Thalassaemia

Relevant physical signs

• Signs of extra-medullary hematopoiesis
  • Frontal bossing
  • Maxillary overgrowth
  • Scoliosis
  • Hepatosplenomegaly
• Signs and complications of chronic haemolysis
  • Conjunctival pallor
  • Scleral icterus
  • Kocher’s scar (previous cholecystectomy)
  • Right ventricular heave, loud P2 (pulmonary hypertension – aetiology not entirely clear)
• Signs of iron overload
  • Slate grey skin
  • Displaced apex beat (congestive cardiac failure)
  • Implantable cardiac device
  • Finger prick blood sugar marks (diabetes mellitus)
  • Diabetic dermopathic changes
  • Signs of chronic liver disease
• Complete examination by:
  • Examining testes (hypogonadotropic hypogonadism from pituitary iron loading)
  • Doing a urine dipstick (glycosuria)
  • Examining the cardiovascular system (iron overload)
  • Examining the musculoskeletal system (arthritis)

Differential diagnosis

• Thalassaemia major
• Thalassaemia intermedia
• Hereditary spherocytosis
• Hereditary elliptocytosis
• Autoimmune haemolytic anaemia

Investigations

• Confirm diagnosis: haemoglobin electrophoresis
  • Beta thalassaemia minor (β⁰/β⁰ or β/β⁺) / intermedia (β⁺/ β⁺)
    • HbA₂ increased (3.5 – 7%)
    • HbF increased in some patients
  • Beta thalassaemia major (β⁰/ β⁰)
    • HbA absent
    • Increased HbA₂ and HbF
  • β⁰ = thalassaemia gene producing no β chain; β⁺ = thalassaemia gene producing some β chain
  • Alpha thalassaemia carrier (αα/α-): asymptomatic, <3% Hb Barts at birth
  • Alpha thalassaemia minor (αα/– or α-/α-): 3 – 8% Hb Barts at birth
  • HbH disease (α-/–): 5 – 30% HbH, 20 – 40% Hb Barts at birth
  • Alpha thalassaemia major (–/–): fetal hydrops, fatal
• Assess severity
  • Full blood count to look at Hb level
  • Markers of haemolysis
    • Unconjugated bilirubin (high)
    • Lactate dehydrogenase (high)
    • Serum haptoglobin (low)
  • Look for complications of iron overload
    • Transthoracic echocardiogram
    • If TTE normal, consider cardiac magnetic resonance imaging
    • Fasting blood glucose and HbA1c
    • Liver function tests and tests of synthetic liver function
    • Anterior pituitary hormone screen (pituitary infiltration)
      • FSH, LH, testosterone / oestrogen
      • TSH, free T4
      • ACTH, 8am cortisol
      • Somatotropin, IGF-1
      • Prolactin
• Bone mineral density studies to screen for osteoporosis

Management

• Multidisciplinary team approach
• Patient education
• Genetic counselling (autosomal recessive)
• Anaemia
  • Chronic transfusion therapy
  • Folic acid supplementation
  • Splenectomy if haemolytic anaemia is severe or if splenomegaly is symptomatic
• Iron chelation for iron overload (may be secondary to repeated transfusions or increased iron absorption)
• Anterior pituitary hormone replacement
• Treatment of diabetes mellitus
• Consider bisphosphonates for patients with osteoporosis

Summary

Sir, this patient has evidence of extra-medullary haematopoiesis. There is frontal bossing and a maxillary prominence. On examination of the abdomen, there is hepatosplenomegaly. There is mild icterus and conjunctival pallor, which suggests that the underlying aetiology is a chronic haemolytic anaemia. There is no evidence of chronic iron overload; the skin is of normal tone, the apex beat is not displaced, there are no dermopathic changes to suggest underlying diabetes, and there are no stigmata of chronic liver disease. I would like to complete my examination by examining the external genitalia. Differentials for this include thalassaemia major and intermedia, hereditary spherocytosis, hereditary elliptocytosis and autoimmune haemolytic anaemia.