目的 用受试者工作特征(ROC)曲线评价胎儿血红蛋白(HbF)和HbA2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HbF和HbA2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 HbF、HbA2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HbF、HbA2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HbA2对应的AUC最大,为0.991。采用ROC曲线法分析得到的截断值,HbF(≥1.05%)、HbA2(≥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HbF(≥1.05)、HbA2(≥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 of biochemical indexes of blood for HbF and HbA2 on the screening and diagnosis of thalassemia in children. Methods The traditional methods (cellulose acetate membrane electrophoresis and single one minute alkaline denaturation) as well as HPLC were used to quantitatively detecting HbF and HbA2 in 200 thalassemic cases and 62 normal controls. With DNA analysis as a golden standard for thalassemia diagnosis, ROC was applied to evaluate the indicators of HbF and HbA2 including areas under the curve (AUC), sensitivity and specificity after different cut-off values chosen. Results In α- and β-thalassemia groups, all of AUC of HbF and HbA2 quantified by HPLC were higher than that detected by the classical method. In the β-thalassemia group, the AUC of HbA2 quantified by HPLC showed the greatest value (0.991). The coincidence rate, sensitivity and specificity of the combined screening scheme of the cut-off value HbF (≥1.05%) and HbA2 (≥3.75%) analyzed by ROC were 99.2%, 99.0%, and 100%, 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 of β-thalassemia. This scheme can improve the sensitivity, coincidence rate and screening efficiency. The internal quality control for the detective process ensured the accuracy and reliability of the results, and reduced the misdiagnosis rates.