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慢性丙型肝炎抗病毒治疗期间因促红细胞生成素α导致的抗体介导的纯红细胞再生障碍性贫血

Antibody-mediated pure red cell aplasia due to epoetin alfa during antiviral therapy of chronic hepatitis C.

作者信息

Stravitz R Todd, Chung Harold, Sterling Richard K, Luketic Velimir A, Sanyal Arun J, Price Angie S, Purrington Amy, Shiffman Mitchell L

机构信息

Section of Hepatology, Division of Gastroenterology and the Division of Hematology/Oncology, Virginia Commonwealth University Medical Center, Richmond, Virginia 23298-0341, USA.

出版信息

Am J Gastroenterol. 2005 Jun;100(6):1415-9. doi: 10.1111/j.1572-0241.2005.41910.x.

Abstract

Anemia frequently complicates the treatment of chronic hepatitis C with interferon and ribavirin (RVN), requiring dose reduction and jeopardizing sustained virologic response. Increasingly, epoetin alfa is used to prevent anemia in this setting. Below, we report the first case of pure red cell aplasia (PRCA) in a patient with chronic hepatitis C who received epoetin alfa (Procrit) to manage anti-viral treatment-induced anemia. Red blood cell transfusion-dependence developed 16 wk after the patient was started on peginterferon alfa-2b and RVN for chronic hepatitis C despite the simultaneous administration of epoetin alfa and subsequent discontinuation of the antiviral medications. Bone marrow biopsy was consistent with PRCA. High-titer erythropoietin antibodies, assayed by two methods, appeared shortly after epoetin alfa was administered, and were associated with a decline in serum erythropoietin to undetectable levels. Erythropoietin antibodies directed toward epoetin alfa were shown to cross react with darbepoetin alfa (Aranesp), and a neutralization assay confirmed that they inhibited cell growth in the presence of erythropoietin. Transfusion-dependence resolved approximately 16 wk after discontinuing epoetin alfa, and 6 wk after starting danazol. PRCA caused by the development of erythropoietin antibodies is a potentially life-threatening complication of administering epoetin alfa to prevent the anemia associated with antiviral therapy in patients with chronic hepatitis C.

摘要

贫血常使慢性丙型肝炎患者使用干扰素和利巴韦林(RVN)治疗变得复杂,需要减少剂量并危及持续病毒学应答。在这种情况下,促红细胞生成素α越来越多地用于预防贫血。下面,我们报告了首例慢性丙型肝炎患者发生纯红细胞再生障碍性贫血(PRCA)的病例,该患者接受促红细胞生成素α(益比奥)来处理抗病毒治疗引起的贫血。尽管同时给予促红细胞生成素α并随后停用抗病毒药物,但该患者在开始使用聚乙二醇干扰素α-2b和RVN治疗慢性丙型肝炎16周后出现了依赖红细胞输血的情况。骨髓活检结果与PRCA相符。通过两种方法检测发现,在给予促红细胞生成素α后不久出现了高滴度的促红细胞生成素抗体,且其与血清促红细胞生成素降至无法检测水平有关。针对促红细胞生成素α的促红细胞生成素抗体被证明与达比加群酯(阿法依泊汀)发生交叉反应,并且中和试验证实它们在有促红细胞生成素存在的情况下抑制细胞生长。在停用促红细胞生成素α约16周后以及开始使用达那唑6周后,输血依赖情况得到缓解。由促红细胞生成素抗体产生引起的PRCA是在慢性丙型肝炎患者中使用促红细胞生成素α预防与抗病毒治疗相关贫血时可能危及生命的并发症。

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