Fetal hemoglobin (α₂γ₂) (HbF)

Fetal hemoglobin (HbF, α₂γ₂) is the principal hemoglobin in the fetus and newborn, responsible for oxygen transport before the switch to adult hemoglobin (HbA) after birth. Unlike adult hemoglobin, HbF has a higher affinity for oxygen, facilitating efficient transfer of oxygen from the mother to the fetus via the placenta. HbF levels rapidly decrease in the first year of life, but certain genetic disorders (such as hereditary persistence of fetal hemoglobin, sickle cell anemia, or beta-thalassemia) can result in persistently elevated levels. Increased expression of HbF in adults with these diseases can markedly ameliorate symptoms by inhibiting sickling in sickle cell disease or reducing ineffective erythropoiesis in thalassemia. Therapeutic strategies are now targeting the reactivation of HbF by modulating key regulatory genes like BCL11A, or with drugs like hydroxyurea, to provide disease-modifying benefits, particularly in sickle cell disease.

Other names

Fetal haemoglobinHemoglobin Fα₂γ₂HbF

Therapeutic agents act by increasing HbF expression, either pharmacologically (e.g., hydroxyurea) or genetically (e.g., downregulating BCL11A to derepress γ-globin genes)