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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。

Patients with Essential Thrombocythemia may be Poor Responders to Enteric-Coated Aspirin, but not to Plain Aspirin.

机构信息

Laboratory of Hemostasis and Thrombosis, Dipartimento di Scienze della Salute, Università degli Studi di Milan, Milan, Lombardia, Italy.

Clinical Biochemistry and Mass Spectrometry, Dipartimento di Scienze della Salute, Università degli Studi di Milan, Milan, Lombardia, Italy.

出版信息

Thromb Haemost. 2020 Oct;120(10):1442-1453. doi: 10.1055/s-0040-1714351. Epub 2020 Jul 27.

Abstract

Essential thrombocythemia (ET) patients are treated with aspirin (acetylsalicylic acid [ASA]) to prevent thrombosis. Previous studies showed that serum thromboxane (Tx) B was high 24 hours after enteric-coated (EC)-ASA in ET patients, due to increased number of noninhibited reticulated platelets (RPs), consequent to high platelet turnover, and that ASA should be given twice a day to ET patients. We studied ET patients ( = 17) and healthy subjects ( = 10) on 100 mg EC-ASA once daily; experiments were repeated after 14-day treatment with 100 mg plain-ASA once daily. Serum TxB, plasma ASA, and salicylic acid (SA) were measured before the morning dose and up to 8 hours thereafter. Blood activity of ASA-deacethylating esterases, in vitro inhibition of collagen-induced TxB production by ASA (10-1,000 µM), and number of RP were measured. TxB inhibition by ASA in vitro and esterases activities were normal in all subjects. EC-ASA elicited highly variable responses; 6 ET patients were poor responders, as their serum TxB was high after EC-ASA; their plasma levels of ASA and SA were low/undetectable. In contrast to EC-ASA, plain ASA decreased serum TxB and increased plasma ASA and SA in all subjects. Serum TxB was high in ET patients at 24 hours and significantly correlated with RP count (but not RP percentage) and platelet count. Plain ASA should be used in ET patients to inhibit platelets efficiently. The identification of ET patients who might benefit from twice a day ASA could simply be based on their platelet count: since their platelet turnover is not increased, ET patients with normalized platelet count should not need twice a day ASA treatment.

摘要

原发性血小板增多症(ET)患者用阿司匹林(乙酰水杨酸[ASA])治疗以预防血栓形成。先前的研究表明,ET 患者服用肠溶(EC)-ASA 后 24 小时血清血栓素(Tx)B 升高,这是由于血小板周转率高导致未被抑制的网织血小板(RPs)数量增加,因此 ASA 应每天两次给予 ET 患者。我们研究了 17 名 ET 患者和 10 名健康受试者,每天一次服用 100mg EC-ASA;在每天一次服用 100mg 普通 ASA 治疗 14 天后重复这些实验。在早晨剂量前和之后最多 8 小时测量血清 TxB、血浆 ASA 和水杨酸(SA)。测量 ASA 去乙酰化酯酶的体外活性、ASA(10-1000µM)抑制胶原诱导的 TxB 产生的活性以及 RPs 的数量。所有受试者的 ASA 体外抑制率和酯酶活性均正常。EC-ASA 产生了高度可变的反应;6 名 ET 患者是反应不良者,因为他们服用 EC-ASA 后血清 TxB 升高;他们的血浆 ASA 和 SA 水平低/无法检测到。与 EC-ASA 相反,普通 ASA 降低了所有受试者的血清 TxB,并增加了血浆 ASA 和 SA。ET 患者在 24 小时时血清 TxB 升高,与 RPs 计数(而非 RPs 百分比)和血小板计数显著相关。普通 ASA 应在 ET 患者中使用,以有效抑制血小板。确定可能受益于每天两次 ASA 的 ET 患者的方法可能仅基于其血小板计数:由于其血小板周转率未增加,血小板计数正常的 ET 患者不应需要每天两次 ASA 治疗。

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