Thalassaemia Flashcards
Normal Hb structure
Haem + 2 alpha + 2 Beta
Foetal Hb structure
Haem + 2 alpha + 2 gamma
Hb delta structure
Haem + 2 alpha + 2 delta chains
Percentage of normal Hb in the blood
97%
Percentage of HbA2 in blood
2%
Percentage of HbF in adult blood
1%
What are thalassaemias
Genetic disease of unbalanced Hb synthesis (no production of one global chain)
Consequence of imbalance in global chains
Cell damage and death of precursors in bone marrow -HAEMOLYSIS
What is Beta and Alpha thalassaemia
Beta - reduced B chain synthesis
Alpha - reduced A chain synthesis
What is the result of Beta thalassaemia having no B chains present
Excess alpha chains combine with delta and gamma chains
Increased HbA2 and HbF
How is Beta thalassaemia caused
Point mutations - porudicing unstable B-globins that can’t be used
What is the most common type of B-thalassaemia
B-thalassaemia minor - hetereozygous state
Symptoms of BT - minor
Asymptomatic
Is anaemia present in BT - nor
YEs but mild/almsot absent
Appearance of RBCs
Hypo chromic
MICROCYTIC
What can BT- minor be confused with
iron-deficiency anaemia
How can this be distinguished from iron-deficiency anaemia
Serum ferritin and iron levels should be normal
Hb electrophoresis shows raised HbA2 and HbF
What is BT- Intermedia
Symptomatic wit h MODERATE ANAEMIA - no transfusion required
Clinical features of BT - Intermedia
Splenomegaly Bone deformities Recurrent leg ulcers Gallstones Infections
When does BT-major present
Children - homozygous
Signs of BT-major
- Recurrent bacterial infections
- Severe anaemia from 3-6 months (when switch from gamma to beta chain usage should occur)
- Extramedullary haemtopoiesis
What is Extramedullary haematopoiesis
Ineffective RBC production outside marrow = hepatosplenomegaly and bone expansion - thalassaemic face
Treatment of BT- major
Transfusion
Result of hypertrophy of ineffective bone marrow in BT-major
Bone abnormalities
What would a skull x-ray in BT-major show
Hair on end sign - increased marrow activity
Blood results for BT-major
Microcytic
Blood films for BT-major
Large + small irregular hypo chromic RBCs
Ferritin levels in BT-major
Normal
How is B-thalassaemia diagnosed
- Hypochromic microcytic anaemia
- Raised reticulocyte
- Nucleated RBC in circulation
Haemoglobin electrophoresis
How is Beta-thalassaemia treated
Every2-4 weeks life-long transfusion + suppress ineffective extra medullary haematopoiesis to allow normal growth
Iron-chelating agents
Ascorbic acid
Splenectomy
Bone marrow transplant
Folic acid
What level should Hb be kept above
90g/L
Name two iron-chelating agents
Oral DEFERIPRONE + SC DESDERRIOXAMINE
Side-effects of iron-chelating agents
Pain
deafness,
cataracts
Retinal damage
Why are iron-chelating agents needed
Stop iron overload
Why do we decrease iron loading
During infusions
Why do we give ascorbic acid
Increase urinary excretion of iron
When do we do a splenectomy
If large spleen persists with increasing transfusion
Complications from transfusion
- Progressive increase in body iron load
- Mainly deposited in the liver + spleen reulsting in liver fibrosis + cirrhosis
- Deposited in endocrine glands and heart = diabetes
How are alpha-thalassaemias caused
Gene deletions
Gene for alpha-globing chains is duplicated on chromosome 16 + one alpha chain (more common) or both alpha-chain genes can be deleted
Clinical presentation of alpha-thalassaemia (in four gene deletion- where both genes on both chromosomes occur)
No alpha chain synthesis
Hb BARTS present (4 gamma chains)
What is the problem with Hb Barts
Can’t carry O2 so incompatible with life
Children are stillborn - pale, oedematous and have enormous livers + spleens)
Consequence of 3 gene deletion in alpha-thalassaemia
Reduction in alpha chains = HbH increase (has four beta-chains)
Symptoms of three gene deletion in alpha-thalaassaemia
MODERATE ANAEMIA
SPLENOMEGALY
(patient is not transfusion dependant)
Two gene deletion alpha-thalassaemia signs
Microcytosis - mild anaemia
One gene deletion alpha-thalassaemia signs
Normal blood
