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 24 year old woman

 Hypochromic, microcytic anaemia
 Iron tablets
 Marries, delivers son
 3 months old – pale, jaundiced, distended abdomen,
spindly limbs, frontal bossing
 Haemoglobin 3!!!
Patient’s CBC
 WBC 5.46 (Ref. range: 4-10)
 RBC 6.22 (Ref. range: 5.5-8.5)
 Hb 10.4 (Ref. range: 12-15)
 MCV 62.1 (Ref. range: 80-100)
 Plt 198 (Ref. range: 150-450)
 Transports oxygen from lungs to tissues
 Located in red cells
 2 pairs of identical subunits, globin chains: α chain cluster – α, ζ
chains, β chain cluster – βδγε
 Embryonic - α2ε2, ζ2ε2, ζ2ɣ2 – 3rd to 10th week gestation
 Foetal – HbF, α2ɣ2 – during pregnancy
 Adult – HbA, α2β2 (98%) α2δ2 (2%)
Globin Genes
 α gene cluster – chromosome 16
 Β gene cluster – chromosome 11
 A heterogeneous group of disorders of haemoglobin synthesis
 Results from decreased production of 1 or more globin chains
which form adult haemoglobin (HbA, α2β2)
 Decreased filling of red cells with haemoglobin and anaemia
 Alpha
 Beta
Globin Chain Synthesis

Mediterranean basin

South-East Asia
Pathophysiology of Alpha Thalassaemia
 Decreased production of alpha polypeptide
chains due to deletion of one or more genes
 Disease classified based on the number of
 Alpha + thalassaemia – Loss of a single gene on one
 Alpha 0 thalassaemia – Loss of both genes on the
same chromosome
Clinical Presentation
Clinical features vary based on the degree of normal haemoglobin
# of α-globin Genotype Haemoglobin Clinical Picture
genes deleted type

4 --/-- Hb Barts (α4) Hydrops fetalis

3 --/-α HbH (α4) Moderate-severe


2 -α/-α or --/αα HbA Mild anaemia

Some HbH bodies

1 αα/-α HbA Very mild anaemia;

Pathophysiology of Beta Thalassaemia
 Decreased production of beta polypeptide chains due to either
mutations or deletion of the beta globin gene
 Results in partial (β + allele) or total loss (β 0 allele) of beta
globin function
 Three types:
 Minor (Beta thalassaemia trait)-heterozygous state; usually
 Intermedia- multiple genotypes; moderate anaemia
 Major (Cooley’s anaemia)-homozygous state; severe anaemia
Clinical Presentation

 Classified based on the degree of impairment of β globin production

 MINOR- asymptomatic; mild anaemia
 INTERMEDIATE- symptomatic moderate anaemia; splenomegaly, bone
deformities, recurrent leg ulcers, gallstones and infections
 MAJOR (Cooley’s anaemia)- presentation within the first year of life with:
 Failure to thrive and recurrent bacterial infection
 Severe anaemia from 3-6 months
 Hepatosplenomegaly and bone expansion  the classical thalassaemic
 CBC – microcytic anaemia
 Peripheral smear – nucleated erythroblasts, target cells,
hypochromic, microcytic RBCs, punctate and diffuse basophilia
 HB Electrophoresis
 DNA testing – prenatal diagnosis
 Bone marrow aspiration- erythroid hyperplasia
Work-up cont’d
 X-ray (skull)- cortical thinning, marrow space widening, areas of
 X-ray (vertebral bodies)- granular or ground glass appearance
Establishing the
 Long-term folic acid supplements
 Blood transfusion
 Suppresses abnormal haematopoesis
 Splenectomy – decreases transfusion requirements for patients
on chronic transfusion
 Iron chelation therapy (standard: desferrioxamine)
 Adjunctive ascorbic acid aids to increase urinary iron excretion
 Curative: allogeneic stem cell transplantation
 Prenatal and gene therapy
 Beta thalassaemia minor; Alpha thalassaemia minor- normal life
 HbH and beta thalassaemia intermedia- varies
 Beta thalassaemia major- usually decreased due to
complications of chronic transfusions
Complications of Iron Overload
Iron overload
(capacity of serum transferrin to bind iron is exceeded)

Non transferrin-bound iron (NTBI) circulates in the plasma

Excess iron promotes free Insoluble iron complexes

radicals, propagate oxygen deposit in the body; end-organ
related tissue damage toxicity occurs
• Cardiac failure • Infertility
• Liver cirrhosis/fibrosis/cancer • Growth failure
Kumar, P. and Clark, M. (2012). Kumar & Clark's clinical medicine. 1st ed. Edinburgh [u.a.]: Saunders, Elsevier.

MSD Manual Professional Edition. (2017). Thalassemias - Hematology and Oncology - MSD Manual
Professional Edition. [online] Available at:
oncology/anemias-caused-by-hemolysis/thalassemias [Accessed 30 Mar. 2017

Vranken, M. (2017). Evaluation of Microcytosis - American Family Physician. [online] Available at: [Accessed 30 Mar. 2017].

Walker, B., Colledge, N., Ralston, S., Penman, I. and Britton, R. (n.d.). Davidson's principles and practice of
medicine. 1st ed.

Essential Haemaology- Multiple Choice Questions. N.p., 2017. Web. 30 Mar.2017
Question 1
Diagnosis of Beta Thalassaemia is established by:
B. Presence of target cells on peripheral smear
C. Hb electrophoresis
D. HbA1C estimation
Question 2
Which ONE of the following is not a feature of thalassaemia
A. It may be due to homozygous β0 thalassaemia
B. It may be associated with splenomegaly
C. It may be associated extramedullary haematopoiesis
D. It may cause iron overload
Question 3
Which one of these statements is TRUE about β-thalassaemia major?
A. The major cause of death is liver failure
B. It requires iron chelation at diagnosis
C. It is usually caused by deletion of β globin genes
D. It may diagnosed antenatally
Question 4
Which ONE of these statements is TRUE about β-thalassaemia major?
A. It presents at birth
B. It is caused by a defect in globin synthesis
C. It is associated with splenomegaly
D. It is associated with an increased risk of bone infarction
Question 5
Which ONE of the following is NOT TRUE about α-thalassaemia?
A. It may cause haemoglobin H disease
B. It causes a microcytic, hypochromic blood picture
C. It ameliorates β-thalassaemia
D. It is a cause of hydrops fetalis
E. It is rare except in the Far East