Sickle Cell Disease

Question 1

What is sickle cell disease?

Answer 1

https://www.youtube.com/watch?v=1ql-X60CUNQ

Sickle-cell disease (SCD) is a group of blood disorders typically inherited from a person’s parents. The most common type is known as sickle-cell anaemia (SCA). It results in an abnormality in the oxygen-carrying protein haemoglobin (haemoglobin S) found in red blood cells. This leads to a rigid, sickle-like shape under certain circumstances

Question 2

What is the pathophysiology of SCD?

Answer 2

Sickle cell haemoglobin (HbS) results from a single-base mutation of adenine to thymine, producing a substitution of valine for glutamic acid at the sixth codon of the β-globin chain. Deoxygenated HbS molecules are insoluble and polymerize. This process is initially reversible but, with repeated sickling, the cells eventually lose their membrane flexibility and become irreversibly sickled. Cells are fragile and prone to haemolysis, and cause small vessel occlusion

Question 3

Which ethnicity is SCD most common in?

Answer 3

Those of african decent

Question 4

Why does the disease not normally manifest until 6 months of age?

Answer 4

As the synthesis of HbF is normal, the disease usually does not manifest itself until the HbF decreases to adult levels at about 6 months of age

Question 5

What does SC trait protect against?

Answer 5

Malaria

Question 6

When can vaso-occlusive crises occur in those with SC trait?

Answer 6

Any hypoxic situations

• Unpressurised aircraft
• Anaesthesia

Question 7

What gene is involved in SCD?

Answer 7

HbS gene

Question 8

Why is the chronic haemolysis normally well tolerated by those with SC anaemia?

Answer 8

HbS releases its oxygen to the tissues more easily than does normal Hb, and patients therefore feel well despite being anaemic (except of course during crises or complications).

Question 9

What are features of SCD?

Answer 9

• Jaundice
• Gallstones
• Mild anaemia
• Crisis syndromes - Bone, Chest, Stroke, Spleen, Liver

Question 10

What is a vaso-occlusive crisis?

Answer 10

Vaso-occlusion of the small vessels. It often affects the marrow of bone

Question 11

What can trigger vaso-occlusive crises?

Answer 11

• Cold
• Dehydration
• Hypoxia
• Infection

Question 12

What is the most common site of pain for vaso-occlusive crises in children?

Answer 12

Hands and feet - dactylitis

Question 13

Why might someone with SC anaemia present with an acute abdomen?

Answer 13

Mesenteric Ischaemia

Question 14

Why can strokes, seizures or cognitive defects occur in those with sickle cell anaemia?

Answer 14

CNS ischaemia

Question 15

How might someone with a sickle cell chest crisis present?

Answer 15

• SOB
• Wheeze
• Cough
• Chest Pain
• Fever
• Worsening hypoxia

Question 16

Why might someone with SCD be at increased risk of infection?

Answer 16

Due to hyposplenism

Organs which are prone to vaso-occlusion are also prone to specific infection

Question 17

What long-term complications can occur in SCD?

Answer 17

• Splenic infarction
• Poor growth
• Chronic renal failure
• Gallstones
• Retinal disease
• Pulmonary fibrosis and hypertension
• Avascular necrosis
• Leg ulcers
• Priapism
• Spontaneous abortion
• Cardiac problems

Question 18

When are sequestration crises most likely to occur?

Answer 18

Childhood - splenic infarction has not occured at this point

Question 19

What is the cause of aplastic crisis in Sickle Cell anaemia?

Answer 19

Parvovirus B19

Question 20

What is acute chest crisis caused by?

Answer 20

• Infection
• Fat embolism - from necrotic bone marrow
• Pulmonary infarction - due to sequestration of sickle cells

Question 21

What are the primary causes of acute chest crisis?

Answer 21

Fat embolism from infarcted bone marrow, or infection from chlamydia, mycoplasma or viruses

Question 22

How would you test a child for suspected sickle cell disease?

Answer 22

• Bloods - FBC, U+E’s, LFTs, reticulocytes, serum bilirubin
• Coombs test
• Blood film
• Hb electrophoresis
• Sickle solubility test
• Genetic study - parents

Question 23

What does a positive sickle solubility test not indicate?

Answer 23

Whether someone is homozygote or heterozygote

Question 24

How would you manage sickle cell anaemia as a chronic disease?

Answer 24

• Hydroxycarbamide
• Prophylactic immunisation
• Folic acid

Question 25

Why is hydroxycarbamide used to treat SCD?

Answer 25

Raises the conc of fetal Hb. This results in reduction in the episodes of pain, the acute chest syndrome, and the need for blood transfusions

Question 26

Why is folic acid used to treat SCD?

Answer 26

Used in patients with severe anaemia

Question 27

How would you manage and acute sickle cell crisis?

Answer 27

• IV opiates
• Rehydrate
• Consider O2 - if hypoxic/sats < 95%
• Antibiotics - if temp >38oC
• Give transfusion - if Hb or retic count fall dramatically

Question 28

What are indications for an exchange transfusion?

Answer 28

• Severe chest crisis
• Suspecte CNS event
• Multiorgan failure

Question 29

How would you manage an acute chest crisis?

Answer 29

• O2
• Analgesia
• Antibiotics
• Bronchodilators - those who are wheezy
• Consider ITU - if PaO2 <9.2 kPa

Question 30

What is the average life expectancy of someone with Sickle Cell disease?

Answer 30

• Males - 42 yrs
• Females - 48 yrs

Question 31

If someone had SCD, what would there reticulocyte count be?

Answer 31

Increased by 10-20%

Question 32

What range does the Hb of someone with SCD normally sit in?

Answer 32

60-90 g/L

Question 33

What might you see when looking at serum bilirubin in someone with SCD?

Answer 33

Increased bilirubin

Question 34

What organisms does splenic atrophy increase the risk of being infected by?

Answer 34

• Pneumococcus
• Salmonella species
• Haemophilus

Question 35

What are the most commonly affected sites of Avascular necrosis in adults?

Answer 35

• Ribs
• Spine
• Pelvis