Thalassaemias Flashcards
Define thalassaemia?
Heterogenous group of recessively inherited (genetic), haematological disorders characterised by abnormal alpha/beta globin chains produced during haemoglobin synthesis
In which 3 ethnicities is thalassaemia most prevalent?
Asian, african, mediterranean ancestry
What are the 2 ways of classifying thalassaemia?
Severity
Which type of globin chain is abnormal
How is is decided whether thalassaemia should be classified as alpha or beta thalassaemia?
Alpha-thalassaemia: Abnormal alpha-globin produced during Hb synthesis
Beta-thalassaemia: Abnormal beta-globin produced during Hb synthesis
What is meant by the classification Thalassaemia major (homozygous)?
Very few or no normal globin chains, which causes severe complications
Why is thalasaemia major also called transfusion-dependent thalassaemia?
Patient dependent on lifelong Packed Red Blood Cell (PRBC) transfusions (transfusion-dependent thalassaemia) every 3-4 weeks
How often will a patient with thalassaemia major require a PRBC transfusion and why?
Every 3-4 weeks
To maintain Hb level above 100g/L to suppress erythropoiesis
Why might a patient with thalassaemia undergo a splenectomy?
To reduce transfusion-dependence
Why might a patient with thalassaemia take iron-chelator drugs?
Erythropoiesis suppression and constant transfusion increases risk of iron overload
What is the only curative method for thalassaemia major, and what are the 2 indications?
Allogeneic bone marrow stem cell transplantation
Severe disease and before onset of end-organ failure
What mutations cause beta thalassemia major (Cooley’s anaemia)?
2 missing/defective beta genes
What is the typical onset age for beta thalassaemia major?
First 2 years of life (infancy)
What is the typical initial clinical feature of beta thalassaemia major, and at what age does it present?
Severe anaemia in 3-6 months old
What are the 2 common presentations of beta thalassaemia major?
Hepato-speglomegaly (liver and spleen swell)
Bone marrow expansion, which causes skull and long bones to deform
How is beta thalassaemia major detected in newborns, and what is the management?
Newborn screening programme to detect disorder
Positive newborns will receive transfusions to prevent symptom manifestation
What mutation causes alpha thalassaemia major (hydrops foetalis)?
Deletion of all 4 alpha genes
Why does alpha thalassaemia major (hydrops foetalis) cause foetal death?
Foetal Hb (HbF) needs alpha-globin to develop into HbA (adult Hb)
But there is no alpha globin as all 4 genes are deleted
What are the 4 common symptoms of alpha thalassaemia major?
Thickened placenta
Large amounts of amniotic fluid
Foetal heart enlarges
Foetal hepato-splenomegaly
Define thalassaemia intermedia and describe its complications?
Clinical presentation between thalassaemia major and minor/trait, but complications are usually more typical of major
What mutation causes alpha-thalassaemia intermedia (Hb H disease)?
Deletion of 3 alpha genes and association of 4 beta-globin chains
Is alpha thalassaemia intermedia transfusion dependent or independent?
Variable presentation, so can be transfusion dependent or independent
What is meant by thalassaemia minor (trait) (heterozygous)?
Reduced normal globin chains, so Hb level is low normal (mild microcytic anaemia) which causes patient to present as asymptomatic
What anaemia typically presents in thalassaemia minor?
Mild microcytic anaemia
In thalassaemia minor, do patients typically present as symptomatic or asymptomatic?
Asymptomatic
Is thalassaemia minor transfusion dependent or independent?
Transfusion-independent thalassaemia
Why is important to identify and provide genetic counselling for patients with thalassaemia minor?
2 people with trait can procreate with 25% chance of child inheriting thalassaemia major
Why is it important to identify thalassaemia minor as the cause of anaemia?
People can undergo unnecessary treatment if mistaken for IDA
eg. given iron supplements
What mutation causes beta thalassaemia trait?
One normal beta gene out of the 2 genes
Compare the presentation of alpha and beta thalassaemia trait?
Very similar but more severe anaemia
What are the classifications of severity for thalassaemia?
Thalassaemia major (homozygous)
Thalassaemia intermedia
Thalassaemia minor (trait) (heterozygous)
