Department of Cardiology, Ruijin Hospital (J.Z., R.Z., X.Y.), Shanghai Jiao Tong University School of Medicine, China.
Department of Biochemistry and Molecular Cell Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education (Y.X., J.L.), Shanghai Jiao Tong University School of Medicine, China.
Arterioscler Thromb Vasc Biol. 2021 Oct;41(10):2523-2537. doi: 10.1161/ATVBAHA.121.316495. Epub 2021 Aug 5.
Objective: Roxadustat is a new medication for the treatment of renal anemia. EPO (erythropoietin)-the current treatment standard-has been reported to enhance platelet activation and production. However, to date, the effect of roxadustat on platelets is unclear. To address this deficiency, herein, we have evaluated the effect of roxadustat on platelet production and function. Approach and Results: We performed several mouse platelet functional assays in the presence/absence of in vitro and in vivo roxadustat treatment. Both healthy and 5/6 nephrectomized mice were utilized. The effect of roxadustat on platelet function of healthy volunteers and chronic kidney disease patients was also evaluated. For platelet production, megakaryocyte maturation and proplatelet formation were assayed in vitro. Peripheral platelet and bone marrow megakaryocyte counts were also determined. We found that roxadustat could not stimulate washed platelets directly, and platelet aggregation, spreading, clot retraction, and P-selectin/JON/A exposure were similar with or without in vitro or in vivo roxadustat treatment among both healthy and 5/6 nephrectomized mice. In vivo mouse thrombosis models were additionally performed, and no differences were detected between the vehicle and roxadustat treatment groups. EPO, which was considered a positive control in the present study, promoted platelet function and production as reported previously. Megakaryocyte maturation and proplatelet formation were also not significantly different between control mice and those treated with roxadustat. After receiving roxadustat for 14 days, no difference in the peripheral platelet count was observed in the mice. Conclusions: Administration of roxadustat has no significant impact on platelet production and function.
罗沙司他是一种治疗肾性贫血的新药。促红细胞生成素（EPO）——目前的治疗标准——已被报道能增强血小板的激活和生成。然而，迄今为止，罗沙司他对血小板的影响尚不清楚。为了解决这一不足，我们在此评估了罗沙司他对血小板生成和功能的影响。
我们在有无体外和体内罗沙司他治疗的情况下进行了几种小鼠血小板功能检测。使用了健康和 5/6 肾切除的小鼠。还评估了罗沙司他对健康志愿者和慢性肾脏病患者血小板功能的影响。对于血小板生成，我们在体外检测巨核细胞成熟和前血小板形成。还测定了外周血小板和骨髓巨核细胞计数。我们发现罗沙司他不能直接刺激洗涤血小板，在健康和 5/6 肾切除的小鼠中，无论有无体外或体内罗沙司他治疗，血小板聚集、扩散、血栓收缩和 P-选择素/JON/A 暴露均相似。还进行了体内小鼠血栓形成模型，在载体和罗沙司他治疗组之间未检测到差异。EPO 被认为是本研究中的阳性对照，如先前报道的那样，促进了血小板功能和生成。巨核细胞成熟和前血小板形成也没有明显的差异。在接受罗沙司他治疗 14 天后，小鼠的外周血小板计数没有差异。
给予罗沙司他对血小板生成和功能没有显著影响。
