Lim S T, Murphy S J X, Smith D R, Collins D R, Coughlan T, Murphy S M, McCarthy A J, Egan B, Lim S-Y, Cox D, McCabe D J H
Department of Neurology, Tallaght University Hospital/The Adelaide and Meath Hospital, Dublin, Incorporating the National Children's Hospital (AMNCH), Dublin, Ireland; Stroke Service, Tallaght University Hospital/The Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital (AMNCH), Dublin, Ireland; Dept. of Clinical and Movement Neurosciences, Royal Free Campus, UCL Queen Square Institute of Neurology, London, UK; Dept. of Clinical Neurophysiology, Kings College Hospital NHS Trust, London, UK.
Department of Neurology, Tallaght University Hospital/The Adelaide and Meath Hospital, Dublin, Incorporating the National Children's Hospital (AMNCH), Dublin, Ireland; Stroke Service, Tallaght University Hospital/The Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital (AMNCH), Dublin, Ireland; Academic Unit of Neurology, School of Medicine, Trinity College Dublin, Ireland.
J Neurol Sci. 2025 Aug 15;475:123540. doi: 10.1016/j.jns.2025.123540. Epub 2025 May 17.
Simultaneously-collected data regarding platelet reactivity and activation in ischaemic cerebrovascular disease (CVD) patients starting antiplatelet agents are limited.
This prospective observational pilot study assessed platelet reactivity and activation in TIA/ischaemic stroke patients before (baseline; N = 73), 14 ± 7 days (14d; N = 59) and ≥ 90 days (90d; N = 38) after commencing aspirin or clopidogrel monotherapy. Platelet reactivity at low shear-stress (Multiplate® Aspirin/ADP assays) and platelet activation status (% expression of CD62P, CD63, and leucocyte-platelet complexes by flow cytometry) were quantified in whole blood. Prevalence of high on-treatment platelet reactivity (HTPR) was determined on Multiplate with 'case-control definitions' (Aspirin-HTPR:>40 U; Clopidogrel-HTPR:>46 U), and innovative 'longitudinal-HTPR definitions' (failure to reduce aggregation compared with the patient's baseline by more than twice the co-efficient of variation of the relevant assay).
Prevalence of case-control aspirin-HTPR was 23.8 % at 14d and 30.8 % at 90d, and of longitudinal aspirin-HTPR was 4.8 % at 14d and 0 % at 90d. Prevalence of clopidogrel-HTPR was significantly higher with case-control than longitudinal definitions at 14d (60.5 % vs. 21 %) and 90d (52 % vs. 24 %) (P ≤ 0.03). % Neutrophil-platelet complexes (P = 0.04) and lymphocyte-platelet complexes (P = 0.002) were higher in patients with vs. without case-control clopidogrel-HTPR at 14d. Median % lymphocyte-platelet complexes significantly decreased between baseline and 14d (P = 0.019), and monocyte-platelet complexes decreased between baseline and 90d (P = 0.017) only in the clopidogrel-patient subgroup whose platelets were adequately inhibited by clopidogrel.
Antiplatelet-HTPR prevalence is higher in CVD patients with case-control than longitudinal definitions on the Multiplate analyser. Quantifying leucocyte-platelet complexes improves our understanding of cellular mechanisms contributing to case-control clopidogrel-HTPR.
关于开始使用抗血小板药物的缺血性脑血管病（CVD）患者血小板反应性和活化的同时收集的数据有限。
这项前瞻性观察性试点研究评估了短暂性脑缺血发作（TIA）/缺血性中风患者在开始阿司匹林或氯吡格雷单药治疗前（基线；N = 73）、治疗后14±7天（14天；N = 59）和≥90天（90天；N = 38）时的血小板反应性和活化情况。在全血中定量低剪切应力下的血小板反应性（Multiplate®阿司匹林/ADP检测）和血小板活化状态（通过流式细胞术检测CD62P、CD63和白细胞-血小板复合物的表达百分比）。使用“病例对照定义”（阿司匹林-高治疗期血小板反应性[HTPR]：>40 U；氯吡格雷-HTPR：>46 U）和创新性的“纵向-HTPR定义”（与患者基线相比，聚集减少未超过相关检测变异系数的两倍）在Multiplate上确定高治疗期血小板反应性（HTPR）的患病率。
病例对照阿司匹林-HTPR的患病率在14天时为23.8%，在90天时为30.8%；纵向阿司匹林-HTPR的患病率在14天时为4.8%，在90天时为0%。氯吡格雷-HTPR的患病率在14天（60.5%对21%）和90天（52%对24%）时，病例对照定义显著高于纵向定义（P≤0.03）。在14天时，有病例对照氯吡格雷-HTPR的患者中中性粒细胞-血小板复合物百分比（P = 0.04）和淋巴细胞-血小板复合物百分比（P = 0.002）高于无该情况的患者。仅在氯吡格雷充分抑制血小板的氯吡格雷治疗患者亚组中，基线至14天期间淋巴细胞-血小板复合物百分比中位数显著降低（P = 0.019），基线至90天期间单核细胞-血小板复合物百分比降低（P = 0.017）。
在Multiplate分析仪上，CVD患者中抗血小板-HTPR患病率采用病例对照定义高于纵向定义。定量白细胞-血小板复合物有助于我们更好地理解导致病例对照氯吡格雷-HTPR的细胞机制。
