Galli Mattia, Terracina Sergio, Schiera Eleonora, Mancone Massimo, Frati Luigi, Angiolillo Dominick J, Pulcinelli Fabio M
Maria Cecilia Hospital, GVM Care & Research, Cotignola, Italy.
Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, Rome, 00161, Italy.
J Thromb Thrombolysis. 2025 Jan;58(1):71-83. doi: 10.1007/s11239-024-03022-w. Epub 2024 Sep 6.
Antiplatelet therapy is crucial for reducing thrombotic events in patients with atherosclerotic disease, but the response vary widely among individuals. The identification of patients at high (HPR), optimal (OPR) or low platelet reactivity (LPR) is dependent on high interlaboratory variability. We report results of a large dataset of patients to assess the gold standard light transmission aggregometry (LTA). A total of 11,913 patients who sequentially underwent LTA assessment using several stimuli (ADP-2µM, collagen-2 µg/ml, arachidonic acid 0.5 mM, epinephrine 10µM) with a standardized methodology between 2004 and 2022 were screened. After application of inclusion-exclusion criteria, 5,901 patients were included and divided into five groups: healthy-volunteers (HV; N = 534); controls (CTR; N = 1073); aspirin-treated patients (ASA; 75-150 mg/die; N = 3280); clopidogrel-treated patients (CLOP; 75 mg/die; N = 495) and patients treated with dual antiplatelet therapy, ASA plus CLOP (DAPT; N = 519). The mean PA% in response to ADP 2 μm was 72.4 ± 33.3 in the CTR population, 40.6 ± 29.9 in the ASA group, 25.1 ± 35.1 in the CLOP group and 10.2 ± 18.5 in the DAPT group. The mean PA% in response to collagen 2 ug/ml was 90.7 ± 10.5 in the CTR population, 40.8 ± 26.3 in the ASA group, 79.4 ± 21.8 in the CLOP group and 17.9 ± 19.9 in the DAPT group. The percentage of patients at OPR following ADP stimuli was 66%, 25%, and 26%, in the ASA, CLOP, and DAPT group, respectively. The percentage of patients at OPR following collagen stimuli was 56%, 22%, and 41%, in the ASA, CLOP, and DAPT group, respectively. LTA was significantly increased in response to ADP (72.4 ± 33.3vs62.7 ± 37.1; p < 0.001) and AA (90.7 ± 15.6vs87.6 ± 20.5; p < 0.001) in CTR compared to HV. Our findings support the concept that a significant proportion of individuals present a hyper- or hypo-reactive platelet phenotype potentially affecting the safety and efficacy of antiplatelet therapy. The variability in response to antiplatelet therapy was particularly evident in patients undergoing single as opposed to dual antiplatelet therapy regimens. These data support ongoing strategies of guided selection of antiplatelet therapy in patients with cardiovascular disease.
抗血小板治疗对于降低动脉粥样硬化疾病患者的血栓形成事件至关重要，但个体之间的反应差异很大。高血小板反应性（HPR）、最佳血小板反应性（OPR）或低血小板反应性（LPR）患者的识别依赖于实验室间的高变异性。我们报告了一个大型患者数据集的结果，以评估金标准光透射聚集法（LTA）。在2004年至2022年期间，共筛选了11913例患者，这些患者使用标准化方法依次接受了几种刺激物（2μM ADP、2μg/ml胶原蛋白、0.5 mM花生四烯酸、10μM肾上腺素）的LTA评估。应用纳入-排除标准后，纳入了5901例患者，并将其分为五组：健康志愿者（HV；N = 534）；对照组（CTR；N = 1073）；阿司匹林治疗患者（ASA；75 - 150 mg/天；N = 3280）；氯吡格雷治疗患者（CLOP；75 mg/天；N = 495）以及接受双重抗血小板治疗（ASA加CLOP）的患者（DAPT；N = 519）。CTR组中对2μm ADP反应的平均PA%为72.4±33.3，ASA组为40.6±29.9，CLOP组为25.1±35.1，DAPT组为10.2±18.5。CTR组中对2μg/ml胶原蛋白反应的平均PA%为90.7±10.5，ASA组为40.8±26.3，CLOP组为79.4±21.8，DAPT组为17.9±19.9。在ASA、CLOP和DAPT组中，ADP刺激后达到OPR的患者百分比分别为66%、25%和26%。在ASA、CLOP和DAPT组中，胶原蛋白刺激后达到OPR的患者百分比分别为56%、22%和41%。与HV相比，CTR组中对ADP（72.4±33.3对62.7±37.1；p < 0.001）和AA（90.7±15.6对87.6±20.5；p < 0.001）的反应中LTA显著增加。我们的研究结果支持这样一种观点，即相当一部分个体呈现出高反应性或低反应性血小板表型，这可能会影响抗血小板治疗的安全性和有效性。与双重抗血小板治疗方案相比，单重抗血小板治疗患者对抗血小板治疗反应的变异性尤为明显。这些数据支持了目前在心血管疾病患者中进行抗血小板治疗指导选择的策略。
