Sickle Cell Disease

Question 1

Where are Haemoglobin found and what is their function?

Answer 1

Found in erythrocytes. Transport oxygen from lungs to peripheral tissues, and CO2 from peripheral tissues to lungs.

Question 2

What chains do haemoglobin have?

Answer 2

They have 2 Alpha chains and 2 Beta chains.

Question 3

What and where is the mutation in Sickle Haemoglobin?

Answer 3

It is an autosomal recessive mutation i the beta glob in (HBB) gene. It is a non-conservative missense mutation, in which the 6th amino acid (Glutamate) is swapped with hydrophobic Valine, making them clump together.

Question 4

Which factors affect Sickle Cell Anaemia?

Answer 4

Acidosis, low O2 concentration, and small radius vessels (as well as hydration, temperature, stress, and exercise).

Question 5

How is sickle cell haemoglobin charged?

Answer 5

Sickle cell haemoglobin is less negative than HbA, so will move the least in electrophoresis.

Question 6

What would you expect to see in a blood film of someone with sickle cell anaemia?

Answer 6

Reticulocytes (immature RBC, larger), target cells (darker patch in centre), normal RBC, and sickle RBC.

Question 7

Why are there reticulocytes in a sickle cell blood film?

Answer 7

Because sickle cells cannot carry oxygen very well, so the bone marrow tries to produce many more that are immature.

Question 8

What are the symptoms of sickle cell anaemia?

Answer 8

Vision loss, strokes, bone crises and splenomegaly.

Question 9

Why is there vision loss?

Answer 9

As the vasculature in the retina is very small, the sickle cells can clot. This increases pressure, and the ischaemia causes chemokine release, angiogenesis, and weak collaterals formed which are easily damaged and can grow over macular.

Question 10

What causes the strokes?

Answer 10

Ischaemic - blocked vessels, infarction. Sometimes silent and asymptomatic.
Haemorrhagic - due to angiogenesis, collaterals formed are easily broken and can cause leakage into tissues.

Question 11

What causes bone crises?

Answer 11

Reduced blood flow to bone marrow due to micro vascular occlusion. Prolonged ischaemia, infarction. Ischaemia causes more sickling.

Question 12

What is splenomegaly?

Answer 12

The spleen filters blood and is very vascular, but lots of blood can cause blockages and an enlarged spleen.

Question 13

What are different methods of diagnosis?

Answer 13

Electrophoresis, screening, and sickle solubility test.

Question 14

What is the sickle solubility test?

Answer 14

Sodium dithionite added as reducing agent to blood, releases haemoglobin, HbS is less soluble than HbA so sickle blood is turbid/cloudy.

Question 15

How can blood transfusions help manage it and how are issues with it resolved?

Answer 15

It supplies functioning erythrocytes. Haemosiderosis (too much iron) can be avoided by chelation therapy.

Question 16

What are short term methods of managing it?

Answer 16

Painkillers and opioids, hydration, warmth, avoiding high altitudes and low oxygen levels.

Question 17

How can hydroxycarbamide help?

Answer 17

Adding Hydroxycarbamide can stimulate the synthesis of fetal haemoglobin. However, it suppresses reticulocyte and neutrophil production.

Question 18

How can bone marrow transplant help?

Answer 18

It can replace mutated haematopoietic stem cells with functioning HSC.

Question 19

How does gene therapy help?

Answer 19

Enzymes can be injected into defective genes to repair mutation in beta glob in chains.
Enzymes can inhibit gene that blocks production of foetal haemoglobin.

Question 20

What are Howell-Jolly Bodies?

Answer 20

Due to Splenomegaly, the checkpoint can be disabled which causes nucleus remnant not to be removed from reticulocytes. Recognised by dark dot in reticulocyte.