Pure red cell aplasia caused by human parvovirus B19 infection after renal transplantation: a report of 2 cases and literature review
-
摘要:
目的 探讨肾移植术后人类微小病毒(HPV) B19感染致纯红细胞再生障碍性贫血(纯红再障)的诊断和治疗特点。 方法 总结南方医科大学南方医院器官移植科收治的2例肾移植术后HPV B19感染致纯红再障的病例, 结合文献复习讨论该病的临床特点、诊断方法、治疗过程及预后。 结果 两例肾移植受者术后早发严重贫血且进行性加重, 输血治疗无效。排除导致贫血的其他原因, 综合骨髓穿刺活检、荧光聚合酶链反应(PCR)检测HPV DNA等方法诊断为HPV B19感染致纯红再障。经调整免疫抑制方案、静脉注射用免疫球蛋白(IVIG)等治疗后2例患者贫血症状明显改善。 结论 对于肾移植术后早期不明原因、进行性加重的贫血患者, 特别是伴随网织红细胞缺乏者, 应考虑HPV B19感染致纯红再障的可能性。骨髓穿刺及荧光PCR检测结果是诊断纯红再障的主要依据, 免疫抑制剂减量和应用IVIG治疗是主要治疗措施。经治疗后, 患者预后较好, 但易复发。 -
关键词:
- 肾移植 /
- 人类微小病毒B19 /
- 纯红细胞再生障碍性贫血 /
- 免疫球蛋白 /
- 复发
Abstract:Objective To investigate the diagnosis and treatment characteristics of pure red cell aplasia (PRCA) caused by human parvovirus (HPV) B19 infection after renal transplantation. Methods Two cases with PRCA caused by HPV B19-induced after renal transplantation, who were treated in the Department of Organ Transplantation, Nanfang Hospital, Southern Medical University, were summarized. Combined with literature review, the clinical characteristics, diagnostic method, course of treatment and prognosis of such disease were investigated. Results Two renal transplant recipients developed severe anemia early after transplantation with progressive deterioration and failed transfusion therapy. Other causes of anemia were ruled out and two patients were diagnosed as PRCA caused by HPV B19 infection according to bone marrow aspiration and biopsy as well as HPV DNA detection by fluorescent polymerase chain reaction (PCR). The symptoms of anemia were improved significantly after adjustment of immunosuppressive treatment protocol and intravenous immunoglobulin (IVIG). Conclusions For patients with unexplained and progressed anemia early after renal transplantation, especially those complicated with reticulocyte deficiency, the possibility of PRCA caused by HPV B19 infection shall be considered. The results of bone marrow aspiration and fluorescent PCR are the main bases for diagnosing PRCA. Immunosuppressive agents reduction and application of IVIG are the major treatment measures. Most of patients have great prognosis after treatment, but this disease is likely to recur. -
Key words:
- Renal transplantation /
- Human parvovirus B19 /
- Pure red cell aplasia /
- Immunoglobulin /
- Relapse
-
表 1 国内HPV B19感染致纯红细胞再生障碍性贫血再障的肾移植受者的病例特点
Table 1. Characteristics of pure red cell aplasia caused by human parvovirus B19 infection in Chinese renal transplant recipients
研究作者 n 基础免疫抑制方案 纯红再障发生距移植时间 最低血红蛋白水平(g/L) 诊断方法 治疗方案 复发情况 Xiao, et al[2] 2 FK506+CsA+MMF 术后第9周 < 60 PCR检测HPV B19 DNA(+) IVIG,停用MMF, FK506减半 1例复发,FK506改为CsA后治愈 李帅阳,等[8] 4 FK506+MMF +泼尼松 术后第4周 56,74,48,42 HPV B19 IgM(+) IVIG,停用MMF或Aza, FK506改为CsA,EPO 4例均复发,其中2例复发2次 Wong, et al[9] 1 FK506+Aza+泼尼松 术后第4周 48 HPV B19 IgM(+),PCR检测HPV B19 DNA (+) IVIG,停用Aza, FK506改为CsA 多次复发,FK506改为CsA后治愈 Lui, et al[10] 3 Csa+Aza+泼尼松 术后第4、4、12周 88,60,60 HPV B19 IgM(+),PCR检测HPV B19 DNA(+) 1例自愈,2例使用IVIG 2例复发,其中1例出现严重并发症,于第4周死亡 黄森林,等(本文) 2 FK506+MMF+甲泼尼龙 术后第4、8周 63,39 PCR检测HPV B19 DNA(+) FK506改为CsA,减量CsA,其中1例使用IVIG和EPO 1例复发 陈燕燕, 等[11] 8 FK506+MMF+泼尼松 术后第4~13 d 50~73 PCR检测HPV B19 DNA(+) IVIG, FK506改为CsA,停用MMF 1例复发 注:Aza为硫唑嘌呤(azathioprine); ATG为抗胸腺细胞球蛋白 -
