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.
J Neurol Sci. 2022 Oct 15;441:120334. doi: 10.1016/j.jns.2022.120334. Epub 2022 Jul 11.
Data are limited on the ability of dipyridamole to additionally inhibit platelet function/reactivity in ischaemic cerebrovascular disease (CVD) patients on aspirin.
To assess inhibition of platelet function/reactivity and platelet activation with dipyridamole in CVD.
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.
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.
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.
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。
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。
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。
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。
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。
