Wei A, Ma H H, Zhang L P, Wu R H, Zhang R, Wang T Y
Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Disease in Children, Ministry of Education, Beijing 100045, China.
Zhonghua Er Ke Za Zhi. 2020 Mar 2;58(3):213-217. doi: 10.3760/cma.j.issn.0578-1310.2020.03.010.
To discuss the clinical characteristics and management approaches to hepatitis associated aplastic anemia (HAAA) presenting as hemophagocytic lymphohistiocytosis (HLH) at onset. The clinical data and laboratory results of hospitalized 5 HAAA patients presenting as HLH at onset in Beijing Children's Hospital from January 2017 to May 2019 were analyzed retrospectively. Among 5 cases, there were 4 males and 1 female. The age of onset was 6.0 (2.7-12.7) years. All patients presented with high fever, hepatomegaly, hepatic dysfunction (aspartate aminotransferase 1 716 (1 409-2 570) U/L, alanine aminotransferase 1 699 (937-2 540) U/L) at onset. After admission, the laboratory results showed pancytopenia (white blood cell 1.2 (0.6-6.7) ×10(9)/L, haemoglobin 94 (65-111) g/L, blood platelet 29 (10-41) ×10(9)/L), decreased fibrinogen (1.3 (1.1-2.5) g/L), significantly elevated triglyceride (4.0 (2.8-5.1) mmol/L), ferritin (1 766 (399-5 253) μg/L) and soluble CD25 (27 457 (9 625-44 000) ng/L). Hemophagocytosis was found in the bone marrow smears of all 5 patients. The diagnosis of acute hepatitis and HLH was confirmed. During the treatment of HLH, the blood cells remain below normal level and the further biopsy of bone marrow (iliac bone) indicated low myeloproliferation. After exclusion of congenital bone marrow failure syndromes and other pancytopenic diseases, HAAA was confirmed. After the diagnosis of HAAA, 1 patient received antithymocyte globulin (ATG) and cyclosporin treatment in our hospital, 1 patient received allogeneic stem cell transplantation (HSCT) in other hospital, 2 patients received ATG in other hospitals. Only 1 patient died of severe infection. HAAA can present as HLH at onset. It is mainly manifested by high fever, acute severe hepatitis, pancytopenia, elevated ferritin and hemophagocytosis in the bone marrow. The diagnosis of HAAA should be considered whenever cytopenia could not completely corrected while apparent improvement of HLH and hepatitis related complications were improved after immunosuppressive therapy. ATG or HSCT treatment should be performed as soon as the diagnosis of severe or transfusion dependent aplastic anemia is confirmed.
探讨以噬血细胞性淋巴组织细胞增生症（HLH）起病的肝炎相关性再生障碍性贫血（HAAA）的临床特点及治疗方法。回顾性分析2017年1月至2019年5月在北京儿童医院住院的5例以HLH起病的HAAA患者的临床资料及实验室检查结果。5例患者中，男4例，女1例。发病年龄为6.0（2.7 - 12.7）岁。所有患者起病时均有高热、肝大、肝功能异常（天冬氨酸氨基转移酶1 716（1 409 - 2 570）U/L，丙氨酸氨基转移酶1 699（937 - 2 540）U/L）。入院后实验室检查显示全血细胞减少（白细胞1.2（0.6 - 6.7）×10⁹/L，血红蛋白94（65 - 111）g/L，血小板29（10 - 41）×10⁹/L），纤维蛋白原降低（1.3（1.1 - 2.5）g/L），甘油三酯显著升高（4.0（2.8 - 5.1）mmol/L），铁蛋白（1 766（399 - 5 253）μg/L）及可溶性CD25（27 457（9 625 - 44 000）ng/L）升高。5例患者骨髓涂片均发现噬血细胞现象。确诊为急性肝炎合并HLH。在HLH治疗过程中，血细胞持续低于正常水平，进一步骨髓（髂骨）活检提示骨髓增殖低下。排除先天性骨髓衰竭综合征及其他全血细胞减少性疾病后，确诊为HAAA。确诊HAAA后，1例患者在我院接受抗胸腺细胞球蛋白（ATG）及环孢素治疗，1例患者在其他医院接受异基因造血干细胞移植（HSCT），2例患者在其他医院接受ATG治疗。仅1例患者死于严重感染。HAAA可起病时表现为HLH。主要表现为高热、急性重型肝炎、全血细胞减少、铁蛋白升高及骨髓噬血细胞现象。当免疫抑制治疗后HLH及肝炎相关并发症明显改善而血细胞减少不能完全纠正时，应考虑HAAA的诊断。一旦确诊为重型或输血依赖型再生障碍性贫血，应尽早进行ATG或HSCT治疗。
