Objectives: To explore the roles of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and hemoglobin A(2) (HbA(2)) 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 Obstetrics 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 HbA(2). 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 HbA(2) alone, combination of MCV and MCH, and combination of MCV, MCH and HbA(2).
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 A(2) alone was 67.4% (275/408) for α thalassemia, 97.5% (593/608) for β thalassemia, and 100% (20/20) for αβ 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 HbA(2) > 3.5% it had a high value in β-thalassemia screening, but when HbA(2) < 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 HbA(2). MCV + MCH was the best for overall screening, but for β thalassemia screening, MCV + MCH + HbA(2) 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.