【作者】 周文华；

【导师】 吴建永；

【作者基本信息】 浙江大学 ， 内科学， 2007， 硕士

【摘要】 目的：肾移植术后合并慢性贫血在临床上十分常见，约占39％。其原因较多，部分患者表现为纯红细胞再生障碍性贫血。文献报道微小病毒B19感染可引起肾移植术后纯红细胞再生障碍性贫血。分析肾移植术后纯红再障的原因，总结肾移植术后微小病毒B19感染所致纯红再障的诊断、治疗和预防经验。方法：对浙江大学附属第一医院肾脏病中心2006年6月诊断的1例肾移植术后微小病毒B19感染所致纯红再障的临床资料进行回顾性分析，同时对国外相关文献进行复习。结果：患者为慢性肾小球肾炎系膜增生型，终末期肾病，接受同种异体肾移植，术后免疫抑制剂治疗包括：术前和术后两周赛尼哌诱导治疗2次；手术当天、术后第一、二、三天甲基强的松龙冲击治疗，随后强的松、骁悉、环孢素三联抗排异治疗；术后29天因血肌酐仍然未降至正常范围停用环孢素，改FK506。术后血红蛋白76g／L，此后血红蛋白进行性下降，给予促红细胞生成素、铁剂、叶酸、集落刺激因子无效，术后53天血红蛋白降至47g／L，输入红细胞4单位。骨髓常规：红系增生欠活跃，仅占4％。骨髓活检：造血组织增生十分低下。考虑到骁悉的骨髓抑制作用，术后64天停用骁悉。因FK506也可导致器官移植后纯红再障，在术后70天停用FK506，改环孢素。术后74天血红蛋白降至42g／L，再次输入红细胞4单位治疗。CT排除胸腺瘤，直接和间接Coobm’s试验均阴性排除溶血。术后76天定量PCR微小病毒B19—DNA测定结果为：5.0×10~9拷贝／ml。EB病毒IgM阴性，IgG阳性。诊断为：微小病毒B19感染致纯红再障。静脉给予大剂量丙种球蛋白，剂量20g／d×5天、25g／d×5天、25g／d×10天，3个疗程后复查微小病毒B19—DNA为：3.8×10~5拷贝／ml。丙球冲击治疗结束21天后血红蛋白升到112g／L。治疗结束3月后复查微小病毒B19—DNA为：5.6×10~3拷贝／ml，再经过3月后复查微小病毒B19—DNA阴性。结论：肾移植术后纯红再障的原因较多，包括免疫抑制剂导致骨髓抑制、病毒感染、促红细胞生成素抵抗、胸腺瘤、缺铁等，病毒感染以微小病毒B19为多见，国外有多例报道。骨髓检查和病毒学检测可明确诊断。治疗以大剂量静脉丙种球蛋白为主，但容易复发。对于复发病例大剂量静脉免疫球蛋白治疗仍有效。微小病毒B19感染致纯红再障经过治疗，一般预后较好。目前尚无特异、有效的预防办法，可能的措施包括避免呼吸道感染、对供体和受体筛查微小病毒B19及开发病毒疫苗。更多还原

【Abstract】 Objective: Chronic aplasia is common in clinic after renal transplantation, maybe 39% of the recipients. Parvovirus B19-induced hematological toxicity, which has been reported in solid organ transplant recipients, may result in anemia episodes especially pure red cell aplasia, reported mainly in kidney transplant recipients. We aim to analyze the causes of pure red cell aplasia after renal transplantation and summarize the experience of diagnosis, treatment and prevention of parvovirus B19 infection causing pure red cell aplasia after transplantation.Methods: We describe the case of a renal transplant recipient with pure red cell aplasia due to parvovirus B19 infection that appeared during immunosuppressive therapy and discuss causes, diagnosis, treatment and prevention of the disease by reviewing relevant literature.Results: A 37-year-old male with mesangial proliferative glomerulonephritis received a renal allograft for end-stage renal disease. Immunosuppression in the first 29 days after the renal transplant was with cyclosporine, mycophenolate, and prednisolone, and thereafter it was changed to tacrolimus, mycophenolate, and prednisolone. After transplantation, this patient suffered from progressive anemia. Fifty-three days later, the hemoglobin had dropped to 47 g/L. Blood transfusions, colony stimulating factor, folate, iron, and erythropoietin supplements failed to raise the hemoglobin levels. And bone marrow biopsy showed selectively inhibited erythropoiesis. The anemia was unresponsive to replacement of tacrolimus by cyclosporine A and discontinuing mycophenolate. Detection of parvovirus B19-DNA with real time polymerase chain reaction revealed a severe parvovirus B19 infection(5.0×10~9 genome copies /ml). A course of intravenous immunoglobulin(20g/d for 5 days) was performed. Ten days after the administration, hemoglobin levels were stably elevated to 76g/L and parvovirus B19-DNA was 4.9 ×10~6 genome copies per milliliter. Ten days later, a remarkable decline of hemoglobin levels(61g/L) and a large amount of parvovirus B19-DNA in blood emerged again(4.8×10~9 genome copies /ml). Another course of intravenous immunoglobulin(25g/d for 5 days) was performed. After the third course of intravenous immunoglobulin(25g/d for 10 days) his hemoglobin level rose to 112 g/L but parvovirus B19-DNA was still detectable in blood with low level (3.8×10~5 genome copies /ml). Three months later, his hemoglobin level was normal. The parvovirus B19-DNA was negative 6 months after the treatment. Conclusions: Parvovirus B19 infection is the most common cause of virus-induced pure red cell aplasia after kidney transplantation. Diagnosis is based on bone marrow examination and detection of parvovirus B19 DNA by polymerase chain reaction in serum and/or bone marrow. Intravenous immunoglobulin is an effective and safe treatment but the disease easily recurs. There is no proven specific strategy available to prevent parvovirus B19 infection after kidney transplantation. We recommend further research on exploring most effective modality of therapy without recurrence and preventative strategies.更多还原