Sickling disorders

Question 1

What are sickling disorders?

Answer 1

Sickling disorders are conditions in which the mutations cause changes to the structure of haemoglobin, leading to distortion of the red cell membrane and thus shape (Sickle shaped)

Question 2

Describe the pathophysiology of sickling disorders

Answer 2

This is caused by point mutations in codon 6 of the ß-globin gene that substitutes glutamine to valine, producing ßS chains

This causes production of HbS, which polymerises if exposed to low oxygen levels for a prolonged period, therefore distorting the red cell and damaging the cell membrane

Question 3

What are the 2 classes of sickling disorder?

Answer 3

• Sickle cell trait
• Sickle cell anaemia

Question 4

What is sickle cell trait?

Answer 4

Sickle cell trait is a form of sickling disorder in which only one of the genes is affected, giving rise to HbA and HbS (HbAS genes)

Despite this, most haemoglobin in the body will be normal HbA

Question 5

Describe the presentation of sickle cell trait

Answer 5

This is an asymptomatic carrier state, with 300million carriers world wide

There are few clinical features as HbS levels will be too low to polymerise and cause damage

But it can lead to sickling, however, in severe hypoxia, such as at high altitude or under anaesthesia

Question 6

What will blood films show in sickle cell trait?

Answer 6

Mostly normal blood cells

Question 7

What will HPLC show in sickle cell trait?

Answer 7

Predominant HbA with little HbS

Question 8

What is sickle cell anaemia?

Answer 8

Sickle cell anaemia is a more severe form of sickling disorder in which both ß-genes are affected giving rise to HbS (HbSS genes)

Question 9

What are some possible complications of sickle cell anaemia?

Answer 9

• Chronic haemolysis
• Sequestration of sickled RBCs in liver and spleen
• Hypoplenism due to repeated splenic infection
• Severe pain in sickle crisis
• Anaemia symptoms

Question 10

What will HPLC show in sickle cell anaemia?

Answer 10

There will often be no HbA and >80% of haemoglobin will be HbS

Question 11

What are some management options used in sickle cell anaemia?

Answer 11

• Prophylactic penicillin (Reduce hyposplenism risk)
• Vaccination (e.g. pneumococcus, meningococcus, haemophilus)
• Folic acid supplementation
• Hydroxycarbamide
• Regular transfusions (Selected cases)

Question 12

Why is folic acid supplementation used in sickle cell anaemia?

Answer 12

To prevent deficiency due to the increased red blood cell turnover that occurs due to chronic haemolysis

Question 13

Why is hydroxycarbamide used in sickle cell anaemia?

Answer 13

It can reduce the severity of disease by inducing the production of HbF

Question 14

Why may regular transfusions be used in sickle cell anaemia ?

Answer 14

To prevent stroke risk in selected cases

Question 15

What is meant by sickle crisis?

Answer 15

Sickle crisis is the name given to episodes of tissue infarction due to vascular occlusion by sickled red blood cells, resulting in severe pain

Question 16

What are some factors that may precipitate sickle crisis?

Answer 16

• Hypoxia
• Dehydration
• Infection
• Cold exposure
• Stress/fatigue

Question 17

What treatments are required in sickle crisis?

Answer 17

• Opiate analgesia
• Hydration
• Rest
• Oxygen
• Antibiotics if evidence of infection
• Red cell exchange transfusion

Question 18

Why is red cell exchange transfusion used in sickle crisis?

Answer 18

Red cell exchange transfusion is required in severe crisis to rapidly reduce proportion of HbS in blood

Question 19

What are some specific forms of sickle crisis?

Answer 19

• Chest crisis (Lung infarction)
• Stroke crisis (Brain infarction)