2. DEFINITION
Hemoglobinopathies are disorders affecting the structure, function or
production of hemoglobin.
These conditions are usually inherited and range in severity from
asymptomatic laboratory abnormalities to death in utero.
Different forms may present as ineffective erythropoiesis, hemolytic anemia,
erythrocytosis, cyanosis or vaso-occlusive stigmata.
3. • All inherited hemolytic anemias are due to intracorpuscular defects except for Familial
hemolytic uremic syndrome (HUS) .
• All acquired hemolytic anemias are due to extracorpuscular defects except for PNH.
4. PROPERTIES OF HUMAN HEMOGLOBINS
HEMOGLOBIN STRUCTURE:
Hemoglobin consists of tetramer of
globin polypeptide chains:
A pair of α like chains – 141 amino acids
A pair of β like chains – 146 amino acids
TYPES:
Adult hemoglobin HbA - α2β2
Fetal hemoglobin HbF - α2γ2
Minor adult hemoglobin HbA2 - α2δ2
6. FUNCTION OF HEMOGLOBIN
To support oxygen transport, hemoglobin must bind O2
efficiently at the partial pressure of oxygen of the alveolus,
retain in the circulation and release it at the tissues at the pO2
of the tissue capillary beds.
At low oxygen tensions, the hemoglobin tetramer is fully
deoxygenated. Oxygen binding begins slowly as oxygen tension
rises.
However, as soon as some oxygen has been bound by the
tetramer, an abrupt increase occurs in the slope of the curve
Thus hemoglobin molecules that have bound some oxygen
develop a higher oxygen affinity, greatly accelerating their
ability to combine with more oxygen.
2.BOHR EFFECT: the ability of hemoglobin to deliver more
oxygen to tissues at low pH
7. 3. 2,3- BISPHOSPHOGLYCERATE
• The major small molecule that alters oxygen
affinity in humans is 2,3-BPG, which lowers
oxygen affinity when bound to hemoglobin.
• HbA has a reasonably high affinity for 2,3-BPG.
• HbF does not bind 2,3-BPG, so it tends to have
a higher oxygen affinity in vivo.
• Normal oxygen transport thus depends on the
tetrameric structure of the proteins, the
arrangement of hydrophilic and hydrophobic
amino acids, and interaction with protons or
2,3-BPG
8. • After 8 weeks of fetal life the embryonic
hemoglobin, Gower-1 (ζ2ε2), Gower-2
(α2ε2), and Portland (ζ2γ2) are formed.
• At 9 weeks of fetal life, the major
hemoglobin is HbF.
• The switch to nearly exclusive synthesis of
adult hemoglobin occurs at about 38
weeks.
• Fetuses and newborns therefore require α
globin but not β globin for normal
gestation
DEVELOPMENT OF HEMOGLOBIN
9. • A few red cell clones called F cells are the progeny of a small pool of
immature committed erythroid precursors (BFU-e) that retain the ability to
produce HbF.
• Profound erythroid stresses, such as severe hemolytic anemias, bone
marrow transplantation, or cancer chemotherapy, cause more of the F-
potent BFU-e to be recruited.
• HbF levels thus rise in some patients with sickle cell anemia or thalassemia
10. EPIDEMIOLOGY:
• Hemoglobinopathies are common in areas in which malaria are endemic.
• Very young children with alpha thalassemia are more susceptible infection with non lethal
plasmodium vivax.
• It might favour protection against infection with the more lethal Plasmodium falciparum.
INHERITANCE AND ONTOGENY:
Hemoglobinopathies are autosomal codominant traits.
DIAGNOSIS:
Diagnosis is best established by recognition of a characteristic history, physical findings,
peripheral blood smear morphology, and abnormalities of CBC.
