Haemoglobinopathy - Thalassaemia

Question 1

What is Thalassaemia?

Answer 1

A haemoglobinopathy due to a genetic autosomal recessive defect in the protein chains that make up Haemoglobin.

Question 2

What is Alpha Thalassaemia caused by?

Answer 2

A defect in the alpha globin chain - the gene coding for this protein is on Chromosome 16.

Question 3

Clinical Severity of Alpha Thalassaemia (3).

Answer 3

1. 1/2 Alleles affected = Hypochromic and Microcytic but Normal Hb.
2. 3 Alleles Affected = Hypochromic Microcytic Anaemia with Splenomegaly (Hb H Disease).
3. 4 Alleles Affected = Death in Utero e.g. Hydrops Fetalis, Bart’s Hydrops.

Question 4

What is Beta Thalassaemia caused by?

Answer 4

A defect in the beta globin chain - the gene coding for this protein is on Chromosome 11.

Question 5

What are the 3 Types of Beta Thalassaemia?

Answer 5

1. Thalassaemia Minor.
2. Thalssaemia Intermedia.
3. Thalassaemia Major.

Question 6

What is Thalassaemia Minor characterised by (4)?

Answer 6

1. Carrier of Abnormally-Functioning Beta-Globin Chain.
2. 1 Abnormal and 1 Normal Gene.
3. Mild Microcytic Anaemia.
4. Monitoring + No Active Treatment.

Question 7

What is Thalassaemia Intermedia characterised by (4)?

Answer 7

1. 2 Abnormal Copies of the Beta Globin Gene.
2. Either 2 Defective Genes or 1 Defective + 1 Deletion Gene.
3. More Significant Microcytic Anaemia.
4. Monitoring + Occasional Blood Transfusions (+ Iron Chelation?).

Question 8

What is Thalassaemia Major characterised by?

Answer 8

1. Homozygous for Deletion Genes.
2. No Functioning Beta Globin Genes.
3. Severe Anaemia and Failure to Thrive in Early Childhood.
4. Regular Transfusions, Iron Chelation, Splenectomy (+ Bone Marrow Transplant).

Question 9

Clinical Features of Thalassaemia.

Answer 9

1. Splenomegaly.
2. Susceptibility to Fractures.
3. Prominent Features e.g. Pronounced Forehead and Malar (Cheek) Eminences.
4. Gallstones.
5. Poor Growth and Development.
6. Jaundice.
7. Anaemia, Fatigue, Pallor.

Question 10

What causes the Splenomegaly?

Answer 10

1. The RBCs are more fragile and are easily broken down.
2. The spleen sieves the blood to remove damaged cells.
3. It works harder and swells.

Question 11

What causes the bone changes?

Answer 11

The Bone Marrow expands to produce extra RBCs to compensate for the chronic anaemia.

Question 12

Investigations in Thalassaemia.

Answer 12

1. FBC - Microcytic (Disproportionate) Hypochromic Anaemia and HbA2 raised.
2. Diagnosis - Haemoglobin Electrophoresis and DNA Testing.
3. Screening - Pregnancy at Booking.

Question 13

Management of Alpha Thalassaemia (5).

Answer 13

1. Monitoring FBC and Complications.
2. Blood Transfusions.
3. Splenectomy.
4. Curative : Bone Marrow Transplant.

Question 14

Why can Iron Overload happen in Thalassaemia?

Answer 14

Faulty creation of RBCs, recurrent transfusions, increased absorption of Iron in response to iron.

Question 15

Management of Iron Overload.

Answer 15

1. Monitor Serum Ferritin levels.
2. Limiting transfusions.
3. Iron Chelation - Desferrioxamine.

Question 16

Clinical Features of Iron Overload in Thalassaemia (7).

Answer 16

• similar to Haemochromatosis :
  1. Fatigue.
  2. Cirrhosis.
  3. Infertility and Impotence.
  4. Heart Failure.
  5. Arthritis.
  6. Diabetes.
  7. Osteoporosis.