fetal health

Fetal Hemoglobin

Biological Role

In the red blood cells of the fetus it is possible to identify a form of hemoglobin different from the adult one.

  • From the structural point of view, the fetal hemoglobin (α 2 γ 2 ) differs from the adult one (α 2 Β 2 ) due to the presence of two gamma chains instead of the two alpha chain

    • In particular, fetal hemoglobin is formed by two α chains and two γ chains, consisting of 141 and 146 amino acids respectively. The two alpha chains are identical to those present in adult hemoglobin, while the gamma ones differ from Beta to 39 amino acids
  • This structural modification gives fetal hemoglobin an affinity for superior oxygen ; in other words, it binds to oxygen more tenaciously than adult hemoglobin

From a functional point of view, the fetal hemoglobin ( HbF or hemoglobin F ) allows the fetus to extract oxygen more effectively from maternal blood .

  • at the low PO 2 value of fetal blood, fetal hemoglobin can carry up to 20-30% more oxygen than the maternal one, as shown by the graph below; this is due to the lower affinity for 2, 3-bisphosphoglycerate compared to adult hemoglobin

The displacement towards the left of the dissociation curve of fetal hemoglobin compared to the adult one is observed

The transfer of oxygen to the fetal blood via the placental barrier is also favored by the higher concentration of hemoglobin, which is about 50% higher than that of maternal blood.

Normal values

The synthesis of fetal hemoglobin begins around the sixth week of gestation, and gradually replaces the embryonic hemoglobins Gower ( 2 ε 2 ), Gower II (α 2 ε 2 ), and Portland (ζ 2 γ 2 ), produced in the first weeks of conception.

Expression in time and in different tissues of different types of human globin chains.

Human globin chains are expressed as a percentage of hemoglobin in the total

The synthesis of Beta globins characterizing adult hemoglobin, barely perceptible during fetal life, reaches the normal regime only towards the end of the third month of extrauterine life.

  • at birth, fetal hemoglobin constitutes about 70-90% of the total hemoglobin present in the red blood cells of the newborn
  • the synthesis of fetal hemoglobin continues even after birth, but gradually decreases going to constitute less than 8% of all hemoglobin at the stroke of the six months of life
  • within the first year of life fetal hemoglobin concentrations fall to levels generally below 1%
  • normal adults have fetal hemoglobin values ​​between 0.3% and 1.2%, less than 3.5% of hemoglobin A2 (α2, δ2), and the remaining percentage (generally> 96%) covered by type A hemoglobin.

The different expression over time, from conception to adult life, of the different globin chains in humans depends on the activation and extinction of specific genes.

High Fetal Hemoglobin

Possible causes of high levels of fetal hemoglobin in the adult
GENETICACQUIRED
Hereditary persistence of fetal hemoglobinPregnancy
Sickle cell anemiaRecovery from bone marrow hypoplasia
Beta thalassemiaLeukemia, particularly chronic juvenile myeloid leukemia
Delta-Beta thalassemiaThyrotoxicosis
Unstable variants of the beta-globin chainHepatoma and choriocarcinoma

Pathological meaning

  • In the uterus, the normal fetus produces a small proportion of adult hemoglobin (2.5-5%). The fetus with thalassemia maior produces even less (less than 2%). To detect during pregnancy if a fetus is affected by thalassemia major, it is possible to determine the amount of adult hemoglobin present in a blood sample taken by cordocentesis.
  • A small percentage of fetal hemoglobin is also expressed during adult life and its levels can also vary greatly under the influence of factors such as age, sex or genomic peculiarities. Some subjects are affected by the so-called hereditary persistence of fetal hemoglobin, a benign condition in which important concentrations of fetal hemoglobin (> 10%) persist even in adulthood. It has been noted that this peculiarity, generally asymptomatic, can alleviate the severity of certain hemoglobinopathies and thalassemias.
  • A drug therapy capable of increasing the concentration of fetal hemoglobin brings significant benefits to some categories of patients, such as those suffering from sickle cell disease or Beta thalassemia. The prototype of these drugs was hydroxyurea, an antineoplastic drug with a myelosuppressive action, which proved to be effective in increasing fetal hemoglobin levels and reducing the incidence of painful crises in patients suffering from sickle cell disease.