fetalhemoglobin

Fetal hemoglobin (HbF) is the dominant form of hemoglobin in the fetus and newborns. It consists of two alpha and two gamma globin chains (α2γ2). HbF replaces the adult beta chains and differs from adult hemoglobin (HbA, α2β2). In healthy newborns, HbF makes up about 70–90% of total hemoglobin and declines after birth, usually falling below 2% by one year of age.

Genetics and regulation: The gamma-globin genes HBG1 and HBG2 encode the HbF gamma chains. A developmental switch from gamma to beta globin production occurs after birth, shifting hemoglobin from fetal to adult forms. The switch is governed by regulatory elements including BCL11A and the HBB gene cluster on chromosome 11; most adults maintain low HbF levels, though hereditary persistence of fetal hemoglobin (HPFH) can sustain higher levels.

Physiology and clinical relevance: HbF binds oxygen with higher affinity than HbA, facilitating fetal oxygen uptake from the maternal circulation and supporting tissue oxygenation in utero. Clinically, higher HbF reduces sickling in sickle cell disease and ameliorates anemia in beta-thalassemia, making HbF a target of therapy. In adults, induction of HbF is pursued with agents like hydroxyurea.

Measurement and therapy: HbF is measured as a percentage of total hemoglobin using electrophoresis, high-performance liquid chromatography (HPLC), or capillary electrophoresis. Therapies aimed at inducing HbF production, such as hydroxyurea, can improve outcomes in some patients with sickle cell disease or beta-thalassemia by increasing HbF levels. HPFH and related conditions illustrate the ongoing regulation of the HbF program.