哌拉西林钠他唑巴坦钠诱导免疫性溶血性贫血一例
A Case of Immune Hemolytic Anemia Induced by Piperacillin Sodium and Tazobactam Sodium
摘要: 目的:探讨哌拉西林钠他唑巴坦钠诱导免疫性溶血性贫血(drug-induced immune hemolytic anemia, DIIHA)的临床特征、血清学诊断方法及诊疗要点,提高临床对该类药物不良反应的识别与处置能力。方法:回顾性分析1例83岁男性患者因肺部感染使用哌拉西林钠他唑巴坦钠后发生免疫性溶血性贫血的临床资料,包括病史、症状体征、实验室指标动态变化及治疗转归。同时采用经典抗人球蛋白法进行体外药物抗体试验,验证药物依赖性抗体的存在及其免疫球蛋白类型。结果:患者于首次使用哌拉西林钠他唑巴坦钠后第8天出现急性溶血,停药并予糖皮质激素治疗后溶血缓解。后因临床需要再次使用该药,第4天溶血迅速复发。体外药物抗体试验证实患者血浆中存在哌拉西林钠他唑巴坦钠依赖性的IgM及IgG型抗红细胞抗体。结论:哌拉西林钠他唑巴坦钠可诱发免疫性溶血性贫血,其诊断需结合用药时间链、血清学动态监测及体外药物抗体试验综合判断。临床使用该药期间应加强血液学监测,一旦疑诊应立即停药并避免再次暴露。输血科在DIIHA的血清学诊断及输血时机决策中具有关键作用,体外药物抗体试验是明确致敏药物的重要手段。
Abstract: Objective: To investigate the clinical characteristics, serological diagnostic methods, and key management points of drug-induced immune hemolytic anemia (DIIHA) induced by piperacillin sodium and tazobactam sodium, thereby enhancing clinical recognition and management of this adverse drug reaction. Methods: A retrospective analysis was conducted on the clinical data of an 83-year-old male patient who developed immune hemolytic anemia after receiving piperacillin sodium and tazobactam sodium for pulmonary infection, including medical history, symptoms and signs, dynamic changes in laboratory parameters, and treatment outcomes. Additionally, a classical anti-human immunoglobulin assay was performed to confirm the presence of drug-dependent antibodies and their immunoglobulin types. Results: The patient developed acute hemolysis on day 8 following initial administration of piperacillin sodium and tazobactam sodium; hemolysis resolved after discontinuation of the medication and glucocorticoid therapy. However, the drug was re-administered due to clinical necessity, leading to rapid hemolytic recurrence on day 4. In vitro antibody testing confirmed the presence of piperacillin sodium and tazobactam sodium-dependent IgM-and IgG-type anti-red blood cell antibodies in the plasma. Conclusion: Piperacillin sodium and tazobactam sodium can induce immune hemolytic anemia, and diagnosis requires comprehensive evaluation of the medication timeline, serological monitoring, and in vitro antibody testing. Hematologic surveillance should be intensified during clinical use; immediate discontinuation and avoidance of re-exposure are warranted upon suspected diagnosis. The transfusion department plays a critical role in serological diagnosis and transfusion decision-making for DIIHA, with in vitro antibody testing serving as a pivotal tool for identifying sensitizing agents.
文章引用:王丽, 杨俊林, 李艾玲, 蒋韬. 哌拉西林钠他唑巴坦钠诱导免疫性溶血性贫血一例[J]. 药物资讯, 2026, 15(5): 505-514. https://doi.org/10.12677/pi.2026.155054

参考文献

[1] 郝宝岚, 王艳. β-内酰胺类抗生素诱导免疫性溶血性贫血的发病机制[J]. 河南医学研究, 2019, 28(8): 1529-1530.
[2] Zantek, N.D., Koepsell, S.A., Tharp, D.R. and Cohn, C.S. (2012) The Direct Antiglobulin Test: A Critical Step in the Evaluation of Hemolysis. American Journal of Hematology, 87, 707-709.
https://doi.org/10.1002/ajh.23218
[3] Wang, Q., He, Z., Wu, X., Wei, Y. and Huang, J. (2020) Hematologic Adverse Effects Induced by Piperacillin-Tazobactam: A Systematic Review of Case Reports. International Journal of Clinical Pharmacy, 42, 1026-1035.
https://doi.org/10.1007/s11096-020-01071-8
[4] 何彦侠, 薛兵. 抗菌药物诱发急性溶血性贫血临床特点分析[J]. 中国医院药学杂志, 2020, 40(19): 2055-2058.
[5] 王晓平, 杨君青. 直接抗人球蛋白试验阳性在贫血患者的分布特征及临床意义[J]. 河北医药, 2016, 38(18): 2796-2798.
