Thalassaemias

Overview – Thalassaemias

Thalassaemias are inherited haemoglobinopathies caused by reduced or absent synthesis of α- or β-globin chains, leading to ineffective erythropoiesis and chronic anaemia. Clinical severity varies from asymptomatic trait carriers to life-threatening transfusion-dependent disease. Complications arise from both the anaemia and the treatment — especially iron overload from chronic transfusions. Understanding the basic classification and pathophysiology of thalassaemias is essential for diagnosing and managing patients with microcytic anaemia.

Definition

• Thalassaemias are genetic disorders of haemoglobin synthesis
• Caused by defective production of either:
  • Alpha chains (α-thalassaemia)
  • Beta chains (β-thalassaemia)
• Leads to imbalanced globin chain production, resulting in ineffective erythropoiesis and chronic haemolysis

Aetiology

Alpha Thalassaemia

• Caused by deletion of 1 or more of 4 α-globin genes
• Severity increases with the number of deletions:
  • 1 gene → silent carrier
  • 2 genes → α-thalassaemia trait
  • 3 genes → HbH disease
  • 4 genes → hydrops fetalis (usually fatal in utero)

Beta Thalassaemia

• Due to point mutations in the β-globin gene
• Results in:
  • β⁺ (partial deficiency)
  • β⁰ (complete absence)
• Clinical forms:
  • β-thalassaemia minor (trait)
  • β-thalassaemia intermedia
  • β-thalassaemia major (Cooley’s anaemia)

Pathophysiology

• ↓ Globin chain production → unmatched chains accumulate
• Unstable unmatched chains → RBC destruction in bone marrow and peripheral blood
• Ineffective erythropoiesis + haemolysis → chronic anaemia
• Bone marrow expands → skeletal deformities
• Compensatory mechanisms → hepatosplenomegaly

Microscopy

• Microcytic, hypochromic RBCs
• Anisopoikilocytosis (variable shape and size)
• Target cells, tear-drop cells, and basophilic stippling may be seen

Clinical Features

Mild Thalassaemia (Trait)

• Asymptomatic or mild anaemia
• Often detected incidentally

Moderate to Severe Disease

• Chronic fatigue, weakness
• Jaundice and dark urine (from haemolysis)
• Splenomegaly
• Delayed growth and puberty
• Skeletal changes: frontal bossing, maxillary overgrowth (due to marrow expansion)

Complications

• Iron overload:
  • From transfusions and increased gut absorption
  • Affects liver, heart, pancreas, pituitary
  • Requires iron chelation therapy (e.g. deferoxamine)
• Infections (especially post-splenectomy)
• Osteoporosis and bone deformities
• Gallstones (from chronic haemolysis)
• Cardiomyopathy and heart failure (iron deposition)

Treatment

• Mild forms:
  • No treatment required
  • Genetic counselling recommended
• Moderate to severe forms:
  • Regular blood transfusions to maintain Hb > 90–100 g/L
  • Iron chelation therapy to prevent iron overload
  • Splenectomy in selected cases
  • Bone marrow transplantation: potential cure in severe cases
• Folic acid supplementation in chronic haemolysis
• Vaccinations (especially post-splenectomy): pneumococcus, meningococcus, Hib

Summary – Thalassaemias

Thalassaemias are inherited anaemias resulting from defective alpha or beta globin chain production. They range from silent carriers to transfusion-dependent disease with significant complications such as iron overload, bone deformities, and organ damage. Recognition and tailored management are crucial to improving quality of life. For a broader context, see our Blood & Haematology Overview page.