Haematology - Thalassaemia

Question 1

Definition

Answer 1

Autosomal recessive haemoglobinopathy which causes a microcytic anaemia.

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

Alpha-Thalassaemia

Answer 3

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 4

Beta-Thalassaemia

Answer 4

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 5

Beta thalassaemia minor

Answer 5

ASx or mild microcytic anaemic symptoms:
- fatigue
Only require monitoring and no active treatment.

Question 6

Beta thalassaemia Intermedia

Answer 6

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 7

Beta thalassaemia major

Answer 7

Homozygous deletion of genes.
- Presentation < 2 years old
= FTT
= Hepatosplenomegaly
= Severe microcytic anaemia (HbA absent)

Question 8

Signs and symptoms

Answer 8

Symptoms:
- Microcytic anaemia (low MCV)
- Fatigue
- Pallor
Signs:
- FTF
- Neonatal Jaundice
- Gallstones
- Hepatosplenomegaly
- Poor growth and development
- Pronounced forehead and malar eminences
- Chipmunk facies : compensatory extramedullary hematopoiesis in the skull causes marrow expansion

Question 9

Diagnosis

Answer 9

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

Women are only offered screening test for thalassaemia at booking

Question 10

Treatment

Answer 10

Alpha and beta thalassaemia trait: mild anaemia which does not require treatment

HbH and beta thalassaemia major:
- Regular blood transfusions: commenced if Hb drops < 70 g/L or if the patient is symptomatic
- Iron chelation: desferrioxamine
- Folate sup
- Stem cell transplantation: the only curative option recommended in those with severe disease

Question 11

Complications

Answer 11

Iron overload: From repeated blood trasfusions. Presents are haemochromatosis symptoms:
- Fatigue
- Liver cirrhosis
- Infertility
- Impotence
- Heart failure
- Arthritis
- Diabetes
- Osteoporosis and joint pain