中国深圳地区孕妇毛细管血红蛋白电泳筛查地中海贫血截断值的探讨

Analysis of Cut-off Value in Screening of Thalassemia by Capillary Hemoglobin Electrophoresis for Pregnant Women from Shenzhen Region of China

目的:了解深圳地区孕妇毛细管血红蛋白电泳筛查地中海贫血的截断值(cut-off值)。方法:回顾性研究2122例产前检查的孕妇毛细管血红蛋白电泳结果与α-和β-地中海贫血基因结果。每个孕妇都抽血做血红蛋白电泳和α-、β-地中海贫血基因检测,用Capillarys 2型全自动毛细管电泳仪进行血红蛋白电泳,采用gap-PCR方法对α基因、反向斑点杂交法对β基因进行基因诊断。通过受试者工作曲线确定筛查地中海贫血的截断值,并以确定的截断值分析Hb A2和Hb F在地中海贫血筛查中的应用价值。结果:Hb A2诊断α-、β-地中海贫血携带者曲线下面积(AUC^(Roc))分别为0.75和0.981,Hb F诊断β-地中海贫血携带者AUC^(Roc)为0.787。Hb A2≤2.55作为诊断α-地中海贫血携带者的最佳临界值时敏感度、特异度、阳性似然比、阴性似然比分别为89.5%、54.8%、1.98、0.19;Hb A2≥3.9作为诊断β-地中海贫血携带者的最佳临界值时敏感度、特异度、阳性似然比、阴性似然比分别为96.1%、99.8%、480.5、0.04;HbF≥0.75作为诊断β-地中海贫血携带者的最佳临界值时敏感度、特异度、阳性似然比、阴性似然比分别为83.6%、61.8%、2.19、0.27。结论:Capillarys 2型全自动毛细管电泳仪在地中海贫血筛查中Hb A2和Hb F的截断值与传统的血红蛋白电泳方法如醋酸纤维薄膜、琼脂糖凝胶电泳不同,实验室应建立各自的截断值。

Objective:To investigate the cut-off value in screening of thalassemia in pregnant women from Shenzhen region by capillary hemoglobin electrophoresis.Methods:The data of capillary hemoglobin electrophoresis and genetic diagnosis of thalassemia from 2122 examined prenatal women were retrospectively analyzed.Capillary hemoglobin electrophoresis and α-,β- genetic diagnosis of thalassemia were carried out for every woman.Hemoglobin electrophoresis was performed using Capillarys 2 full-auto mated electrophoresis instrument.Gap polymerase chain reaction and reverse dot blot were used for genetic diagnosis of thalassemia genotyping test.The cut-off value in screening of thalassemia was determined by receiver operating characteristic curve and next to analyze the value of HbA2 and HbF in screening of thalassemia using the decided cut-off value.Results:The areas under the curve(AUCRoc) of HbA2 for diagnosis of α-,β- thalassemia were 0.75 and 0.981 respectively,and the AUCRoc of HbF for diagnosis of β-thalassemia was 0.787.When HbA2≤2.55 was taken as the cut-off value of HbA2 for diagnosis of α-thalassemia,the sensitivity,specificity positive likelihood ratio（LR+） and negative likelihood ratio（LR） were 89.5%,54.8%,1.98,0.19 respectively.When HbA2 ≥ 3.9 was taken as the cut off value of HbA2 for diagnosis of β-thalassemia,the sensitivity,specificity,LR+ and LR- were 96.1%,99.8%480.5,0.04,respectively.When HbF ≥0.75 was taken as the cut off value of HbF for diagnosis of β-thalassemia,the sensitivity,specificity,LR+ and LR- were 83.6%,61.8%respectively.Conclusion:The cut-off value in screening of thalassemia by capillarys 2 full automated electrophoresis instrument is different from that of the traditional method of hemoglobin electrophoresis,such as cellulose acetate membrane electrophoresis and agarose gel electrophoresis.Each laboratory should establish their own respective cut off value.