MCV、MCH和血红蛋白A2检测在地中海贫血筛查中的价值

The value of MCV, MCH and HbA2 in laboratory screening of thalassemia

目的 探讨平均红细胞体积（MCV）、平均红细胞血红蛋白（Hb）含量（MCH）及HbA2等3项指标在地中海贫血（地贫）筛查中的价值,以及临床不同情况下地贫筛查的最佳策略.方法 选择2008年9月-2011年5月南方医科大学南方医院妇产科及内科门诊进行地贫筛查和地贫基因诊断的受检者1384例,其中1036例确诊地贫基因携带者为地贫组（包括α地贫408例、β地贫608例、αβ复合型地贫20例）；348例确诊非地贫基因携带者为非地贫组.所有受检者均进行了血液学表型指标筛查,并分别对单独应用MCV、MCH和HbA2作为地贫筛查指标、MCV＋ MCH联合应用作为地贫筛查指标以及MCV＋ MCH＋ HbA2联合筛查在两组受检者中诊断地贫的灵敏度、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.结果 （1）地贫组MCV筛查的灵敏度分别为：α地贫92.9％ （379/408）；β地贫99.3％（ 604/608）；αβ复合型地贫100.0％（ 20/20）.非地贫组MCV的特异度为75.0％ （261/348）.（2）地贫组MCH筛查灵敏度分别为：α地贫92.9％（ 379/408）；β地贫99.0％ （602/608）；αβ复合型地贫100.0％ （20/20）.非地贫组MCH特异度为72.7％ （253/348）.（3）地贫组HbA2筛查的灵敏度分别为：α地贫67.4％（ 275/408）,β地贫97.5％ （593/608）,αβ复合型地贫100.0％ （20/20）；非地贫组HbA2的特异度为72.4％（ 252/348）.（4）单独以MCV、MCH或MCV＋MCH为表型筛查指标,而以HbA2作为地贫分型结果显示,HbA2＞ 3.5％作为β地贫的分型标准对临床有重要指导意义,而以HbA2＜2.5％作为α地贫的分型标准则有较高的假阴性率.（5）MCV、MCH和HbA2单独作为地贫筛查指标时,MCV和MCH的灵敏度、特异度、阳性预测值、阴性预测值和诊断符合率均高于HbA2.结论 MCV、MCV＋MCH及MCV＋MCH＋HbA23种不同的地贫筛查策略中,MCV＋MCH的初筛效果最优；而MCV＋ MCH＋ HbA2在β地贫筛查中效果最优.但针对MCV和MCH筛查阳性的孕妇,可直接行α及β地贫基因诊断.

Objectives To explore the roles of mean corpuscular volume（MCV）,mean corpuscular hemoglobin（MCH） and hemoglobin A2 （HbA2） in the laboratory screening of thalassemia,and to find optimal screening modality for different conditions.Methods From September 2008 to May 2011,1384 subjects underwent thalassemia screening at Department of Obstertrics and Gynecology of Nanfang Hospital.Of them,1036 cases were diagnosed with thalassemia （408 α-thalassemia,608 β-thalassemia,and 20 αβ compound thalassemia,thalassemia group） and 348 without thalassemia,non-thalassemia group.All subjects were screened respectively for MCV,MCH and HbA2.Analyses were performed in all subjects to assess the sensitivity,specificity,positive predictive value,negative predictive value and diagnostic accuracy respectively associated with MCV,MCH and HbA2 alone,combination of MCV and MCH,and combination of MCV,MCH and HbA2.Results （ 1 ） In the thalassemia group,the sensitivity of MCV alone was 92.9% （379/408） for α thalassemia,99.3% （604/608） for β thalassemia and 100.0% （20/20） for αβ compound thalassemia.In the non-thalassemia group,the specificity of MCV alone was 75.0% （261/348）.（2） In the thalassemia group,the sensitivity of MCH alone was 92.9% （379/408） in α thalassemia,99.0% （602/608） in β thalassemia and 100.0% （20/20） in αβ compound thalassemia.In the non-thalassemia group,the specificity of MCH alone was 72.7 % （253/348）.（3） The sensitivity of Hb A2 alone was 67.4% （275/408） for α thalassemia,97.5% （593/608） for 3 thalassemia,and 100% （20/20） for α3 compound thalassemia while it＇s specificity was 72.4% （252/348） in the non-thalassemia group.（4）With positive indexes of MCV,MCH and MCV ＋ MCH,when HbA2 〉 3.5% it had a high value in [β-thalassemia screening,but when HbA2 〈 2.5% it had little value in α-thalassemia screening.（5） As a single marker,MCV and MCH had better sensitivity,specificity,positive predictive value,negative predictive value and diagnosis accuracy than HbA2.MCV ＋ MCH was the best for overall screening,but for [β thalassemia screening,MCV ＋ MCH ＋ HbA2 was the best.Conclusions MCV and MCH are suitable for epidemic screening in a large population,physical examination and premarital check-up.Hb electrophoresis and thalassemia gene diagnosis are recommended for subjects with positive MCV and MCH indexes.Diagnoses of α and β-thalassemia gene are recommended for pregnant women with positive MCV and MCH indexes.