Thalassaemia

Definition | Types | Aetiology | Pathophysiology | Risk Factors | Signs and Symptoms | Investigations | Management | References

Definition

Thalassaemia is a group of inherited blood disorders characterised by the abnormal formation of haemoglobin. This results in the destruction of a large number of red blood cells, which leads to anaemia.

Types

Thalassaemia can be broadly classified into two main types:

• Alpha Thalassaemia: Caused by mutations in the HBA1 and HBA2 genes, leading to reduced or absent alpha-globin production.
• Beta Thalassaemia: Caused by mutations in the HBB gene, leading to reduced or absent beta-globin production. It includes:
  • Thalassaemia Major (Cooley's Anaemia): Severe form requiring regular blood transfusions.
  • Thalassaemia Intermedia: Milder form with less frequent transfusion needs.
  • Thalassaemia Minor (Trait): Carrier state with mild anaemia.

Aetiology

Thalassaemia is caused by genetic mutations that affect the production of haemoglobin chains:

• Alpha Thalassaemia: Deletions or mutations in the HBA1 and HBA2 genes.
• Beta Thalassaemia: Mutations in the HBB gene affecting beta-globin production.

Pathophysiology

The pathophysiology of thalassaemia involves:

• Imbalance in the production of globin chains, leading to ineffective erythropoiesis and haemolysis.
• Accumulation of unpaired globin chains causing damage to red blood cell membranes.
• Increased destruction of abnormal red blood cells in the spleen.
• Expansion of bone marrow to compensate for anaemia, leading to bone deformities.

Risk Factors

• Family history of thalassaemia
• Ethnicity (more common in people of Mediterranean, Middle Eastern, Indian, and Southeast Asian descent)
• Consanguinity (marriage between close relatives)

Signs and Symptoms

Common signs and symptoms of thalassaemia include:

• Fatigue and weakness
• Pale or yellowish skin (jaundice)
• Facial bone deformities
• Slow growth and development
• Abdominal swelling due to splenomegaly
• Dark urine
• Frequent infections

Key Examination Findings

During physical examination, look for:

• Pallor
• Jaundice
• Splenomegaly
• Hepatomegaly
• Bone deformities, particularly in the facial bones
• Growth retardation

Investigations

Specific blood tests and investigations include:

• Full blood count (FBC): Low haemoglobin levels, microcytic hypochromic anaemia.
• Peripheral blood smear: Target cells, anisopoikilocytosis, basophilic stippling.
• Haemoglobin electrophoresis: Abnormal haemoglobin patterns, increased HbA2 and HbF in beta thalassaemia.
• Genetic testing: To identify mutations in the HBA1, HBA2, and HBB genes.
• Iron studies: To differentiate from iron deficiency anaemia (serum ferritin, transferrin saturation).
• Reticulocyte count: Elevated in response to anaemia.
• Liver function tests (LFTs): To assess liver involvement.
• Bilirubin levels: Elevated indirect bilirubin indicating haemolysis.

Management

Primary Care Management

• Referral to a specialist: Patients with suspected thalassaemia should be referred to a haematologist for further evaluation and management.
• Initial management: Supportive care including folic acid supplementation and monitoring of haemoglobin levels.

Specialist Management

• Regular blood transfusions: To maintain haemoglobin levels and prevent complications of anaemia in severe cases.
• Iron chelation therapy: To prevent iron overload from frequent transfusions (e.g., deferoxamine, deferasirox).
• Bone marrow transplant: Potential curative treatment for severe cases.
• Gene therapy: Emerging treatment aimed at correcting the genetic defect.
• Management of complications: Monitoring and treating complications such as heart failure, liver disease, and endocrine dysfunction.

References

1. NHS. (2024). Thalassaemia. Retrieved from NHS
2. Thalassaemia International Federation. (2024). Thalassaemia Guidelines. Retrieved from TIF
3. British Society for Haematology. (2024). Guidelines on the Management of Thalassaemia. Retrieved from BSH

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