Haemoglobinopathies

Question 1

What is the structure of haemoglobin?

Answer 1

tetramer of 2 alpha and 2 beta globin chains
1 haem group attached to each globin chain
each contains an Fe2+ ion

Question 2

What are the major forms of Hb?

Answer 2

HbA - 2 alpha, 2 beta
HbA2 - 2 alpha, 2 delta
HbF - 2 alpha, 2 gamma

Question 3

What are the thalassaemias?

Answer 3

genetic diseases with under production or no production of one globin chain

Question 4

What does unbalanced accumulation of globin chains cause?

Answer 4

It is toxic

Ineffective erythropoiesis and haemolysis

Question 5

What kind of anaemia do you get in thalassaemias?

Answer 5

microcytic and hypo chromic (as inadequate Hb production)

Question 6

What are the classifications of alpha thalassaemias?

Answer 6

unaffected
a thalassaemia trait
HbH disease
Hb Barts hydrops fetalis

Question 7

What are a thalassaemias?

Answer 7

deletion of one (-a) or both (–) a genes from chromosome 16

Question 8

What is Hb Barts hydrops fetalis?

Answer 8

death occurs in utero 
all 4 a genes are deleted 
--/--  
(should be aa/aa)
HbA can't be made

Question 9

What is HbH disease?

Answer 9

3 genes deleted

–/-a

Question 10

What is a thalassaemia trait?

Answer 10

1 or 2 genes missing 
(aa/-a) 
(--/aa) 
(a-/a-) 
asymptomatic, no treatment
decreased MCV

Question 11

What are the clinical features of HbH disease?

Answer 11

moderate anaemia, features of haemolysis
hepatosplenomegaly
leg ulcers
jaundice

Question 12

What is HbH in HbH disease?

Answer 12

excess B chains form tetramers (B4) 
called HbH (can't carry oxygen)

Question 13

What are B thalassaemias?

Answer 13

disorder of B chain synthesis

Question 14

What are the classifications of B thalassaemias?

Answer 14

B thalassaemia trait
B thalassaemia intermedia
B thalassaemia major

Question 15

What is B thalassaemia trait?

Answer 15

B-/BB
asymptomatic, no or mild anaemia
decreased MCV

Question 16

What is B thalassaemia intermedia?

Answer 16

B-/B-
moderate anaemia
splenomegaly

Question 17

What usually causes B thalassaemias?

Answer 17

point mutations in B globin genes on chromosome 11

Question 18

What Hb is affected in B thalassaemia?

Answer 18

only HbA

Question 19

What Hb is affected in a thalassaemia?

Answer 19

HbA
HbA2
HbF
(all)

Question 20

What is B thalassaemia major?

Answer 20

(–/–) - no B genes

lifelong transfusion dependency

Question 21

What is the management of B thalassaemia major?

Answer 21

regular transfusion

watch for iron overload (give iron chelating drugs e.g. desferroxamine)

Question 22

How is reduced B or a written?

Answer 22

B+

a+

Question 23

How is absent B or a written?

Answer 23

B0
a0
(small zero)

Question 24

How does B thalassaemia major present?

Answer 24

first year of life

severe anaemia and failure to thrive

Question 25

What is sickle cell anaemia?

Answer 25

autosomal recessive disorder | production of abnormal B chains

Question 26

What is the mutation in sickle cell anaemia?

Answer 26

point mutation - codon 6 of B globin gene substitutes glutamine for valine produces HbS not HbA

Question 27

What is the pathogenesis of sickle cell anaemia?

Answer 27

HbS polymerises when deoxygenated RBCs deform producing sickle cells fragile and haemolyse also block small vessels

Question 28

What is sickle trait?

Answer 28

one normal, one abnormal B gene (B/Bs) | asymptomatic carrier state

Question 29

When may someone with sickle trait experience symptoms of sickling?

Answer 29

in severe hypoxia e.g. anaesthesia, high altitude

Question 30

What is a sickle crisis?

Answer 30

episodes of tissue infarction due to vascular occlusion

Question 31

What are the symptoms of a sickle crisis?

Answer 31

depends on site and severity severe pain e.g. CNS, lung, spleen, bone marrow

Question 32

Why is there hyposplenism in sickle cell anaemia?

Answer 32

repeated splenic infarcts | sequestration of sickled RBC in liver and spleen

Question 33

What can trigger a sickle crisis?

Answer 33

cold dehydration infection hypoxia

Question 34

What is it called when hands/feet are affected in a sickle crisis?

Answer 34

dactylitis

Question 35

What is the long term management of sickle cell anaemia?

Answer 35

hydroxycarbimide - if frequent crises prophylactic penicillin and vaccination - for hyposplenism folic acid supplements