Survival of F-reticulocytes in sickle cell disease

Fetal hemoglobin, Hb F, is known to be an important factor for clinical course of sickle cell disease, as it suppresses polymerization of sickle hemoglobin. To investigate the effect of Hb F on the survival of sickle reticulocytes (young red cells) in circulation, Hb F levels in individual reticulocytes and mature erythrocytes were quantified via fluorescence image cytometry. We first examined unfractionated SS cells from 3 patients with different Hb F levels, and found that Hb F levels in reticulocyte populations were always lower than those in erythrocyte populations. This suggests that subsets of reticulocytes with lower Hb F levels are removed during maturation while those with higher Hb F levels tend to survive to become erythrocytes. The distribution of Hb F in reticulocytes was different among these patients and seems to strongly affect the survival of F-reticulocytes. We also analyzed density-separated fractions, and found that Hb F levels in reticulocytes found in the densest fraction were lower than those in lighter fractions. This suggests that reticulocytes with lower Hb F levels are susceptible to quick dehydration within their maturation period (1-2 days) in circulation.