Compound heterozygosity for hemoglobin S and D: what do we need to know?

Abstract

Hemoglobinopathies are among the most common hereditary blood diseases worldwide and are considered a public health problem in some regions. In Brazil, hemoglobin S (Hb S) has a variable frequency between different regions mainly due to the ethnic composition of local populations. Due to the multiethnic characteristics of the Brazilian people, some regions reflect scenarios that allow us to consider the inheritance of the symptomatic forms of Hb S, namely sickle cell disease (SCD) a serious public health problem. These clinically significant forms include the homozygous inheritance of Hb S – sickle cell anemia (Hb SS), inheritance with thalassemia, especially beta thalassemia (Hb S/beta thalassemia) and compound heterozygotes in which Hb S is inherited in combination with another hemoglobin variant; the most common in Brazil are Hb SC and Hb SD. The application of accurate laboratory methodologies associated to routine techniques such as electrophoresis and high pressure liquid chromatography (HPLC) along with hematologic information and family data are essential for the correct identification of SCD and, consequently, adequate clinical and family guidance that can guarantee a promising prognosis. However, the differentiation between Hb SS and the Hb SD profile is not possible by simple tests such as electrophoresis in alkaline pH as, in these conditions, the migrations of the variants overlap. Additional methods are needed to elucidate this double heterozygosity. Automated systems such as capillary electrophoresis, HPLC cation exchange, isoelectric