Introduction:
Hemoglobin (Hb) is a type of protein present in the red blood cells (RBCs) of the body. This is responsible for transporting oxygen in the body through the blood. It picks up the oxygen in the lungs and then transports it through the blood. This is a tetrameric protein, which means it has a quaternary structure of four subunits and a heme group attached to each subunit. In the fetus, hemoglobin is slightly different because it picks up the oxygen in the placenta from the mother’s hemoglobin and has a different structure as compared to adult hemoglobin.
What Are the Types of Hemoglobin?
The normal types of hemoglobin include -
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Hemoglobin A (HbA) - This is the most common type of hemoglobin seen in adults. Adult hemoglobin (HbA) has two alpha and two beta subunits.
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Hemoglobin F (HbF, Fetal Hemoglobin) - This type of hemoglobin is commonly found in unborn babies (fetuses) and newborns, and it gets replaced soon after the birth into adult hemoglobin. Fetal hemoglobin has two alpha and two gamma subunits.
If the levels of both HbA and HbF are high or low. This indicates a certain type of anemia.
The abnormal types of hemoglobin include -
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Hemoglobin C (HbC) - This type of hemoglobin is not able to carry oxygen efficiently and may lead to a mild form of anemia.
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Hemoglobin E (HbE) - This type of hemoglobin is mostly found in people of Southeast Asian origin. People with this type of hemoglobin usually have no symptoms of anemia or may only show mild symptoms.
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Hemoglobin S (HbS) - This type of hemoglobin is usually found in patients with sickle cell anemia. This is a type of inherited disorder that leads to the abnormal formation of red blood cells into a sickle shape, which may get stuck in the blood vessels, causing severe pain, infections, and other various complications.
What Is Fetal Hemoglobin?
Fetal hemoglobin (HbF) is a type of hemoglobin that is commonly found during fetal life and can be markedly increased in concentration for many weeks, even after birth. This hemoglobin was first found by E. von Korber in 1866. The structure of this hemoglobin is different from adult hemoglobin, as the gamma subunits present in HbF contain either alanine or glycine proteins, which are nonpolar amino acids. This change in structure causes several physiological differences in oxygen delivery that are critical in fetal circulation.
What Is the Function of Fetal Hemoglobin?
Fetal hemoglobin has a stronger oxygen affinity as compared to adult hemoglobin. This factor helps in increasing the transport of oxygen to the fetus inside the uterus by capturing the oxygen from the placenta, a temporary organ that grows in the uterus during pregnancy, and helps in providing oxygen and nutrients to a growing baby. The decline in the production of fetal hemoglobin can be seen later on after six months of birth, leading to a reduction in the exchange of oxygen between the blood vessels and other parts of the body.
What Are the Effects of Fetal Hemoglobin at the Cellular Level?
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High Affinity With Oxygen - Fetal hemoglobin plays a critical role in transporting oxygen by taking oxygen from the mother’s body. The transfer of oxygen from maternal to fetal circulation is only possible due to the high affinity for oxygen and decreased affinity to 2,3-bisphosphoglycerate, which is related to adult hemoglobin.
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Oxygen Dissociation Curve - In the oxygen dissociation curve, it can be found that the partial pressure of fetal hemoglobin with oxygen is 19 mm Hg compared to 27 mm Hg in the case of adult hemoglobin. This clearly shows that HbF has a high affinity for oxygen, thus increasing its high binding capacity with oxygen.
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Low Affinity - HbF has a low affinity for 2,3-bisphosphoglycerate (2,3-DPG), which is the opposite in adult hemoglobin. This molecule is responsible for unloading oxygen from the blood cells, which ultimately leads to a low affinity for oxygen in adult hemoglobin and vice-versa in fetal hemoglobin.
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Fetal Hematocrit - Hematocrit means the ratio of the volume of red blood cells to the total volume of blood. In the case of fetal circulation, the fetal hematocrit (15g/dL) is higher than that in the mother (12g/dL), leading to inducing a higher potential for oxygen content per liter of blood.
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Lower Oxygen Tension - This factor helps in fetal systemic circulation and helps in the proper unloading of oxygen, which helps in the development of the fetus.
What Are the Normal Fetal Hemoglobin Levels?
The normal blood fetal hemoglobin levels are -
What Conditions Cause Increased Levels of Fetal Hemoglobin?
The levels of fetal hemoglobin can be increased by some inherited (genetic) or acquired conditions, which include -
Genetic Conditions -
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Beta thalassemia (blood disorder causing reduced production of hemoglobin because of decreased synthesis of the hemoglobin subunit beta).
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Delta-beta thalassemia (caused by decreased production (or total absence) of delta- and beta-globin).
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Hereditary persistence of fetal hemoglobin (HPFH - a benign condition causing fetal hemoglobin production even into adulthood).
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Sickle cell disease (abnormally shaped red blood cells).
Acquired Conditions -
1. Developmental -
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Prematurity.
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Children of diabetic mothers.
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Trisomy 13 (Patau syndrome - condition with extra 13 chromosomes, three instead of two).
2. Increased Erythropoiesis (Production of RBCs) -
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After critical blood loss.
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Acute hemolysis (destruction of RBCs).
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After iron replacement for severe iron deficiency.
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During chemotherapy.
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Transient erythroblastopenia of childhood (TEC - slowly developing form of anemia in early childhood).
3. Inherited Bone Marrow Failure Syndromes -
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Fanconi anemia (genetic blood disorder affecting all types of blood cells).
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Diamond-Blackfan anemia (inherited blood disorder affecting the ability of the bone marrow to produce red blood cells).
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Shwachman-Diamond syndrome (disorder causing bone-marrow failure).
4. Malignancies -
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Juvenile myelomonocytic leukemia (JMML - a rare blood cancer affecting young children).
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Adenocarcinoma of the lung (cancer of glandular tissue).
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Hepatoma (cancer of liver cells).
Which Test Can Be Done to Determine Fetal Hemoglobin Levels?
Some of the following methods can be used to determine the HbF levels such as -
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Kleihauer Test or Acid Elution Test - This is used to check the quantity of fetal hemoglobin transmitted from a fetus to a mother's bloodstream.
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Flow Cytometry - In this technique, a laser is used to detect and examine the chemical and physical attributes of cells or particles.
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Electrophoresis - In this test, an electric current is applied to a blood sample, which separates the normal and abnormal types of hemoglobin.
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Alkali Denaturation Method - This test is used to differentiate fetal blood from maternal blood.
Conclusion:
Fetal hemoglobin plays a vital role in the development of the child. The increased or decreased levels of fetal hemoglobin can help determine the various medical conditions in the body. Various methods exist to check the levels of this hemoglobin and to differentiate it from other abnormal forms of hemoglobin. Currently, multiple studies are going on to develop drugs to increase the level of HbF in conditions with low HbF production.
