临床常用直接抗凝血剂的头对头体内外比较

Jaka Fadraersada, Raúl Alva-Gallegos, Pavel Skořepa, František Musil, Lenka Javorská, Kateřina Matoušová, Lenka Kujovská Krčmová, Markéta Paclíková, Alejandro Carazo, Vladimír Blaha, Přemysl Mladěnka
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摘要

凝血失衡与心血管事件有关。为了预防和治疗,目前主要使用抗凝剂,如沙班和加特兰。由于目前还没有直接评估这些新型抗凝剂的研究,因此本研究的目的是进行正面比较。此外,本研究还旨在了解某些人类学和生化因素是否会影响以固定剂量使用的这些药物的抗凝特性。在这项横断面研究中,研究人员收集了 50 名身体健康的献血者的血液,分析了他们对浓度为 1 μM 的达比加群、阿加曲班、利伐沙班和阿哌沙班的凝血反应。肝素用作阳性对照。测量并比较了以国际标准化比值(INR)表示的凝血酶原时间(PT)和活化部分凝血活酶时间(aPTT)。根据 PT/INR 值,利伐沙班的活性最高,而根据 aPTT 值,阿加曲班的活性最高。在所有四种测试的抗凝剂中,用 INR 测量的体内抗凝效果与体重指数(BMI)成反比。aPTT 缩短与胆固醇和甘油三酯水平升高有关。在对抗凝剂的反应方面,没有观察到与性别有关的差异。由于这是一项体外研究,且不包括药代动力学因素,因此 BMI 的影响在治疗方面具有重要意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Head-to-head ex vivo comparison of clinically used direct anticoagulant drugs

An imbalance in coagulation is associated with cardiovascular events. For prevention and treatment, anticoagulants, currently mainly xabans and gatrans, are used. The purpose of the present study was to provide a head-to-head comparison since there are no studies directly evaluating these novel anticoagulants. An additional aim was to find whether selected anthropological and biochemical factors can affect their anticoagulant properties as they are used in fixed doses. In this cross-sectional study, blood from 50 generally healthy donors was collected, and coagulation responses to dabigatran, argatroban, rivaroxaban, and apixaban, at a concentration of 1 μM, were analyzed. Heparin was used as a positive control. Prothrombin time (PT) expressed as international normalized ratio (INR) and activated partial thromboplastin time (aPTT) were measured and compared. Rivaroxaban was the most active according to PT/INR while argatroban according to aPTT. The ex vivo anticoagulant effect measured by INR correlated inversely with body mass index (BMI) in all four anticoagulants tested. Shortening of aPTT was associated with higher cholesterol and triglyceride levels. No sex-related differences were observed in response to the anticoagulant treatments. As this was an ex vivo study and pharmacokinetic factors were not included, the influence of BMI is of high therapeutic importance.

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