Haemoglobinopathies

Question 1

what are the haemoglobinopathies (2)

Answer 1

thalassaemia

sickle cell

Question 2

where are haemoglobinopathies common (not UK)

Answer 2

SE asia

Africa

Question 3

what is the primary problem in thalassaemia

Answer 3

abnormal globin production

Question 4

what type of anaemia does thalassaemia cause

Answer 4

microcytic anaemia (same as iron deficiency)

Question 5

in alpha thalassaemia, which chromosome is the mutation on

how many alpha genes are on this chromosome
hence how many alpha genes do we have in total (x2 for each parent)

clinical significance of this

Answer 5

16

2 alpha genes on each chromosome 16
so 4 alpha genes altogether

means you need 2 copies of gene to have complete failure of alpha chain synthesis (if one copy = just reduced synthesis)

Question 6

what type of haemoglobin (HbF, HbA HbA2) does alpha thlassaemia affect

Answer 6

all! bc they all contain alpha subunits

Question 7

how many of the 4 alpha genes is someone missing if they have alpha thalassaemia trait

Answer 7

one or 2

Question 8

treatment of alpha thalassaemia trait

Answer 8

nothing - theyre fine

Question 9

how many of the 4 alpha genes is someone missing if they have HbH disease (type of alpha thalassaemia)

Answer 9

3 missing = only 1 of the 4 remains

Question 10

what happens in HbH disease (type of alpha thalassaemia)

Answer 10

all the unbound beta chains form a HbH haemoglobin (not functional)

Question 11

how many of the 4 alpha genes is someone missing if they have Hb barts hydrops (hydrops fetalis)

what does this mean

Answer 11

all 4 missing = no alpha genes

cant make any HbA

Question 12

most severe form of alpha thalassaemia

prognosis

Answer 12

Hb bart hydrops (hydrops fetalis)

most die in utero

Question 13

management of HbH disease (type of alpha thalassaemia)

Answer 13

transfusion

splenectomy

Question 14

presentation of HbH disease (type of alpha thalassaemia)

why does this happen

Answer 14

splenomegaly and jaundice

from hemolysis - breakdown of RBCs (HbH) bc theyre useless

Question 15

in beta thalassaemia, which chromosome is the mutation on

how many beta genes are on this chromosome
hence how many beta genes do we have in total (x2 for each parent)

Answer 15

chromosome 11

1 beta gene on each chromosome 11
so 2 beta genes altogether

Question 16

what type of haemoglobin (HbF, HbA HbA2) does beta thalassemia affect

what does this mean

Answer 16

only affects HbA
doesn’t affect HbA2 or HbF

can compensate for loss of HbA by increasing HbF/HbA2

Question 17

what kind of chains are in HbA2

Answer 17

4 alpha chains

Question 18

what are the 3 classifications of beta thalassaemia

Answer 18

beta thalasaemia trait
beta thalasaemia intermedia
beta thalasaemia major

Question 19

investigations for beta thalassaemia

what are the results

Answer 19

gel electrophoresis/HPLC (high performance liquid chromatography)
will see raised HbA2

Question 20

management of beta thalasaemia trait

Answer 20

nothing

Question 21

management of beta thalasaemia intermedia

Answer 21

occasional transfusions

Question 22

management of beta thalasaemia major

Answer 22

life long RBC transfusion with iron chelating drugs (desferrioxamine) to prevent iron overload

OR

bone marrow transplant - curative but rarely done

Question 23

presentation of beta thalasaemia major

at what age

Answer 23

age 6-24 months, whenever the HbF runs out

pallor
failure to thrive
extramedullary haemotopoiesis - splenomegaly, bony deformities

Question 24

what xray appearance of beta thalasaemia major

Answer 24

cortical thinning

‘hair on end’ bone appearance

Question 25

how many of the beta genes is someone missing if they have beta thalasaemia major what does this mean

Answer 25

them all no beta chain production = no HbA

Question 26

cortical thinning | 'hair on end' bone appearance

Answer 26

extramedullary haematopoiesis in beta thalasaemia major

Question 27

blood film cells in beta thalasaemia major

Answer 27

target cells nucleated RBCs alpha chain precipitates (bc loads are unbound)

Question 28

what type of haemoblogin in sickle cell trait

Answer 28

HbAS half HbA half HbS

Question 29

presentation of sickle cell trait

Answer 29

asymptomatic unless sickle cell crisis

Question 30

triggers of sickle cell crisis

Answer 30

``` high altititude (hypoxia) under anaesthesia dehydration infection stress ```

Question 31

inheritance pattern of sickle cell | hence what are the possible outcomes

Answer 31

autosomal recessive sickle cell trait (1 copy of abnormal gene) - HbAS sickle cell anaemia (2 copies of abnormal gene) - HbS

Question 32

what is wrong with the haemoglobin in sickle cell | what causes this

Answer 32

Bs globin chains instead of B globin chains | mutation in globin chain synthesis

Question 33

what happens to HbS in a sickle cell crisis

Answer 33

it polymerises = distorts RBC shape to be sickle cells = RBC damage = haemolysis

Question 34

what do sickle cells do to vasculature

Answer 34

vascular occlusion = tissue infarction

Question 35

investigations for sickle cell

Answer 35

gel electrophoresis/HPLC (high performance liquid chromatography) will see raised HbS

Question 36

what type of RBCs are made in sickle cell

Answer 36

reticulocytes sickle cell = haemolysis = reticulocyte formation to compensate

Question 37

presentation of sickle cell anaemia in fingers

Answer 37

dactylitis = painful swollen digits (v painful)

Question 38

presentation of sickle cell anaemia in penis

Answer 38

priapism - painful erection

Question 39

blood film of sickle cell (3)

Answer 39

target cells sickle cells reticulocytes

Question 40

acute management of sickle cell crisis

Answer 40

hydration opiate analgesia for pain red cell exchange transfusion (replace HbS with donor HbA)

Question 41

chronic management of sickle cell anaemia

Answer 41

folic acid - bc chronic haemolysis | hydroxycarbamide - induces HbF (fetal haemoglobin) production