【摘要】 目的确定高效液相色谱法(HPLC)检测血红蛋白A2(HbA2)诊断β-地中海贫血(β地贫)携带者的最佳阈值,以提高HbA2作为β地贫携带者诊断指标的应用价值,减少漏诊与误诊。方法以反向点杂交技术(RDB)为金标准方法,将近两年来已确诊的1007例β地贫携带者和606例正常对照采用HPLC检测HbA2的结果按不同阈值界定的范围分为真阳性、假阳性、真阴性和假阴性,并评估出敏感度、特异度、阳性似然比、阴性似然比、尤登(Youden)指数等评价指标,同时绘制受试者工作特征曲线(ROC),确定HPLC诊断β地贫携带者HbA2的最佳阈值。结果以HbA2≥4.0%作为HPLC诊断β地贫携带者的阈值时,其敏感度为99.21%,特异度为99.34%,阳性似然比为150.30,阴性似然比为0.008,尤登指数为0.99,其中尤登指数优于其它阈值,且对应的切点在ROC曲线上最靠近左上方。结论HbA2≥4.0%为HPLC诊断β地贫携带者的最佳阈值,其敏感度与特异度的综合评价性能最理想,诊断试验的真实性最好。更多还原

【Abstract】 Objective To determine the best threshold value of hemoglobin A2 (HbA2) for diagnosis of β-thalassemia (β-thal) carriers by using high performance liquid chromatography (HPLC), and to improve the application value of HbA2 as a diagnostic index for β-thal carriers to reduce the rates of missed diagnosis and misdiagnosis. Methods Using reverse dot blot (RDB) as a gold standard method, HbA2 results of 1 007 β-thal carriers and 606 normal controls in the past two years determined by HPLC were divided into true positive, false positive, true negative, and false negative based on the different threshold values of HbA2 results. Then, the evaluation indexes such as sensitivity, specificity, positive and negative likelihood ratio, and Youden’s index were evaluated. Next, the receiver operator characteristic (ROC) curve was drawn to determine the best threshold value of HbA2 for diagnosis of β-thal carriers by HPLC. Results If ≥ 4.0% was taken as the threshold value of HbA2 for diagnosis of β-thal carriers by HPLC, the evaluation indexes values were shown as follows: sensitivity 99.21%, specifi city 99.34%, positive likelihood ratio 150.30, negative likelihood ratio 0.008, and Youden’s index 0.99. The Youden’s index was better than the other threshold values, and the corresponding tangent point was the peak point of the ROC curve. Conclusion When ≥ 4.0% serves as the best threshold value of HbA2 for diagnosis of β-thal carriers using HPLC, integrated evaluation performance of the corresponding sensitivity and specifi city is the most ideal, and the authenticity of the diagnostic test is the best.更多还原