Table 1.

Terminology.

(HbA, α2β2): consists of 2 α-globin and 2 β-globin chains and is the most common human hemoglobin tetramer, accounting for about 97% of the total red blood cell hemoglobin in adulthood

(HbF, α2γ2): consists of 2 α-globin and 2 γ-globin chains. This is the predominant form in the fetus and declines in the first weeks after birth

(HbS, α2βS2): consists of 2 α-globin and 2 mutant β-globin chains. HbS is the most common type of hemoglobin variant and the basis of sickle cell trait and sickle cell anemia

Sickle cell disease is caused by the presence of HbS, and includes different sickle genotypes classified according to the hemoglobin abnormality:

HbSS: homozygous mutation in β-globin (Glu to Val at position 6)

HbSC: compound heterozygotes of HbS (Glu to Val at position 6 and Glu to Lys at position 6)

HBS/β thal: compound heterozygotes of HbS with beta thalassemia, the latter can be either beta zero or beta plus, depending on whether beta globin is absent of present but in reduced amounts, respectively

Other less common sickle genotypes include compound heterozygotes of HbS with HbD Punjab (HbSD Punjab) and HbS with HbE (HbSE)

HbAS refers to heterozygotes or carriers of the HbS mutation: these individuals have HbS of 30%–40% and are asymptomatic. Under extreme conditions, such as physically stressful sports and severe dehydration, HbAS individuals may suffer vaso-occlusive episodes and pain. HbAS individuals are protected against falciparum malaria and can pass the mutant allele to their children

HbA = hemoglobin A; HbD = hemoglobin D; HbE = hemoglobin E; HbF = hemoglobin F; HbS = hemoglobin S; HbSC = hemoglobin SC; HbSS = hemoglobin SS.