• Group of genetic disorders characterised by abnormal globin chains of haemoglobin due to mutations
  • Two main types (based on the chain affected
    • β-thalassaemia (most common in the Mediterranean, middle east and in central and south Asia area)
      • Autosomal recessive condition of abnormal β-globin.  Can further be classified as
        • Major (homozygote)
        • Intermedia (βo/- or β+/β+)
        • Minor (heterozygote) (around 1.5% of the world population)
    • α-thalassaemia (most common in SE Asia, Africa and India)
      • Slightly different pattern of inheritance as there are 2 alleles responsible for α-chain production
        • α+ heterozygous (α,-/α,α)- clinically asymptomatic
        • α+ homozygous (α,-/α,-)- slightly anaemic, low MCV and MCH, clinically asymptomatic
        • αo heterozygous (α,α/-,-)- as α+ homozygous
        • HbH disease (α,-/-,-)- HbH, anaemia, very low MCV and MCH, splenomegaly, variable bone changes
          • Under the microscope, RBCs appear ‘golf-ball like’ with characteristic ‘Heinz bodies’ (dense bodies of precipitated Hb)
        • α thalassaemia major (-,-/-,-)- usually fatal (hydrops fetalis)


Beta-thalassaemia minor

  • Usually presents as a mild, microcytic anaemia which fails to respond to iron therapy

Beta-thalassaemia intermedia

  • Characterised by later/milder onset of symptoms of β-thalassaemia major
    • Patients will maintain an Hb >70g/l at the cost of intense bone marrow hyperplasia and splenomegaly

Beta-thalassaemia major

  • Usually presents within the first few months of life once foetal haemoglobin depletes
    • Profound hypochromic anaemia can present as failure to thrive: vomiting feeds, sleepiness, stunted growth and irritability
    • Patients can also have problems with associated iron overload and splenomegaly


  • Traits will only usually develop a mild anaemia non-responsive to iron treatment
  • HbH disease can present with moderate-severe anaemia, splenomegaly, jaundice


  • FBC
    • Hypochromic, microcytic anaemia
    • Haemoglobin fractionation
  • Genetic testing


  • Asymptomatic carriers require no treatment (avoid iron therapy)
  • Thalassaemia intermedia and HbH disease
    • Monitor closely for complications of chronic haemolytic anaemia
    • Transfusions may be required
      • Hb <50g/l
      • Falling Hb with profound spleen enlargement
      • Growth failure or poor performance at school
      • Diminished exercise tolerance
      • Failure of secondary development in parallel with bone age*
      • Severe bone changes e.g. deformity, frontal bossing etc*
      • Pregnancy
      • Infection
      • Other compllications e.g. heart failure; pulmonary complications; hypertension; thromboembolic disease; leg ulcers; priapism
        • * cause for regular transfusion
    • Splenectomy can be considered if splenomegaly is problematic, although this carries risk of life-threatening infection, pulmonary hypertension and thrombosis
  • Thalassaemia major
    • Can be cured by HSCT
    • Regular hypertransfusion to maintain Hb >95g/l
    • Iron chelation to prevent overload
      • e.g. deferoxamine or deferasirox
      • Main and most important side-effect is iron overload causing heart failure
    • Immunisations and prompt treatment of all infections
    • Splenectomy
    • Hydroxyurea (cytotoxic agent used to increase production of gamma-chains)

Haemoglobinopathies in Pregnancy

  • For women with thalassaemia, there are detailed guidelines about management during pregnancy published by RCOG (see here)
  • Haemoglobinopathies such as thalassaemia and sickle cell disease are routinely screened for antenatally
    • If there is a high risk of thalassaemia major/HbS disease then prenatal testing can provide a diagnosis
      • TOP can be offered for affected pregnancies

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