血小板生成素受体激动剂治疗慢性肝病伴血小板减少症的最新进展:以阿伐曲波帕为重点

IF 3 Q2 Medicine
Jemal Abdela
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引用次数: 13

摘要

慢性肝病(CLD)是一种随着时间的推移而发展到晚期疾病状态的疾病,即肝硬化。肝硬化在世界各地的人们中导致危险的健康问题。在大约75%的肝硬化患者中观察到的一个这样的问题是血小板减少症;这反过来又与CLD的预后和恢复不良有关。除此之外,肝硬化患者的血小板减少导致凝血级联功能受损,并显著影响CLD治疗有效机制的使用。从本质上讲,CLD的治疗涉及侵入性诊断和治疗程序;因此,在存在血小板减少的情况下,由于出血和死亡风险增加,实施这些方法将患者的生命置于严重的健康问题中。由于这些原因,预防性输血小板被认为是降低需要接受侵入性手术的CLD患者出血风险的最有效选择之一。尽管血小板输注在促进CLD患者侵入性手术方面具有显著优势,但反复使用的难治性和输注相关的各种问题限制了这一重要选择的持续使用。面对这些挑战和目前血小板生成知识的进步,开发相对安全的替代药物,通过与血小板生成素受体激动剂相互作用来增强血小板的产生,为血小板输注提供了一个有希望的选择。romiplostim和eltrombopag分别于2008年8月和2008年11月被发现并批准用于治疗慢性免疫性血小板减少症,随后美国食品和药物管理局(FDA)于2018年批准了两种潜在优势药物lusutrombopag和avatrombopag,用于治疗需要接受选择性手术的CLD患者的血小板减少症。因此,本综述旨在评估血小板减少的发病机制及其在肝脏相关问题管理中的挑战,更重要的是,通过介绍各种试验中最常见的不良事件,强调阿伏曲波帕在治疗CLD所致的血小板减少中的潜在应用,其药代动力学和药效学以及毒理学概况。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Current Advance in Thrombopoietin Receptor Agonists in the Management of Thrombocytopenia Associated With Chronic Liver Disease: Focus on Avatrombopag
Chronic liver disease (CLD) is a condition that progresses over time toward advanced disease state which is known as liver cirrhosis. Liver cirrhosis leads to dangerous health problems among people living across the world. One such problem that observed in about 75% of cirrhotic patients is thrombocytopenia; which in turn associated with poor prognosis and recovery from CLD. Beyond these, thrombocytopenia in cirrhotic patients led to impairment of coagulation cascade and significantly influenced the utilization of effective mechanism in the management of CLD. By nature, treatment of CLD involves invasive diagnostic and treatment procedures; therefore, in the presence of thrombocytopenia implementing these methods put the lives of patients in a critical health problem due to increased risk of bleeding and mortality. Because of these reasons, prophylactic transfusion of platelets is considered to be one of the most effective options that reduce the risk of bleeding in patients with CLD that required to undergo an invasive procedure. Although platelet transfusion presented with significant advantages in facilitating the invasive procedure in patients with CLD, refractoriness with repeated use and various problems associated with its transfusion limit the continuous utilization of this important option. With these challenges and current advance in the knowledge of thrombopoiesis, the development of relatively safe and alternative drugs that enhance the production of platelets by interacting with thrombopoietin receptor agonists provides a promising option to platelet transfusion. The discovery and approval of romiplostim and eltrombopag in August 2008 and November 2008, respectively, for the treatment of chronic immune thrombocytopenia paved a way and followed by the Food and Drug Administration (FDA) approval of 2 potentially advantageous drugs, lusutrombopag, and avatrombopag, in 2018 for the treatment of thrombocytopenia in patients with CLD that required to undergo elective surgery. Therefore, this review aims to assess pathogenesis of thrombocytopenia and its challenges in the management of liver-related issues and, more importantly, gives emphasis to address the potential use of avatrombopag in the treatment of thrombocytopenia underlying CLD, its pharmacokinetics and pharmacodynamics, as well as its toxicological profiles by presenting the most commonly reported adverse events in various trials.
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CiteScore
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