Fetal Hemoglobin Decrease During Voxelotor Treatment.

Voxelotor modifies hemoglobin-oxygen affinity improving anemia and reducing hemolysis in sickle cell patients. However, the impact of Voxelotor on fetal hemoglobin (HbF) levels is unknown. We describe here variations of percentage of HbF measured by high performance liquid chromatography and mean corpuscular fetal Hb in a cohort of sickle cell patients treated with Voxelotor at Henri Mondor Sickle Cell Referral Center. Our data show a decrease in HbF levels in sickle cell patients after 6 months of treatment with Voxelotor, which is likely to be associated with an increase in the lifespan of red blood cells that are no longer prematurely removed from the circulation, particularly those with low HbF. This work raises the question of the risk of a rebound effect when stopping Voxelotor, which has a short half-life, during the time it takes to increase HbF.