Thalassaemias Flashcards
What is a thalassaemia?
Autosomal recessive disorder causing reduced globin chain synthesis -> impaired Hb production
What condition does thalassaemia lead to?
Microcytic anaemia
What are the types of thalassaemia?
Alpha- affects α chains
Minor, moderate and major
Beta- affects β chains
Minor and major
What does alpha thalassaemia affect?
HbA, HbA2, and HbF
Pathophysiology of alpha thalassaemia
Unaffected people have 4 alpha genes on chromosome 16
Alpha thalassaemia involves deletion of one or both α chains from chromosome 16 -> defective alphaglobin chains
What is α thalassaemia silent carrier?
One deleted chain
Usually asymptomatic
What is α thalassaemia trait (minor)?
1 or 2 deleted chains
Patients usually experience mild anaemia with no need for treatment
What is HbH disease?
Moderate α thalassaemia
Both chains deleted, excess β chains form tetramers called HbH
Very low MCV and MCH, with moderate-severe anaemia symptoms
Common in SE Asia
Presents with jaundice and splenomegaly
What is Hydrops Fertalis?
All chains deleted
Gamma chains form tetramers of Hb Barts (𝛾4) and HbH (β4)
Usually incompatible with life- fatal before or shortly after birth
What does β thalassaemia affect?
β globin chain deletion on chromosome 11
Only affects HbA
How is β thalassaemia classified?
Trait, intermedia, or major
Dependent on clinical severity, usually caused by point mutations
What is β thalassaemia trait?
One defetive β chain present
Typically asymptomatic, but MCV/MCH low and HbA2 high
What is β thalassaemia intermedia
2 defective chains or one defective and one absent
Both genes affected, so more severe and may require occasional transfusion
What is β thalassaemia major?
Both chains absent
Severe presentation and requires lifelong transfusion dependency
How do thalassaemias present?
Minor forms often asymptomatic
Major forms:
Present in early life
Pallor, failure to thrive
Anaemia symptoms
Chipmunk faeces
Hepatosplenomegaly and jaundice
Not much HbA on analysis
Investigations for thalassaemia
Bloods show microcytic anaemia, low MCV, low Hb and low MCH
Electrophoresis can be used to quantify types of Hb present
How is thalassaemia treated?
Minor may be left untreated
Major requires lifelong transfusion to maintain Hb levels, and monitoring iron levels to prevent overload
Bone marrow transplants may be curative
What is iron overload?
Complication of transfusion
Can cause:
endocrine dysfunction eg diabetes
Cardiac disease eg arrhythmias
Liver disease eg cirrhosis
Osteoporosis
How is iron overload treated?
Iron chelation
Via drugs eg desferrioxamine
