Haemoglobinopathies

Question 1

What are haemoglobinopathies?

Answer 1

Haemoglobinopathies → group of recessively inherited conditions affecting the haemoglobin component of blood
a. Change in Structure and Quality Hb ⇒ haemoglobin variants such as HbS (sickle cell disease), HbO, HbE
b. Reduction in Quantity Hb ⇒ alpha or beta thalassaemia (reduced globin synthesis)

Question 2

What are the causes/ risk factors of haemoglobinopathies?

Answer 2

Thalassaemia (Autosomal Recessive):
1. Beta Thalassaemia → most commonly seen in people of mediterranean descent
2. Αlpha Thalassaemia → most commonly seen in people of asian and african descent
- Cause ⇒ gene mutations:
1. Beta Thalassaemia → beta-globin chains are coded by a total of two alleles, so there are two main forms of the disease. Beta thalassaemia minor (one defective allele) or beta thalassaemia major (two defective alleles)
- HbA (2 alpha and 2 beta chains) can not be produced, hence rise in HbA2 and HbF
2. Αlpha Thalassaemia → α-globin chains are coded by a total of four alleles, so there are four forms of the disease. Silent carrier (one defective allele), alpha thalassaemia trait (two defective alleles), haemoglobin H disease (three defective alleles), haemoglobin bart disease (four defective alleles).

Question 3

What are the presenting symptoms/ signs of haemoglobinopathies?

Answer 3

1. Beta Thalassaemia:
   - Minor → mild microcytic hypochromic anaemia. Asymptomatic.
   - Major → severe haemolytic anaemia, hepatosplenomegaly, skeletal deformities
2. Αlpha Thalassaemia:
   - Silent Carrier → asymptomatic. No anaemia.
   - Αlpha Thalassaemia Trait → microcytic hypochromic red cells. No anaemia.
   - Haemoglobin H (HbH) Disease → microcytic hypochromic anaemia with splenomegaly
   - Haemoglobin Bart Disease → intrauterine death

Question 4

What investigations are used to diagnose/ monitor haemoglobinopathies?

Answer 4

1. Hb-Electrophoresis→ HbA2 levels useful for diagnosis (raised in beta thalassaemia trait + major). HbH band in alpha thalassaemia.
2. Beta Thalassaemia → raised HbA2, raised HbF, absent HbH
3. FBC → microcytic hypochromic anaemia
4. Raised Reticulocytes

Question 5

How are haemoglobinopathies managed?

Answer 5

1. Thalassaemia Major → Transfusion Therapy (ie. lifelong blood transfusions).
   - May lead to iron overload which can cause organ failure, hence iron chelation therapy is important (deferoxamine)
2. Genetic Counselling & Screening Tests for relative.

Question 6

What complications may arise following haemoglobinopathies?

Answer 6

• Thrombotic complications
• Transfusion-acquired infection
• Gallstones
• Pulmonary hypertension
• Aplastic crisis