[6] 胡丽华, 王学锋, 阎石, 等. 临床输血学检验技术[M]. 第6版. 北京: 人民卫生出版社, 2015: 36-40.
[7] 沈伟, 陈伟, 刘凤霞, 等. 红细胞血清学技术[M]. 长沙: 中南大学出版社, 2022: 17-19.
[8] 亓玲, 魏丽, 李静. 哌拉西林钠他唑巴坦钠联合布地奈德雾化吸入治疗新生儿肺炎的临床研究[J]. 中国临床药理学杂志, 2023, 39(14): 1979-1982.
[9] 中华医学会呼吸病学分会感染学组. 中国铜绿假单胞菌下呼吸道感染诊治专家共识(2022年版) [J]. 中华结核和呼吸杂志, 2022, 45(8): 739-752.
[10] 中华医学会血液学分会红细胞疾病(贫血)学组. 中国成人自身免疫性溶血性贫血诊疗指南(2023年版) [J]. 中华血液学杂志, 2023, 44(1): 12-18.
[11] Renard, D. and Rosselet, A. (2017) Drug-Induced Hemolytic Anemia: Pharmacological Aspects. Transfusion Clinique et Biologique, 24, 110-114.
https://doi.org/10.1016/j.tracli.2017.05.013
[12] Arndt, P.A., Garratty, G., Hill, J., Kasper, M. and Chandrasekaran, V. (2002) Two Cases of Immune Haemolytic Anaemia, Associated with Anti‐Piperacillin, Detected by the “Immune Complex” Method. Vox Sanguinis, 83, 273-278.
https://doi.org/10.1046/j.1423-0410.2002.00188.x
[13] Thickett, K.M., Wildman, M.J., Fegan, C.D., et al. (1999) Haemolytic Anaemia Following Treatment with Piperacillin in a Patient with Cysticfibrosis. Journal of Antimicrobial Chemotherapy, 43, 435-436.
https://doi.org/10.1093/jac/43.3.435
[14] Nagao, B., Yuan, S. and Bon Homme, M. (2012) Sudden Onset of Severe Anemia in a Patient with Cystic Fibrosis. Clinical Chemistry, 58, 1286-1289.
https://doi.org/10.1373/clinchem.2011.167213
[15] McDonald, L., Brodie, R., Murphy, K., Wright, P., Webster, R. and Fitzgerald, J. (2019) Piperacillin‐Tazobactam Drug‐Induced Immune Haemolysis in a Case of Paroxysmal Nocturnal Haemoglobinuria. Transfusion Medicine, 29, 138-140.
https://doi.org/10.1111/tme.12592
[16] Gerhardy, B. and Bowler, S. (2021) Piperacillin-Tazobactam‐Induced Haemolytic Anaemia after Multiple Courses of Therapy. Internal Medicine Journal, 51, 458-458.
https://doi.org/10.1111/imj.15243
[17] 何彦侠, 赵慧敏, 薛兵. 药源性溶血性贫血临床及误诊分析[J]. 临床误诊误治, 2019, 32(6): 1-4.
[18] Garratty, G. and Arndt, P.A. (1998) Positive Direct Antiglobulin Tests and Haemolytic Anaemia Following Therapy with Beta‐Lactamase Inhibitor Containing Drugs May Be Associated with Nonimmunologic Adsorption of Protein onto Red Blood Cells. British Journal of Haematology, 100, 777-783.
https://doi.org/10.1046/j.1365-2141.1998.00615.x
[19] 许志连, 郑颖, 何飞燕. 哌拉西林他唑巴坦诱发溶血性贫血的文献病例分析[J]. 药物流行病学杂志, 2024, 33(6): 688-696.
[20] Kerkhoff, A.D., Patrick, L., Cornett, P., Kleinhenz, M. and Brondfield, S. (2017) Severe Piperacillin-Tazobactam‐Induced Hemolysis in a Cystic Fibrosis Patient. Clinical Case Reports, 5, 2059-2061.
https://doi.org/10.1002/ccr3.1256
[21] Ge, J.B., Wang, C. and Xu, Y.J. (2018) Internal Medicine. 9th Edition, People’s Medical Publishing House, 558-560.
[22] 郑歌, 白雪, 马子坤, 等. 直接抗人球蛋白检测阳性分型对输注红细胞后临床疗效的影响[J]. 标记免疫分析与临床, 2025, 32(10): 2047-2052, 2122.
[23] 江峰锦, 白乐, 余泽波, 等. 自身免疫性溶血性贫血的诊疗进展[J]. 临床输血与检验, 2023, 25(5): 692-698.
[24] 魏戌, 谢雁鸣. 国内外不良反应因果判断原则及评价方法解读[J]. 中国中药杂志, 2012, 37(18): 2744-2747.