Vamifeport induced iron-restricted erythropoiesis with reduced hemoglobin (Hb) concentration in RBCs of HbSS mice. (A) Administration of vamifeport (60 mg/kg) twice daily (BID) for 6 weeks in 6- to 7-week-old HbSS mice resulted in iron-restricted erythropoiesis, as shown by decreased CHCM, mean corpuscular hemoglobin (MCH), MCV, hematocrit, and total Hb without lowering RBC counts. (B) Likewise, reticulocyte counts remained stable with marked reductions in reticulocyte Hb and spleen size. (C) RBC scatterplots revealed a significant increase in the proportion of hypochromic and microcytic RBCs after vamifeport treatment. Results are presented as individual values with mean ± standard deviation (n = 6-8 mice per group). Analysis was performed by using one-way analysis of variance with Dunnett’s multiple comparison of all groups vs the HbSS vehicle group: *P < .05, **P < .01, ***P < .001.