Haemoglobinopathies

Question 1

Which type of haemoglobin is predominant in adults and what are its components?

Answer 1

HbA –> 2 alpha + 2 beta chains

Question 2

What is HbA2 composed of?

Answer 2

2 alpha + 2 delta chains

Question 3

What is HbF and what is it composed of?

Answer 3

Foetal Hb –> 2 alpha + 2 gamma chains

Question 4

When will a child usually reach adult levels of HbA?

Answer 4

Age 6-12 months (so beta chain problems wont manifest until then)

Question 5

What are haemoglobinopathies?

Answer 5

Hereditary, autosomal recessive conditions

Affecting globin chain synthesis

Question 6

What are the two main groups of haemoglobinopathies?

Answer 6

Thalassaemias (decreased rate of globin synthesis)

Structural Hb variants (normal production of abnormal globin chain e.g. HbS)

Question 7

What are the two main types of thalassaemia?

Answer 7

Alpha thalassaemia

Beta thalassaemia

Question 8

Describe the different severities of alpha thalassaemia

Answer 8

Alpha chain has 2 genes, so 4 alleles:

• 1 allele affected = silent carrier
• 2 alleles affected = trait
• 3 alleles affected = HbH disease
• 4 alleles affected = Hb Barts

Question 9

Describe the different severities of beta thalassaemia

Answer 9

Beta chain has 1 gene, so 2 alleles:

• 1 allele affected = trait
• 2 partially functioning alleles = thalassaemia intermedia
• 2 non-functioning alleles = thalassaemia major

Question 10

What are the features of Hb Bart?

Answer 10

Causes intrauterine haemolytic anaemia + hydrops fetalis –> usually fatal

Question 11

In which geographical areas is alpha thalassaemia most common?

Answer 11

SE Asia
Africa
India

Question 12

In which geographical areas in beta thalassaemia most common?

Answer 12

Mediterranean
Middle East
Central/South Asia
China

Question 13

Which signs/symptoms are seen in both alpha and beta thalassaemia?

Answer 13

Haemolytic anaemia:

• SOB
• fatigue
• pallor
• murmur from increased CO
• splenomegaly +/- hepatomegaly
• failure to thrive, reduced growth

Question 14

Which additional features might be seen in beta thalassaemia?

Answer 14

Jaundice
Facial dysmorphia:
- frontal bossing
- maxillary hypertrophy
- large head
Osteopenia

Question 15

Which sign might be the only feature in thalassaemia trait/minor?

Answer 15

Microcytic anaemia

Question 16

How is thalassaemia diagnosed?

Answer 16

Hb electrophoresis or chromatography

Question 17

Which electrophoresis finding is characteristic of beta thalassaemia trait?

Answer 17

Increased HbA2

Question 18

What would be seen on electrophoresis in beta thalassaemia major?

Answer 18

Mainly HbF, no HbA

Question 19

What would be seen on electrophoresis in HbH disease?

Answer 19

HbH –> excess beta chains form B4 tetramers (HbH)

Question 20

What is the management for beta thalassaemia intermedia and HbH disease?

Answer 20

Occasional transfusions

Question 21

What is the management for beta thalassaemia major?

Answer 21

Lifelong regular transfusions

–> maintain Hb 95-105

Question 22

What is the main cause of mortality in beta thalassaemia major?

Answer 22

Iron overload from regular transfusions

Question 23

How is iron overload managed in thalassaemia?

Answer 23

Iron chelating drugs e.g. desferrioxamine (SC/IV)

venesection not possible as patient is already anaemic

Question 24

Which side effects of iron chelating drugs is it important to monitor closely for?

Answer 24

Hearing and vision loss

Question 25

What is the pathophysiology behind 'sickling'?

Answer 25

Recessive mutation in gene for beta-globin --> HbS (altered structure) HbS polymerises if exposed to low oxygen levels for a prolonged period --> distorted shape of red cell

Question 26

What are the consequences of HbS red cells?

Answer 26

Breakdown easily --> haemolytic anaemia Occlude the microvasculature Are sequestered in liver + spleen --> splenic dysfunction + immunosuppression

Question 27

What is the lifespan of a HbS red cell?

Answer 27

20 days (HbA is 120 days)

Question 28

What are the features of sickle cell trait?

Answer 28

Asymptomatic carrier | May sickle in severe hypoxia e.g. high altitude, under anaesthesia

Question 29

What would be seen on the blood film and electrophoresis in sickle cell trait?

Answer 29

Film normal | Mainly HbA, HbS < 50%

Question 30

Which parts of the world have the highest rates of sickle cell anaemia?

Answer 30

Afro-Caribbean Middle East Mediterranean Indian

Question 31

How would sickle cell anaemia appear of electrophoresis?

Answer 31

HbS > 80%, no HbA

Question 32

What are the chronic features of sickle cell anaemia?

Answer 32

Haemolytic anaemia: pallor, fatigue, jaundice Chronic pain Painful dactylitis (in age 6-18 months) Splenomegaly Hyposplenism due to repeated infarcts Pigment gallstones from chronic haemolysis (affects 70%) Raised CO --> systolic murmur + cardiomegaly

Question 33

What is a sickle cell crisis?

Answer 33

Episode of tissue infarction due to vascular occlusion

Question 34

What might trigger a sickly cell crisis?

Answer 34

``` Cold Dehydration Stress Infection Pregnancy Acidosis Hypoxia ```

Question 35

Give some examples of symptoms of sickle cell crisis?

Answer 35

Acute painful limb, abdomen or chest Stroke Visual floaters Chest pain + pneumonia --> acute chest syndrome (common in kids)

Question 36

Which type of infection may precipitate an aplastic crisis in a patient with sickle cell anaemia?

Answer 36

Parovirus B19

Question 37

Which type of infections are sickle cell patients particularly susceptible to?

Answer 37

Encapsulated bacteria --> due to hyposplenism (spleen responsible for removing encapsulated bacteria)

Question 38

How is sickle cell disease diagnosed?

Answer 38

Electrophoresis High performance liquid chromatography (HPLC) Hb isoelectric focusing (IEF)

Question 39

What is the general management of sickle cell anaemia?

Answer 39

Avoid alcohol + smoking Prophylactic penicillin + all vaccinations Folic acid supplements (especially in pregnancy) Transfusions if symptomatic anaemia Splenectomy if 2 sequestration crises Hydroxycarbamide can reduce severity by inducing HbF production

Question 40

How is a sickle cell crisis treated?

Answer 40

``` Opiates Hydration Rest Oxygen Antibiotics if infection Red cell exchange transfusion if chest crisis or stroke ```

Question 41

How are haemoglobinopathies screened for?

Answer 41

Antenatal screening to identify carriers - family origin questionaire + FBC - further testing if from high risk area or abnormal red cell indices