Sickle Cell Disease

Question 1

What causes sickle cell disease?

Answer 1

• a haemoglobin variant which causes abnormal haemoglobin
• mutation at a point in beta gene (chromosome 11)
• single amino acid substitution at point 6
• glutamine for valine = HbS
• another variant (west Africa) glutamine for lysine = HbC

Question 2

What happens to the Hb molecule due to the sickle cell disease variant?

Answer 2

• instead of normal HbA you have 2 alpha chains and 2 sickling beta chains
• continuous polymerisation causes rigid Hb which is prone to blockage through small vessels

Question 3

What factors affect the rate of sickling of the red cells?

Answer 3

• Hb concentration
• HbF
• deoxygenating rate
  (Infection, hypoxia, dehydration and the cold can exacerbate)

Question 4

What is a sign seen in blood films of sickle cell disease?

Answer 4

Howell jolly bodies

Question 5

What are the clinical consequences of sickle cell disease?

Answer 5

• anaemia (from reduced red cell survival)
• haemolysis (from chronic endothelial cell dysfunction)
• vaso-occlusion (from tissue hypoxia and infarction)
  ^ - causes pain from tissue damage (risk of strokes, kidney damage etc.)

Question 6

What is a significant consequence of untreated sickle cell disease in children?

Answer 6

• 10% will have a stroke which can cause Moyà Moyà
• new vessel formation (from new collaterals forming around the circle of Willis)
• vessels are very fragile and can risk formation of aneurysms and cerebral haemorrhage

Question 7

How can lung infections easily happen in patients with sickle cell disease?

Answer 7

• vaso-occlusion from blockage of sickle cells causes tissue damage and pain on full inspiration
• results in hypoventilation (from patient compensating from pain)
• areas of the lunch are receiving blood but not oxygen (V/Q mis-match) causing decreased O2 delivery
• results in hypoxia which exacerbates sickling process

Question 8

What is the management of sickle cell disease?

Answer 8

1. Prevent crises: patient education, hydration, analgesia, early intervention
2. Prophylactic vaccinations and antibiotics
3. Folic acid (because red cells are breaking down fast)
4. Hydroxycarbamide therapy (increases HbF and reduces sickling)
5. Prompt management of any crises: O2, fluids, antibiotics, specialist care
6. Transfusion/red cell exchange (remove sickling red cells)
7. Bone marrow transplantation (for few)