Thalassaemia

Question 1

What?

Answer 1

Genetic diseases of unbalanced Hb synthesis
Underproduction of one globin chain -> unmatched globins precipitate -> damage to RBC membranes -> haemolysis whilst still in BM
Common in Mediterranean to Far East
Beta chain problem

Question 2

Types

Answer 2

Beta thalassaemia minor or trait - heretozygous, carrier
Beta thalassaemia media - intermediate stage
Beta thalassaemia major (Cooley’s anaemia)

Question 3

Minor

Answer 3

Carrier state
Usually aymptomatic
Mild, well-tolerated anaemia -may worsen in pregnancy
Often confused with iron deficiency anaemia

Question 4

Intermedia

Answer 4

Moderate anaemia - not requiring transfusions
Splenomegaly
Mild homoxygous mutation or heterozygous, two different mutations

Question 5

Major (Cooley’s)

Answer 5

Homozygous
Presents in 1st year
Severe anaemia and FTT
Extramedullary haematopoiesis occurs in response to anaemia -> frontal bossing and hepatosplenomegaly (also due to haemolysis)
Skull xray: hair on end sign due to increased marrow activity
Life long blood transfusions needed
After about 10 years old, the transfusions result in iron deposition -> endocrine failure (pituitary, thyroid, pancreas); liver disease and cardiac toxicity
Film: hypochromic, microcytic cells + target cells + nucleated cells

Question 6

Inv

Answer 6

FBC
MCV
Film
Iron
HbA2, HbF
Hb electrophoresis
MRI to monitor myocardial siderosis

Question 7

Treatment

Answer 7

Promote fitness and healthy diet; folate supplements
Regular (2-4x/week) transfusions -> Hb >90, allow growth, stop extramedullary haematopoiesis
Iron-chelators to prevent overload (-> hypothyroid, hypogonadism): Oral deferiprone and SC desferrioxamine 2x/week. SE: pain, deafness, cataracts, retinal damage
Large doses of ascorbic acid -> urinary excretion of iron
Splenectomy if hypersplenism persists - wait until >5yo due to risk of infection
Hormonal replacement/treatment for endocrine complications
Histocompatible SCT

Question 8

Prevention

Answer 8

Genetic counselling

Antenatal diagnosis using fetal DNA

Question 9

Alpha thalassaemias

Answer 9

Due to deletions
There are 4 alpha genes
All four deleted -> death in utero (barts hydrops)
3 deleted -> moderate anaemia, haemolysis (hepatosplenomegaly, leg ulcers, jaundice)
2 deleted -> asymptomatic carrier state, low MCV
1 deleted -> clinically normal