Sickle Cell Anaemia

“Autosomal recessive disorder in which production of abnormal haemoglobin results in vaso-occlusive crises”

• HbSS- homozygotes, have sickle cell disease
• HbAS- heterozygotes, have sickle cell trait

Risk Factors

• Most commonly in people of African origin (1:700 people of African descent)
• Family history (parents with sickle cell trait

Aetiology

• Amino acid substitution in the gene coding for the β chain (Glu → Val at position 6) leading to the production of HbS instead of HbA

Pathophysiology

• HbS polymerizes when deoxygenated → RBCs to deform → produces sickle cells which are fragile and haemolyse, also block small vessels

Clinical Presentation

Sickle Cell Crisis

• Vaso-occlusive crises
  • Most common crisis
  • Precipitated by cold, infection, dehydration, exertion, ischaemia
  • Occlusion of small vessels
  • Swollen painful joints, tachypnoea, acute abdominal distension and pain, loin pain, retinal occlusion
  • Large vessels à stroke, acute sickle chest syndrome, placental infarction
  • Acute chest syndrome- vaso-occlusive in the lungs, infections in children, infarcts in adults
• Aplastic crisis
  • Temporary cessation of erythropoiesis causing severe anaemia
  • Usually caused by infection with parvovirus B19
  • Drop-in Hb
  • Spontaneous recovery but may require a transfusion
• Sequestration crisis
  • Sudden enlargement of the spleen
  • The pooling of blood in spleen ± liver with severe anaemia
  • Urgent transfusion needed

Investigations

• FBC
• Blood film
• Sickle solubility test
• Hb electrophoresis
• Other tests:
  • Renal function tests
  • LFTs
  • Lung function tests

Management

• Neonatal screening for sickle cell disease
• Conservative:
  • Parental and patient education
  • Avoid triggers of crises- cold, dehydration, exhaustion
  • Avoid alcohol and smoking
• Medical:
  • Hydroxycarbamide (hydroxyurea)
  • Folic acid supplementation
  • Zinc supplementation if growth is restricted
  • Vit D supplementation especially in non-white children in the UK
  • Oral penicillin prophylaxis started at diagnosis
  • Routine childhood vaccinations
  • Malaria chemoprophylaxis (malaria significant cause of morbidity and mortality in patients)
  • Blood transfusion therapy in severe anaemia
• Surgical:
  • Bone marrow transplantation only in severe disease and a matched sibling donor
• Prevention:
  • Genetic counselling
  • Prenatal tests

Complications

• Splenic infarction before 2 years old → increased susceptibility to infection
• Poor growth
• Chronic renal failure
• Gallstones due to chronic haemolytic anaemia
• Eye- retinopathy, retinal infarcts, retinal haemorrhage, retinal detachment
• Stroke
• Chronic pain
• Nocturnal enuresis
• Iron overload
• Leg ulcers Lung damage → hypoxia → fibrosis → pulmonary hypertension