受试者工作特征曲线分析在地中海贫血筛查中的应用价值  

Clinical significance of receiver operating characteristic curve analysis in the screening of thalassemia

作　　者：夏超然[1] 黄英[1] 任兆瑞[1] XIA Chaoran;HUANG Ying;REN Zhaorui(Shanghai Institute of Medical Genetics; Shanghai Children’s Hospital, Shanghai Jiao Tong University School of Medicine; Key Lab of Medical Embryo Molecular Biology; Ministry of Health, and Shanghai Lab of Embryo and Reproduction Engineering, Shanghai 200040, China)

机构地区：[1]上海交通大学附属儿童医院,上海市儿童医院,上海交通大学医学遗传研究所,卫生部医学胚胎分子,生物学重点实验室,上海市胚胎与生殖工程重点实验室,上海200040

出　　处：《临床儿科杂志》2017年第5期340-344,共5页Journal of Clinical Pediatrics

基　　金：国家科技支撑计划资助项目(No.2012BAI09B04)

摘　　要：目的用受试者工作特征(ROC)曲线评价胎儿血红蛋白(Hb F)和HbA_2在儿童地中海贫血筛查和诊断中的临床应用价值。方法分别采用经典法(醋纤法和Singer一分钟碱变性实验)和高效液相法(HPLC)对经基因检查确诊的200例地贫患儿和62例正常对照者进行Hb F和HbA_2定量检测。以基因检测结果为金标准,采用ROC曲线分析法,分析Hb F、HbA_2曲线下面积(AUC)以及选择不同切值对应的灵敏度和特异度,确定可行性筛查方案。结果α-和β-地中海贫血组中,HPLC法定量Hb F、HbA_2值的AUC均大于对应的经典方法定量结果的AUC;β-地中海贫血组中,HPLC法定量HbA_2对应的AUC最大,为0.991。采用ROC曲线法分析得到的截断值,Hb F(≥1.05%)、HbA_2(≥3.75%)组成的联合筛查方案的诊断符合率、灵敏度、特异度可分别达到99.2%、99.0%和100.0%。结论在进行大规模β-地中海贫血筛查时,采用HPLC定量的截断值Hb F(≥1.05)、HbA_2(≥3.75)与血液学有关指标联合的筛查方案可提高筛查的灵敏度、符合率和筛查效率。Objective The aim of this study was to evaluate the application of receiver operating characteristic(ROC)curve ofbiochemical indexes of blood for HbF and HbA2on the screening and diagnosis of thalassemia in children.Methods The traditionalmethods(cellulose acetate membrane electrophoresis and single one minute alkaline denaturation)as well as HPLC were used toquantitatively detecting HbF and HbA2in200thalassemic cases and62normal controls.With DNA analysis as a golden standardfor thalassemia diagnosis,ROC was applied to evaluate the indicators of HbF and HbA2including areas under the curve(AUC),sensitivity and specificity after different cut-off values chosen.Results Inα-andβ-thalassemia groups,all of AUC of HbF andHbA2quantified by HPLC were higher than that detected by the classical method.In theβ-thalassemia group,the AUC of HbA2quantified by HPLC showed the greatest value(0.991).The coincidence rate,sensitivity and specificity of the combined screeningscheme of the cut-off value HbF(≥1.05%)and HbA2(≥3.75%)analyzed by ROC were99.2%,99.0%,and100%,respectively.Conclusions It is suggested that the combined screening scheme,the cut-off value of HbF(≥1.05)and HbA2(≥3.75)measured by HPLC,together with the related hematological indexes,may be applied to the large-scale screening ofβ-thalassemia.This scheme can improve the sensitivity,coincidence rate and screening efficiency.The internal quality control for the detectiveprocess ensured the accuracy and reliability of the results,and reduced the misdiagnosis rates.

关 键 词：地中海贫血 受试者工作特征曲线 筛查指标 血红蛋白 

分 类 号：R725.5[医药卫生—儿科]