Haemoglobinopathy

Question 1

What causes HbS to form?

Answer 1

Missense mutation in the beta globin gene

Substitution of glutamic acid by valine

Question 2

What happens to HbS at low oxygen levels?

Answer 2

Deoxy Hb polymerises into long intracellular fibres called tactoids

This conforms the RBC into an inflexible sickle chape which cannot flow easily through blood vessels

Question 3

What is the solubility like of HbS?

Answer 3

Highly insoluble

Question 4

Which condition does the distribution of the Sickle Cell gene match?

Answer 4

Plasmodium falciparum malaria

Question 5

Where is HbS particularly prevalent?

Answer 5

In tropical Africa and some parts of the Miditerranean, Middle East and India

Question 6

What is the phenotype of person carrying two copies of the Beta sickle gene?

Answer 6

Sickle Cell Anaemia

Question 7

What is the lifespan of a sickled red blood cell like compared with a normal one?

Answer 7

10-20 days, compared with the 120 normal days

Question 8

Why might a patient with sickle cell anaemia have a high reticulocyte count?

Answer 8

The bone marrow compensates for the destruction of sickle cells by producing more red blood cells, hence an increase in immature RBCs

Question 9

Which type of blood cells might specifically be seen on a blood film in a sickle cell anaemia patient?

Answer 9

Reticulocytes
Target cells (with Howell-Jolly Bodies)
Sickle cells

Question 10

What are Howell-Jolly Bodies (in target cells) and what are they caused by?

Answer 10

Clusters of DNA still present in circulating RBCs

Arises when patients have reduced splenic function

Question 11

Why does sickle cell disease lead to splenic complications?

Answer 11

Sickling vaso-occlusion can occur in the microvasculature of the spleen

Repeated occlusions leads to destruction and splenic sequestration

Question 12

Why does splenic sequestration occur in SCD?

Answer 12

The RBCs have a shorter life span (20 days), and therefore are destroyed more quickly

When the spleen cannot cope with this high load, it can lead to blood pooling in the spleen

Question 13

Why might you find elevated gall stones in patients with SCD?

Answer 13

Increased haemolysis leads to increased bilirubin production and increased gall stone formation

Question 14

Why might jaundice occur in patients with SCD?

Answer 14

More haemolysis of RBC thus more bilirubin

Leaves yellow tint to skin and sclera of eye

Question 15

What is a common early manifestation of SCD?

Answer 15

Dactylitis which is inflammation of the digits

Question 16

What is hyposplenism?

Answer 16

Reduced splenic function due to repeated vaso-occlusion

Question 17

What can hyposplenism lead to in terms of infection?

Answer 17

Increased succeptibility to encapsulated bacterial infections

Question 18

What are sickle cell crises?

Answer 18

Vaso-occlusive crises which are a hallmark of sickle cell diease

They are acute episodes of pain, usually felt in the lower back, pelvis and legs

Question 19

Why are SCD patients given hydroxyurea?

Answer 19

Hydroxyurea stimulates HbF production which has higher O2 affinity

This reduces recurrent vaso-occlusive crises

Question 20

In patients heterozygous for the beta sickle gene, what is seen on gel electrophoresis?

Answer 20

Both HbA and HbS are seen

Question 21

What is acute chest syndrome in SCD?

Answer 21

Vaso-occlusion of the pulmonary vasculature, which should be treated as a medical emergency

Question 22

How is acute chest syndrome diagnosed?

Answer 22

Chest X-ray shows new pulmonary infiltrate
With fever, cough, chest pain, tachypnoea

Question 23

What other conditions can SCD cause?

Answer 23

Acute chest syndrome
Avascular necrosis of femoral head
Hyposplenism
Jaundice
Stroke
Osteomyelitis

Question 24

How does the sickle solubility test work in diagnosing SCD?

Answer 24

In presence of reducing agent (sodium dithionite), oxyHb is converted to deoxyHb

HbA dissolves easily but HbS is insoluble and solution becomes turbid

Question 25

What is the problem with the sickle solubility test in the diagnosis of SCD?

Answer 25

Does not differentiate AS from SS

Question 26

What does the definitive diagnosis of SCD require?

Answer 26

Electrophoresis or high performance liquid chromatography to separate proteins according to charge