Thalassemia is a genetic haemoglobinopathy (A disease of the red blood pigment haemoglobin). The name thalassemia is derived from the Greek thalassa = sea and (h)aima = blood. The disease was discovered and described first by an American Doctor Cooley who treated Italian patients.

The haemoglobin is the transport molecule of oxygen in the blood. It consists of four globin chains. Adults have 2 α- and 2 β-globin chains. Thalassemia is characterised by many different mutations (genetic errors) which cause a change in the structure of the haemoglobin protein. (A gene is the construction plan for a protein. Every protein has a specific task. The protein haemoglobin binds oxygen in the lungs and transports it to the places in the body which need the oxygen, e.g. the muscles.) Depending on whether the α- or the β- globin chain contains the mutation, one describes the α- or β- Thalassemia. As a safety precaution, the body has various copies of these genes. If however both parents pass on the same mutated gene, the consequences and constraints are much more serious for the patient. If a person has sufficient functioning copies of the gene, and if only one faulty gene is inherited from the mother or the father, a thalassemia minor is described. With the thalassemia minor the patients seldom have symptoms, a slightly low haemoglobin value occurs and a treatment is not required. These patients are called carriers. If however, no or only few functioning gene copies are present (also if haemoglobin mutations are inherited from both mother and father), a serious thalassemia or a Thalassemia major is described. Often a treatment from the 9th-12th month of life is inevitable. The consequences of the disease are otherwise grave or even fatal. Thalassemia intermedia is an intermediate form of the disease, which requires treatment only in certain stages of life. The β- Thalassemia is more common than the α-Thalassemia. A possible explanation for the existence of the grave Thalassemia major is, that the carriers have a benefit against Malaria disease.

The most important Thalassemias

General Clinical Classification:

(Aufgrund der Symptomatik/Erscheinen der Krankheit)

Thalassemia minor

- 1 faulty gene copy (mutated gene inherited from 1 parent only = heterozygote)
- Mild microcytic anaemia, maybe a slightly enlarged spleen, no further symptoms.

Thalassemia major

- 2 faulty gene copies (mutated gene inherited from both parents = homozygote)
- Seldom, but grave. Patients need regular blood transfusions.

Thalassemia intermedia

- 2 faulty gene copies (mutations inherited from both parents = homozygote)
- Special type of homozygoteous Thalassemia (gene inherited from both parents, but alleviating additional changes in the blood production, e.g. lifelong production of HbF, and other changes)

Patients with Thalassemia intermedia need blood transfusions only occasionally.

β – Thalassemia (occurs often in the Mediterranean Regions)

2 gene copies exist which code for the β-globin chain

β-Thalassemia minor
Microcytic Anaemia, slightly enlarged spleen, no other symptoms.

β-Thalassemia major
Synonym: Cooley-Anaemia
Patients have no normal β-globin chains at all.
Grave form of Thalassemia Blood transfusions are necessary from the 6th-12th month of life. Children without blood transfusions cannot survive middle termly. Foetal Haemoglobin (HbF) consists of' 2 α- and 2 γ –globin chains, and contains no β-globin chains. It is produced in the early months of life and is successively replaced by adult Haemoglobin with β-globin chains. HbF is the reason that children do not need blood transfusions directly after birth and in the first few months of life. When the production of the γ-globin chains decreases, the need for β-globin chains increases. Because the β-globin chains cannot be produced sufficiently, the deficit becomes clinically noticeable, when symptoms arise.

β-Thalassemia intermedia
Special type of homozygoteous Thalassemia
Patients with Thalassemia intermedia need blood transfusions only occasionally from the first year of life, in specific phases or with complications (infections, pregnancy or during growth).

α – Thalassemia (occurs often in Asia and Africa)

4 gene copies exist which code for the α-globin chain; because of the 4 copies, α – Thalassemia presents itself differently.

α – Thalassemia minima: 1 faulty gene copy, no symptoms

α – Thalassemia minor: 2 faulty gene copies, no symptoms, maybe a slight change in blood tests

α – Thalassemia intermedia: 3 faulty gene copies Synonym: HbH-disease = Haemoglobin H disease. HbH consists of 4 β-globin chains. (Normal haemoglobin: 2 α and 2 β – globin chains). Mild to severe symptoms: Anaemia, Hepatosplenomegaly (enlargement of liver and spleen), deficiency of folic acid, gall stones.

α – Thalassemia major:  4 faulty gene copies, non-viable form of Thalassemia, Affected children mostly die before birth.

Causes of α- and β-Thalassemia

Thalassemia is inherited from the mother and/or father. The parents pass on a mutation to their child (gene fault). This mutation is situated in the gene, which is responsible for the protein haemoglobin (either for the α- or for the β-globin chain). Haemoglobin is the red blood pigment which binds oxygen in the lungs and transports it in the body. Because the construction plan for the protein haemoglobin is faulty in Thalassemia, the protein cannot fulfil its function of transporting oxygen in the body.

