Studies on genetic testing for the possible diagnosis of aspirin resistance

最近的研究表明，对阿司匹林和其他抗血小板药物的抵抗是一种公认的状态。那些接受阿司匹林治疗的人对这种药物有抵抗力，更容易复发血栓。因此，研究发现导致阿司匹林抵抗的基因对于预防动脉粥样硬化血栓形成事件是极其重要的，动脉粥样硬化血栓事件是这个国家的主要死亡原因。本研究的目的是分析阿司匹林抵抗与血栓形成和止血相关基因变异的关系，为血栓的个体化治疗提供基础数据。我们首先利用血小板功能分析仪PFA100建立了体外评估阿司匹林抵抗的最佳实验条件。在大多数情况下，在正常的富含血小板的血浆中加入高浓度的阿司匹林会延长闭塞时间。然而，添加低浓度的阿司匹林也起到了作用，但约30%的正常人对阿司匹林没有反应(即保持在临界值范围内)。那些对阿司匹林“耐受”的人的特征是基础血小板反应性高，通过其他血小板功能测试(全血聚集仪的胶原刺激的血小板功能WBA-Neo和传统的光学聚集仪使用富含血小板的血浆)评估的高血小板功能。我们发现了几个可能与阿司匹林抵抗有关的基因多态。我们的研究结果对抗血小板治疗的处方前疗效评估有一定的参考价值。有必要进行前瞻性研究，以确定基因多态与抗血小板治疗结果之间的关系和原因。

Recent studies have revealed that resistance to aspirin and other antiplatelet drugs is a commonly recognized status. Those on aspirin therapy who are resistant to this drug are more prone to the recurrence of thrombosis. Thus, research to find genes responsible for aspirin resistance is extremely important to prevent atherothrombotic events, which are the leading cause of death in this country. The purpose of this study was to analyze the mechanisms of aspirin resistance in relationship with the variability in genes responsible for thrombosis and hemostasis, and to obtain basic data for individualized treatment of thrombosis. We first established the optimal experimental conditions for the in vitro assessment of aspirin resistance, using a platelet function analyzer, PFA100. Addition of aspirin at high concentration to normal platelet-rich plasma prolonged the occlusion time over the cut-off range in most cases. Addition of low concentration of aspirin, however, also did so but 〜30% of normal individuals failed to respond to aspirin (i.e., remained within the cut-off range). Those who are "resistant" to aspirin were characteristic as having high basal platelet reactivity, high platelet function as assessed by other platelet function tests (collagen-stimulated platelet function in a whole-blood aggregometer WBA-Neo and conventional optical aggregometer using platelet rich plasma). We found several genetic polymorphisms that are possibly associated with aspirin resistance. Our results are suggestive for the pre-prescription assessment of the efficacies of antiplatelet therapies. Prospective studies are necessary to establish the relationship and causation between genetic polymorphisms and the outcome of antiplatelet therapies.