Increased platelet activation in early symptomatic vs. asymptomatic carotid stenosis and relationship with microembolic status: results from the Platelets and Carotid Stenosis Study
Increased platelet activation in early symptomatic vs. asymptomatic carotid stenosis and relationship with microembolic status: results from the Platelets and Carotid Stenosis Study
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DOI：
10.1111/jth.12277
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发表时间：
2013-07-01
影响因子：
10.4
通讯作者：
McCabe, D. J. H.
中科院分区：
文献类型：
--
作者：
Kinsella, J. A.;Tobin, W. O.;McCabe, D. J. H.
背景脑微栓子信号(MES)可预测颈动脉狭窄患者卒中风险的增加。方法对无症状颈动脉狭窄早期(TIA/卒中后4周)和晚期(3个月，50%)患者的血小板计数和血小板活化状态与MES的关系进行了前瞻性、先导性观察研究。全血计数，全血流式细胞仪定量检测血小板表面活化标志物CD62p和CD63的表达及循环白细胞-血小板复合体。双侧大脑中动脉同时经颅多普勒超声监测1h，将患者分为MES阳性或阴性患者。结果31例无症状患者与46例有症状患者的早期资料进行比较，其中35例患者在症状出现后随访至晚期。早期有症状患者的血小板计数中位数(211vs.200×10~(-9)，L(-1)，P=0.001)和淋巴细胞-血小板复合体的中位数百分比(2.8vs.2.4%，P=0.03)均高于无症状患者。早期症状者淋巴细胞-血小板复合体百分率高于颈动脉狭窄70%的无症状者(P=0.0005)和发病7d内有症状者(P=0.028)。25例无症状、31例早期有症状和27例晚期有症状的患者可获得完整的TCD数据。无症状组的MES阳性率为12%，早期症状组为32%(P=0.02)，晚期症状组为19%(P=0.2)。早期有症状的MES阴性患者的淋巴细胞-血小板复合体比例高于无症状的MES阴性患者(2.8%vs.2.3%；P=0.0085)。MES在早期有症状的患者中比无症状的患者更常见，但晚期有症状和无症状的患者之间的差异并不显著。最近有症状的MES阴性患者与无症状的MES阴性患者相比，淋巴细胞-血小板复合体的形成增加表明这一早期症状亚群的血小板活化增强。在无症状和有症状的颈动脉狭窄患者中，血小板生物标志物与经颅多普勒超声相结合，有可能有助于风险分层。
Background Cerebral microembolic signals (MES) may predict increased stroke risk in carotid stenosis. However, the relationship between platelet counts or platelet activation status and MES in symptomatic vs. asymptomatic carotid stenosis has not been comprehensively assessed.Setting University teaching hospitals.Methods This prospective, pilot observational study assessed platelet counts and platelet activation status, and the relationship between platelet activation and MES in asymptomatic vs. early (4weeks after TIA/stroke) and late phase (3months) symptomatic moderate or severe (50%) carotid stenosis patients. Full blood count measurements were performed, and whole blood flow cytometry was used to quantify platelet surface activation marker expression (CD62P and CD63) and circulating leucocyte-platelet complexes. Bilateral simultaneous transcranial Doppler ultrasound monitoring of the middle cerebral arteries was performed for 1h to classify patients as MES positive or MES negative.Results Data from 31 asymptomatic patients were compared with 46 symptomatic patients in the early phase, and 35 of these patients were followed up to the late phase after symptom onset. The median platelet count (211 vs. 200x10(9)L(-1); P=0.03) and the median percentage of lymphocyte-platelet complexes was higher in early symptomatic than asymptomatic patients (2.8 vs. 2.4%; P=0.001). The percentage of lymphocyte-platelet complexes was higher in early symptomatic than in asymptomatic patients with 70% carotid stenosis (P=0.0005) and symptomatic patients recruited within 7days of symptom onset (P=0.028). Complete TCD data were available in 25 asymptomatic, 31 early phase symptomatic and 27 late phase symptomatic patients. Twelve per cent of asymptomatic vs. 32% of early phase symptomatic (P=0.02) and 19% of late phase symptomatic patients (P=0.2) were MES positive. Early symptomatic MES-negative patients had a higher percentage of lymphocyte-platelet complexes than asymptomatic MES-negative patients (2.8 vs. 2.3%; P=0.0085).Discussion Recently, symptomatic carotid stenosis patients have had higher platelet counts (potentially reflecting increased platelet production, mobilization or reduced clearance) and platelet activation status than asymptomatic patients. MES were more frequently detected in early symptomatic than asymptomatic patients, but the differences between late symptomatic and asymptomatic groups were not significant. Increased lymphocyte-platelet complex formation in recently symptomatic vs. asymptomatic MES-negative patients indicates enhanced platelet activation in this early symptomatic subgroup. Platelet biomarkers, in combination with TCD, have the potential to aid risk-stratification in asymptomatic and symptomatic carotid stenosis patients.