The significance of the hemoglobin A(2) value in screening for hemoglobinopathies.
OBJECTIVE
The inherited hemoglobinopathies are a large group of disorders that include thalassemias and hemoglobin variants. Accurate determination of the carrier phenotype is essential for detecting couples at risk for producing offspring with hemoglobinopathy. Heterozygous beta-thalassemia is usually silent at the clinical level. His phenotype is characterized by microcytosis and hypochromia with increased hemoglobin A(2) (HbA(2)) value. Therefore, HbA(2) determination plays a key role in screening programs for hemoglobinopathy. The aim of this review is to address and suggest an approach for reducing or abolishing hemoglobinopathy screening mistakes.


METHODS
Quantitative methods for HbA(2) value determination, comment on the accuracy of the test and on the interpretation of data were discussed. The most probable diagnostic conclusion based on the HbA(2) level, hemoglobin pattern, hematological parameters and iron markers was suggested in this review.


RESULTS
Hemoglobinopathies are the only genetic disease where it is possible to detect carriers using hematological findings rather than DNA analysis. However, hematological diagnosis is sometimes presumptive, and in these cases, DNA analysis becomes necessary. Complete screening is based on the detection of red cell indices, HbA(2), HbF and hemoglobin variant values. In particular, HbA(2) determination plays a key role in screening programs for beta-thalassemia because a small increase in this fraction is one of the most important markers of beta-thalassemia heterozygous carriers.


CONCLUSIONS
Genetic factors both related and unrelated to the beta- and alpha-globin gene clusters, iron metabolism, endocrinological disorders, and some types of anemia, together with intra- and inter-laboratory variations in HbA(2) determination, may cause difficulties in evaluating this measurement in screening programs for hemoglobinopathies. Therefore, knowledge of all these issues is important for reducing or eliminating the risk of mistakes in screening programs for hemoglobinopathies.
Giambona
Antonino
A
U.O.C. Ematologia II con Talassemia, Azienda Ospedaliera Vincenzo Cervello, via Trabucco 180, 90146 Palermo, Italy. giambic@libero.it
Passarello
Cristina
C
Renda
Disma
D
Maggio
Aurelio
A
D005820:Genetic Testing; D006443:Hemoglobin A2 / Q000032:analysis*; D006453:Hemoglobinopathies / Q000175:diagnosis* / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D010641:Phenotype
D006443:Hemoglobin A2