Hemoglobin (Hb), Fetal, Quantitative

Whole blood

1 mL

0.5 mL (Note: This volume does not allow for repeat testing.)

Lavender-top (EDTA) tube

Fasting or fluid restriction is not necessary.

Evaluate hemoglobinopathies, hemolytic anemia; diagnose hereditary persistence of fetal hemoglobin; diagnose thalassemia; evaluate sickling hemoglobins

Capillary electrophoresis (CE)

See table.

Fetal hemoglobin is formed of two α-chains and two γ-chains. It is the major hemoglobin during fetal life. Hb F levels decrease after birth by about 3% to 4% per week. In two to three weeks, fetal hemoglobin is about 65%. By six months of age, fetal hemoglobin is <2% of the total hemoglobin. See graph. The oxygen dissociation curve of Hb F is shifted to the left as compared with normal Hb A. This may be due to decreased binding of 2,3-DPG by Hb F (γ-chains). This facilitates placental oxygen transfer. With erythroblastosis fetalis and anoxic states of the newborn; however, Hb F is proportionally lower than in a normal newborn. Some 15 inherited abnormalities of γ-chain structure have been described¹ but most are without clinical significance (fetal Hb normally forms <2% of total hemoglobin). An exception is Hb F Poole, which has been reported as a cause of hemolytic disease of the newborn.²

In the adult, hereditary persistence of fetal hemoglobin (HPFH) of multiple varieties is associated with varying elevations of Hb F. The homozygous form of HPFH is found only in black individuals. In the heterozygous state, the Hb F level is 15% to 35% in the black type, and 5% to 20% in the Greek type. Homozygous β-thalassemia is associated with Hb F levels <10% to >90%. About 50% of heterozygotes for β-thalassemia have elevated levels around 2%, rarely >5%. The remainder have normal Hb F. Heterozygous S/β-thalassemia may have Hb F in the 5% to 20% range. With homozygous Hb S disease, the level of Hb F varies from 0% to 20%.³ Other conditions associated with elevated Hb F include various anemias: spherocytosis, Fanconi, acquired aplastic, hemolytic hypoplastics, megaloblastic, myelophthisic, and untreated pernicious anemia; all types of leukemia (especially erythroleukemia and juvenile chronic myelogenous leukemia), multiple myeloma and lymphomas, metastatic disease of the bone marrow; pregnancy; miscellaneous disorders reported include infants small for gestational age, infants with chronic intrauterine anoxia with developmental anomalies; during anticonvulsant drug therapy; diabetes; hyper- and hypothyroidism; and macroglobulin. Elevation of Hb F should, then, raise the question of possible underlying disease.