Haematology - Thalassaemia

Question 1

Definition

Answer 1

Genetic defect in the protein chains that make up haemoglobin
- Normal chain consists of 2 alpha and 2 beta globin chains
- Both alpha and beta thalassaemia are autosomal recessive conditions = overall effect is varying degrees of anaemia, depending on the type of mutation

Question 2

Pathophysiology

Answer 2

The red blood cells are more fragile and break down more easily. The spleen filters the blood and removes older blood cells, collecting all the destroyed red blood cells = splenomegaly.

The bone marrow expands to produce extra red blood cells to compensate for the chronic anaemia. This causes a susceptibility to fractures and prominent features, such as a pronounced forehead and malar eminences (cheek bones).

Question 3

Signs and symptoms

Answer 3

• Microcytic anaemia (low MCV)
• Fatigue
• Pallor
• Jaundice
• Gallstones
• Splenomegaly
• Poor growth and development
• Pronounced forehead and malar eminences

Question 4

Diagnosis

Answer 4

FBC shows microcytic anaemia
Haemoglobin electrophoresis is used to diagnose globin abnormalities
DNA testing = genetic abnormalities

Women are only offered screening test for thalassaemia at booking

Question 5

Iron Overload

Answer 5

Iron overload occurs in thalassaemia as a result of the faulty creation of red blood cells, recurrent transfusions and increased absorption of iron in the gut in response to anaemia.
Px with thalassaemia have serum ferritin levels monitored to check for iron overload.
Management of iron overload = limiting transfusions and performing iron chelation

Question 6

Signs and symptoms of iron overload

Answer 6

Similar effects to haemochromatosis:
- Fatigue
- Liver cirrhosis
- Infertility
- Impotence
- Heart failure
- Arthritis
- Diabetes
- Osteoporosis and joint pain

Question 7

Alpha-Thalassaemia

Answer 7

Defects in alpha globin chains = the gene coding for this protein is on chromosome 16
Treatment:
- Monitoring the full blood count
- Monitoring for complications
- Blood transfusions
- Splenectomy may be performed
- Bone marrow transplant can be curative

Question 8

Beta-Thalassaemia

Answer 8

Caused by defects in beta-globin chains.
The gene coding for this protein is on chromosome 17.
The gene defect can either consist of abnormal copies that retain some function or deletion genes where there is no function in the beta globin proteins at all.
Beta thalassaemia can be split into three types:
- Thalassaemia minor
- Thalassaemia intermedia
- Thalassaemia major

Question 9

Thalassaemia minor

Answer 9

Patients with beta thalassaemia minor are carriers of an abnormally functioning beta globin gene. They have one abnormal and one normal gene.
Thalassaemia minor causes a mild microcytic anaemia and usually patients only require monitoring and no active treatment.

Question 10

Thalassaemia Intermedia

Answer 10

Beta thalassaemia intermedia = Px have two abnormal copies of the beta globin gene. This can be either two defective genes or one defective gene and one deletion gene.
Thalassaemia intermedia causes a more significant microcytic anaemia.
Patients require monitoring and occasional blood transfusions. When they require more transfusions, they may require iron chelation to prevent iron overload.

Question 11

Thalassaemia major

Answer 11

Homozygous deletion of genes.
They have no functioning beta globin genes at all. This is the most severe form and usually presents with severe anaemia + failure to thrive in early childhood