Sickle Cell Disease

Question 1

Definition of sickle cell disease

Answer 1

A chronic condition caused by an autosomal recessive single defect in the beta chain of haemoglobin, which results in the production of sickle cell haemoglobin (HbS) and increases the risk of vaso-occlusive crises

Question 2

Aetiology of sickle cell disease

Answer 2

• Most commonly seen in people of African origin and those with Family history

• Sickling occurs when RBCs containing sickle haemoglobin become rigid and disotorted into a crescent shape when the HbS polymerises due to deoxygenation

• It occurs due to a point mutation in the beta-glob in gene that results in an amino acid substitution (Valine replaces glutamic acid in position 6)
‣ This results in the formation of HbS rather than HbA

• Homozygotes for HbS (HbSS)= Sickle cell anaemia (no protection against malaria)
• Heterozygous for HbS (HbAS)= Sickle cell trait (carrier). They have no disability and are also protected from falciparum malaria. But may still experience sickling in hypoxic conditions

Question 3

Pathophysiology of sickle cell disease

Answer 3

• Deoxygenation of HbS can alter its shape and result in the sickle cell RBCs
• The sickle shape increases the risk of:
◦ Sequestration and destruction (become fragile and haemolysis), contributes to anaemia
◦ Occlusion of small blood vessels can cause painful crises, reduced O2 to tissue, damage to organs and increased risk of infections

Question 4

Risk factors for sickle cell crisis

Answer 4

• Factors that increase the risk of sickling/crisis:
◦ Infection
◦ Hypoxia
◦ Dehydration
◦ Acidosis
◦ Cold temperatures
◦ Stress

Question 5

History and examination for sickle cell disease

Answer 5

• Painful sickle cell crises secondary to vaso-occlusion:
◦ Persistent pain in skeleton, chest and/or abdomen
◦ Bone pain: due to bone infarction and a vascular necrosis as a result of vaso-occlusion
• Dactylitis: swollen dorsa of the hands and feet can be presenting symptoms in young infants and children
• Increased risk of infections: due to damage to spleen (splenic atrophy and infarction)
◦ High temperature

• Symptoms of a SEQUESTRATION CRISIS:
◦ Occurs due to the pooling of RBCs in the spleen can lead to splenomegaly
◦ Anaemia: haemolysis of RBCs
◦ Jaundice
◦ Tachycardia
◦ Lung problems: sickling of blood in pulmonary system leads to acute chest syndrome (chest pain, SOB, fever etc)

• Visual defects: Visual loss can be due to occlusion of small retinal arterioles; hence leading to ischaemia

Question 6

Investigations for sickle cell disease

Answer 6

• FBC: would show low Hb and high reticulocytes
• Blood film: would show the presence of sickle-shaped RBCs , target cells and Howell-Jolly bodies
• DNA-based assays: provides accurate diagnosis, but reserved for antenatal diagnosis
• Hb electrophoresis: can differentiate between sickle cell trait (HbAS) and sick cell disease (HbSS)
• Haemoglobin solubility test: will be positive for the gene, but cannot differentiate between trait and disease
• Iron studies: differentiates iron deficiency from haemolytic anaemia (iron study will be normal)

Question 7

Treatment for sickle cell disease

Answer 7

Vaso-occlusive (pain) crisis:
1) Analgesia: May need strong analgesia (e.g IV opiates), but refer to personalised analgesia plan
+ Oxygen: O2 sats are checked and O2 is given accordingly
+ Hydrate with IV fluids
+ keep warm
+ Folic acid: if severe haemolysis
CONSIDER
Blood transfusions: for severe anaemia, can give deferasirox (iron chelator) if repeated transfusions needed
Antibiotics: for infectious presentations
Hydroxycarbamide; Increases HbF levels; therefore decreases frequency of pain episodes, transfusion requirements etc

Ongoing:
Avoid triggers: Reduce risk of infections by ensuring pneumococcal and influenza vaccinations are done, antibiotics prophylaxis if needed, keeping warm, maintaining hydration etc
CONSIDER
Hydroxycarbamide

Question 8

Prevention and prognosis of sickle cell disease

Answer 8

Genetic counselling, prenatal testing, parental education
Avoiding triggers (secondary)

Reduced life span, risk of chronic organ damage (can be managed)
Risk of pulmonary or neurological complications in adults

Question 9

Complications of sickle cell disease

Answer 9

Reduced life span, risk of chronic organ damage (can be managed)
Risk of pulmonary or neurological complications in adults