病例报告

发热伴血小板减少综合征合并噬血细胞综合征2例诊疗分析

  • 乔靓 ,
  • 张婷娟 ,
  • 冯媛 ,
  • 杨磊 ,
  • 钱军 ,
  • 周静东
展开
  • 1.江苏大学附属人民医院血液科,镇江 212002
    2.江苏省镇江市血液病临床医学研究中心,镇江 212002
    3.江苏省镇江市血液系统恶性肿瘤精准诊断与治疗重点实验室,镇江 212002
周静东,副主任医师,博士;电子信箱:zhoujingdong@ujs.edu.cn

收稿日期: 2025-04-09

  录用日期: 2025-06-19

  网络出版日期: 2025-10-28

基金资助

国家自然科学基金(82270179);江苏省自然科学基金(BK20221287);江苏省卫生健康员会科研项目(M2022123)

Diagnosis and treatment analysis of two cases of severe fever with thrombocytopenia syndrome complicated with hemophagocytic lymphohistiocytosis

  • QIAO Liang ,
  • ZHANG Tingjuan ,
  • FENG Yuan ,
  • YANG Lei ,
  • QIAN Jun ,
  • ZHOU Jingdong
Expand
  • 1.Department of Hematology, Affiliated People's Hospital of Jiangsu University, Zhenjiang 212002, China
    2.Zhenjiang Clinical Research Center of Hematology, Jiangsu Province, Zhenjiang 212002, China
    3.The Key Lab of Precision Diagnosis and Treatment of Zhenjiang City, Jiangsu Province, Zhenjiang 212002, China
ZHOU Jingdong, E-mail: zhoujingdong@ujs.edu.cn.

Received date: 2025-04-09

  Accepted date: 2025-06-19

  Online published: 2025-10-28

Supported by

National Natural Science Foundation of China(82270179);Jiangsu Provincial Natural Science Foundation(BK20221287);Jiangsu Commission of Health Scientific Research Project(M2022123)

摘要

病例1,患者男性,69岁,因“头晕乏力、恶心腹泻伴口腔出血10 d”就诊,近期有田间劳作史。患者出现白细胞、血小板减少,同时伴有凝血功能障碍、肝功能异常、胃肠道紊乱、心肌损伤、呼吸衰竭等多器官功能障碍的临床表现,骨髓穿刺涂片结果见噬血现象,外送新型布尼亚病毒检测显示阳性,确诊为发热伴血小板减少综合征(severe fever with thrombocytopenia syndrome,SFTS)合并噬血细胞综合征(hemophagocytic lymphohistiocytosis,HLH)。确诊后启动糖皮质激素联合利巴韦林治疗,但随访得知患者死亡,原因可能与患者就诊偏晚、高龄、病毒复制未能较好控制等因素有关。病例2,患者男性,73岁,因“乏力1周”就诊,近期有田间劳作史。患者同样有白细胞、血小板减少,合并肝功能、凝血功能异常,骨髓穿刺涂片可见噬血现象,考虑患者高度疑似SFTS伴HLH。予经验性抢先使用法维拉韦抗病毒联合糖皮质激素抗炎治疗,早期抑制新型布尼亚病毒复制及炎症因子风暴。其后检测结果显示患者新型布尼亚病毒核酸定量2.69×103半数组织细胞感染剂量(50% tissue culture infective dose,TCID50)/mL,确诊SFTS伴发HLH。患者最终临床症状及各项指标总体改善。通过2例类似病例复习提示临床上早期经验性抢先使用法维拉韦控制病毒复制可改善SFTS合并HLH患者的治疗与预后。

本文引用格式

乔靓 , 张婷娟 , 冯媛 , 杨磊 , 钱军 , 周静东 . 发热伴血小板减少综合征合并噬血细胞综合征2例诊疗分析[J]. 上海交通大学学报(医学版), 2025 , 45(10) : 1400 -1406 . DOI: 10.3969/j.issn.1674-8115.2025.10.016

