Haemoglobinopathies

Question 1

What are haemoglobinopathies?

Answer 1

Hereditary conditions affecting globin chain synthesis

Question 2

What are the two main groups of haemoglobinopathies?

Answer 2

Thalassaemias

Structural haemoglobin variants - sickle diseases

Question 3

What are thalassaemias?

Answer 3

A decreased rate of globin chain synthesis

Question 4

What are structural haemoglobin variants?

Answer 4

Normal production of abnormal globin chains

Question 5

Describe the structure of haemoglobin?

Answer 5

A tetramer made up of up 2 alpha chains and 2 beta globin chains

Has one haem group attached to each globin chain

Question 6

What makes up foetal haemoglobin (HbF) ?

Answer 6

2 alpha chains and 2 gamma chains

Question 7

What makes up HbA2 ?

Answer 7

2 alpha chains and 2 delta chains

Question 8

What chromosome are alpha like genes found on?

How many genes per chromosome / cell?

Answer 8

Chromosome 16

Two alpha genes per chromosome so 4 per cell

Question 9

What chromosome are beta like genes found on?

How many genes per chromosome / cell?

Answer 9

Chromosome 11

One beta gene per chromosome so 2 per cell

Question 10

When are adult haemoglobin levels typically reached?

Answer 10

By 6-12 months of age

Question 11

When are beta chain problems commonly identified in a patient?

Answer 11

Between 6-12 months of age as this is when it is developed

Question 12

How do haemoglobinopathies behave genetically?

Answer 12

They behave as autosomal recessive disorders

Question 13

What is alpha thalassaemia?

Answer 13

Reduced globin chain synthesis of alpha globin chains

Question 14

What is beta thalassaemia?

Answer 14

Reduced globin chain synthesis of beta globin chains

Question 15

What is a well known consequence of inadequate Hb production?

Answer 15

Microcytic hypochromic anaemia

Question 16

What are the classifications for alpha thalassaemias?

Answer 16

Unaffected (four normal alpha genes)

Alpha thalassaemia trait (one or two alpha genes missing)

HbH disease (one alpha gene left)

Hb Barts hydrops fetalis (no functional alpha genes)

Question 17

What can be seen in alpha thalassaemia trait patients?

Answer 17

Microcytic hypochromic red cells with mild anaemia

Ferritin will be normal - distinguish from iron deficiency anaemia

Question 18

What can be seen in HbH patients?

Answer 18

Anaemia with very low MCV and MCH

Question 19

Give properties of HbH disease?

Answer 19

Excess beta chains form tetramers called HbH

Common in SE Asia

Patients may be jaundiced and have splenomegaly

Question 20

Which alpha thalassaemia is severely life-threatening?

Answer 20

Hb Barts Hydrops Foetalis syndrome

Question 21

Clinical features of Hb Barts Hydrops Foetalis syndrome?

Answer 21

Profound anaemia, cardiac failure, growth retardation, severe hepatosplenomegaly, skeletal and cardiovascular abnormalities

Question 22

What is the classification of beta thalassaemias?

Answer 22

Beta thalassaemia trait

Beta thalassaemia intermedia

Beta thalassaemia major

Question 23

Which form(s) of beta thalassaemia require transfusions?

Answer 23

Beta thalassaemia intermedia (requires occasional transfusion)

Beta thalassaemia major
(requires life-long transfusions)

Question 24

Give clinical features of beta thalassaemia major?

Answer 24

Pallor, failure to thrive

Extramedullary haematopoiesis causing hepatosplenomegaly, skeletal changes, organ damage

Question 25

When will beta thalassaemia major patients tent to be diagnosed?

Answer 25

Between 6-24 months of life (as HbF levels fall)

Question 26

What is the management option for beta thalassaemia major patients?

Answer 26

Regular transfusion programmes

Question 27

What complication can cause mortality in beta thalassaemia patients receiving transfusions?

Answer 27

Iron overload

Question 28

What can be a treatment option in beta thalassaemia major patients who are diagnosed before complications develop?

Answer 28

Bone marrow transplant

Question 29

What are the main consequences of iron overload?

Answer 29

Endocrine dysfunction (impaired growth, diabetes, osteoporosis) Cardiac disease (cardiomyopathy, arrhythmias) Liver disease (cirrhosis, hepatocellular cancer)

Question 30

What can be given to patients with iron overload?

Answer 30

Iron chelating drugs - desferrioxamine

Question 31

What serious infection is more likely to be seen in iron overload patients?

Answer 31

Sepsis

Question 32

What occurs in codon 6 that leads to sickling disorders?

Answer 32

A point mutation that substitutes glutamine to valine - produces Bs

Question 33

What is sickle cell trait (HbAS) ?

Answer 33

Having one normal and one abnormal beta gene, asymptomatic carrier state

Question 34

Give examples of situations of severe hypoxia that can cause cells to sickle?

Answer 34

High altitude, under anaesthesia

Question 35

What is sickle cell anaemia (HbSS)?

Answer 35

Two abnormal beta genes

Question 36

What is sickle crisis?

Answer 36

Episodes of tissue infarction due to vascular occlusion - severe pain

Question 37

What can be seen in patients with sickle cell anaemia?

Answer 37

Sickle crisis (severely painful) Chronic haemolysis (shortened RBC lifespan) Hyposplenism (due to repeated splenic infarcts)

Question 38

Give 5 common precipitants of sickle cell crisis? (Use CHIDS to help remember)

Answer 38

Hypoxia Dehydration Infection Cold exposure Stress / fatigue

Question 39

How is sickle crisis treated?

Answer 39

Opiate analgesia, hydration, rest, oxygen, antibiotics if needed Red cell exchange transfusion used in severe crisis (lung / brain)

Question 40

What drugs are given to sickle cell patients?

Answer 40

Folic acid supplementation Hydroxycarbamide

Question 41

What investigations are used to diagnose haemoglobinopathies?

Answer 41

FBC + blood film History (ethnic origin) High performance liquid chromatography (HPLC) or electrophoresis

Question 42

What investigations can be used to quantify haemoglobins present?

Answer 42

High performance liquid chromatography (HPLC) or electrophoresis

Question 43

What screening has become standardised to identify carrier parents of haemoglobinopathies?

Answer 43

Antenatal screening