[1] Macdougall IC, Casadevall N, Locatelli F, et al. Incidence of erythropoietin antibody-mediated pure red cell aplasia:the Prospective Immunogenicity Surveillance Registry (PRIMS)[J]. Nephrol Dial Transplant, 2015, 30(3):451-460. doi: 10.1093/ndt/gfu297 [2] Xiao C, Wang CX, Liu LS, et al. Clinical investigation of human parvovirus B19 infection after renal transplantation in China[J]. Transplant Proc, 2013, 45(4):1593-1599. doi: 10.1016/j.transproceed.2013.02.040 [3] Chang HJ, Sinn DH, Cho SG, et al. Pure red-cell aplasia and autoimmune hemolytic anemia in a patient with acute hepatitis A[J]. Clin Mol Hepatol, 2014, 20(2):204-207. doi: 10.3350/cmh.2014.20.2.204 [4] Hirokawa M, Sawada K, Fujishima N, et al. Long-term outcome of patients with acquired chronic pure red cell aplasia (PRCA) following immunosuppressive therapy:a final report of the nationwide cohort study in 2004/2006 by the Japan PRCA collaborative study group[J]. Br J Haematol, 2015, DOI:10.1111/bjh.13376[Epub ahead of print]. [5] Kelleher E, Mcmahon C, Mcmahon CJ. A case of parvovirus B19-induced pure red cell aplasia in a child following heart transplant[J]. Cardiol Young, 2015, 25(2):373-375. doi: 10.1017/S1047951114000225 [6] Varshney P, Verma V, Verma N, et al. An unusual case of post-renal transplant anemia induced by parvovirus B19[J]. Indian J Transpl, 2014, 8(2):54-56. doi: 10.1016/j.ijt.2014.04.003 [7] 李栋林, 梁廷波.实体器官移植后纯红细胞再生障碍性贫血的病因与诊治[J].中华医学杂志, 2007, 86(42):3020-3022. http://www.cnki.com.cn/Article/CJFDTOTAL-ZHYX200642023.htmLi DL, Liang TB. Diagnosis and etiology treatment of pure red blood cell aplastic anemia after solid organ transplantation[J]. Natl Med J China, 2007, 86(42):3020-3022. http://www.cnki.com.cn/Article/CJFDTOTAL-ZHYX200642023.htm [8] 李帅阳, 沈兵, 刘志宏, 等.肾移植术后人微小病毒B19感染导致纯红细胞增生障碍性贫血[J].现代生物医学进展, 2012, 12(14):2698-2702. http://www.cnki.com.cn/Article/CJFDTOTAL-SWCX201214025.htmLi SY, Shen B, Liu ZH, et al. Human parvovirus B 19-induced pure red cell aplasia in patients with allograft renal transplantation[J]. Prog Mod Biomed, 2012, 12(14):2698-2702. http://www.cnki.com.cn/Article/CJFDTOTAL-SWCX201214025.htm [9] Wong TY, Chan PK, Leung CB, et al. Parvovirus B19 infection causing red cell aplasia in renal transplantation on tacrolimus[J]. Am J Kidney Dis, 1999, 34(6):1132-1136. doi: 10.1016/S0272-6386(99)70021-1 [10] Lui SL, Luk WK, Cheung CY, et al. Nosocomial outbreak of parvovirus B19 infection in a renal transplant unit[J]. Transplantation, 2001, 71(1):59-64. doi: 10.1097/00007890-200101150-00010 [11] 陈燕燕, 黄洪锋, 彭文翰, 等.肾移植后微小病毒B19感染导致纯红细胞再生障碍性贫血八例[J].