Hb and Thalassaemia Flashcards
What is on the x and y axis of the Hb dissociation curve?
x = ppO2 y = HbO2(%)
How does a left/ right shift of the O2 dissociation curve describe a change in affinity for oxygen?
Left = higher affinity Right = lower affinity
Recall 5 factors that affect the position of the O2 dissociation curve
[2,3-DPG] pH [CO2] %HbS %HbF
Which direction does the O2 dissociation curve move in when the concentration of 2,3-DPG increases?
right
Describe the effect of HbS/ HbF on the position of the oxygen dissociation curve
HbS increase –> right
HbF increase –> left
What is the normal concentration of Hb in adults?
120-165g/L
What mass of iron is contained within one gram of Hb?
3.4mg
Recall the structure of haem
Protoporphyrin ring + central iron (usually ferrous)
Where is haem synthesised and what enzyme is used?
Mitochondria - ALAS
How many amino acids are in an alpha globin chain?
141
How many amino acids are in a non-alpha globin chain?
146
Recall the location and arrangement of the globin genes
Arrangement: 2 clusters - alpha = 2 x alpha and an epsilon gene, beta = beta, gamma and delta globin genes
Location: alpha = c16, beta = c11
What globin chains make up foetal Hb?
alpha and gamma
What is the normal adult concentration of erythrocytes?
3.5-5x10^12/ L
When is Hb synthesised?
During development of erythrocyte: begins in pro-erythroblast stage and completed in reticulocyte stage
Where are globin chains synthesised?
ribosomes
Which globin chains make up HbA2?
2 alpha and 2 delta
Recall the aetiology of beta thalassaemia
Defective/ absent beta globin chains
Recall the inheritance of beta thalassaemia
recessive
What is required to cause beta thalassaemia major?
2 copies of thalassaemia gene
Which 3 tests can be done in the laboratory for beta thalassaemia
FBC
Blood film
HPLC
Recall 2 findings in an FBC of someone with beta thalassaemia
- Microcytic hypochromic indices
2. Increased RBC: Hb ratio
Recall 3 features of a blood film in beta thalassaemia
Target cells
Poikilocytosis
NO anisocytosis
How do beta and alpha thalassaemia differ when subjected to HPLC
Beta = raised hbA2 and HbF Alpha = fairly inconspicuous
What causes severe alpha thalassaemia?
Defect in 3 out of 4 alpha genes (4 is fatal in utero)
What is the MAIN clinical presentation of thalassaemia?
severe anaemia
What is the cause of hepatosplenomegaly in thalassaemia?
extramedullary haematopoiesis
Describe the blood film in SEVERE thalassaemia
Gross hypochromia
Poikiliocytosis
Many nucleated erythrocytes
How are iron levels affected by thalassaemia major?
Iron OVERLOAD
Recall 3 possible effects of iron overload
Cholelithiasis
Cardiac failure
Endocrinopathies
What are the first-line treatments for thalassaemia?
Blood transfusions
Iron chelation
When should iron chelation be started?
When serum ferritin is >1000mcg/L
As early as poss to avoid iron overload
Recall the 3 available drugs for iron chelation
Desferrioxamine
Deferprone
Deferasirox
Compare the administration methods of each available iron chelator drug
Desferrioxamine is parenteral but deferiprone and defasirox are administered orally
Compare the toxicity of each available iron chelator drug
Deferrioxamine: toxic to eyes, ears and bones
Deferiprone: causes agranulocytosis, arthropathy and Zn deficiency
Deferasirox has limited toxicity
