Group of genetic disorders that affect the structure of haemoglobin, resulting in the production of HbS

Aetiology

• Genetic - point mutation in codon 6 of the β globin gene that substitutes glutamine to valine producing βS

Pathophysiology

• Mutation alters the structure of the resulting Hb → HbS (⍺2βS2)
• HbS polymerises if exposed to low oxygen levels for a prolonged period → distorts the red cell, damaging the RBC membrane

Sickle cell trait (HbAS)

• One normal, one abnormal β gene
• Asymptomatic carrier state
• Few clinical features as HbS level too low to polymerase
• May sickle in severe hypoxia e.g. high altitude, under anaesthesia
• Blood film normal
• Mainly HbA, HbS <50%

Sickle cell anaemia (HbSS)

• Two abnormal β genes (βS/βS)
• HbS >80%, no HbA
• Episodes of tissue infarction due to vascular occlusion - sickle crisis
  • Symptoms depend on site and severity
  • Pain may be extremely severe
  • Precipitants include hypoxia, dehydration, infection, cold exposure, stress/fatigue
• Chronic haemolysis - shortened RBC lifespan
• Sequestration of sickled RBCs in liver and spleen
• Hyposplenism due to repeated splenic infarcts