Thalassaemia Flashcards
What are the normal chains in a haemoglobin molecule?
2 alpha chains and 2 beta chains
What are haemoglobinopatheis?
Inherited conditions resulting in a relative lack of normal globin chains due to absent genes or a variant globin chain
What does the severity of haemoglobinopathies depend on?
- Amount of abnormal haemoglobin
- Type of abnormal haemoglobin
- Ameliorating factors
What does the severity of haemoglobinopathies depend on?
- Amount of abnormal haemoglobin
- Type of abnormal haemoglobin
- Ameliorating factors
Describe the genetics of Hb production
- Globin chains are produced on ribosomes
* control of production is mainly at the transcription level and depends on the availability of haem
What happens if there is a problem with one of the alpha chain genes?
There are problems in utero, resulting in miscarriage early on in the pregnancy
What happens if there are problems with the beta genes?
They will experience problems in early childhood
Describe the haemoglobin chains from conception to childhood
•At conception:
- Gower 1: theta and epsilon chains
- Gower 2: alpha and epsilon
- Portland 1: theta and gamma
•Then produce Hb F: Alpha and gamma
•Then Hb A (majority after 3 months post partum): alpha and beta
•Small amount of Hb A2 produced just before birth and remains at less than 5% of Hb: alpha and delta
What is thalassaemia?
Relative lack of globin genes
What globin genes are we meant to have?
- 4 alpha globin genes on 2 Ch16
* 2 beta globin genes of 2 Ch 11
State the alpha gene permutations from least harmful to most harmful
- lacking on alpha gene: α+ thalassaemia trait
- Lacking 2 alpha genes, one on each chromosome: homozygous α+ thalassaemia trait
- Lacking 2 alpha genes on one chromosome: αo thalassaemia trait
- Lakcing 3 alpha genes: HbH disease
- No alpha genes: Alpha thalassaemia major
Describe the clinical significance of α+ thalassaemia trait
Will not be anaemic but may have mild microcytosis
Describe the clinical significance of homozygous α+/ αo thalassaemia trait
Microcytosis, increased red cell count and sometimes a very mild asymptomatic anaemia
Describe the clinical aspect of HbH disease
Significant anaemia (Hb approx 75g/l) and abnormal shaped small red blood cells
Describe the clinical significance of alpha thalassaemia major
not compatible with life as need alpha chains for foetal haemoglobin
Explain the pathogenesis of HbH disease
Because of the lack of alpha genes there is an excess of beta chains that join together
Describe the treatment of HbH disease
- Asymptomatic most of the time but may need treatment during periods of stress e.g. post op or pregnancy
- Blood transfusion
What is beta thalassaemia major?
- Autosomal recessive disorder
- Missing both beta genes
- Unable to make HbA (adult haemoglobin) resulting in significant dyserythropoiesis (abnormal red cells)
Describe a blood film in beta thalassaemia major
- Many different shapes
- Hypochromic
- microcytic cells
Describe a blood film in beta thalassaemia major
- Many different shapes
- Hypochromic
- microcytic cells
What may you see on a head x ray of someone with beta thalassaemia major?
Hair on end appearance due to bone changes
Describe the clinical management of beta thalassaemia major
- Transfusion dependent from a young age - first couple of years: 2-3 units every 3 weeks (consider venous port)
- Why it is also called transfusion dependent thalassaemia
- Due to transfusions will have iron overload - iron chelation and monitor organs affected by iron overload (heart, liver, endocrine, thyroid etc.)
- Consider bone marrow transplantation in childhood if sibling match
