LAUSR

The WHO estimates that more than 270 million individuals are carriers of thalassemia. Each year, 500 000 births are registered with a thalassemia gene or a hemoglobin variant. Eighty percent of those are born in developing countries, 83% concern sickle-cell disease, and 17% severe thalassemias [1]. Identification of hemoglobinopathies is easier to perform by routine hematological or biochemical tests than by DNA analysis [2]. When routine test is abnormal, additional investigations might be needed for definitive diagnosis and DNA analysis required in cases of risk assessment [3]. Identification of carriers for thalassemias and other hemoglobinopathies associates determination of red cell indices with qualitative and quantitative analysis of Hb fractions. Microcytosis with mean cellular volume (MCV) < 80 fL, hypochromia with mean cellular hemoglobin (MCH) < 27 pg, and a relatively elevated RBC count suggest either a thalassemia mutation or a structural variant with thalassemic effects, such as Hb E (b26 Glu > Lys) or Hb Knossos (b27 Ala > Ser). Abnormal findings on the complete blood count (CBC) should prompt additional testing [4]. As the most common Hb variants (Hb S and Hb C) present usually with normocytic indices, an analysis of the Hb fractions should always be performed together with CBC specially in populations with high prevalence of these traits. During the second year of life, HbA2 is raised in most carriers of b-thalassemia to values between 4% and 8%. Low or borderline values (3.2–3.9%) in a microcytic patient may indicate iron depletion or ‘normal HbA2 bthalassemia’ conditions. Levels higher than 8% may indicate Hb Lepore or Hb E requiring further investigation. Several methods are available for HbA2 testing, but the two most frequently used are automated high performance liquid chromatography (HPLC) and capillary electrophoresis (CE). While measurement of HbA2 is essential for routine identification of b-thalassemia carriers, DNA analysis is needed to characterize the mutation[4]. Often more information is required for interpretation of the hematological condition and should be considered: (i) iron studies to exclude iron-deficiency anemia [e.g., measurement of serum iron transferrin, ferritin, or zinc-protoporphyrin (ZnPP)], (ii) recent blood transfusion (3 months), (iii) ethnic origin, (iv) clinical history, (v) drug therapy (e.g., hydroxyurea, antiretroviral drugs).