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PH-HE04

Thalassaemia

How an imbalance between alpha and beta globin chains damages developing red cells, why the marrow expands and the spleen enlarges, why iron accumulates, and how the inherited forms range from silent trait to transfusion dependence.

By the end, you can

  • Describe the normal balance of globin chains in adult and fetal haemoglobin.
  • Distinguish alpha- from beta-thalassaemia by the genes affected and the chains in excess.
  • Explain how excess unpaired chains cause ineffective erythropoiesis and haemolysis.
  • Explain the bone changes, enlarged spleen and iron overload of severe thalassaemia.
  • Explain why thalassaemia trait can be mistaken for iron deficiency.
  • Recognise the classic blood film, skull and laboratory features and the alpha and beta classifications of thalassaemia, and explain how transfusion, chelation and curative treatments act on its mechanism.

What it is

Thalassaemias are inherited disorders in which one type of globin chain is made in reduced amounts or not at all. Too few chains of one kind leaves the other kind unpaired. In beta-thalassaemia beta chains are reduced and alpha chains accumulate; in alpha-thalassaemia alpha chains are reduced. Severity ranges from a symptomless trait to severe, transfusion-dependent anaemia.

3 types to tell apart
Beta-thalassaemia trait (minor)
One affected beta gene: mild microcytic anaemia or none, with raised HbA2. Usually no symptoms.
Beta-thalassaemia major
Both beta genes severely affected: severe anaemia from late infancy, needing regular transfusion. Intermediate forms need transfusion only sometimes.
Alpha-thalassaemia
Four alpha genes: losing one is silent, two gives trait, three gives HbH disease (moderate haemolytic anaemia), and four gives Hb Barts hydrops fetalis, usually fatal before or soon after birth.

US spelling: thalassaemia → thalassemia, thalassaemias → thalassemias, anaemia → anemia, haemoglobin → hemoglobin, haem → hem.

Normal function

Balanced globin chains

Haemoglobin is built from four globin chains, each holding a haem. Adult haemoglobin, HbA, has two alpha and two beta chains; small amounts of HbA2 (two alpha, two delta) are also present. Before birth the main haemoglobin is HbF (two alpha, two gamma), which is replaced by HbA over the first months of life.

Alpha chains are made from four genes (two on each chromosome 16); beta chains from two genes (one on each chromosome 11). Normally the two kinds of chain are made in matching amounts, so almost every chain finds a partner.

Developing red cells live in the bone marrow, which in adults is found in the flat bones such as the skull, sternum, ribs, vertebrae and pelvis. In childhood the marrow of almost all bones makes blood.