Tiu Ramon V, Sekeres Mikkael A
Cleveland Clinic Taussig Cancer Center, Department of Hematologic Oncology and Blood Disorders, 9500 Euclid Avenue R35, Cleveland, Ohio 44195, USA.
Expert Opin Biol Ther. 2008 Jul;8(7):1021-30. doi: 10.1517/14712598.8.7.1021.
Thrombocytopenia can be seen in a variety of disease states, including immune mediated thrombocytopenic purpura (ITP) and myelodysplastic syndromes (MDS). The most concerning complication is the development of hemorrhagic complications that may contribute to patient morbidity and mortality. The ligand thrombopoeitin (TPO) and its interaction with its receptor (c-mpl) are important in platelet production. Thrombopoietic agonists can help in the management of thrombocytopenia related to these conditions. Amgen Megakaryopoiesis Protein 531 (AMG-531) (Romiplostim) is a recombinant TPO with a peptide fragment that shares no sequence homology with endogenous TPO, preventing the production of neutralizing antibodies. Recent studies have shown that it is effective in raising platelet counts, and is well tolerated in ITP and MDS patients. In this review, we discuss thrombopoiesis regulation by TPO; the chemistry, pharmacokinetics and pharmacodynamics of AMG-531 in animals and humans; the pathophysiological mechanisms leading to thrombocytopenia in ITP and MDS; and clinical trials demonstrating its efficacy in treating thrombocytopenia.
血小板减少症可见于多种疾病状态，包括免疫介导的血小板减少性紫癜（ITP）和骨髓增生异常综合征（MDS）。最令人担忧的并发症是出血并发症的发生，这可能导致患者发病和死亡。配体血小板生成素（TPO）及其与受体（c-mpl）的相互作用在血小板生成中很重要。血小板生成激动剂有助于管理与这些病症相关的血小板减少症。安进巨核细胞生成蛋白531（AMG-531）（罗米司亭）是一种重组TPO，其肽片段与内源性TPO没有序列同源性，可防止产生中和抗体。最近的研究表明，它能有效提高血小板计数，并且在ITP和MDS患者中耐受性良好。在这篇综述中，我们讨论了TPO对血小板生成的调节；AMG-531在动物和人类中的化学性质、药代动力学和药效学；ITP和MDS中导致血小板减少的病理生理机制；以及证明其治疗血小板减少症疗效的临床试验。
