高效液相色谱技术检测地中海贫血的临床价值

Clinical value of high performance liquid chromatography in detection of thalassemia

目的探讨高效液相色谱技术应用于α地贫、β地贫、αβ复合型地贫以及其它异常血红蛋白病诊断的临床价值。方法选择受检者1 872例进行地中海贫血基因检测,同时应用高效液相色谱法分析血红蛋白组分;根据基因检测结果将受检者分为α地贫、β地贫、αβ复合型地贫3个实验组以及对照组,计算Hb A2值对各实验组的诊断灵敏度、特异度、阳性预测值、阴性预测值和诊断准确率,进行对比分析、评价HPLC法对各类型地贫的诊断效能,同时结合高效液相色谱分析的峰型图谱对异常血红蛋白病进行诊断。结果 11 872例样本中,地贫基因携带者783例(α地贫508例,β地贫262例,αβ复合型地贫13例),非地贫基因携带者1 089例(对照组)。2高效液相色谱分析法对α地贫检测的灵敏度为28.3%(144/508)、特异度80.1%(872/1 089)、阳性预测值39.9%(144/361)、阴性预测值70.6%(872/1 236)和诊断准确率63.6%(1 016/1 597);对β地贫检测的灵敏度为97.3%(255/262)、特异度99.5%(1 084/1 089)、阳性预测值98.1%(255/260)、阴性预测值99.4%(1 084/1 091)和诊断准确率99.1%(1 339/1 351);对αβ复合地贫检测的灵敏度为100.0%(13/13)。3结合高效液相色谱分析的峰型图谱共诊断异常血红蛋白病7例,包括2例Hb J-Bangkok、2例Hb E、1例镰型红细胞贫血、1例Hb D、1例Hb Abruzzo。结论 HPLC法适用于临床对地中海贫血疾病的筛查,其中对β地贫的筛查效率好于α地贫;HPLC法在诊断地贫的同时对发现其他异常血红蛋白病也有重要的临床价值。

Objective To explore the clinical value of high performance liquid chromatography（ HPLC） in diagnosis of α- thalassemia,β- thalassemia,αβ composite type thalassemia,and other abnormal hemoglobin diseases. Methods A total of 1 872 patients underwent thalassemia gene detection,HPLC was used to analyze constituents of hemoglobin; the patients were divided into α- thalassemia group,β- thalassemia group,composite type group,and control group according to gene detection results; sensitivity,specificity,positive predictive value,negative predictive value,and accuracy of hemoglobin A2（ Hb A2） levels in α- thalassemia group,β- thalassemia group,and composite type group were calculated and compared; the diagnostic efficacy of HPLC for different types of thalassemia was evaluated;peak profile of HPLC was used to diagnose abnormal hemoglobin diseases. Results Among 1 872 patients,783 patients were thalassemia gene carriers,including 508 α- thalassemia gene carriers,262 β- thalassemia gene carriers,and 13 αβ composite type thalassemia gene carriers; 1 089 patients were not thalassemia gene carriers（ control group）. The sensitivity,specificity,positive predictive value,negative predictive value,and accuracy of HPLC for α- thalassemia were 28. 3%（ 144 /508）,80. 1%（ 872 /1 089）,39. 9%（ 144 /361）,70. 6%（ 872 /1 236）,and 63. 6%（ 1 016 /1 597）,respectively; the sensitivity,specificity,positive predictive value,negative predictive value,and accuracy of HPLC for β- thalassemia were 97. 3%（ 255 /262）,99. 5%（ 1 084 /1 089）,98. 1%（ 255 /260）,99. 4%（ 1 084 /1091）,and 99. 1%（ 1 339 /1 351）,respectively; the sensitivity of HPLC for αβ composite type thalassemia was 100. 0%（ 13 /13）. Combining with peak profile of HPLC,seven patients were diagnosed as abnormal hemoglobin diseases,including two patients with Hb J-Bangkok,two patients with Hb E,one patient with sickle cell anemia,one patient with Hb D,and one patient with Hb Abruzzo. Conclusion HPLC is suitable for thalassemia screening,the screening efficacy for β- thalassemia is better than α- thalassemia; HPLC has important clinical value for diagnosing other abnormal hemoglobin diseases at the same time of diagnosing thalassemia.