万古霉素致非霍奇金淋巴瘤患儿免疫性溶血及凝血功能障碍分析

Analysis of immune hemolysis and coagulation dysfunction induced by Vancomycin in children with non-Hodgkin′s lymphoma

目的探讨万古霉素对非霍奇金淋巴瘤患儿免疫性溶血和凝血功能的影响,为诊断和治疗万古霉素所致溶血性贫血和凝血功能障碍提供依据,指导儿童合理用药。方法选取2018年1月至2019年1月首都医科大学附属北京儿童医院单纯使用万古霉素的非霍奇金淋巴瘤患儿31例,采集其使用万古霉素后1周内的血浆,微柱凝胶法检测万古霉素抗体,并分析用药前后溶血性贫血及凝血功能相关实验室诊断指标。根据资料性质采用组内配对样本t检验进行统计学分析。结果31例患儿中,14例万古霉素抗体阳性,其中10例直接抗人球蛋白试验(DAT)阳性。万古霉素抗体阳性患儿用药后红细胞计数(RBC)[(2.75±0.07)×10^(12)/L]、血小板计数(PLT)[(64.29±14.87)×10^(9)/L]、红细胞比容(HCT)[(23.02±0.83)%]与用药前RBC[(3.18±0.07)×10^(12)/L]、PLT[(91.36±16.84)×10^(9)/L]、HCT[(29.19±1.98)%]相比均明显下降(均P<0.01);用药后总胆红素(TB)[(51.96±15.52)μmol/L]、结合胆红素(DB)[(31.30±13.98)μmol/L]、未结合胆红素(IB)[(21.81±2.89)μmol/L]、乳酸脱氢酶(LDH)[(208.6±16.85)U/L]与用药前TB[(39.34±13.40)μmol/L]、DB[(26.38±12.61)μmol/L]、IB[(13.75±1.63)μmol/L]、LDH[(60.93±16.00)U/L]相比均显著上升(均P<0.05);用药后凝血酶原时间(PT)[(13.94±0.58)s]、部分凝血活酶时间(APTT)[(36.01±2.64)s]与用药前PT[(11.66±0.30)s]、APTT[(28.09±0.98)s]相比均显著延长(均P<0.01),用药后国际标准化比值(INR)(1.25±0.05)与用药前(1.05±0.02)相比明显增大(P<0.0001);万古霉素抗体阴性的患儿除了用药后PT[(12.99±0.35)s]比用药前[(11.82±0.27)s]延长,用药后INR(1.18±0.03)比用药前(1.07±0.03)增高(均P<0.01)外,其他上述指标无显著变化。结论万古霉素抗体可能导致患儿免疫性溶血及凝血功能障碍。用药过程中应结合临床症状及时检测药物抗体和实验室指标,防止药物抗体导致严重不良反应的发生。

Objective To explore the effect of Vancomycin on immune hemolysis and coagulation in children with non-Hodgkin′s lymphoma(NHL),thus providing the basis for the diagnosis and treatment of hemolytic anemia and coagulation dysfunction caused by Vancomycin,and guiding the rational use of drugs in children with NHL.Methods From January 2018 to January 2019,31 children with NHL treated with monotherapy of Vancomycin in Beijing Children′s Hospital,Capital Medical University were collected.Plasma samples within 1 week of Vancomycin medication were collected for detecting the anti-Vancomycin antibody by microcolumn gel method.The laboratory diagnostic and coagulation function indexes of hemolytic anemia before and after Vancomycin medication were analyzed using the paired sample t test.Results Fourteen out of 31 children with NHL were positive for the anti-Vancomycin antibody,and among them,10 cases had positive direct antiglobulin test(DAT).In NHL children with positive anti-Vancomycin antibody,their red blood cell count(RBC)[(2.75±0.07)×10^(12)/L vs.(3.18±0.07)×10^(12)/L],platelet count(PLT)[64.29±14.87)×10^(9)/L vs.(91.36±16.84)×10^(9)/L]and hematocrit(HCT)[(23.02±0.83)%vs.(29.19±1.98)%]were significantly reduced after Vancomycin medication than those before treatment(all P<0.01).On the contrary,total bilirubin(TB)[(51.96±15.52)μmol/L vs.(39.34±13.40)μmol/L],direct bilirubin(DB)[(31.30±13.98)μmol/L vs.(26.38±12.61)μmol/L],indirect bilirubin(IB)[(21.81±2.89)μmol/L vs.(13.75±1.63)μmol/L]and lactate dehydrogenase(LDH)[(208.6±16.85)U/L vs.(60.93±16.00)U/L]in them were significantly enhanced after Vancomycin medication than those before treatment(all P<0.05).Prothrombin time(PT)[(13.94±0.58)s vs.(11.66±0.30)s]and partial thromboplastin time(APTT)[(36.01±2.64)s vs.(28.09±0.98)s]were significantly prolonged in them after vancomycin medication than those before treatment(all P<0.01).A higher international normalized ratio(INR)(1.25±0.05 vs.1.05±0.02)was detected in NHL children with positive anti-Vancomycin antibody after medication(P<0.0001).In NHL children with negative anti-Vancomycin antibody,significantly higher PT(12.99±0.35)s vs.(11.82±0.27)s and INR(1.18±0.03 vs.1.07±0.03)were detected after Vancomycin medication(all P<0.0001),while other indexes were similar before and after treatment.Conclusions The anti-Vancomycin antibody may cause immune hemolysis and coagulation dysfunction in children with NHL.In order to prevent serious adverse events caused by drug antibodies,comprehensively clinical symptoms should be considered,drug antibodies and laboratory test results should be detected.