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Editors

UllaWartiovaara-Kautto
KirsiJahnukainen

Thalassaemias

Essentials

  • Thalassaemias are non-immunological, haemolytic, hereditary disorders typically causing microcytic anaemia.
  • Iron supplementation should not be begun unless the patient has iron deficiency confirmed by low ferritin levels or Prussian blue staining of a bone marrow sample. N.B.! For anaemia during pregnancy in immigrants, see separate instructions below here.
  • Patients with severe thalassaemia or symptomatic, moderately severe thalassaemia belong in specialized care.
  • Globin gene mutation carriers of fertile age require genetic counselling.

Aetiology

  • Thalassaemia is caused by a genetic defect in the alpha or beta globin gene, leading to insufficient or imbalanced production of globin molecules and haemolysis (cf. sickle cell anaemia Sickle Cell Anaemia).

Epidemiology

  • Carriership of globin gene mutations is most frequent in regions endemic for malaria in the Mediterranean countries, Africa, India and the Far East. With immigration, thalassaemias are encountered also in other countries.

Symptoms

  • For types of thalassaemia, see Table T1.
  • Thalassaemia minor is usually clinically asymptomatic.
  • Thalassaemia intermedia
    • Anaemia (mild or moderate) may cause fatigue, a lowered exercise tolerance and, in children, delayed growth and pubertal development. Some patients will need red blood cell transfusions temporarily during pregnancy or the period of most rapid growth.
    • There may be enlargement of the spleen, causing pressure symptoms, pain and cytopenias.
    • Chronic haemolysis may lead to cholelithiasis.
    • With age, some people develop an iron overload that may cause disturbances in, for instance, liver or heart function or in hormonal activity.
  • Thalassaemia major
    • Red blood cell transfusion dependent severe anaemia (Hb usually below 70 g/l)
    • Even without red cell transfusion, significant iron overload may develop, leading to functional disturbances (for instance, of the liver or the heart or hormonal activity)
    • Skeletal changes (deformation, pain), symptomatic enlargement of the spleen, biliary and neurocognitive problems.

Types of thalassaemia

Severity of thalassaemiaType of thalassaemia
Thalassaemia minor
(or asymptomatic carriership)
  • Alpha globin gene defect in one or two of four alleles
  • Beta globin gene defect causing a mild form of the disease in one of two alleles
Thalassaemia intermedia
  • HbH disease
  • Some heterozygous carriers of the beta-0 mutation
  • Most combination thalassaemias
Thalassaemia major
  • Homozygous carriers of beta globin mutations; symptoms from infancy
  • Some patients with combination thalassaemia or HbH disease; symptoms from teenage or adulthood

Laboratory findings

  • Thalassaemia minor
    • Haemoglobin normal or no more than slightly lower than normal
    • MCV low (70±5 fl) despite normal iron stores
    • Mild erythrocytosis
    • Possibly slight changes in haemolysis parameters
  • Thalassaemia intermedia and major
    • Findings consistent with chronic haemolytic anaemia (LD elevated, haptoglobin cannot be measured) but no significant reticulocytosis
    • Microcytosis
    • Elevated plasma ferritin
    • N.B.! Plasma transferrin receptor levels are also elevated but the patients do not have iron deficiency. Instead, the elevated levels are due to haemolysis.

Diagnosis of thalassaemia

  • Analysis of blood haemoglobin fractions, plasma ferritin and basic blood count with platelet count
    • Analysis of haemoglobin fractions can only identify mutations in the beta globin gene. If suspicion of clinically significant alpha thalassaemia (symptomatic thalassaemia intermedia) arises, a gene test will be needed.
  • If the patient needs specialized care or genetic counselling, the diagnosis should be confirmed by gene testing in specialized care.
  • Measurement of spleen size by ultrasound examination, if thalassaemia is suspected

Treatment and follow-up Desferrioxamine Mesylate for Iron Overload in Transfusion-Dependent Thalassaemia, Oral Deferiprone for Iron Chelation in People with Thalassaemia

  • Patients with thalassaemia (minor, intermedia or major) should not be given iron supplementation unless they have confirmed iron deficiency anaemia.
  • If ferritin levels are low, the cause of the iron deficiency must be established and treatment started normally (cf. Iron Deficiency Anaemia).
  • If there are signs of active haemolysis, folic acid supplementation (1-5 mg/day) should be started.
  • Nearly all patients will need calcium/vitamin D supplementation.
  • If a patient with thalassaemia needs a red blood cell transfusion, it should be performed, in order to reduce immunization risk, using phenotyped red blood cells, if only possible.

Treatment chain

  • Thalassaemia minor
    • There is no need for monitoring but if the patient is of fertile age and, particularly, if his/her spouse is genetically from a region where haemoglobin mutations occur, genetic counselling should be kept in mind.
    • For pregnant women, see below here
  • Thalassaemia intermedia
    • Asymptomatic patients (Hb exceeding 90 g/l, P-Ferrit below 500 µg/l, no splenic symptoms) should be followed up at a primary health care centre (e.g. blood count and ferritin levels once a year). If anaemia increases, ferritin levels rise or the patient develops splenic symptoms, refer to specialized care.
    • Symptomatic thalassaemia or thalassaemia intermedia (fulfilling one or more of the following criteria: Hb below 90 g/l, ferritin above 500 µg/l, splenic or general symptoms): specialized care should be consulted
    • Pregnant women: as asymptomatic thalassaemia intermedia usually becomes symptomatic during pregnancy, haemoglobin levels need to be monitored more frequently at the maternal health centre, consulting the maternity outpatient department within specialized care, as necessary (see below here).
  • Thalassaemia major
    • The patients need specialized care.

Pregnant women

  • If anaemia develops (Hb below 90 g/l or significant decrease from previous level), check plasma ferritin level. If there is iron deficiency, start iron supplementation.
  • If there is no iron deficiency, refer the patient to a maternity outpatient department in specialized care.
  • After pregnancy, the patient will again become asymptomatic.
  • N.B.! A pregnant thalassaemia patient's spouse's blood count and haemoglobin fractions should be checked as early in the pregnancy as possible if the family has not been given genetic counselling and the spouse is from a region endemic for thalassaemia.
  • Patients with thalassaemia should start using folic acid supplementation already when planning pregnancy, unless they already use it (dosage 5 mg once daily).

Genetic counselling

  • Carriers of a thalassaemia gene who are of fertile age should be given genetic counselling. It is important to identify couples at risk of having a child with thalassaemia major or intermedia (e.g. if both parents are carriers).