Thalassaemia

Question 1

Definition of beta thalassaemia

Answer 1

Genetic disease that leads to decreased or absent beta globin chain synthesis. This would lead to ineffective erythropoiesis; hence microcytic anaemia

Question 2

Aetiology of beta thalassaemia

Answer 2

• Occurs due to a mutation in the beta-globin chain on chromosome 11
• This therefore leads to decreased/absent beta globin chain production

• Follows an AUTOSOMAL RECESSIVE inheritance pattern
◦ Heterozygous individuals would have the trait (can experience mild symptoms)
◦ Some can be silent carriers (experience no symptoms and have no haematological changes)

Question 3

Pathophysiology of beta thalassaemia

Answer 3

• Reduction/absence in beta globin chains leads to ineffective erythropoiesis
◦ This is due to RBC membrane damage and cell destruction
◦ This would lead to erythroid hyperplasia (contributes to boney changes of the skull and Hepatosplenomegaly)

• Split into 3 types:
◦ Beta-thalassaemia major: complete/near-complete lack of beta-globin, leading to transfusion dependent severe anaemia

			◦ Beta-thalassaemia intermedia: moderate reduction in beta-globin, leading to less severe anaemia 

			◦ Beta thalassaemia minor/trait: heterozygous individuals that have mild anaemia with compensatory overexpression of normal gene

Question 4

History and Examination of beta thalassaemia

Answer 4

• Beta thalassaemia Major and sometimes intermedia:
◦ Lethargy: due to anaemia
◦ Abdominal distention: due to organomaly
◦ Hepatosplenomegaly: due to haemolysis
◦ Pallor: of the conjunctive, nail beds and mucosa
◦ Presenting in 1st year with failure to thrive: very common for Major, low height and weight
◦ Skull bossing + large head: due to extra-medullary haematopoiesis . ‘Hair on end’ skull X-Ray sign
◦ Hypochromic, microcytic anaemia
◦ Raised HbF and absent HbA

• Beta thalassaemia minor/trait:
◦ Usually asymptomatic
◦ Can have mild anaemia

Question 5

Investigations for beta thalassaemia

Answer 5

• FBC: would see microcytic anaemia
• Peripheral blood smear: hypochromic microcytic cells, target cells, large number of nucleated red cells
• Reticulocyte count: Elevated
• Haemoglobin analysis: no HbA and elevated HbF in Major
• LFTs: can see hyperbilirubinaemia
• X-Ray of skull: ‘hair on end’ sign

Question 6

Treatment of beat thalassaemia

Answer 6

Beta thalassaemia trait:
• 1) Genetic counselling + iron advice: family planning and avoid iron supplementation unless actually iron deficienct

Beta thalassaemia intermedia: non-transfused-dependent:
1) Transfusion when symptomatic anaemia: unlikely to need transfusion as most have moderate anaemia. But may need it at times of major stress (surgery or serious illness/infection)

Beta Thalassaemia major:
1) Regular transfusion: Main treatment to maintain Hb level that allows normal growth and reduces risk of organ damage from chronic hypoxia. Has to be maintained lifelong

+ Iron monitoring + chelation: repeated transfusions can lead to iron overload and toxicity (can cause organ failure). Can take Desferrioxamine or Deferasirox for iron chelation therapy

+ Genetic counselling

+ consider Splenectomy: if massive

Question 7

Complications of beta thalassaemia

Answer 7

• Severe anaemia
• Thrombotic complications
• Iron overload

Question 8

Prognosis of beta thalassaemia

Answer 8

Normal life expectancy with trait and intermedia (may have some reduced quality of life due to cosmetic changes)
Major is fatal in first few years if untreated
Leading cause of death is heart failure due to iron overload

Question 9

Definition of alpha thalassaemia

Answer 9

the deficiency of alpha chains in haemoglobin, due to deletions in at least 1 of the 4 alpha-globin genes. Lack of chains would lead to anaemia and haemolysis

Question 10

Aetiology of alpha thalassaemia

Answer 10

• If 1 or 2 alpha globin alleles are affected, then there would be hypochromic microcytic cells (reduced MCV) (BUT Hb would be normal). Would be asymptomatic and can be completely normal

• If 3 alpha globin alleles are affected, then there would be moderate hypochromic microcytic anaemia with hepatosplenomegaly, leg ulcers and jaundice. Known as Hb H disease

• If all 4 alpha globin alleles there is death in utero

• Family history is a risk factor

Question 11

History and Examination of alpha thalassaemia

Answer 11

• Anaemia: fatigue, dizziness and SOB
• Splenomegaly
• Symptoms of gallstones
• Jaundice

Question 12

Investigations of alpha thalassaemia

Answer 12

• Hb: normal to low
• MCV: low
• Peripheral blood smear: hypochromic, microcytosis, target cells

Question 13

Treatment of alpha thalassaemia

Answer 13

1) Folic acid supplementation + supportive care: genetic counselling needed, avoid unnecessary iron supplementation

Consider RBC transfusion if severe anaemia