Sickle cell Anemia & thalassemia

SICKLE-CELL
ANAEMIA &
THALASSAEMIAS
Dr Akshay Shetty
Asst. Professor
SSRAMCH INCHAL

Contents
Objectives
Introduction of
Sickle-cell
Anaemia
Epidemiology
of Sickle-cell
Anaemia
Pathogenesis of
Sickle-cell
Anaemia
Clinical features
of Sickle-cell
Anaemia
Investigations
of Sickle-cell
Anaemia
26/05/2020 Sickle-cell Anemia & Thalassemia (Dr Akshay Shetty) 3

Contd…
Introduction
of
Thalassemia
Types of
Thalassemia
Alpha-
thalassaemia
Beta-
thalassaemia
Summary References

Objectives
By the end of the presentation the students must be able to---
• Discuss Introduction of Sickle-cell Anaemia
• State Epidemiology of Sickle-cell Anaemia
• Explain Pathogenesis of Sickle-cell Anaemia
• Enumerate Clinical features of Sickle-cell Anaemia
• Quote Investigations of Sickle-cell Anaemia
• Discuss Introduction of Thalassemia
• Classify Types of Thalassemia
• Discuss Alpha-thalassaemia
• Discuss Beta-thalassaemia

Introduction of Sickle-
cell Anaemia
• Sickle-cell disease results from a single glutamic acid
to valine substitution at position 6 of the beta globin
polypeptide chain.
• It is inherited as an autosomal recessive trait.
• Homozygotes only produce abnormal beta chains that
make haemoglobin S (HbS, termed SS), and this
results in the clinical syndrome of sickle-cell disease.
• Heterozygotes produce a mixture of normal and
abnormal beta chains that make normal HbA and HbS
(termed AS), and this results in the clinically
asymptomatic sickle trait.

Epidemiology of Sickle-cell
Anaemia
• The geographical distribution of sickle-cell anaemia and
the other common haemoglobinopathies.
• The greatest prevalence of haemoglobinopathies occurs
in tropical Africa, where the heterozygote frequency is
over 20%.
• In black American populations, sickle-cell trait has a
frequency of 8%.
• Individuals with sickle-cell trait are relatively resistant to
the lethal effects of falciparum malaria in early
childhood.

Contd..

Pathogenesis of Sickle-cell
Anaemia
• When haemoglobin S is deoxygenated, the molecules of
haemoglobin polymerise to form pseudocrystalline structures
known as 'tactoids’.
• These distort the red cell membrane and produce
characteristic sickle-shaped cells.
• The polymerisation is reversible when reoxygenation occurs.
• The distortion of the red cell membrane, however, may
become permanent and the red cell 'irreversibly sickled’.

Contd…
• The greater the concentration of sickle-cell
haemoglobin in the individual cell, the more easily
tactoids are formed, but this process may be
enhanced or retarded by the presence of other
haemoglobins.
• Thus haemoglobin C participates in the
polymerisation more readily than haemoglobin A,
whereas haemoglobin F strongly inhibits
polymerisation

Clinical features of Sickle-cell Anaemia

Investigations of Sickle-cell
Anaemia
• The blood film shows sickle cells, target cells and
features of hyposplenism.
• A reticulocytosis is present.
• The presence of HbS can be demonstrated by exposing
red cells to a reducing agent such as sodium dithionite;
HbA gives a clear solution, whereas HbS polymerises to
produce a turbid solution.
• The definitive diagnosis requires haemoglobin
electrophoresis to demonstrate no HbA, 2-20% HbF and
the predominance of HbS.

Introduction of Thalassemia
• Thalassaemia is an inherited impairment of
haemoglobin production, in which there is partial or
complete failure to synthesise a specific type of globin
chain.
• In alpha-thalassaemia, the alpha genes are deleted; loss
of one gene (α-/α) or both genes (α-/α-) from each
chromosome 16 may occur, in association with the
production of some or no alpha globin chains.
• In beta-thalassaemia defective production usually
results from disabling point mutations causing no (β0) or
reduced (β-) beta chain production.

Types of Thalassemia
Alpha-thalassaemia
Beta-thalassaemia

Alpha-thalassaemia
• The reduction or absence of alpha-chain synthesis is
common in Southeast Asia.
• There are two alpha gene loci on chromosome 16 and
therefore four alpha genes. If one is deleted there is
no clinical effect.
• If two are deleted there may be a mild hypochromic
anaemia.
• If three are deleted the patient has haemoglobin H
disease and if all four are deleted the baby is stillborn
(hydrops fetalis).

Contd…
Age and sex
incidence Both sexes from birth onward
Genetics
Two alpha-chain genes from each parent
Presentation
• Hydrops fetalis if all genes deleted
• Haemoglobin H if three genes deleted
• Mild hypochromic microcytic anaemia if two genes
deleted

Beta-thalassaemia
• Failure to synthesise beta chains (beta-thalassaemia) is
the most common type of thalassaemia and is seen in
highest frequency in the Mediterranean area.
• Heterozygotes have thalassaemia minor, a condition in
which there is usually mild anaemia and little or no
clinical disability.
• Homozygotes (thalassaemia major) either are unable to
synthesise haemoglobin A or at best produce very little
and, after the first 4 months of life, develop a profound
hypochromic anaemia.

Contd…
Major
• Profound hypochromic anaemia
• Evidence of severe red cell dysplasia
• Erythroblastosis
• Absence or gross reduction of the amount of
haemoglobin A
• Raised levels of haemoglobin F
• Evidence that both parents have thalassaemia minor

Contd…
Minor
• Mild anaemia
• Microcytic hypochromic erythrocytes (not iron-deficient)
• Some target cells
• Punctate basophilia
• Raised resistance of erythrocytes to osmotic lysis
• Raised haemoglobin A2 fraction
• Evidence that one parent has thalassaemia minor

Summary
Pathogenesis & Clinical
features of Sickle-cell
Anaemia
Investigations of Sickle-cell
Anaemia
Introduction of Thalassemia
Types of Thalassemia
Alpha-thalassaemia
Beta-thalassaemia
Introduction &
Epidemiology of
Sickle-cell Anaemia

References
• Davidson Principles Of Medicine & Practice Of
Medicine .20th Ed.

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Sickle cell Anemia & thalassemia

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