Thalassaemia Flashcards
Definition
A group of genetic disorders characterised by reduced globin chain synthesis
Aetiology
- Autosomal recessive
- Result in an imbalance of globin chain production and deposition in erythroblasts and erythrocytes
• This leads to: o Ineffective erythropoiesis o Haemolysis o Anaemia o Extramedullary haematopoiesis
Types (alpha)
o ALPHA THALASSEMIA - reduction in alpha-globin chain synthesis. There are
FOUR alpha-globin genes on the chromosome.
• 4 gene deletion = Haemoglobin Barts Hydrops Fetalis (intrauterine death)
• 3 gene deletion = Haemoglobin H –> microcytic hypochromic anaemia and
splenomegaly
• 2 gene deletion = Alpha 0 thalassemia –> microcytic hypochromic red cells, NO ANAEMIA
• 1 gene deletion = Alpha+ thalassemia –> microcytic hypochromic red cells, NO ANAEMIA
Types (beta)
o BETA THALASSEMIA
• Beta Thalassemia Major (homozygous beta thalassemia) –> little or no
beta-chain synthesis
• Beta Thalassemia Intermedia - mild defect in beta-chain synthesis leads to:
▪ Microcytic anaemia
▪ Reduced alpha-chain synthesis
▪ Increased gamma-chain synthesis
• Beta Thalassemia Trait (heterozygous carrier state)
▪ ASYMPTOMATIC
▪ Mild microcytic anaemia
▪ Increased red cell count
Epidemiology
- WORLDWIDE
* Most common in the MEDITERRANEAN and areas of the Middle-East
Presenting symptoms
• Beta Thalassemia Major o Anaemia o Presenting at 3-6 months • This is when the change from HbF to HbA takes place • Failure to thrive • Prone to infection
• Alpha or Beta Thalassemia Trait
o May be ASYMPTOMATIC
o Detected during routine blood tests or due to family history
Signs on physical examination
Beta Thalassemia Major
o Pallor
o Malaise
o Dyspnoea
o Mild jaundice
o Frontal bossing
o Thalassaemia facies (facial features caused by marrow hyperplasia)
o Hepatosplenomegaly (due to erythrocyte pooling and extramedullary
haematopoiesis)
o Patients with beta-thalassemia intermedia may also have these signs
Investigations (bloods)
o FBC
- Low Hb
- Low MCV (microcytic anaemia)
- Low MCH
Investigations (blood film)
o Hypochromic microcytic anaemia
o Target cells
o Nucleated red cells
o High reticulocyte count
Investigations (other)
• Hb Electrophoresis
o Absent or reduced HbA
o High HbF
• Bone Marrow
o Hypercellular
o Erythroid hyperplasia
• Genetic Testing (rarely used)
• Skull X-Ray
o ‘Hair on end’ appearance in beta thalassemia major
• This is caused by expansion of marrow into the cortex