Hb and Thalassaemia

Question 1

What is on the x and y axis of the Hb dissociation curve?

Answer 1

x = ppO2
y = HbO2(%)

Question 2

How does a left/ right shift of the O2 dissociation curve describe a change in affinity for oxygen?

Answer 2

Left = higher affinity
Right = lower affinity

Question 3

Recall 5 factors that affect the position of the O2 dissociation curve

Answer 3

[2,3-DPG]
pH
[CO2]
%HbS
%HbF

Question 4

Which direction does the O2 dissociation curve move in when the concentration of 2,3-DPG increases?

Answer 4

right

Question 5

Describe the effect of HbS/ HbF on the position of the oxygen dissociation curve

Answer 5

HbS increase –> right

HbF increase –> left

Question 6

What is the normal concentration of Hb in adults?

Answer 6

120-165g/L

Question 7

What mass of iron is contained within one gram of Hb?

Answer 7

3.4mg

Question 8

Recall the structure of haem

Answer 8

Protoporphyrin ring + central iron (usually ferrous)

Question 9

Where is haem synthesised and what enzyme is used?

Answer 9

Mitochondria - ALAS

Question 10

How many amino acids are in an alpha globin chain?

Answer 10

141

Question 11

How many amino acids are in a non-alpha globin chain?

Answer 11

146

Question 12

Recall the location and arrangement of the globin genes

Answer 12

Arrangement: 2 clusters - alpha = 2 x alpha and an epsilon gene, beta = beta, gamma and delta globin genes
Location: alpha = c16, beta = c11

Question 13

What globin chains make up foetal Hb?

Answer 13

alpha and gamma

Question 14

What is the normal adult concentration of erythrocytes?

Answer 14

3.5-5x10^12/ L

Question 15

When is Hb synthesised?

Answer 15

During development of erythrocyte: begins in pro-erythroblast stage and completed in reticulocyte stage

Question 16

Where are globin chains synthesised?

Answer 16

ribosomes

Question 17

Which globin chains make up HbA2?

Answer 17

2 alpha and 2 delta

Question 18

Recall the aetiology of beta thalassaemia

Answer 18

Defective/ absent beta globin chains

Question 19

Recall the inheritance of beta thalassaemia

Answer 19

recessive

Question 20

What is required to cause beta thalassaemia major?

Answer 20

2 copies of thalassaemia gene

Question 21

Which 3 tests can be done in the laboratory for beta thalassaemia

Answer 21

FBC
Blood film
HPLC

Question 22

Recall 2 findings in an FBC of someone with beta thalassaemia

Answer 22

1. Microcytic hypochromic indices

2. Increased RBC: Hb ratio

Question 23

Recall 3 features of a blood film in beta thalassaemia

Answer 23

Target cells
Poikilocytosis
NO anisocytosis

Question 24

How do beta and alpha thalassaemia differ when subjected to HPLC

Answer 24

Beta = raised hbA2 and HbF
Alpha = fairly inconspicuous

Question 25

What causes severe alpha thalassaemia?

Answer 25

Defect in 3 out of 4 alpha genes (4 is fatal in utero)

Question 26

What is the MAIN clinical presentation of thalassaemia?

Answer 26

severe anaemia

Question 27

What is the cause of hepatosplenomegaly in thalassaemia?

Answer 27

extramedullary haematopoiesis

Question 28

Describe the blood film in SEVERE thalassaemia

Answer 28

Gross hypochromia Poikiliocytosis Many nucleated erythrocytes

Question 29

How are iron levels affected by thalassaemia major?

Answer 29

Iron OVERLOAD

Question 30

Recall 3 possible effects of iron overload

Answer 30

Cholelithiasis Cardiac failure Endocrinopathies

Question 31

What are the first-line treatments for thalassaemia?

Answer 31

Blood transfusions | Iron chelation

Question 32

When should iron chelation be started?

Answer 32

When serum ferritin is >1000mcg/L | As early as poss to avoid iron overload

Question 33

Recall the 3 available drugs for iron chelation

Answer 33

Desferrioxamine Deferprone Deferasirox

Question 34

Compare the administration methods of each available iron chelator drug

Answer 34

Desferrioxamine is parenteral but deferiprone and defasirox are administered orally

Question 35

Compare the toxicity of each available iron chelator drug

Answer 35

Deferrioxamine: toxic to eyes, ears and bones Deferiprone: causes agranulocytosis, arthropathy and Zn deficiency Deferasirox has limited toxicity