Sickle cell anaemia

Question 1

What is sickle cell anaemia?

Answer 1

A genetic condition that causes sickle (crescent) shaped RBCs. The abnormal shape makes the RBCs more fragile and easily destroyed, leading to haemolytic anaemia.

Question 2

What are patients with sickle cell anaemia prone to?

Answer 2

Various sickle cell crises.

Question 3

What type of condition is sickle cell anaemia and what gene does it affect?

Answer 3

It is an autosomal recessive condition. Two abnormal copies result in sickle cell disease, while one results in sickle cell trait. It affects the gene for the beta globin on chromosome 11.

Question 4

What is sickle cell trait and are these patients symptomatic?

Answer 4

One abnormal copy of the gene results in sickle cell trait. These patients are asymptomatic and are carriers of the condition.

Question 5

What is Hb?

Answer 5

A protein in the RBCs that transports oxygen.

Question 6

When does HbF decrease and HbA increase?

Answer 6

Around 32-36 weeks gestation, with a gradual transition from HbF to HbA. At birth, around half of the Hb is HbF and half is HbA. By 6 months, very little HbF is produced and RBCs contain almost entirely HbA.

Question 7

Where is sickle cell disease more common?

Answer 7

In areas traditionally affected by malaria, like Africa, India, the Middle East, and the Caribbean.

Question 8

What is the relation between sickle cell and malaria?

Answer 8

Having one copy of the gene (sickle cell trait) reduces the severity of malaria. Patients with sickle cell trait are more likely to survive malaria and pass on their genes, giving a selective advantage to having the sickle cell gene in areas of malaria.

Question 9

When is sickle cell screened for?

Answer 9

On the newborn blood spot around 5 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
• priapism (painful and persistent penile erections)
• sickle cell crises
• acute chest syndrome
• stroke
• CKD
• CNS complications - CVAs, seizures, hearing loss
• visual problems
• avascular necrosis in large joints eg. the hip
• renal papillary necrosis (can lead to haematuria, renal tubular defects and difficulty concentrating urine
• pulmonary hypertension
• gallstones

Question 11

What is a sickle cell crisis?

Answer 11

A spectrum of acute exacerbations caused by sickle cell disease, ranging from mild to life-threatening.

Question 12

What causes a sickle cell crisis?

Answer 12

It can occur spontaneously or be triggered by dehydration, infection, stress, or cold weather.

Question 13

What is the management for a sickle cell crisis?

Answer 13

Supportive

• low threshold for admission to hospital
• treating infections that may have triggered the crisis
• keep warm
• good hydration (IV fluids may be needed)
• analgesia (avoid NSAIDs if there’s renal impairment)

Question 14

What is a vaso-occlusive crisis (VOC)?

Answer 14

Also known as a painful crisis, it is the most common type of sickle cell crisis.

Question 15

What causes a vaso-occlusive crisis?

Answer 15

Sickle shaped RBCs clogging capillaries, causing distal ischaemia

Question 16

How does a vaso-occlusive crisis present?

Answer 16

• pain and swelling in the hands or feet
• can affect the chest, back or other body areas
• can be associated with fever
• can cause priapism by trapping blood in the penis → painful and persistent erection (urological emergency - treated by aspirating blood from the penis)

Question 17

What is a splenic sequestration crisis?

Answer 17

Caused by RBCs blocking blood flow within the spleen.

Question 18

What does a splenic sequestration crisis cause?

Answer 18

An acutely enlarged and painful spleen, blood pooling in the spleen can lead to severe anaemia and hypovolaemic shock.

Question 19

What is the management for a splenic sequestration crisis?

Answer 19

• emergency?
• supportive management
• blood transfusions
• fluid resuscitation to treat anaemia and shock

Question 20

What can splenic sequestration crisis lead to?

Answer 20

splenic infection, leading to hyposplenism and susceptibility to infections, particularly encapsulated bacteria (eg. streptococcus pneumoniae and haemophilus influenza)

Question 21

What is an aplastic crisis?

Answer 21

Temporary absence of the creation of new RBCs.

Question 22

What usually triggers an aplastic crisis?

Answer 22

Infection with parvovirus B19

Question 23

What does an aplastic crisis lead to?

Answer 23

Anaemia (aplastic anaemia).

Question 24

What is the management for an aplastic crisis?

Answer 24

Supportive management with blood transfusions if necessary, usually resolves spontaneously within around a week.

Question 25

When does acute chest syndrome occur?

Answer 25

When the vessels supplying the lungs become clogged with RBCs, it is a medical emergency.

Question 26

What can trigger acute chest syndrome?

Answer 26

A vaso-occlusive crisis, fat embolism, or infection.

Question 27

How does acute chest syndrome present?

Answer 27

Fever, shortness of breath, chest pain, cough, and hypoxia.

Question 28

What would a chest X-ray show in acute chest syndrome?

Answer 28

Pulmonary infiltrates.

Question 29

What is the management for acute chest syndrome?

Answer 29

- **analgesia** - good **hydration**, may need IV fluids - **antibiotics** or **antivirals** for infection - **blood transfusions for anaemia** - **incentive spirometry** using a machine that encourages **effective and deep breathing** - **respiratory support with oxygen, NIV or mechanical ventilation**

Question 30

What is the definitive diagnosis of sickle cell disease made by?

Answer 30

By haemoglobin electrophoresis.

Question 31

What are the general principles of management for sickle cell disease?

Answer 31

Avoid triggers for crises, such as dehydration, and ensure up-to-date vaccines.

Question 32

What medications can be given for sickle cell disease?

Answer 32

- **antibiotic prophylaxis** to protect against infection, typically with **Penicillin V** - **hydroxycarbamide/hydroxyurea** (stimulates HbF) - **Crizanlizumab** - **blood transfusions** for severe anaemia - **bone marrow transplants** can be curative

Question 33

How does hydroxycarbamide/hydroxyurea work?

Answer 33

- **stimulates HbF** - fetal Hb **doesn’t lead to the sickling of RBCs** (unlike HbS) - it **reduces the frequency of vaso-occlusive crises**, improves anaemia and may extend lifespan

Question 34

How does Crizanlizumab work?

Answer 34

- a **MCA** that **targets P-selectin** - this is an **adhesion molecule** found on **endothelial cells** on the **inside of blood vessels and platelets** - it **prevents RBCs from** **sticking to the blood vessel wall** and **reduces the frequency** of **vaso-occlusive crisis**