Thalassemias Flashcards
What is the normal structure of haemaglobin?
Tetramer made up of 2 alpha globin like chains and 2 beta globin like chains.
One haem group is attached to each globin chain. Different haemoglobin chains are:
- 2 alpha and 2 bea
- 2 alpha and 2 delta
- 2 alpha and 2 gamma
What are thalassemias?
These are genetic diseasses of unbalanced Hb synthesis, with underprodution or no production of one globin chain. Unmatched globins precipitate, damaging RBC membranes, causing their haemolysis while still in the marrow.
What are the main types of thalassemia?
- Alpha thalassemia - reduced alpha chain synthesis
- Beta Thalassemia - reduced beta chain synthesis
What is alpha thalassaemia?
Mutations affecting the apla globin chain synthesis. Alpha chains present in all adult forms of Hb therefore HbA, HbA2 and HbF all affected.
What are three forms of alpha thalassaemia?
- A thalassaemia - one or two genes missing, asymptmatic.
- HbH disease - only one alpha gene left. Severe form of a thalassaemia.
- Hb Barts hydrops fetalis - no functional a genes so HbA cannot be made.
Clinical features of Hb Barts hydrops fetalis
- Severe anaemia
- Cardiac failure, oedema
- Growth retardation
- Severe hepatosplenomegaly
- Skeletal and cardiac abnormalties
- Most die in utero
What is the main issue in Beta thalassemia?
Homozygous β-thalassaemia - either no normal β chains are produced (β0) or β-chain production is very reduced (β+). There is an excess of α chains, which precipitate in erythroblasts and red cells causing ineffective erythropoiesis and haemolysis. The excess α chains combine with whatever β, δ and γ chains are produced, resulting in increased quantities of HbA2 and HbF and, at best, small amounts of HbA.
Heterozygous β-thalassaemia - usually symptomless microcytosis with or without mild anaemia.
What are the main genetic defects involved in beta thalassemia?
Mainly point mutations rather than gene deletions
How is beta thalassemia subdivided clinically?
- Thalassaemia minor
- Thalassaemia intermedia
- Thalassaemia major
What are features of beta thalassemia minor?
- Asymptomatic
- Mild hypochromic microcytic anaemia
What are features of beta thalassemia intermedia?
- Moderate anaemia - not requiring transfusion
- Splenomegaly
- Boney deformity
What are clinical features of B-thalassemia Major?
Presents in 1st year
- Severe anaemia
- Recurrent bacterial infections
- Failure to thrive
- Boney deformity - extramedullary haemopoeisis
- Hepatosplenomegaly - due to haemolysis
- Osteopenia
Extramedullary haemoptysis: hepatosplenomegaly, skeletal cahnges, organ damage
Why do individuals with thalassemia get bony deformities?
Chipmunk Facies
Extramedullary haematopoiesis (EMH) is the cause of the facies in this setting.
This leads to decreased normal haemoglobin synthesis and increased red blood cell destruction. To compensate for the low Hb, the bone marrow increases activity (hyperplasia) and haematopoiesis also takes place outside the bone marrow.
What are the most commonly affected bones in thalassemia (for bony deformity)?
- Skull
- Facial bone
- Ribs
- Limbs
- Extremities
- Spine
What investigations might you do for someone who you suspected had thalassemia?
- Bloods - FBC, Ferritin, Serum Iron, TIBC
- Blood film - Hypochromic, microcytic cells + target cells + nucleated RBCs
- X-ray - characteristic ‘hair on end’ appearance of bony trabeculation as a result of expansion of the bone marrow into cortical bone
- Haemoglobin assays - HbF increased
