短暂性脑缺血发作和缺血性脑卒中后早期和晚期加用双嘧达莫后高和低切应力下治疗中的血小板反应性和血小板活化状态的评估。
Assessment of on-treatment platelet reactivity at high and low shear stress and platelet activation status after the addition of dipyridamole to aspirin in the early and late phases after TIA and ischaemic stroke.
机构信息
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; Department of Clinical Neurosciences, Royal Free Campus, UCL Queen Square Institute of Neurology, 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.
出版信息
J Neurol Sci. 2022 Oct 15;441:120334. doi: 10.1016/j.jns.2022.120334. Epub 2022 Jul 11.
BACKGROUND
Data are limited on the ability of dipyridamole to additionally inhibit platelet function/reactivity in ischaemic cerebrovascular disease (CVD) patients on aspirin.
AIMS
To assess inhibition of platelet function/reactivity and platelet activation with dipyridamole in CVD.
METHODS
This prospective, observational study assessed TIA/ischaemic stroke patients before (baseline; N = 60), at 14 ±7 days (14d, N = 39) and ≥ 90 days (90d, N = 31) after adding dipyridamole to aspirin. Platelet function/reactivity at high shear stress (PFA-100® C-ADP) and low shear stress (VerifyNow® P2Y12 and Multiplate® ADP assays), and platelet activation status (% expression of CD62P, CD63 and leucocyte-platelet complexes on whole blood flow cytometry) were quantified. 'Dipyridamole-high on-treatment platelet reactivity (HTPR)' was defined as failure to inhibit ADP-induced platelet aggregation +/- adhesion compared with the patient's baseline on aspirin monotherapy by more than twice the coefficient-of-variation of the assay after adding dipyridamole to aspirin.
RESULTS
Dipyridamole-HTPR was identified in 71.4-75% of patients on PFA-100 C-ADP, 83.9-86.8% of patients on VerifyNow P2Y12, and 81.5-83.3% of patients on Multiplate ADP assays. There were no changes in CD62P/CD63 expression (P ≥ 0.18), or consistent changes in leucocyte-platelet complexes in CVD patients overall at 14d or 90d vs. baseline after commencing dipyridamole. Monocyte-platelet complexes increased in the patient subgroup with dipyridamole-HTPR at 14d and 90d on PFA-100, and at 14d on VerifyNow (P ≤ 0.04), but not in those without dipyridamole-HTPR.
DISCUSSION
Additional antiplatelet effects of dipyridamole are detectable under high and low shear stress conditions with user-friendly platelet function/reactivity tests ex vivo. Increasing circulating monocyte-platelet complexes over time are associated with dipyridamole-HTPR.
背景
在服用阿司匹林的缺血性脑血管病（CVD）患者中，双嘧达莫抑制血小板功能/反应性的能力数据有限。
目的
评估 CVD 患者中双嘧达莫对血小板功能/反应性和血小板激活的抑制作用。
方法
这项前瞻性观察性研究在添加双嘧达莫至阿司匹林前（基线；N=60）、14±7 天时（14d，N=39）和≥90 天时（90d，N=31）评估短暂性脑缺血发作/缺血性卒中患者。使用高剪切应力（PFA-100®C-ADP）和低剪切应力（VerifyNow®P2Y12 和 Multiplate®ADP 测定法）检测血小板功能/反应性，并通过全血流式细胞术检测血小板激活状态（%表达 CD62P、CD63 和白细胞-血小板复合物）。将“双嘧达莫高治疗血小板反应性（HTPR）”定义为与阿司匹林单药治疗时的基线相比，在添加双嘧达莫后，ADP 诱导的血小板聚集/粘附抑制作用未能超过检测方法变异系数的两倍。
结果
在 PFA-100 C-ADP 上，71.4%-75%的患者存在双嘧达莫-HTPR，在 VerifyNow P2Y12 上，83.9%-86.8%的患者存在双嘧达莫-HTPR，在 Multiplate ADP 测定法上，81.5%-83.3%的患者存在双嘧达莫-HTPR。在总体 CVD 患者中，在添加双嘧达莫后 14 天或 90 天时，CD62P/CD63 表达无变化（P≥0.18），白细胞-血小板复合物也无一致变化。在接受双嘧达莫治疗的患者亚组中，在 PFA-100 上的 14 天和 90 天，以及在 VerifyNow 上的 14 天，单核细胞-血小板复合物增加（P≤0.04），但在无双嘧达莫-HTPR 的患者中则没有。
讨论
在使用体外血小板功能/反应性检测的高剪切和低剪切条件下，可以检测到双嘧达莫的额外抗血小板作用。随着时间的推移，循环中单核细胞-血小板复合物的增加与双嘧达莫-HTPR 相关。
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