23rd May 2023

Alpha thalassaemia

Alpha thalassaemia is due to reduced or absent alpha chain production and accumulation of beta-like chains. There are two alpha chain genes (HBA1 and HBA2) on each copy of chromosome 16, thus four alleles exist. The number of deleted alpha-globin alleles determines which of the four different traits seen in alpha thalassaemia results.

Alpha thalassaemia minima (silent carrier)

• One affected alpha chain
• Asymptomatic
• No anaemia
• Normal haemoglobin analysis

Alpha thalassaemia minor (alpha thalassaemia trait)

• Loss of two alpha chains
• Homozygous if one alpha chain on each chromosome affected
• Heterozygous if both alpha chains on one chromosome affected
• Mild asymptomatic microcytic hypochromic anaemia
• Homozygous patients are more affected – mild anaemia, low MCV, splenomegaly

Haemoglobin H disease

• Three alpha chains affected
• Variable clinical severity
• Symptomatic from birth but typically do not require regular blood transfusion
• Periods of increased haemolysis and aplastic crises e.g. during infection, may require blood transfusion
• Risk of iron overload even in absence of regular blood transfusion

Haemoglobin Bart’s Hydrops Foetalis (Homozygous alpha thalassaemia)

• Deletion of all alpha chains
• Severe anaemia during foetal development causing foetal hydrops
• Often in-utero death occurs

Management of alpha thalassaemia

• Patient education and counselling, particularly around family planning is important.
• Avoid iron supplementation unless proven to be iron deficient, due to risk of iron overload.
• Blood transfusion, depending on the clinical severity and symptoms of anaemia.
• Iron chelating therapy, as these patients are at risk of iron overload from repeated blood transfusions or from increased absorption from the gastrointestinal tract. Careful monitoring of cardiac, endocrine, and hepatic function is required.
• Splenectomy may be considered in patients with painful splenomegaly, hypersplenism with pancytopenia, increased transfusion requirement, and worsening anaemia.
• Haematopoietic stem cell transplant is the only curative treatment and should be considered in severe transfusion dependent patients.