血红蛋白电泳联合地中海贫血基因检测对地中海贫血的早期诊断价值

Value of hemoglobin electrophoresis combined with thalassemia gene detection in early diagnosis of thalassemia

目的分析血红蛋白电泳联合地中海贫血(地贫)基因检测对地中海贫血的早期诊断价值,并探讨血红蛋白A2(Hb A2)在不同类型地中海贫血早期诊断中的应用价值。方法选取2021年7月1日至2021年7月30日于广东省鹤山市人民医院就诊的疑似地中海贫血患者208例作为研究对象。将血红蛋白电泳筛查结果为阳性的标本进一步进行地贫基因检测,并根据地贫基因检测结果进行分组,比较各组血红蛋白指标。通过全自动毛细血管血红蛋白电泳分析Hb A2水平,绘制受试者工作曲线(ROC)评估Hb A2在不同类型地中海贫血早期诊断中的价值。结果血红蛋白电泳筛查208例疑似地中海贫血的患者,结果显示,阳性例数共50例(24.03%,50/208),其中疑似α-地中海贫血41例(82.00%,41/50),疑似β-地中海贫血9例(18.00%,9/50)。将50例血红蛋白电泳呈阳性患者进一步进行地贫基因检测,结果显示,确诊为地中海贫血28例(56.00%,28/50),其中α-地中海贫血20例(71.42%,20/28),与血红蛋白电泳筛查符合率为48.78%;β-地中海贫血确诊为8例(28.57%,8/28),与血红蛋白电泳筛查符合率为88.88%。将地贫基因检测结果为阳性的28例地中海贫血分为α-地中海贫血组20例[静止型α-地中海贫血17例,中间型α-地中海贫血3例]与β-地中海贫血组8例[轻型β-地中海贫血6例,其他2例],并将地贫基因检测结果为阴性的22例作为阴性对照组。分别比较各组血红蛋白指标,发现β-地中海贫血组Hb A2高于阴性对照组、α-地中海贫血组(P<0.05);α-地中海贫血组、β-地中海贫血组血红蛋白F均高于阴性对照组(P<0.05);阴性对照组血红蛋白A高于α-地中海贫血组、β-地中海贫血组,但差异未见统计学意义(P>0.05)。Hb A2指标在诊断静止型、轻型、中间型α-地中海贫血和轻型β-地中海贫血的AUC分别为0.708、0.834、0.957、0.987;最佳截断值为2.83%、2.60%、2.20%、3.43%;敏感度为48.16%、72.66%、95.31%、99.30%;特异度为83.33%、83.70%、92.90%、96.90%。结论血红蛋白电泳联合地贫基因检测可提高非地中海贫血的排除率及地中海贫血的检出率,尤其是β-地中海贫血在血红蛋白电泳检出率更高,且Hb A2指标对诊断中间型α-地中海贫血和轻型β-地中海贫血准确性高,可用于早期诊断地中海贫血。

Objective To analyze the significance of hemoglobin electrophoresis combined with thalassemia gene detection in the early diagnosis of thalassemia,and to investigate the application value of hemoglobin A2(HBA2)in the early diagnosis of different types of thalassemia.Methods A total of208 patients with suspected thalassemia treated in Heshan People’s Hospital of Guangdong Province from July 1,2021 to July 30,2021 were selected as the research objects.The samples with positive hemoglobin electrophoresis screening results were further tested for thalassemia gene,grouped according to the results of thalassemia gene test,and the hemoglobin indexes of each group were compared.The level of HBA2 was analyzed by automatic capillary hemoglobin electrophoresis,and the receiver operating curve(ROC)was drawn to evaluate the value of HBA2 in the early diagnosis of different types of thalassemia.Results The 208 patients with suspected thalassemia were screened by hemoglobin electrophoresis.The results showed that there were 50 positive cases(24.03%),including 41 cases(82.00%)of suspected thalassemiaα-Thalassemia,and 9 cases(18.00%)of suspectedβ-Thalassemia.The 50 patients with positive hemoglobin electrophoresis were further tested for thalassemia gene.The results showed that 28 cases(56.00%)were diagnosed as thalassemia,20 cases(71.42%)were diagnosed asα-Thalassemia,and the coincidence rate with hemoglobin electrophoresis screening was 48.78%;β-Thalassemia was diagnosed in 8 cases(28.57%),and the coincidence rate with hemoglobin electrophoresis screening was 88.88%.The 28 cases of thalassemia with positive thalassemia gene test were divided intoα-Thalassemia group:20 cases(17 cases of stationary typeα-Thalassemia,3 cases of intermediate typeα-Thalassemia),β-Thalassemia group:8 cases(mildβ-Thalassemia was found in 6 cases and the others were found in 2 cases),and 22 cases with negative thalassemia gene test results were used as the negative control group.The hemoglobin indexes of each group were compared.The level ofβ-HBA2 in thalassemia group was higher than that in negative control group andα-Thala ssemia group(P<0.05).The levels ofβ-HbF inα-Thalassemia group andβ-Thalassemia group were higher than those in negative control group(P<0.05).The level of HbA in negative control group was higher than that inα-Thalassemia group andβ-Thalassemia group,but the differences were not significant(P>0.05).HBA2 index was used in the diagnosis of static type,light type and intermediate typeα-Thalassemia and mildβ-thalassemia.The AUCs were 0.708,0.834,0.957 and 0.987 respectively;the best cut-off values are 2.83%,2.60%,2.20%and 3.43%;the sensitivity was 48.16%,72.66%,95.31%and 99.30%;the specificity was 83.33%,83.70%,92.90%and 96.90%.Conclusions Hemoglobin electrophoresis combined with thalassemia gene detection can improve the exclusion rate of non thalassemia and the detection rate of thalassemia,especiallyβ-Thalassemia has a higher detection rate in hemoglobin electrophoresis,and HBA2 index has high accuracy for the diagnosis of intermediate typeα-Thalassemia and mildβ-Thalassemia,and can be used for early diagnosis of thalassemia.