Thalassaemia

Background/Epidemiology

• 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)

Presentation

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

Alpha-thalassaemia

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

Investigations

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

Management

• 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