Galli Mattia, Terracina Sergio, Schiera Eleonora, De Corci Simone, Sangiorgi Diego, Mancone Massimo, Frati Luigi, Sciarretta Sebastiano, Angiolillo Dominick J, Pulcinelli Fabio M
Cardiovascular Department, Maria Cecilia Hospital, GVM Care & Research, Cotignola 48033, Italy.
Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina 04100, Italy.
Eur Heart J Cardiovasc Pharmacother. 2025 Sep 22;11(6):509-517. doi: 10.1093/ehjcvp/pvaf034.
Emerging evidence suggests sex-specific differences in platelet biology and clinical responses to antiplatelet agents. Light transmission aggregometry (LTA) represents the historical gold standard for the assessment of platelet reactivity but is influenced by pre-analytical and analytical variables. We analysed a large dataset of patients undergoing LTA using a standardized methodology to investigate the impact of sex on platelet reactivity with or without antiplatelet therapy.
Between 2004 and 2022, 11,913 patients sequentially underwent LTA assessments following stimulation with adenosine diphosphate (ADP) (2 µM), collagen (2 µg/mL), arachidonic acid (AA, 0.5 mM), and epinephrine (10 µM). After applying study entry criteria, 5687 patients were included: 428 healthy volunteers (HV, F = 273; M = 155), 1055 controls (CTR; F = 725; M = 330), 3289 aspirin-treated patients (ASA; F = 2058; M = 1231), 430 clopidogrel-treated patients (CLOP; F = 272; M = 158), and 485 patients on dual antiplatelet therapy (DAPT; F = 166; M = 319). Within each group, results were analysed and compared between males and females.Females exhibited significantly greater platelet reactivity in response to ADP compared to males in the HV (P = 0.004), CTR (P < 0.0001), ASA (P < 0.0001), and CLOP (P < 0.018) groups, but not in the DAPT group. Among aspirin-treated patients, females showed increased platelet reactivity (P < 0.0001) in response to collagen, compared with males.
Females exhibit heightened baseline ADP-dependent platelet reactivity and a diminished response to aspirin and clopidogrel monotherapy compared to males.
新出现的证据表明血小板生物学及抗血小板药物临床反应存在性别差异。光透射聚集法（LTA）是评估血小板反应性的历史金标准，但受分析前和分析变量的影响。我们使用标准化方法分析了大量接受LTA检测的患者数据集，以研究性别对接受或未接受抗血小板治疗时血小板反应性的影响。
2004年至2022年期间，11913例患者先后接受了用二磷酸腺苷（ADP，2 μM）、胶原蛋白（2 μg/mL）、花生四烯酸（AA，0.5 mM）和肾上腺素（10 μM）刺激后的LTA评估。应用研究纳入标准后，纳入了5687例患者：428例健康志愿者（HV，女性=273例；男性=155例），1055例对照者（CTR；女性=725例；男性=330例），3289例接受阿司匹林治疗的患者（ASA；女性=2058例；男性=1231例），430例接受氯吡格雷治疗的患者（CLOP；女性=272例；男性=158例），以及485例接受双联抗血小板治疗（DAPT）的患者（女性=166例；男性=319例）。在每组中，对男性和女性的结果进行了分析和比较。在HV组（P = 0.004）、CTR组（P < 0.0001）、ASA组（P < 0.0001）和CLOP组（P < 0.018）中，女性对ADP刺激的血小板反应性显著高于男性，但在DAPT组中并非如此。在接受阿司匹林治疗的患者中，与男性相比，女性对胶原蛋白刺激的血小板反应性增加（P < 0.0001）。
与男性相比，女性表现出更高的基线ADP依赖性血小板反应性，且对阿司匹林和氯吡格雷单药治疗的反应减弱。
