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Haemoglobinopathies
Ahmad Sh. Silmi
Msc Haematology, FIBMS
Hemoglobinopathy
definition
definition
An inherited mutation of the globin
genes leading to a qualitative or
quantitative abnormality of globin
synthesis
Structural hemoglobinopathy
Amino acid substitution in the globin
chain e.g. sickle hemoglobin (HbS)
Sickle Cell Anaemia
• Sickle cell anaemia (SCA) is the homozygous form
of the disease, in which the individuals inherits a
double dose of the abnormal gene that encodes
for haemoglobin S.
• Haemoglobin S is a tetramer composed of two αchains and two β-chains.
• The β -chains, however, are abnormal, containing
a valine instead of a glutamine at position 6.
• The structural formula for sickle cell anaemia (Hb
SS) is α 2 β 26 glu-val. The formula alternatively may
be written as α 2 β 2s or α 2 β 26 val.
Sickle Cell Anemia – blood film
Sickle Cells
Erythroblasts
Howell-Jolly Body
Pathophysiology
• Haemoglobin S is soluble and usually
causes no problem when properly
oxygenated.
• However, when the oxygen tension
decreases, haemoglobin S polymerizes
and forming fluid polymers.
• As these polymers realign, they cause the
characteristic sickle shape into the red
cells.
Sickle Cell
Anemia –
EM of red
cell
showing
‘tactoids’
Fibres of Sickle Hemoglobin
Fibres of Sickle Hemoglobin –
cross section
Factors Affecting Sicklling process
•
•
•
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The degree of oxygenation
PH
Dehydration of the patient
The concentration of other
types of haemoglobins.
(When these factors are decreases the sickling process is promoted.)
Pathophysiology
sicklling
Lower PH & Decrease
O2 tension &
increase sicklling
viscocity
promote further
sicklling
Slow blood
circulation
hypoxia
• All of this leads to hypoxia, painful crises, and infarction
of the organs.
• It should be noted that the presence of HbA and HbF
modify the degree, or the severity of sickling.
Clinical Picture
•
Symptoms of sickle cell anaemia are
seldom manifested before the age of 6
months when the level of circulating Hb
F falls to the adult level. Usually the
condition is characterized by a chronic
haemolytic state with jaundice and
relatively constant haemoglobin level of
7-8 g/dl.
Clinical Picture
Patients with sickle cell anaemia usually
manifest the following symptoms:
•
•
•
•
Stomach, arm, legs, and joint pain.
Tired, tense, and nervous.
Short trunk, ulcers in legs, thin arms
and tower-shaped head.
Enlarged liver and heart.
The Complication of Sickle Cell
Disease
• Acute Chest Syndrome - A serious
condition caused by infection or trapped
red blood cells in the lungs.
• Anemia (low red blood cell count)
• Aplastic Crisis - Temporary lack of
production of red blood cells.
• Bone Necrosis - Degradation of bone
tissue which can lead to hip replacements
and other complications.
The Complication of Sickle Cell
Disease (cont.’)
• Hand and Foot Syndrome - Painful swelling in the hands and
feet.
• Severe Infections - Sepsis (blood stream infection),
meningitis, and pneumonia. The risk of infection is increase
because the spleen does not function properly.
• Splenic Sequestration Crisis - The spleen is the organ that
filters blood. Rapid enlargement can result due to
entrapment of sickled cells in the spleen. This condition can
be life threatening.
• Stroke - Occurs when sickled cells create a blockage within
the brain. Signs include seizure, weakness in the arms and
legs, speech problems, and loss of consciousness.
Sickle cell trait
• Sickle cell trait is the heterozygous form of
the disease, represents a combination of
HbA and HbS. The structural formula is
α2β1 β16 glu-val.
• Individuals with HbS trait are usually
asymptomatic, but occasional haematuria
occurs as a complication of the disorder.
Factors promote sickling
•
•
The drastic lowering PH
Reduction in oxygen tension
These conditions are caused in:
•
•
•
•
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Sever respiratory infections.
Air travel in unpressurized aircraft
Anesthesia
Congestive heart failure.
Excessive exercise which leads to accumulation of
lactic acid.
Laboratory Findings
1.
Sickle cell anaemia
Normochromic normocytic anaemia with haemoglobin level
ranging between 6 and 8 g/dl. The peripheral blood can be
striking with:
•
•
•
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Numerous target cells
Fragmented red cells
Polychromasia and nucleated red cells
Sickle cells ( common)
Reticulocyte average count 5-20% but will reduce during
the aplastic crises.
Leukocytosis and thrombocytosis is common.
The bone marrow reflects a marked erythroid hyperplasia,
except during aplastic crises.
•
•
Screening Procedures
•
Solubility Test-Special tubes that precipitate the
abnormal haemoglobin S.
•
Sodium metabisulfite- an old screening test, in which
Na-metabisulfite induces sickling. It's important to
remember that some rare abnormal Hb's also sickle,
such as variants of HbC.
•
The definitive test is haemoglobin electrophoresis; the
patient with sickle cell anaemia produces no beta chain.
Thus, the result is:
Hb S = 80% and Hb F ranges from 1-20%. Increasing
haemoglobin F value is lowering the severity of the
disease. This is seen in newborns and in combination of
HbS with hereditary persistence of foetal haemoglobin
(HPFH). Haemoglobin A2 is slightly increased.
•
Sickle Cell Trait
• The peripheral blood smear is usually normal,
with the exception of target cells. Solubility
screening tests are positive. Haemoglobin
electrophoresis shows:
• Hb A = 60%, Hb S = 40%, Hb A2 usually
elevated.
• Sickle cells usually are not seen in peripheral
blood smear except during crises.
Treatment
• One of the most important measures in treating
sickle cell is to minimize the number of crises by
educating sufferers and their families about
circumstances, which may trigger sickling crises.
They should be advised to avoid sudden cold,
dehydration, hypoxic conditions, and infections.
• Hypertransfusion or even exchange transfusion
with normal blood can lower the proportion of
haemoglobin S sufficiently to reduce greatly the
incidence of sickling crises. This is most useful
as a short-term measure, for example in
pregnancy or before and during major surgery.