Fadraersada Jaka, Alva-Gallegos Raúl, Skořepa Pavel, Musil František, Javorská Lenka, Matoušová Kateřina, Krčmová Lenka Kujovská, Paclíková Markéta, Carazo Alejandro, Blaha Vladimír, Mladěnka Přemysl
Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Hradec Králové, Czech Republic.
3rd Department of Internal Medicine-Metabolic Care and Gerontology, University Hospital and Faculty of Medicine in Hradec Králové, Charles University, Sokolská 581, 50005, Hradec Králové, Czech Republic.
Naunyn Schmiedebergs Arch Pharmacol. 2024 Jun;397(6):4461-4470. doi: 10.1007/s00210-023-02891-x. Epub 2023 Dec 19.
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.
凝血失衡与心血管事件相关。为了预防和治疗，目前主要使用抗凝剂，即利伐沙班和达比加群酯。由于尚无直接评估这些新型抗凝剂的研究，本研究旨在进行直接比较。另一个目的是确定在固定剂量使用时，选定的人体学和生化因素是否会影响其抗凝特性。在这项横断面研究中，收集了50名一般健康供体的血液，并分析了浓度为1 μM时达比加群、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，利伐沙班活性最高，而根据aPTT，阿加曲班活性最高。在所有四种测试的抗凝剂中，通过INR测量的体外抗凝作用与体重指数（BMI）呈负相关。aPTT缩短与较高的胆固醇和甘油三酯水平相关。在抗凝治疗反应中未观察到性别差异。由于这是一项体外研究，未纳入药代动力学因素，BMI的影响具有重要的治疗意义。
