Sickle Cell

• What type of genetic condition is sickle cell anaemia (SCA)?


  Autosomal recessive condition
• What mutation leads to the production of HbS in sickle cell anaemia?


  A point mutation in the beta chain on chromosome 11
• What happens to HbS when it is deoxygenated?


  It polymerises, leading to sickled red blood cells
• What are the consequences of sickled red blood cells?

  They are fragile and sticky, causing vaso-occlusive crises
• What is the most common acute presentation of sickle cell anaemia?


  Painful vaso-occlusive crises
• What is the most dangerous acute presentation of sickle cell anaemia?


  Acute chest crises
• How is sickle cell anaemia typically diagnosed in the UK?


  Via a national screening programme postnatally
• What may investigations reveal in sickle cell anaemia?


  Microcytic anaemia with variable degrees of haemolysis
• What is the definitive diagnosis for sickle cell anaemia?


  Haemoglobin electrophoresis +/- genetic testing
• What management strategies are used for acute crises in sickle cell disease?


  High-flow oxygen, IV fluids, and analgesia
• What is the genetic basis of sickle cell anaemia?


  It is caused by a mutation where glutamic acid is replaced by valine at the 6th position of the β chain
• What happens to HbS in its deoxygenated state?


  It undergoes polymerisation, forming crystals
• What is the consequence of the abnormal shape of RBCs in sickle cell disease?


  It causes clotting in the microvasculature, leading to vaso-occlusive crises
• How does chronic haemolysis affect the body's nitric oxide levels?


  It decreases the body's nitric oxide, affecting vasoregulation
• What is the inheritance pattern of sickle cell anaemia?


  Autosomal recessive
• What is the most severe form of sickle cell disease?

  Homozygous HbS (HbSS)
• What happens to sickled red cells in the spleen?

  They undergo phagocytosis by the reticular endothelial system
• What is the result of splenic infarction in sickle cell disease?


  It leads to hyposplenism and reduced immune function
• Why are individuals with sickle cell disease prone to bacteraemia?


  Due to reduced immune function from hyposplenism
• What vaccinations should individuals with sickle cell disease have?


  Vaccinations for S. pneumoniae, H. influenzae B, and N. meningitidis
• What triggers painful vaso-occlusive crises in sickle cell anaemia?


  Microvascular obstruction due to RBC sickling and inflammation
• What is the mortality rate associated with acute chest crises?


  3% mortality rate
• What are the common presentations of acute chest crises?

  Tachypnoea, wheeze, cough, hypoxia, and pulmonary infiltrates
• What are some complications of sickle cell disease?


  Splenic infarction, osteomyelitis, stroke, and chronic renal disease
• How does the amount of HbF affect clinical severity in sickle cell disease?


  Higher levels of HbF reduce the severity of clinical complications
• How do patients with Hb SC disease compare to those with Hb SS disease?


  Patients with Hb SC disease have milder anaemia and fewer crises
• Why do patients with Hb SC disease require annual ophthalmological review?


  They are more prone to sickle cell retinopathy
• What bedside investigation is essential for monitoring patients with chest crisis?


  Peak flow measurement
• What typical blood film findings are associated with sickle cell disease?


  Characteristic sickle cells, target cells, and reticulocytosis
• What is the role of haemoglobin electrophoresis in sickle cell disease diagnosis?


  It provides a definitive diagnosis
• How is sickle cell disease screened in the UK?


  Typically diagnosed postnatally by the national screening programme
• What treatments are included for acute sickle cell crisis?


  High-flow oxygen, IV fluids, and analgesia
• What is the purpose of hydroxycarbamide in chronic sickle cell disease management?


  It increases fetal haemoglobin concentrations
• What newer therapies are available for sickle cell disease?


  Crizaniluzumab and voxelotor
• What are potential curative options for sickle cell disease?


  Bone marrow transplant and gene-editing techniques
• What are the management strategies for chronic sickle cell disease?


  • Hydroxycarbamide for frequent crises
  • Regular exchange transfusions for severe cases
  • Vaccinations and antibiotic prophylaxis
  • Newer therapies: crizaniluzumab and voxelotor
  • Bone marrow transplant and gene-editing techniques as curative options