中华器官移植杂志, 2013, 34(4):231-234. http://d.wanfangdata.com.cn/Periodical/zhqgyz98201304010Chen YY, Huang HF, Peng WH, et al. Pure red cell apalsia caused by infection of human parvovirus B19 post-renal transplantation:8 cases report and review[J]. Chin J Organ Transplant, 2013, 34(4):231-234. http://d.wanfangdata.com.cn/Periodical/zhqgyz98201304010 [12] Kooistra K, Mesman HJ, de Waal M, et al. Epidemiology of high-level parvovirus B19 viraemia among Dutch blood donors, 2003-2009[J]. Vox Sang, 2011, 100(3):261-266. doi: 10.1111/vox.2011.100.issue-3 [13] Eis-Hübinger AM, Oldenburg J, Brackmann HH, et al. The prevalence of antibody to parvovirus B19 in hemophiliacs and in the general population[J]. Zentralbl Bakteriol, 1996, 284(2/3):232-240. https://www.researchgate.net/publication/14368779_The_Prevalence_of_Antibody_to_Parvovirus_B19_in_Hemophiliacs_and_in_the_General_Population [14] Abdollahi A, Shoar S, Sheikhbahaei S, et al. Status of immunity against PVB19 in HIV-infected patients according to CD4(+) cell count, and antiretroviral therapy regimen groups[J]. Niger Med J, 2014, 55(1):20-23. doi: 10.4103/0300-1652.128153 [15] Niccoli G, Severino A, Pieroni M, et al. Parvovirus B19 at the culprit coronary stenosis predicts outcome after stenting[J]. Eur J Clin Invest, 2014, 44(2):209-218. doi: 10.1111/eci.2014.44.issue-2 [16] 井丽萍, 邵宗鸿.获得性纯红细胞再生障碍发病机制及治疗[J].中华血液学杂志, 2004, 25(8):510-512. http://www.cnki.com.cn/Article/CJFDTOTAL-ZHXY200408023.htmJing LP, Shao ZH. Pathogenesis and treatment of acquired pure red blood cell regeneration barrier[J]. Chin J Hematol, 2004, 25(8):510-512. http://www.cnki.com.cn/Article/CJFDTOTAL-ZHXY200408023.htm [17] Reindl-Schwaighofer R, Oberbauer R. Blood disorders after kidney transplantation[J]. Transplant Rev, 2014, 28(2):63-75. doi: 10.1016/j.trre.2013.10.001 [18] Atalay A, Gökahmetoğ lu S, Durmaz S, et al. Investigation of Epstein-Barr virus and parvovirus b19 DNA in allogeneic stem cell transplant patients[J]. Turk J Haematol, 2014, 31(2):155. doi: 10.4274/tjh [19] Green LK, Fraire AE. Parvovirus[M]. Berlin:Springer, 2014:133-140. [20] Eid AJ, Chen SF, AST Infectious Diseases Community of Practice. Human parvovirus B19 in solid organ transplantation[J]. Am J Transplant, 2013, 13(s4):201-205. doi: 10.1111/ajt.2013.13.issue-s4 [21] Choi SH, Chang SP, Won JC, et al. A case of persistent anemia in a renal transplant recipient:association with parvovirus B19 infection[J]. Scand J Infect Dis, 2002, 34(1):71-75. doi: 10.1080/003655402753395247 [22] Crabol Y, Terrier B, Rozenberg F, et al. Intravenous immunoglobulin therapy for pure red cell aplasia related to human parvovirus B19 infection:a retrospective study of 10 patients and review of the literature[J]. Clin Infect Dis, 2013, 56(7):968-977. doi: 10.1093/cid/cis1046 [23] Pascual J, Jiménez C, Franco A, et al. Early-onset anemia after kidney transplantation is an independent factor for graft loss:a multicenter, observational cohort study[J]. Transplantation, 2013, 96(8):717-725. doi: 10.1097/TP.0b013e31829f162e [25] 王丹妹.人类微小病毒B19感染与乙型肝炎的关系[J].实用预防医学, 2006, 13(5):1334-1335. http://www.cnki.com.cn/Article/CJFDTOTAL-SYYY200605113.htmWang DM. Hepatitis B and human parvovirus B19 infection[J]. Pract Prev Med, 2006, 13(5):1334-1335. http://www.cnki.com.cn/Article/CJFDTOTAL-SYYY200605113.htm