Iron incorporation in red blood cells of pediatric sickle cell anemia: a stable isotope pilot investigation

Abstract

Sickle cell anemia (SCA) is marked by hypoxia, inflammation, and secondary iron overload (IO), which potentially modulate hepcidin, the pivotal hormone governing iron homeostasis. The aim was to evaluate the iron incorporation in red blood cells (RBC) in SCA pediatric patients, considering the presence or absence of IO. SCA children (n = 12; SCAtotal) ingested an oral stable iron isotope (57Fe) and iron incorporation in RBC was measured after 14 days. Patients with ≥1000 ng/mL serum ferritin were considered to present IO (SCAio+; n = 4) while the others were classified as being without IO (SCAio−; n = 8). Liver iron concentration (LIC) was determined by Magnetic Resonance Imaging (MRI) T2* method. The SCAio+ group had lower iron incorporation (mean ± SD: 0.166 ± 0.04 mg; 3.33 ± 0.757%) than SCAio− patients (0.746 ± 0.303 mg; 14.9 ± 6.05%) (p = 0.024). Hepcidin was not different between groups. Iron incorporation was inversely associated with serum ferritin level (SCAtotal group: r = −0.775, p = 0.041; SCAio− group: r = −0.982; p = 0.018) and sickle hemoglobin (HbS) presented positive correlation with iron incorporation (r = 0.991; p = 0.009) in SCAio− group. LIC was positively associated with ferritin (SCAtotal: r = 0.921; p = 0.026) and C reactive protein (SCAio+: r = 0.999; p = 0.020). SCAio+ group had lower iron incorporation in RBC than SCAio− group, suggesting that they may not need to reduce their intake of iron-rich food, as usually recommended. Conversely, a high percentage of HbS may indirectly exacerbate hypoxia and seems to increase iron incorporation in RBC. This trial was registered at www.ensaiosclinicos.gov.br . Identifier RBR-4b7v8pt.