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

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。

Objective To analyze the affinity ofβ-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 ofβ-lactam drug use were selected for detection of ABO and Rh blood group,direct antiglobulin test(DAT),irregular antibody identification(IAT)andβ-lactam drug antibody and titer.Erythrocytes of DAT positive patients were dispersed with acid andβ-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 ofβ-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 wereβ-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 threeβ-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.