Sickle cell anaemia (zero to finals)

Question 1

What is sickle cell anaemia?

Answer 1

A genetic condition that causes sickle (crescent) shaped red blood cells.

Question 2

Why is the red blood cells being in a sickle shape a bad thing?

Answer 2

The abnormal shape makes the red blood cells more fragile and easily destroyed, leading to haemolytic anaemia.

Patients with sickle cell anaemia are prone to various sickle cell crises.

Question 3

What is haemoglobin?

Answer 3

Haemoglobin is the protein in red blood cells that transports oxygen.

Question 4

At what point of gestation does production of foetal haemoglobin decrease and adult haemoglobin increase?

Answer 4

During fetal development, at around 32-36 weeks gestation, fetal haemoglobin (HbF) production decreases, and adult haemoglobin (HbA) increases.

Question 5

When does HbF gradually change to HbA in young children?

Answer 5

There is a gradual transition from HbF to HbA.

At birth, around half the haemoglobin is HbF, and half is HbA.

By six months of age, very little HbF is produced, and red blood cells contain almost entirely HbA.

Question 6

What haemoglobin type is present in sickle cell disease?

Answer 6

Patients with sickle-cell disease have an abnormal variant called haemoglobin S (HbS).

HbS results in sickle-shaped red blood cells.

Question 7

What is the inheritance pattern for sickle cell disease and what chromosome does it act on?

Answer 7

Sickle cell anaemia is an autosomal recessive condition affecting the gene for beta-globin on chromosome 11.

One abnormal copy of the gene results in sickle-cell trait.

Patients with sickle-cell trait are usually asymptomatic. They are carriers of the condition. Two abnormal copies result in sickle-cell disease.

Question 8

What is the relation between sickle cell disease and malaria and where is sickle cell disease most prevalent?

Answer 8

More common in patients from areas traditionally affected by malaria, such as Africa, India, the Middle East and the Caribbean.

Having one copy of the gene (sickle cell trait) reduces the severity of malaria.

As a result, patients with sickle cell trait are more likely to survive malaria and pass on their genes.

Therefore, there is a selective advantage to having the sickle cell gene in areas of malaria, making it more common.

Question 9

When is sickle cell disease screened for?

Answer 9

Sickle cell disease is tested for on the newborn blood spot screening test at around five days of age.

Pregnant women at high risk of being carriers of the sickle cell gene are offered testing.

Question 10

What are the complications of sickle cell anaemia?

Answer 10

Anaemia

Increased risk of infection

Chronic kidney disease

Sickle cell crises

Acute chest syndrome

Stroke

Avascular necrosis in large joints such as the hip

Pulmonary hypertension

Gallstones

Priapism (painful and persistent penile erections)

Question 11

What is a sickle cell crisis?

Answer 11

Sickle cell crisis refers to a spectrum of acute exacerbations caused by sickle cell disease.

These range from mild to life-threatening. They can occur spontaneously or triggered by dehydration, infection, stress or cold weather.

Question 12

How is sickle cell crisis managed?

Answer 12

There is no specific treatment for sickle cell crisis. They are managed supportively, with:

• Low threshold for admission to hospital
• Treating infections that may have triggered the crisis
• Keep warm
• Good hydration (IV fluids may be required)
• Analgesia (NSAIDs should be avoided where there is renal impairment)

Question 13

What is a vaso-occlusive crisis?

Answer 13

Vaso-occlusive crisis (VOC) is also known as painful crisis and is the most common type of sickle cell crisis. It is caused by the sickle-shaped red blood cells clogging capillaries, causing distal ischaemia.

Question 14

What are the features of a vaso-occlusive crisis?

Answer 14

It typically presents with pain and swelling in the hands or feet but can affect the chest, back, or other body areas. It can be associated with fever.

It can cause priapism in men by trapping blood in the penis, causing a painful and persistent erection.

Priapism is a urological emergency, treated by aspirating blood from the penis.

Question 15

What is a Splenic sequestration crisis and what can blood pooling in the spleen cause?

Answer 15

Splenic sequestration crisis is caused by red blood cells blocking blood flow within the spleen.

It causes an acutely enlarged and painful spleen.

Blood pooling in the spleen can lead to severe anaemia and hypovolaemic shock.

Question 16

Splenic sequestration crisis is considered an emergency. True/false?

Answer 16

True

Question 17

Management of splenic sequestration crisis?

Answer 17

Management is supportive, with blood transfusions and fluid resuscitation to treat anaemia and shock.

Question 18

What can Splenic sequestration crisis lead to and how can a splenectomy be beneficial?

Answer 18

Splenic sequestration crisis can lead to splenic infarction, leading to hyposplenism and susceptibility to infections, particularly by encapsulated bacteria (e.g., Streptococcus pneumoniae and Haemophilus influenzae).

Splenectomy prevents sequestration crises and may be used in recurrent cases.

Question 19

What is an aplastic crisis and what infection would trigger this?

Answer 19

Aplastic crisis describes a temporary absence of the creation of new red blood cells.

It is usually triggered by infection with parvovirus B19

Question 20

What can an aplastic crisis lead to?

Answer 20

It leads to significant anaemia (aplastic anaemia).

Question 21

Management of aplastic crisis in sickle cell disease?

Answer 21

Management is supportive, with blood transfusions if necessary. It usually resolves spontaneously within around a week.

Question 22

What is acute chest syndrome?

Answer 22

Acute chest syndrome occurs when the vessels supplying the lungs become clogged with red blood cells.

A vaso-occlusive crisis, fat embolism or infection can trigger it.

Question 23

How does an acute chest crisis present?

Answer 23

Acute chest syndrome presents with fever, shortness of breath, chest pain, cough and hypoxia.

Question 24

What does a chest x-ray show for an acute chest crisis?

Answer 24

A chest x-ray will show pulmonary infiltrates.

Question 25

Acute chest crisis is usually benign. True/false?

Answer 25

False

Acute chest syndrome is a medical emergency with high mortality.

Question 26

Management for acute chest crisis?

Answer 26

It requires prompt supportive management and treatment of the underlying cause:

Analgesia
Good hydration (IV fluids may be required)
Antibiotics or antivirals for infection
Blood transfusions for anaemia
Incentive spirometry using a machine that encourages effective and deep breathing
Respiratory support with oxygen, non-invasive ventilation or mechanical ventilation

Question 27

A specialist MDT will manage sickle cell disease. What are the general principles to abide by?

Answer 27

Avoid triggers for crises, such as dehydration

Up-to-date vaccinations

Antibiotic prophylaxis to protect against infection, typically with penicillin V (phenoxymethylpenicillin)

Hydroxycarbamide (stimulates HbF)

Crizanlizumab

Blood transfusions for severe anaemia

Bone marrow transplant can be curative

Question 28

How can hydroxycarbamide help with sickle cell disease?

Answer 28

Hydroxycarbamide works by stimulating the production of foetal haemoglobin (HbF).

Foetal haemoglobin does not lead to the sickling of red blood cells (unlike HbS). It reduces the frequency of vaso-occlusive crises, improves anaemia and may extend lifespan.

Question 29

How can Crizanlizumab help with sickle cell disease?

Answer 29

Crizanlizumab is a monoclonal antibody that targets P-selectin.

P-selectin is an adhesion molecule found on endothelial cells on the inside walls of blood vessels and platelets.

It prevents red blood cells from sticking to the blood vessel wall and reduces the frequency of vaso-occlusive crises.

Question 30

Inheritance pattern for sickle cell disease?

Answer 30

Autosomal recessive