Sickle Cell Disease

Question 1

What is sickle cell disease.

Answer 1

Autosomal recessive genetic disease due to haemoglobin chain mutation.

Question 2

What are the characterisitcs of sickle cell disease.

Answer 2

Abnormal haemoglobin (HbS) has a tendency to become rigid and sickle, causing occlusion of small vessels.

Question 3

What can occlusion of small vessels in sickle cell disease lead to.

Answer 3

Sickle cell crisis.

Question 4

What can a sickle cell crisis be precipitated by. (5)

Answer 4

Infection. 
Dehydration. 
Hypoxia. 
Acidosis. 
Cold.

Question 5

What are the clinical systems most affected by sickle cell disease. (6)

Answer 5

Ocular. 
Pulmonary. 
Renal. 
Musculoskeletal. 
CNS. 
Cardiac.

Question 6

What investigations should be carried out to diagnose sickle cell disease. (2)

Answer 6

Blood film.

Hb electrophoresis.

Question 7

What kind of treatment is used for sickle cell disease.

Answer 7

Treatment is supportive.

Question 8

What is involved in the supportive treatment of sickle cell disease. (3)

Answer 8

When needed:
Aggressive analgesia.
Antibiotics.
Fluids.

Question 9

What are the complications of sickle cell disease. (10)

Answer 9

Gallstones. 
Leg ulcers. 
Avascular necrosis of the femoral head. 
Pulmonary hypertension. 
Splenic infarction (in children). 
Poor growth. 
Retinal disease. 
Iron overload. 
Lung damage. 
Chronic renal disease.

Question 10

What is the mutation involved in sickle cell disease.

Answer 10

A single glutamic acid to valine substitution at position 6 of the beta globin polypeptide chain

Question 11

What do sickle cell homozygotes produce.

Answer 11

They only produce the abnormal beta chains that make HbS.

This results in the clinical syndrome of sickle cell disease.

Question 12

What do sickle cell heterozygotes produce.

Answer 12

They produce a mixture of normal and abnormal beta chains that make both normal HbA and HbS.
This results in the clinically asymptomatic sickle cell trait.

Question 13

What is the heterozygote frequency of sickle cell in tropical Africa.

Answer 13

20%.

Question 14

What ethnic minority has the largest rate of sickle cell trait.

Answer 14

Black American population - at 8%.

Question 15

What is sickle cell trait protective against.

Answer 15

It is protective against the lethal effects of falciparum malaria in early childhood.
You are not granted a greater resistance against malaria if you are a homozygote for sickle cells.

Question 16

What gives HbS its characteristic ‘sickle’ shape.

Answer 16

When HbS is deoxygenated, the molecules of Hb polymerise to form pseudocrystalline structures known as ‘tactoids’.
These distort the RBC membrane.

Question 17

What are the ocular clinical features of sickle cell disease. (3)

Answer 17

Background retinopathy.
Proliferative retinopathy.
Vitreous bleeds.

Question 18

What are the pulmonary features of sickle cell disease. (3)

Answer 18

Sickle chest syndrome.
Infection.
Pulmonary hypertension.

Question 19

What are the cardiac features of sickle cell disease. (3)

Answer 19

Sickle myocardium.
Cardiomegaly.
Transfusional iron overload (eg splenic infarction).

Question 20

What are the CNS features of sickle cell disease. (2)

Answer 20

Subarachnoid bleed.

Fits.

Question 21

What are the renal features of sickle cell disease. (4)

Answer 21

Enuresis.
Haematuria.
Papillary necrosis.
Chronic renal failure.

Question 22

What are the musculoskeletal features of sickle cell disease. (6)

Answer 22

Osteomyeitis. 
Dactylitis. 
Arthropathy. 
Vertebral collapse. 
Osteoporosis. 
Avascular necrosis of the femoral head.

Question 23

What other features are there of sickle cell disease. (4)

Answer 23

Leg ulcerations.
Priapism.
Hepatic sequestration.
Choleslithiasis.

Question 24

What is seen on the blood film of a patient with sickle cell disease. (2)

Answer 24

Sickle cells.

Nucleated red cells.

Question 25

What is the cause behind the sickle cell crises that can occur.

Answer 25

Irreversibly sickled cells have a shortened survival and plug vessels in the microcirculation. This plugging results in a number of acute syndromes, leading to chronic organ damage.

Question 26

What is the most common form of sickle cell crisis.

Answer 26

Painful vaso-occlusive crisis.

Question 27

What usually accompanies the bone pain of a vaso-occlusive crisis. (3)

Answer 27

A systemic response with sweating, fever and tachycardia.

Question 28

What is significant about a sickle chest syndrome.

Answer 28

It may follow a vaso-occlusive crisis. | It is the most common cause of death in adult sickle cell disease.

Question 29

What is sickle chest syndrome.

Answer 29

Bone marrow infarction results in fat emboli to the lungs, which cause further sickling and infarction, leading to ventilatory failure if left untreated.

Question 30

What is involved in a painful vaso-occlusive crisis.

Answer 30

Plugging of small vessels in the bone produces acute severe bone pain.

Question 31

What is the most common symptom of a vaso-occlusive crisis in children.

Answer 31

Dactylitis.

Question 32

What is a sequestation crisis. (3)

Answer 32

Thrombosis of the venous outflow from an organ causes loss of function and acute painful enlargement. In children, the spleen is the most common site. In adults, the liver may undergo sequestration.

Question 33

What is an aplastic crisis.

Answer 33

Infection with human parovovirus B19 results in a severe but self-limiting red cell aplasia. It produces a very low Hb, which may cause heart failure. The reticulocyte count is low in this crisis.

Question 34

What are the types of sickle cell crisis. (4)

Answer 34

Painful vaso-occlusive crisis. Sickle chest syndrome. Sequestration crisis. Aplastic crisis.

Question 35

What is the definitive investigation to diagnose sickle cell disease.

Answer 35

Electrophoresis to demonstrate the absence of HbA, HbF and the predominance of HbS.

Question 36

What is the treatment for sickle cell disease. (3)

Answer 36

All patients with sickle cell disease should receive prophylaxis with daily folic acid and penicillin V to protect against pneumococcal infection. Hydroxycarbamide if frequent crises. Treatment is otherwise supportive when needed.

Question 37

How are vaso-occlusive crises managed. (5)

Answer 37

``` Aggressive rehydration. Oxygen therapy. Adequate analgesia. Antibiotics. If transfusions are necessary, they should be fully genotyped wherever possible. ```

Question 38

How many hospitlal admissions can a patient with relatively severe sickle cell disease,

Answer 38

Around 3 a year from painful vaso-occlusive crisis.

Question 39

In what percentage of patents with sickle cell disease is pulmonary hypertension also present.

Answer 39

30-40%.

Question 40

What do sickle cell homozygotes have.

Answer 40

Sickle cell anaemia.

Question 41

What do sickle cell heterozygotes have.

Answer 41

Sickle cell trait.

Question 42

What is the prevalence of sickle cell disease.

Answer 42

1 in 700 people of African heritage.

Question 43

What is the limitation of the sickle solubility test.

Answer 43

It does not distinguish between HbS and HbAS.

Question 44

What tests should be carried out in a patient with sickle cell. (4)

Answer 44

Blood film. FBC. Sickle solubility test. Hb electrophoresis.