Thalassaemia

Question 1

Thalassaemia general overview

Answer 1

Related to genetic defect in protein chains that make up haemoglobin

Normal haemoglobin consists of 2 alpha- and 2 beta- globin chains

defect in alpha/ beta leads to alpha/ beta thalassaemia

Both are Autosomal Recessive

SPLEEN:
RBCs are more fragile and break down more easily
- Spleen collects damaged/ destroyed RBCs
- results in splenomegaly

MARROW:

• Marrow expands to produce extra bood cells to compensate for chronic anaemia
• Causes suceptibility to fractures
• Features such as pronounced forehead and malar eminences (cheek bones)

Question 2

Signs and symptoms of thalassaemia

Answer 2

Microcytic anaemia (low MCV)

Fatigue

Pallor

Jaundice

Gallstones

Splenomegaly

Poor growth and development

Pronounced forehead and malar eminences

Question 3

Diagnosis of thalassaemia:

Answer 3

FBC - shows microcytic anaemia

Haemoglobin electrophoresis - used to diagnose globin abnormalities

DNA testing - can be used to look for the genetic abnormality

SCREENING - offered to pregnant women

Question 4

Iron overload in thalassaemia:

Answer 4

result of faulty creation of RBCs, recurrent transfusions, increased absorption of iron in response to the anaemia

Patients with thalassaemia have serum ferritin levels mornitored to check for iron overload.

Question 5

Management of iron overload:

Answer 5

Patients with thalassaemia have serum ferritin levels monitored to check for iron overload

Management involves:

• limiting transfusions
• Iron chelation

Effects of iron overload similar to haemochromatosis

Question 6

Effects of iron overload in thalassaemia

Answer 6

Similar to those of haemochromatosis:

Fatigue
Liver cirrhosis
Infertility and impotence
Heart failure
Arthritis
Diabetes
Osteoporosis and joint pain

Question 7

Alpha-thalassaemia

Answer 7

Alpha-thalassaemia is caused by defects in alpha-globin chains. The gene coding for this protein is on chromosome 16.

Question 8

Management of Alpha-thalassaemia

Answer 8

Monitoring the full blood count

Monitoring for complications

Blood transfusions

Splenectomy may be performed

Bone marrow transplant can be curative

Question 9

Beta-thalassaemia

Answer 9

Beta-thalassaemia is caused by defects in beta-globin chains.

The gene coding for this protein is on chromosome 11.

Gene defects can either consist of:

• abnormal copies (retains some function)
• Deletion genes (where there is no function in beta-globin protein at all)

Subdivided into 3 types:

• Thalassaemia minor
• Thalassaemia intermedia
• Thalassaemia major

Question 10

Thalassaemia minor

Answer 10

beta thalassaemia minor are carriers of an abnormally functioning beta globin gene. They have one abnormal and one normal gene.

Causes:
- mild microcytic anaemia

Patients usually only require monitoring and no active treatment

Question 11

Thalassaemia major

Answer 11

Patients with beta thalassaemia major are homozygous for the deletion genes.

No functioning beta-globin genes at all

most severe form and resents with severe anaemia and failure to thrive in early childhood

Results in:
- Severe microcytic anaemia
Splenomegaly
Bone deformities

Management:
regular transfusions

iron chelation

splenectomy.

Bone marrow transplant - can potentially be curative.

Question 12

Management of thalassaemia major:

Answer 12

Regular transfusions

Iron chelation

Splenectomy

Bone marrow transplant - potentially curative

Question 13

Thalassaemia intermedia

Answer 13

Patients with beta thalassaemia intermedia have two abnormal copies of the beta-globin gene

Either:

• two defective genes
• one defective gene and one deletion gene

Causes:
- more significant microcytic anaemia

Patients require monitoring and occasional blood transfusion
- If more transfusions needed, they may also require iron chelation to prevent iron overload