Haemaglobinopathies Flashcards
What are haemoglobinopathies?
group of recessively inherited genetic conditions affected haemoglobin
What is the epidemiology of haemaglobinopathies?
- Not gender linked
- More prevalent in parts of world
What are 2 examples of haemaglobinopathies?
- sickle cell disease
2. thalassaemia
What are different types of thalassaemia?
- alpha thalassaemia (AT)
- Haemoglobin H disease
- Beta thalassaemia major (BT)
- Beta thalassaemia intermedia
What happens in thalassaemia?
Globin chain mutations causing quantitative defects
What are the possible alpha defects in AT and what do they lead to?
- Alpha + (mild anaemia)
- Alpha degree (mild anaemia)
- Hb H (significant anaemia )
- Hb Barts (death in utero no alpha genes)
What are the possible beta defects in BT and what are the effects?
- Beta minor (mild anaemia but v low MCV)
- Beta intermedia
- Beta major (severe anaemia presents first few months of life)
What does thalassaemia minor lead to?
resistance to falciparum malaria
What type of thalassaemia is rarer?
alpha
What are risk factors for AT?
- Found in malarial regions of world
2. FHx of AT
What are symptoms and signs of AT?
clinically well and asymptomatic
What are symptoms and signs of Hb H?
clinically well but risk of acute haemolytic epispdes, aplastic crisis etc
What anaemia symptoms may present with AT?
- fatigue
- Dizziness
- SOB
- Splenomegaly
What are symptoms and signs of BT?
- asymptomatic
- FHx
- ancestory
- If major can have hepatosplenomegaly, anaemia , growth retardation (show up in first 3-6 months of life) and jaundice
- Can lead to hemochromatosis
- Chipmunk face
- Hair on end on skull x ray
What are differential diagnosis for AT?
- Iron deficiency anaemia
- Beta-thalassamia
- Variant haemoglobins
- Anaemia of chronic disease
- Lead poisoning
SA - B12 deficiency anaemia
- Folate deficiency
- Other haemolytic anaemia
- Haematological malignancies
What investigations are done for AT?
- Hb
- MCV
- MCH
- RBC count
- Peripheral smear
- Reticulocyte percentage
- Serum iron
- Serum ferritin
What is Hb like in AT?
normal to low
What is MCV like in AT?
low
What is MCH like in AT?
low
What is rbc count like in AT?
increased
What would peripheral smear show in AT?
abnormal shape and size of cells, microcytic and hypochromic + target cells
What is reticulocyte percentage like in AT?
increased
What investigations do you do for BT?
- FBC
- Peripheral smear
- Reticulocyte count
- Haemoglobin analysis
- LFTs
- Plain X ray of skull
- Abdominal US
- Plain X ray of long bones
What is FBC like in BT?
microcytic anaemia
What is peripheral smear like in BT?
microcytic red cells, tear drops
What is reticulocyte count like in BT?
elevated
What are LFTs like in BT?
elevated total and unconjugated bilirubin and high LDH
How do you treat a crisis?
rbc transfusion
What is management of AT silent carrier or trait?
- avoidance of unnecessary iron supplementation
- if severe can have iron chelating e.g. deferoxamine
What is management of Hb H?
folic acid supplement
What is management of BT?
- Promote fitness, healthy diet, folate supplements
- Lifelong transfusions to keep Hb >90g/L
- Iron monitoring
What is life expectancy for BT trait?
normal
What chromosome is affected in AT?
16
What chromsome is affect in BT?
11
How do you confirm BT diagnsois?
Confirmed with Hb electrophoresis (low HbA and high HbF and HbA2)
How can you tell AT on Hb electrophoresis?
see HbH ahead of HbA with AT
What are the key investigations of thalassaemia?
- Microcytic anaemia + Film
- Normal Iron studies
- Gel Electrophoresis
What is the management of thalassaemia?
Regular red cell transfusions every 2-4 weeks with iron chelation regime
What makes up HbA1?
2 alpha and 2 beta
What makes up HbA2?
2alpha and 2delta
What makes up HbF?
2 alpha and 2 gamma
Where is thalassaemia common?
cyrpus (screening programme)
What gene is affected in alpha thalassaemia?
Chr 16
What gene is affected in alpha thalassaemia?
Chr11
Which thalassaemia is lethal?
Hb Barts
Which thalassaemia require life long transfusion?
- Hb H
2. Beta major
When do you have alpha chains?
before birth
When does beta chain synthesis increase?
have some when born but beta from early infancy
What is gamma synthesis like?
most gamma at birth and decreases
