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临床患者血浆中β-内酰胺类药物&抗体致输血无效及对供者红细胞亲和力的研究

Study on β-lactam Drugs and Antibodies in Clinical Patients’ Plasma Causing Blood Transfusion Inefficiency and Affinity for Donor Red Blood Cells

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【作者】 梁延连; 杨燕; 吴明磊; 方泰石; 苏宇清; 吴亚飞; 彭龙; 吴凡; 梁爽; 刘嘉婧; 徐筠娉;

【Author】 LIANG Yan-lian;YANG Yan;WU Ming-lei;FANG Tai-shi;SU Yu-qing;WU Ya-fei;PENG Long;WU Fan;LIANG Shuang;LIU Jia-jing;XU Yun-ping;Institute of Transfusion Medicine,Shenzhen Blood Center;the Third People’s Hospital of Shenzhen;Jiangsu Zhongji Wantai Biomedical Co.LTD;

【通讯作者】 徐筠娉;

【机构】 深圳市血液中心输血医学研究所; 深圳市第三人民医院; 江苏中济万泰生物医药有限公司;

【摘要】 目的 分析临床患者血浆中β-内酰胺类药物&抗体对供者红细胞的亲和力,探究药源性溶血性贫血及输血无效的临床特点。方法 选择2021年11月~2022年4月期间临床送检的4例有β-内酰胺类药物用药史的临床患者,检测ABO与Rh血型,直接抗球蛋白试验(direct antiglobulin test,DAT)、不规则抗体鉴定(identification of irregular antibodies,IAT)与β-内酰胺类药物抗体及效价,对DAT阳性的患者红细胞进行酸放散并检测放散液中β-内酰胺类药物抗体。选择ABO和Rh同型的供者红细胞与患者血浆在37℃无菌条件下体外致敏,监测β-内酰胺类药物&抗体在0,24,48和72 h与供者红细胞的亲和力,并观察加入补体后的溶血程度。结果 4例患者血浆中均存在β-内酰胺类药物抗体,停药前输血无效,停药后输血效果良好。患者1:A型,RhCCDee,DAT阳性(3+W),IAT阴性,血浆中存在头孢哌酮药物抗体(效价:1∶64)、阿莫西林药物抗体(效价:1∶16),放散液中存在头孢哌酮药物抗体。患者2:A型,RhCcDee,DAT阳性(4+W),IAT阴性,血浆中存在头孢哌酮药物抗体(效价:1∶128),放散液中存在头孢哌酮药物抗体。患者3:A型,RhCcDee,DAT阳性(4+),IAT阳性,鉴定为抗E抗体,血浆中存在阿莫西林药物抗体(效价:1∶16)、亚胺培南药物抗体(效价:1∶64)、头孢哌酮药物抗体(效价:1∶128),放散液中存在亚胺培南、头孢哌酮药物抗体。患者4:A型,RhCCDee,DAT阳性(1+),IAT阳性,鉴定为抗-E.c抗体,血浆中存在阿莫西林药物抗体(效价:1∶32),放散液中未检测到药物抗体。4例患者血浆与供者红细胞体外致敏24 h后DAT均为阳性,48和72 h内逐渐增强,加入补体后均可引起红细胞溶解。结论 头孢哌酮、阿莫西林和亚胺培南三种β-内酰胺类药物&抗体可迅速结合到供者红细胞表面并随时间延长而增强,有补体存在的条件下可在24~72 h内破坏供者红细胞引起溶血,导致输血无效。

【Abstract】 Objective To analyze the affinity of β-lactam drugs & antibodies in plasma of clinical patients to donor erythrocytes, and explore the clinical characteristics of drug-induced hemolytic anemia and ineffective transfusion. Methods From November 2021 to April 2022, 4 clinical patients with a history of β-lactam drug use were selected for detection of ABO and Rh blood group, direct antiglobulin test(DAT), irregular antibody identification(IAT) and β-lactam drug antibody and titer.Erythrocytes of DAT positive patients were dispersed with acid and β-lactam antibodies were detected in the dispersed solution.ABO, Rh isotype donor erythrocytes and patient plasma were sensitized in vitro under sterile conditions of 37 ℃. The affinity of β-lactam drugs & antibodies to donor erythrocytes at 0, 24, 48 and 72 h were monitored, and the degree of hemolysis after complement addition was observed. Results There were β-lactam antibodies in the plasma of 4 patients. Blood transfusion was ineffective before drug withdrawal, but the blood transfusion effect was good after drug withdrawal. Patient 1: type A,RhCCDee, DAT positive(3+W), IAT negative, cefoperazone drug antibody in plasma(titer:1∶64), amoxicillin drug antibody(titer:1 ∶ 16), cefoperazone drug antibody in the discharge fluid. Patient 2: type A, RhCcDee, DAT positive(4+W), IAT negative, cefoperazone drug antibody in plasma(titer:1∶128), cefoperazone drug antibody in the discharge fluid. Patient 3: type A, RhCcDee, DAT positive(4+), IAT positive, identified as anti-E antibody, amoxicillin drug antibody(titer:1∶16), imipenem drug antibody(titer:1∶64), cefoperazone drug antibody(titer:1∶128) in plasma, imipenem drug antibody and cefoperazone drug antibody. Patient 4: type A, RhCCDee,DAT positive(1+), IAT positive, identified as anti-E.c antibody and amoxicillin antibody was present in plasma(titer:1∶32), but no drug antibody was detected in the release fluid. After sensitization of plasma and donor erythrocytes in vitro for 24 h, DAT was positive in all the 4 patients, and it was gradually enhanced within 48 h and 72h. The addition of complement could cause erythrocyte lysis in all the 4 patients. Conclusion Cefoperazone, amoxicillin and imipenem were three β-lactam drugs & antibodies can bind to the surface of donor erythrocytes rapidly and enhance with time.In the presence of complement, they could destroy donor erythrocytes and cause hemolysis within 24 h to 72 h, resulting in ineffective transfusion.

【基金】 广东省医学基金(项目编号:B2020179);深圳市医学三名工程(项目编号:SZSM201811092);深圳市医学重点学科(项目编号:SZXK070)
  • 【文献出处】 现代检验医学杂志 ,Journal of Modern Laboratory Medicine , 编辑部邮箱 ,2023年01期
  • 【分类号】R457.1
  • 【下载频次】26
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