Occurrence and frequency


- 5 Mio affected people world wide
- α – Thalassemia: South-East Asia, Africa, Middle-East, Mediterranean Region
- β – Thalassemia: Mediterranean Region (Thalassemia und iron-deficiency are the most common causes for hypochromic anaemia)


Switzerland: Especially immigrants and their descendants


β – Thalassemia major: (Thalassemia intermedia could show similar symptoms, however not as severe).

Enlargement of spleen and liver (hepatosplenomegaly)

- Visibly large Abdomen: normally the blood production (erythropoiesis) in the red bone marrow is sufficient, and after birth the blood production in the spleen and liver terminates. However in Thalassemia patients, the blood production in the bone marrow does not produce functioning red blood cells (erythrocytes), whereupon the body requires more blood cells from the spleen and liver. Because Thalassemia is a genetic disease, the red blood cells from the spleen and liver are also non-functioning. This abnormal production of blood cells results in enlargement of bone marrow, but also of spleen (splenomegaly) and liver (hepatomegaly).

Bone deformation

- Increase of bone volume: the bones grow broader and become more brittle. Due to anaemia (deficit of red blood cells), the bone marrow produces even more non-functioning red blood cells and enlarges. The bones become thicker or broader and unstable. Due to the structural changes of the bone, it can no longer fulfil its other functions, e.g. its stability. This leads to fractures.

- Tower skull (oxycephaly), hair-on-end sign in radiography, high arched palate.

Impaired growth

- Consequence of iron-overload after repeated blood transfusions

Differential diagnosis - What else could it be?

The iron-deficiency anaemia can resemble Thalassemia. With Thalassemia the ferritin level can be normal or high. The diagnosis of iron-deficiency is more common and should hence be eliminated before diagnosing Thalassemia.


- Blood test

- Analysis of blood cells (erythrocytes, leucocytes, thrombocytes), their structure and number
- Hypochromic, microcytic, hyper regenerative anaemia (small, pale erythrocytes; higher reticulocyte levels (young erythrocytes))
- Metzner Index (Ratio of MCV in fl and erythrocytes in mio/ul) <13

Conservative Therapy / Medication an blood transfusions

Necessary with severe symptoms (symptoms which restrict the patient in daily activities): daily intake of medication or injections are inevitable.

Blood transfusions

by transfusing blood, the patient receives enough red blood cells and stops producing his own. This leads to the amelioration of all symptoms (incl. hepatosplenomegaly, bone fractures, etc.) and prevents further symptoms.

- Iron-overload after repeated transfusions

When transfusing the patient regularly, he also receives the iron from the donor which is situated in the erythrocytes. The human body however does not have an opportunity to get rid of its excess iron. The iron hence sediments in the organs. In the past this lead to grave organ damage, and was the most common cause of death before the discovery of chelators.

Iron elimination with iron chelators

Chelators bind the excess iron in the body. The body can then eliminate the iron via the kidneys and urine. The adverse effects of blood transfusions are manageable with this treatment and a normal life can be lived. However, chelators do not treat the cause of the disease. Up to date, only 3 chelators are available on the market, each with its own benefits and adverse effects. The medical doctor decides upon the treatment for each patient individually.


-  Component: Deferoxamin / Name: Desferal

- Iron is eliminated via the bowel or the kidney
- Injection or intravenous therapy
- Time-consuming therapy during the whole night
- Today not as commonly used, as there are newer therapies available which are easier to use.
- Best known and safest chelator therapy

- Component: Defarasirox / Name: Exjade

- Once daily
- Dissolve in water and take orally
- Could lead to reversible kidney disease
- Relatively new but safe chelator therapy

- Component: Deferipron / Name: Ferriprox

- If patient does not tolerate Desferal or Defarasirox
- 3 times daily
- Can be used to eliminate iron out of the heart muscle
- Many tablets o Can lead to pain in joints
- Decreases amount of white blood cells – patients become prone to infections
- Blood tests every 4-12 weeks

All patients with iron overload should go for an organ screening check-up once to twice yearly. The heart, the kidneys and the lungs are examined. The dosage and intake of the chelator therapy is adjusted according to the iron sediments in the organs, and to the Ferritin value in the blood test.

Hormone Therapy

If the iron overload reaches an iron intoxication and affects hormone producing organs, the hormones have to be substituted pharmaceutically. This is essential for child growth and to ensure metabolism regulation.

Causal Therapy

syn. Kausaltherapie

The only chance for a full healing and recovery of Thalassemia major is a Stem cell-Transplant, or a bone marrow transplant. The donor can either be a sibling or an unknown person. The transplant can omit the long term adverse effects of blood transfusions.

The success of the therapy is >90% with a sibling donor, and 80-85% with an unknown donor if the transplantation is done before the 16th year of life. Each child should receive a transplant if an identical donor exists. The suitable donor is determined in specific laboratory tests.


A few decades ago: No survival of Thalassemia major without regular transfusions
Today: all children reach adulthood. With new treatments and therapies life expectancy is barely affected.

Choose your language! Wähle deine Sprache! Scegli la tua lingua! Choisissez votre langue!

© by Swiss Haemoglobinopathy Platform - Impressum

Questions? Contact the webmaster!