Abstract

Case 1, a 69-year-old male patient, was admitted to our hospital due to "dizziness, fatigue, nausea, diarrhea, and oral bleeding for 10 d", with a recent history of field farming work. The patient exhibited leukopenia, thrombocytopenia, and clinical manifestations of multi-organ dysfunction, including coagulation dysfunction, liver function abnormalities, gastrointestinal disorders, myocardial injury, and respiratory failure. Bone marrow aspiration smear revealed hemophagocytosis, and out-of-hospital testing for the severe fever with thrombocytopenia syndrome bunyavirus was positive. The patient was diagnosed with severe fever with thrombocytopenia syndrome (SFTS) complicated by hemophagocytic lymphohistiocytosis (HLH). After diagnosis, glucocorticoid combined with ribavirin treatment was initiated. However, the patient still died, which may be related to factors such as delayed medical consultation, advanced age, and poor control of viral replication. Case 2, a 73-year-old male patient, was admitted to our hospital due to "fatigue for 1 week", with a recent history of field farming work. The patient also presented with leukopenia and thrombocytopenia, combined with liver and coagulation function abnormalities. Bone marrow aspiration smear showed hemophagocytosis, and the patient was highly suspected of SFTS with HLH. We empirically initiated preemptive treatment with favipiravir for antiviral therapy, combined with glucocorticoid for anti-inflammation, to early inhibit novel bunyavirus replication and cytokine storm. Subsequent testing reported the severe fever with thrombocytopenia syndrome bunyavirus nucleic acid quantification as 2.69×10³ 50% tissue culture infective dose (TCID50)/mL, confirming the diagnosis of SFTS with HLH. The patient's clinical symptoms and various indicators generally improved. Review of these two similar cases suggests that early empirical preemptive use of favipiravir to control viral replication in clinical practice may improve the treatment and prognosis of patients with SFTS complicated by HLH.

