HbF

HbF, or fetal hemoglobin, is the predominant form of hemoglobin in the fetus and newborns. It is an α2γ2 tetramer, consisting of two alpha (α) and two gamma (γ) globin chains, encoded by genes in the beta-globin gene cluster on chromosome 11. In contrast, most adult hemoglobin (HbA) is α2β2, containing beta chains. HbF has a higher intrinsic oxygen affinity than HbA.

The higher oxygen affinity of HbF is due in part to its reduced interaction with 2,3-bisphosphoglycerate (2,3-BPG), which normally decreases HbA’s affinity for oxygen. This allows HbF to sequester oxygen more effectively from the mother’s blood across the placenta, supporting fetal development in a relatively low-oxygen environment. After birth, HbF levels decline as gamma-globin expression wanes and beta-globin production increases, giving rise to predominantly HbA.

Developmental regulation and clinical relevance are closely linked. HbF is the major hemoglobin during fetal life and typically constitutes up to 75% of total hemoglobin at birth, dropping to less than 1–2% in healthy adults. Some individuals retain higher HbF levels throughout life, a condition known as hereditary persistence of fetal hemoglobin (HPFH). Clinically, elevated HbF can lessen the severity of sickle cell disease and beta-thalassemia by inhibiting HbS polymerization or compensating for deficient beta-globin production. Treatments such as hydroxyurea aim to increase HbF production, and research explores gene-based strategies to reactivate gamma-globin expression.

Laboratory assessment of HbF is common in newborn screening and hemoglobin analysis, often quantified by HPLC or capillary electrophoresis. Normal adult HbF levels are low, whereas newborns have substantially higher HbF which gradually declines with age.