Thalassaemia

Question 1

What is Thalassaemia?

Answer 1

The reduced production or failure to produce one of the globin chains required to make Hb, which can result in anaemia

Note:

• alpha-thalassaemia relates to alpha-globin
• beta-thalassaemia relates to beta-globin

Question 2

What may Thalassaemia be protective against?

Answer 2

Malaria

Question 3

Which people is alpha-thalassaemia most prevalent in?

Answer 3

Mediterraean
Middle East
South Asia

Question 4

Which people is beta-thalassaemia most prevalent in?

Answer 4

West African

Question 5

Describe the genetics of Thalassaemia?

Answer 5

Inherited in an autosommal-recessive pattern due to allele mutations on HBA1 and HBA2 genes (alpha-thalassaemia), and HBB gene (Beta-thalassaemia)

Leads to a deficiency in the respective globin chain

Question 6

Describe the globin chains in someone with alpha-thalassaemia.

Answer 6

Excess Beta-chains (or gamma-chains in foetus) due to a lack of alpha-chains

Question 7

Describe the negative effect alpha-thalassaemia has on Hb and RBCs?

Answer 7

Microcytic anaemia (small hypochromic blood cells) due to decreased Hb production

Inefficient Hb due to excess beta/gamma-chains forming tetramers resulting in inefficient O2 dissociation curves

Haemolysis due to damaged RBCs

(Note: severity varies depending on amount of alpha-chains that can be made)

Question 8

Describe the globin chains in someone with beta-thalassaemia.

Answer 8

Excess alpha-chains due to a lack of beta-chains

Question 9

Describe the negative effect beta-thalassaemia has on Hb and RBCs?

Answer 9

Microcytic anaemia (small hypochromic blood cells) due to decreased Hb production

Excess alpha-chains bind to eyrthropoietic cells often preventing RBP production

Haemolysis due to damaged RBCs

Question 10

Describe the severity of Beta-thalassaemia

Answer 10

No thalassaemia = Normal beta-globin production

B+ = reduced beta-globin production due to 1 faulty allele

B(0) = no beta-globin production due to 2 faulty alleles

Question 11

What are the clinical features of thalassaemia?

Answer 11

Mild (trait carriers) = often asymptomatic

Mod/severe = ususally symptomatic at birth/shortly afterwards

• Jaundice (due to haemolysis)
• Anaemia
• Splenomegaly
• Hepatomegaly
• Frontal bossing & maxillary prominence
• Shortened fingers/limbs
• Leg ulcers (due to microinfarction)

Hydrops Fetalis (alpha-thalassaemia only)
 - still birth nenoatal death due to complete failure to make alpha-globin => no Hb

Question 12

Why do thalassaemia patients often become jaundiced?

Answer 12

Due to haemolysis

Question 13

Why do thalassamia patients often have shortened fingers/limbs?

Answer 13

Due to infarction/premature closing of epiphyseal plates

Question 14

What will investigations tell us about a patient with thalassaemia?

Answer 14

Bloods: Microcytic, hypochromic anaemia
- Nucleated RBCs sometimes present (let out too early)

Genetic testing

X-rays
- bones esp. skull are thickened with thin cortices and have “hair on end” appearance due to increased marrow space

Question 15

How is thalassaemia managed?

Answer 15

Often not necessary for mild sufferers

For major sufferers:

• long term transfusion therapy to maintain Hb>9.0
• iron chelation to reduce free Fe in blood from haemolysis (which can be damaging)
• marrow transplant ?