Abnormalities with blood cells

Question 1

What makes up haemoglobin?

Answer 1

2 alpha chains
2 beta chains
Both associated with a haem group

Question 2

Which type of hemoglobin is most common?

Answer 2

Hb A

Question 3

What is different about Hb A2?

Answer 3

Less common variety

2 delta chains instead of 2 beta chains

Question 4

How can haemoglobinopathies be classified?

Answer 4

Structural variants

Thalassaemia

Question 5

What causes a structural variant?

Answer 5

Mutation changes an amino acid in the globin chain

Question 6

What causes a thalassaemia?

Answer 6

Mutation that results in a reduced production of the globin chain

Question 7

What are the types of thalassaemia?

Answer 7

Alpha

Beta

Question 8

What causes alpha thalassaemia?

Answer 8

Mostly caused by a mutation to one of the 4 alpha globin genes?

Question 9

What are the 3 severities of alpha thalassaemia?

Answer 9

Alpha thalassaemia trait
Hb H disease
Hb Bart’s hydrops fetalis

Question 10

What causes alpha thalassaemia trait?

Answer 10

The loss of 1/2 alpha globin genes

Question 11

What causes Hb H disease?

Answer 11

The loss of 3 alpha globin genes

Question 12

What causes Hb Bart’s hydrops fetalis?

Answer 12

The loss of all 4 alpha globin genes

Question 13

What are the symptoms of Hb H disease?

Answer 13

Moderately severe microcytic anaemia

Splenomegaly

Question 14

What does Hb Bart’s hydrops fetalis result in?

Answer 14

No production of Hb F, Hb A or Hb A2 without alpha globin

Incompatible with life

Question 15

What causes beta thalassaemia?

Answer 15

Mostly point mutations which results in the reduced production of the beta globin chain
Either no amount of chain synthesised (βo) or small amounts synthesised (β+)
Leads to an excess of alpha chains which causes ineffective erythropoiesis and haemolysis

Question 16

What does the excess of alpha chains in beta thalassaemia cause?

Answer 16

Ineffective erythropoiesis and haemolysis

Question 17

What are the severities of beta thalassaemia? (including potential phenotypes)

Answer 17

Beta thalassaemia trait (o ββ+ or ββo)
Beta thalassaemia intermedia (o βoβ+ or β+β+)
Beta thalassaemia major (o βoβo)

Question 18

What are the symptoms of beta thalassaemia major?

Answer 18

Severe anaemia preseting in early life - will lead to death within first decade if untreated
Bony deformation
Splenomegaly and hepatomegaly
Wasting of limbs and stunted growth

Question 19

What are the symptoms of beta thalassaemia intermedia?

Answer 19

Mild-moderate anaemia

Question 20

What are the symptoms of beta thalassaemia trait?

Answer 20

Mild anaemia

Question 21

What causes sickle cell disease?

Inherit what and what is different about it

Answer 21

Inheritance of homozygous recessive sickle beta globin gene (Hb BS)
Substitution of valine for glutamic acid in position 6 in the beta chain

Question 22

Why is sickle cell so well maintained?

Answer 22

Being a carrier doesn’t normally produce symptoms

Seems to give a degree of protection against malaria

Question 23

In what conditions may sickle cell carriers exhibit symptoms?

Answer 23

At very low oxygen tensions
Under anaesthetics
At altitude

Question 24

What are the clinical features of sickle cell disease?

Answer 24

Haemolytic anaemia punctured with crises

Question 25

What type of crises are seen in sickle cell disease?

Answer 25

Vaso-occlusive crises

Visceral sequestration crises

Question 26

Vaso-occlusive crises in sickle cell

Answer 26

Most frequent of crises
Reduced solubility of Hb S at low oxygen tensions causes polymerisation of globin chain molecules
RBCs lose their biconcave shape and block blood vessels and reduce O2 supply

Question 27

Visceral sequestration crises in sickle cell

Answer 27

Caused by sickling inside organs and pooling of blood