Fetal hemoglobin and hemolysis markers in sickle cell anemia☆

It has been known for many years that high levels of fetal hemoglobin (Hb F) have an important clinical benefit in patients with sickle cell anemia (SCA). This knowledge was initially based on the observation that populations of Indian and Arabian SCA patients with high Hb F levels have a milder clinical form of the disease.1 Later on, epidemiological studies demonstrated that patients with Hb F levels above 20% had consistently lower rates of recurrent clinical events such as vaso-occlusive crises, acute chest syndrome and hospitalizations, and patients with Hb F levels above 10% had reduced occurrence of aseptic necrosis and strokes.2 A significant increase of 1.0 g/dL in hemoglobin levels in the high Hb F group was also noted, indicating a reduction in the rate of hemolysis.2 A study of life expectancy in sickle cell disease (SCD) patients demonstrated an improved survival of patients with Hb F levels above 8.6% and an increased risk of early death in patients with low Hb F levels.3 The presence of Hb F in red blood cells (RBCs) alters contact between RBCs with hemoglobin S (Hb S) and inhibits the formation of polymers in deoxygenated RBCs. Hb F is produced by a fraction of RBCs denominated F-cells, which contain variable concentrations of Hb F.4 Studies suggest that when F-cells contain around 10 pg of Hb F there is complete inhibition of polymer formation even when oxygen saturation is from 40% to 70%.5 F-cells are RBCs that have a much longer survival than non-F-cells, with their survival being related to their Hb F content: the higher the Hb F content the longer the life span of F-cells.6 The survival of non-F-cells is inversely correlated