FRCA Notes

Thalassaemia

This topic fulfils the curriculum item requiring knowledge of 'haemoglobin and its variants including abnormal haemoglobins e.g. thalassaemia'.

Resources

  • In health, equal numbers of ɑ-globin and β-globin chains are produced - for example 'normal' HbA consists of 2 ɑ-globin and 2 β-globin chains
  • Thalassaemia describes an abnormality in the ratio of globin chains, typically due to under-production of one type
  • It can be classified by whether the abnormality is in ɑ-globin or β-globin chain production, and further by the number of missing chains
  • Occurs due to deletions of the alpha-globin chain genes on chromosome 16
  • The severity of the disease correlates with the number of deleted genes
  1. Alpha thalassaemia trait (ɑ0, ɑ+, homozygous ɑ+)
    • Microcytic, hypochromic picture without necessarily anaemia
    • Raised RBC count
    • Normal HbA2 level
    • Hb electrophoresis is normal and normal alpha: beta chain ratio
    • Requires molecular analysis to diagnose

  2. Alpha thalassaemia trait

  3. HbH disease
    • β4 disease detectable by Hb electrophoresis
    • Moderately severe microcytic, hypochromic anaemia
    • Splenomegaly develops
    • Normal development
    • Doesn't usually require transfusions

  4. Hydrops Foetalis
    • Non-compatible with life and death in utero occurs

Β thalassaemia trait/minor (β+)

  • Reduced production of β chains
  • Causes a mild, hypochromic, microcytic anaemia which may resemble IDA
  • [Hb] is typically 20 - 30 g/L below the normal range for the age group

Β thalassaemia intermedia

  • Mutations in both β globin genes but patient able to maintain [Hb] 70 - 100g/L without transfusion
  • There may still be bone deformities and extramedullary haemopoiesis
  • Can remain dormant until stress states e.g. pregnancy

Β thalassaemia major (β0) a.k.a. Cooley's anaemia

  • Absent production of β chains
  • Becomes clinically apparent at 6 months when the transfer from HbF to HbA starts
  • The excess ɑ-globin chains combine with whichever other chains there are available, leading to increased HbA2 and HbF concentrations

  • Clinical features include:
    • Bone marrow hyperplasia
      • Thalassaemic facies (frontal bossing)
      • Cortical thinning and increased susceptibility to fractures
    • Extramedullary haemopoiesis
    • Hepatosplenomegaly

  • Leads to severe, transfusion-dependent anaemia
  • Transfusions can lead to normal development although iron overload becomes an issue

Airway

  • Difficult airway may arise due to:
    • Oro-facial malformation which results from bone marrow hypertrophy e.g. frontal bossing, maxillary overgrowth
    • Osteopaenic facial fractures
    • Poor dentition

Respiratory

Cardiovascular

  • High cardiac output state due to chronic anaemia
  • Cardiomyopathy e.g. due to haemochromatosis

Renal

  • Fluid overload state from compensatory mechanisms ± repeated transfusions

Gastrointestinal

  • Hepatomegaly
  • Splenomegaly
  • Increased incidence of cholelithiasis
  • Diabetes
  • Jaundice from haemolysis

Haematological

  • Anaemia
    • May have chronic haemolytic anaemia
  • Increased risk of thromboembolic events
  • Haemochromatosis due to repeated transfusions
  • Thrombocytopaenia from splenomegaly

Perioperative management of the patient with thalassaemia


  • MDT approach including Haematology input
  • Investigate coalescing cardiorespiratory disease e.g. lung function tests, TTE
  • Evaluate anaemia and ensure optimised Hb prior to surgery
  • Ensure adequate cross-matching as may have alloimmunisation due to repeated transfusion

Monitoring and access

  • AAGBI
  • Consider invasive BP monitoring, especially if cardiovascular sequelae of the disease
  • Consider CVC ± CO monitoring to help avoid fluid overload

Anaesthetic technique

  • Plan for difficult airway
  • Neuraxial anaesthesia may also be difficult if there have been osteopaenic vertebral fractures/collapse

  • Standard measures to minimise intra-operative bleeding
  • Minimise risk of thrombotic events e.g. intra-operative VTE prophylaxis, warming

  • Avoid oxidant drugs may precipitate haemolysis
    • Prilocaine
    • Nitroprusside
    • Vitamin K
    • Aspirin
    • ± Penicillins

  • Consider HDU environment
  • Ongoing management to minimise bleeding