Division of Cardiology, Department of Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, USA.
Division of Cardiology, Department of Medicine, Duke University, Durham, NC, USA.
J Thromb Thrombolysis. 2021 Feb;51(2):249-259. doi: 10.1007/s11239-020-02327-w. Epub 2020 Nov 6.
Platelet gene polymorphisms are associated with variable on-treatment platelet reactivity and vary by race. Whether differences in platelet reactivity and aspirin or ticagrelor exist between African-American and European-Americans remains poorly understood. Biological samples from three prior prospective antiplatelet challenge studies at the Duke Clinical Research Unit were used to compare platelet reactivity between African-American and European-American subjects. Platelet reactivity at baseline, on-aspirin, on-ticagrelor, and the treatment effect of aspirin or ticagrelor were compared between groups using an adjusted mixed effects model. Compared with European-Americans (n = 282; 50% female; mean ± standard deviation age, 50 ± 16), African-Americans (n = 209; 67% female; age 48 ± 12) had lower baseline platelet reactivity with platelet function analyzer-100 (PFA-100) (p < 0.01) and with light transmission aggregometry (LTA) in response to arachidonic acid (AA), adenosine diphosphate (ADP), and epinephrine agonists (p < 0.05). African-Americans had lower platelet reactivity on aspirin in response to ADP, epinephrine, and collagen (p < 0.05) and on ticagrelor in response to AA, ADP, and collagen (p < 0.05). The treatment effect of aspirin was greater in European-Americans with an AA agonist (p = 0.002). Between-race differences with in vitro aspirin mirrored those seen in vivo. The treatment effect of ticagrelor was greater in European-Americans in response to ADP (p < 0.05) but with collagen, the treatment effect was greater for African-Americans (p < 0.05). Platelet reactivity was overall lower in African-Americans off-treatment, on aspirin, and on ticagrelor. European-Americans experienced greater platelet suppression on aspirin and on ticagrelor. The aspirin response difference in vivo and in vitro suggests a mechanism intrinsic to the platelet. Whether the absolute level of platelet reactivity or the degree of platelet suppression after treatment is more important for clinical outcomes is uncertain.
血小板基因多态性与治疗中的血小板反应性变化有关，并且因种族而异。非裔美国人和欧洲裔美国人之间在血小板反应性和阿司匹林或替格瑞洛方面是否存在差异尚不清楚。使用杜克临床研究单位之前三项前瞻性抗血小板挑战研究的生物样本，比较了非裔美国人和欧洲裔美国受试者之间的血小板反应性。使用调整后的混合效应模型比较了两组之间的基线血小板反应性、阿司匹林治疗后、替格瑞洛治疗后以及阿司匹林或替格瑞洛的治疗效果。与欧洲裔美国人（n=282；50%为女性；平均年龄±标准差，50±16）相比，非裔美国人（n=209；67%为女性；年龄 48±12）的血小板反应性较低，血小板功能分析仪-100（PFA-100）（p<0.01）和花生四烯酸（AA）、二磷酸腺苷（ADP）和肾上腺素激动剂反应的光透射聚集（LTA）（p<0.05）。非裔美国人在阿司匹林治疗后对 ADP、肾上腺素和胶原的反应性较低（p<0.05），在替格瑞洛治疗后对 AA、ADP 和胶原的反应性较低（p<0.05）。AA 激动剂时，欧洲裔美国人的阿司匹林治疗效果更大（p=0.002）。体外阿司匹林的种族间差异与体内所见相似。ADP 反应时，欧洲裔美国人的替格瑞洛治疗效果更大（p<0.05），但胶原时，非裔美国人的治疗效果更大（p<0.05）。治疗后，非裔美国人的血小板反应性总体较低，服用阿司匹林和替格瑞洛时也是如此。欧洲裔美国人在阿司匹林和替格瑞洛治疗中血小板抑制作用更大。体内和体外的阿司匹林反应差异表明，血小板存在内在机制。对于临床结果，血小板反应性的绝对水平或治疗后的血小板抑制程度更重要尚不清楚。
