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以血小板聚集异常为首发表现的原发性血小板增多症:肠溶剂阿司匹林降低血小板过度激活失败。

Aberrant Platelet Aggregation as Initial Presentation of Essential Thrombocythemia: Failure of Entero-Coated Aspirin to Reduce Platelet Hyperactivation.

机构信息

Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole, 10, Orbassano, I-10043 Turin, Italy.

Laboratory of Clinical and Microbiological Analyses, San Luigi Gonzaga Hospital, Orbassano, I-10043 Turin, Italy.

出版信息

Int J Mol Sci. 2023 Dec 22;25(1):176. doi: 10.3390/ijms25010176.

DOI:10.3390/ijms25010176
PMID:38203347
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10778871/
Abstract

Essential thrombocythemia (ET) is a myeloproliferative neoplasm variant characterized by excessive production of platelets. Since the most common cause of mortality and morbidity in ET patients is thrombosis, the excessive production of platelets may cause thrombotic events. However, little is known about the function of platelets in ET. We report a female patient who presented as asymptomatic, without a remarkable medical history, and ET was diagnosed after an incidental finding of moderate thrombocytosis. Notably, together with thrombocytosis, an abnormal platelet phenotype was found for the presence of a massive, rapid and spontaneous formation of aggregates and platelet hypersensitivity to subthreshold concentrations of aggregating agonists. Bone marrow histopathological examination and genetic analysis with the (V617F) gene mutation findings confirmed the initial suspicion of ET. Although the ET patient was placed on aspirin, the persistence of the platelet hyperactivation and hyperaggregability prompted a switch in antiplatelet medication from entero-coated (EC) to plain aspirin. As result, platelet hypersensitivity to agonists and spontaneous aggregation were no longer found. Collectively, our study demonstrates that platelet function analysis could be a reliable predictor of ET and that plain aspirin should be preferred over EC aspirin to attenuate platelet hyperreactivity.

摘要

原发性血小板增多症(ET)是一种骨髓增殖性肿瘤变异,其特征为血小板过度生成。由于 ET 患者最常见的死亡和发病原因是血栓形成,因此血小板的过度生成可能导致血栓事件。然而,关于血小板在 ET 中的作用知之甚少。我们报告了一名女性患者,其表现为无症状,无明显病史,在偶然发现中度血小板增多症后被诊断为 ET。值得注意的是,除了血小板增多症外,还发现了一种异常的血小板表型,存在大量、快速和自发性聚集形成以及血小板对亚阈值聚集激动剂浓度的超敏反应。骨髓组织病理学检查和基因分析发现 (V617F) 基因突变证实了对 ET 的初步怀疑。尽管 ET 患者服用了阿司匹林,但血小板过度激活和高聚集性持续存在,促使抗血小板药物从肠溶(EC)阿司匹林转换为普通阿司匹林。结果,发现血小板对激动剂的超敏反应和自发性聚集不再存在。总之,我们的研究表明,血小板功能分析可能是 ET 的可靠预测指标,并且应该优先使用普通阿司匹林而不是 EC 阿司匹林来减轻血小板高反应性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c712/10778871/ce53bba794a4/ijms-25-00176-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c712/10778871/d3929f2e0e94/ijms-25-00176-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c712/10778871/ce53bba794a4/ijms-25-00176-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c712/10778871/d3929f2e0e94/ijms-25-00176-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c712/10778871/ce53bba794a4/ijms-25-00176-g002.jpg

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本文引用的文献

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Validation of thrombotic risk factors in 1381 patients with essential thrombocythaemia: A multicentre retrospective real-life study.1381 例原发性血小板增多症患者血栓危险因素的验证:一项多中心回顾性真实研究。
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Lower Antiplatelet Effect of Aspirin in Essential Thrombocythemia than in Coronary Artery Disease.
阿司匹林在原发性血小板增多症中的抗血小板作用低于冠状动脉疾病。
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Platelet Function and Turnover in Essential Thrombocythemia: A Systematic Review.原发性血小板增多症中的血小板功能和周转率:系统评价。
Semin Thromb Hemost. 2021 Feb;47(1):90-101. doi: 10.1055/s-0040-1718873. Epub 2021 Feb 1.
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Patients with Essential Thrombocythemia may be Poor Responders to Enteric-Coated Aspirin, but not to Plain Aspirin.原发性血小板增多症患者对肠溶阿司匹林反应不佳,但对普通阿司匹林反应良好。
Thromb Haemost. 2020 Oct;120(10):1442-1453. doi: 10.1055/s-0040-1714351. Epub 2020 Jul 27.
6
A randomized double-blind trial of 3 aspirin regimens to optimize antiplatelet therapy in essential thrombocythemia.一项随机双盲试验,比较三种阿司匹林方案优化原发性血小板增多症的抗血小板治疗。
Blood. 2020 Jul 9;136(2):171-182. doi: 10.1182/blood.2019004596.
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Essential Thrombocythemia.原发性血小板增多症
N Engl J Med. 2019 Nov 28;381(22):2135-2144. doi: 10.1056/NEJMcp1816082.
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Benefits and Risks of Antithrombotic Therapy in Essential Thrombocythemia: A Systematic Review.原发性血小板增多症抗血栓治疗的获益与风险:系统评价。
Ann Intern Med. 2017 Aug 1;167(3):170-180. doi: 10.7326/M17-0284. Epub 2017 Jun 27.
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Do we need antiplatelet therapy in thrombocytosis? Contra. Proposal for an individualized risk-adapted treatment.血小板增多症患者是否需要抗血小板治疗?反对意见。关于个体化风险适应性治疗的提议。
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