Department of Neurology, Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital, Trinity College Dublin, Dublin, Ireland.
Eur J Neurol. 2013 Feb;20(2):344-52. doi: 10.1111/j.1468-1331.2012.03861.x. Epub 2012 Sep 20.
The prevalence of ex vivo 'high on-treatment platelet reactivity' (HTPR) to antiplatelet regimens in patients with ischaemic cerebrovascular disease (CVD) is uncertain.
HTPR was assessed with PFA-100 collagen-epinephrine (C-EPI) and collagen-ADP (C-ADP) cartridges. Platelet activation (CD62P, CD63 and leucocyte-platelet complex formation) was assessed with whole-blood flow cytometry. Patients were assessed at baseline [≤ 4 weeks of transient ischaemic attack (TIA) or ischaemic stroke], and at 14 days and ≥ 90 days after changing treatment from (i) no medication to aspirin monotherapy (N = 26) or (ii) aspirin to clopidogrel monotherapy (N = 22). HTPR was defined in a novel, 'longitudinal fashion' as failure to prolong relevant closure times compared with the patient's 'baseline value' before he/she underwent an antiplatelet change by more than twice the coefficient of variation of the assay.
(i) C-EPI closure times increased at 14 days and 90 days after commencing aspirin (P = 0.002); 24% at 14 days and 18% at 90 days demonstrated HTPR on aspirin. (ii) C-ADP closure times increased at 14 days (P = 0.001) but not 90 days (P = 0.09) after changing from aspirin to clopidogrel; 41% at 14 days, and 35% at 90 days demonstrated HTPR on clopidogrel. Platelet activation was unaffected by aspirin (P = 0.09). The percentage neutrophil-platelet complexes decreased at 14 days (P = 0.02), but this reduction was not maintained 90 days after changing to clopidogrel (P = 0.3). No patient had a recurrent vascular event during prospective follow-up.
Longitudinal definitions of HTPR in patients with ischaemic CVD who are undergoing a change in antiplatelet therapy have the potential to provide more clinically meaningful information than traditional 'cross-sectional definitions' of HTPR which are usually based on the comparison of patients' values with those in healthy controls. Using our novel, longitudinal definition of HTPR, the PFA-100 could be used to monitor ex vivo responsiveness to aspirin, and larger, prospective studies are warranted to assess the clinical predictive value of this and other platelet function tests in patients with ischaemic CVD.
缺血性脑血管病（CVD）患者体外“高治疗血小板反应性”（HTPR）的流行情况尚不确定。
使用 PFA-100 胶原-肾上腺素（C-EPI）和胶原-ADP（C-ADP）试剂盒评估 HTPR。使用全血流动 cytometry 评估血小板活化（CD62P、CD63 和白细胞-血小板复合物形成）。在基线时（≤ 4 周短暂性脑缺血发作（TIA）或缺血性中风），以及改变治疗方案后 14 天和≥90 天，评估患者（i）从不服用药物改为阿司匹林单药治疗（N = 26）或（ii）阿司匹林改为氯吡格雷单药治疗（N = 22）。HTPR 采用新的“纵向”方法定义为与患者在接受抗血小板药物变化之前的“基线值”相比，相关闭合时间未能延长两倍以上，而检测的变异系数则超过两倍。
（i）开始服用阿司匹林后 14 天和 90 天，C-EPI 闭合时间增加（P = 0.002）；14 天时有 24%，90 天时有 18%的患者对阿司匹林出现 HTPR。（ii）从阿司匹林改为氯吡格雷后 14 天 C-ADP 闭合时间增加（P = 0.001），但 90 天无变化（P = 0.09）；14 天时有 41%，90 天时有 35%的患者对氯吡格雷出现 HTPR。阿司匹林对血小板活化无影响（P = 0.09）。中性粒细胞-血小板复合物的百分比在 14 天减少（P = 0.02），但在改用氯吡格雷后 90 天并未保持（P = 0.3）。在前瞻性随访期间，没有患者发生血管再发事件。
正在改变抗血小板治疗的缺血性 CVD 患者中，HTPR 的纵向定义有可能比通常基于患者值与健康对照组值比较的传统“横断面定义”提供更有临床意义的信息。使用我们新的、纵向的 HTPR 定义，PFA-100 可用于监测体外对阿司匹林的反应性，需要进行更大的前瞻性研究来评估这种和其他血小板功能测试在缺血性 CVD 患者中的临床预测价值。