参考文献

[1] YU X J, LIANG M F, ZHANG S Y, et al. Fever with thrombocytopenia associated with a novel bunyavirus in China[J]. N Engl J Med, 2011, 364(16): 1523-1532.
[2] 郑昕. 发热伴血小板减少综合征的再认识[J]. 中华传染病杂志,2024, 42(4): 193-197.
  ZHENG X, Fever with thrombocytopenia syndrome recognized[J]. Chinese Journal of Infectious Diseases, 2024, 42(4): 193-197.
[3] LUO N, LI M D, XU M, et al. Research progress of fever with thrombocytopenia syndrome[J]. Intensive Care Res, 2023: 1-10.
[4] WU Y J, SUN X, KANG K, et al. Hemophagocytic lymphohistiocytosis: current treatment advances, emerging targeted therapy and underlying mechanisms[J]. J Hematol Oncol, 2024, 17(1): 106.
[5] 中国医师协会血液科医师分会, 中华医学会儿科学分会血液学组, 噬血细胞综合征中国专家联盟, 等. 中国噬血细胞综合征诊断与治疗指南(2022年版)[J]. 中华医学杂志, 2022, 102(20): 1492-1499.
  Hematology Branch of Chinese Medical Doctor Association, Hematology Group, Pediatric Branch, Chinese Medical Association, Chinese Expert Alliance on Hemophagocytic Syndrome, et al. Guidelines for the diagnosis and treatment of hemophagocytic syndrome in China (2022 edition)[J]. Chinese Medical Journal, 2022, 102(20):1492-1499.
[6] 黄晓霞, 杜珊珊, 李阿茜, 等. 2018—2021年中国发热伴血小板减少综合征流行特征分析[J]. 中华流行病学杂志, 2024, 45(1): 112-116.
  HUANG X X, DU S S, LI A Q, et al. Epidemiological characteristics of fever with thrombocytopenia syndrome in China, 2018?2021[J]. Chinese Journal of Epidemiology, 2024, 45(1):112-116.
[7] 中华医学会感染病学分会. 发热伴血小板减少综合征诊疗共识[J]. 中华传染病杂志, 2022, 40(12): 711-721.
  Chinese Society of Infectious Diseases. Consensus on the diagnosis and treatment of fever with thrombocytopenia syndrome[J]. Chinese Journal of Infectious Diseases, 2022, 40(12): 711-721.
[8] 陈广, 陈韬, 舒赛男, 等. 重症发热伴血小板减少综合征诊治专家共识[J]. 中华临床感染病杂志, 2022, 15(4): 253-263.
  CHEN G, CHEN T, SHU S N, et al. Expert consensus on the diagnosis and treatment of severe fever with thrombocytopenia syndrome[J]. Chinese Journal of Clinical Infectious Diseases, 2022, 15(4): 253-263.
[9] LI M M, ZHANG W J, LIU J, et al. Dynamic changes in the immunological characteristics of T lymphocytes in surviving patients with severe fever with thrombocytopenia syndrome (SFTS)[J]. Int J Infect Dis, 2018, 70: 72-80.
[10] SONG P X, ZHENG N, LIU Y, et al. Deficient humoral responses and disrupted B-cell immunity are associated with fatal SFTSV infection[J]. Nat Commun, 2018, 9(1): 3328.
[11] KIM N, KIM K H, LEE S J, et al. Bone marrow findings in severe fever with thrombocytopenia syndrome: prominent haemophagocytosis and its implication in haemophagocytic lymphohistiocytosis[J]. J Clin Pathol, 2016, 69(6): 537-541.
[12] 周鑫, 朱建勇, 曾宪聪. 新型布尼亚病毒感染继发嗜血细胞综合征1例报道[J]. 中国临床研究, 2021, 34(4): 531-533.
  ZHOU X, ZHU J Y, ZENG X C. A case report of haemophilic syndrome secondary to novel bunyavirus infection[J]. Chinese Journal of Clinical Research, 2021, 34(4): 531-533.
[13] YOO J R, HEO S T, SONG S W, et al. Severe fever with thrombocytopenia syndrome virus in ticks and SFTS incidence in humans, south Korea[J]. Emerg Infect Dis, 2020, 26(9): 2292-2294.
[14] LIANG B Y, XU L, LI M Y, et al. The association between elevated myocardial injury-related biomarker (TnI) and increased mortality in patients with severe fever with thrombocytopenia syndrome[J]. Crit Care Med, 2024, 52(10): 1509-1519.
[15] FURUTA Y, GOWEN B B, TAKAHASHI K, et al. Favipiravir (T-705), a novel viral RNA polymerase inhibitor[J]. Antiviral Res, 2013, 100(2): 446-454.
[16] SHIRAKI K, DAIKOKU T. Favipiravir, an anti-influenza drug against life-threatening RNA virus infections[J]. Pharmacol Ther, 2020, 209: 107512.
[17] TANI H, FUKUMA A, FUKUSHI S, et al. Efficacy of T-705 (favipiravir) in the treatment of infections with lethal severe fever with thrombocytopenia syndrome virus[J]. mSphere, 2016, 1(1): e00061-15.
[18] TAKAYAMA-ITO M, SAIJO M. Antiviral drugs against severe fever with thrombocytopenia syndrome virus infection[J]. Front Microbiol, 2020, 11: 150.
[19] TANI H, KOMENO T, FUKUMA A, et al. Therapeutic effects of favipiravir against severe fever with thrombocytopenia syndrome virus infection in a lethal mouse model: dose-efficacy studies upon oral administration[J]. PLoS One, 2018, 13(10): e0206416.
[20] LI H, JIANG X M, CUI N, et al. Clinical effect and antiviral mechanism of T-705 in treating severe fever with thrombocytopenia syndrome[J]. Signal Transduct Target Ther, 2021, 6(1): 145.
[21] YUAN Y, LU Q B, YAO W S, et al. Clinical efficacy and safety evaluation of favipiravir in treating patients with severe fever with thrombocytopenia syndrome[J]. EBioMedicine, 2021, 72: 103591.
[22] SONG R, CHEN Z H, LI W. Severe fever with thrombocytopenia syndrome (SFTS) treated with a novel antiviral medication, favipiravir (T-705)[J]. Infection, 2020, 48(2): 295-298.
[23] 金灵薇. 法维拉韦治疗重症发热伴血小板减少综合征病例报道1例[J]. 世界最新医学信息文摘, 2021, 21(51): 301-302.
  JIN L W. A case report of severe fever with thrombocytopenia syndrome treated with favipiravir[J]. World Latest Medical Information Abstracts, 2021, 21(51): 301-302.
[24] 刘亚萍, 臧玮. 法维拉韦治疗发热伴血小板减少综合征1例[J]. 中国新药与临床杂志, 2022, 41(11): 697-699.
  LIU Y P, ZANG W. Favipiravir in treatment of severe fever with thrombocytopenia syndrome: a case report[J]. Chinese Journal of New Drugs and Clinical Remedies, 2022, 41(11): 697-699.
[25] ZHANG Y, MIAO W, XU Y H, et al. Severe fever with thrombocytopenia syndrome in Hefei: clinical features, risk factors, and ribavirin therapeutic efficacy[J]. J Med Virol, 2021, 93(6): 3516-3523.
[26] SHIMOJIMA M, FUKUSHI S, TANI H, et al. Effects of ribavirin on severe fever with thrombocytopenia syndrome virus in vitro[J]. Jpn J Infect Dis, 2014, 67(6): 423-427.
[27] YAMAUCHI N, HONGO T, KAWAKAMI M, et al. Successful recovery from severe fever with thrombocytopenia syndrome and hemophagocytic lymphohistiocytosis with standard treatment and a calcium channel blocker of nicardipine hydrochloride[J]. Intern Med, 2023, 62(9): 1365-1369.
[28] BANG M S, KIM C M, KIM D M, et al. Effective drugs against severe fever with thrombocytopenia syndrome virus in an in vitro model[J]. Front Med (Lausanne), 2022, 9: 839215.
[29] ZHOU D, HUANG X B, ZHU L X, et al. Ruxolitinib combined with dexamethasone for adult patients with newly diagnosed hemophagocytic lymphohistiocytosis in China[J]. Blood, 2025, 146(3): 318-327.
文章导航

/