Thalassaemia

• Thalassaemia is caused by a genetic defect in the protein chains that make up haemoglobin. Normal haemoglobin consists of two alpha-globin and two beta-globin chains.
• Defects in alpha-globin chains lead to alpha thalassaemia. Defects in the beta-globin chains lead to beta thalassaemia. Both conditions are autosomal recessive. 
• In patients with thalassaemia, the red blood cells are more fragile and break down easily, causing haemolytic anaemia. The spleen acts as a sieve, filtering the blood and removing older cells. The spleen collects all the destroyed red blood cells, resulting in splenomegaly.
• The severity of features depends on the type. Universal features include:

  • Microcytic anaemia (low mean corpuscular volume)
  • Fatigue
  • Pallor
  • Jaundice
  • Gallstones
  • Splenomegaly
  • Poor growth and development
• Investigations:

  • Microcytic anaemia
  • Raised ferritin suggests iron overload - repeated transfusions and increased reabsorption
  • Raised bilirubin
  • Haemoglobin electrophoresis is used to diagnose globin abnormalities
  • All pregnant women in the UK are offered screening
• Iron overload may occur in thalassaemia due to: 

  • Increased iron absorption in the gastrointestinal tract
  • Blood transfusions
• Iron overload in thalassaemia can cause symptoms and complications of:

  • Liver cirrhosis
  • Hypogonadism
  • Hypothyroidism
  • Heart failure
  • Diabetes
  • Osteoporosis
• Alpha thalassaemia:

  • Defects in the alpha-globin chains
  • Genes that code for alpha-globin are on chromosome 16
  • Can be a carrier
  • Moderate = haemoglobin H disease
  • Major = intrauterine death due to severe fetal anaemia
  • Management = transfusions, splenectomy, bone marrow transplant
• Defects in beta-globin chains cause beta-thalassaemia. The gene coding for this protein is on chromosome 11. The gene defects can either consist of abnormal copies that retain some function or deletion genes with no function in the beta-globin. Based on this, beta-thalassaemia can be split into three types:

  • Thalassaemia minor
  • Thalassaemia intermedia
  • Thalassaemia major
• Beta thalassaemia minor:

  • Thalassaemia trait
  • One abnormal and one normal gene
  • Mild microcytic anaemia
  • Usually only requires monitoring
• Beta thalassaemia intermedia:

  • Two abnormal copies - two defective gene or one defective + one deletion
  • More significant microcytic anaemia
  • Monitoring and may need occasional blood transfusions
  • May require iron chelation to prevent iron overload
• Beta thalassaemia major:

  • Homozygous for the deletion gene - no functioning beta-globin genes
  • Severe anaemia and failure to thrive in early childhood
  • Bone marrow expands as trying to compensate - increased risk of fractures and changes to appearance e.g. frontal bossing and enlarged maxilla
  • Management - regular transfusions, iron chelation and splenectomy
  • Bone marrow transplant may be curative
• Clinical features of beta thalassaemia major:

  • Severe anaemia
  • Splenomegaly and hepatomegaly - presents as swollen abdomen in children
  • Bone expansion
  • Iron overload - can lead to organ failure
• Complications:

  • Infection - hyposplenism increases the risk of pneumococcal, Haemophilus and meningococcal infection.
  • Osteoporosis - vitamin D and calcium given to prevent
  • Transfusion reactions
  • Alloimmunisation with repeated transfusions
  • Endocrine complications - due to iron overload - delayed sexual maturation, infertility, thyroid dysfunction and parathyroid dysfunction
  • Cardiovascular complications - iron induced cardiomyopathy
  • Thrombosis
• The leading cause of death in these diseases remains heart failure, secondary to iron-induced cardiomyopathy