1 and COX -2 in elderly patients, to provide individualized intervention guidance for clinical APT. Methods From January 2011 to December 2012, a total of 114 patients （aged over 60 years） having taken bayaspirin over 1 year were enrolled in this study, including 55 with thrombotic high - risk factors （ group A）, 59 who ever had artery thrombosis incidence （group B）, another 55 healthy subjects enrolled as control group. Blood platelet count （PLT）, mean platelet volume （MPV）, thromboelastogram （TEG - MA）, arachidonic acid - induced platelet inhibition rate （TEG - AA）, COX - 1 - 1676A 〉 G and COX - 2 - 765G 〉 C SNP were determined in 3 groups. Results There was no significant difference in PLT in 3 groups （P 〉 0.05 ）. MPV, TEG - MA were greater in group B than in groups A, control （P 〈 0. 05 ）. All participants were divided, according to TEG - AA, into groups non - aspirin - sensitive （ NAS, n = 66）, aspirin - sensitive （ AS, n = 103） ; there were significant differences in COX - 1 - 1676A 〉 G genotype and allele frequencies between 2 groups （ P 〈 0. 05）, there was no in COX - 2 - 765G 〉 C genotype and allele frequencies （ P 〉 0. 05 ）. Conclusion Increased activity of PLT, a major cause for thrombogenesis, has aspirin resistance （AR） in elderly patients having APT due to thrombotic high - risk factors or ever having artery thrombosis incidence. COX - 1 - 1676A 〉 G SNP may be related to AR, COX -2 -765G 〉 G SNP may not.