Sickle cell disease

Definition | Aetiology | Pathophysiology | Risk Factors | Signs and Symptoms | Investigations | Management

Definition

Sickle cell disease (SCD) is an inherited haemoglobinopathy caused by a mutation in the beta-globin gene, leading to abnormal haemoglobin S (HbS) production. It results in chronic haemolytic anaemia, vaso-occlusive crises, and end-organ damage.

Aetiology

  • Genetic mutation: autosomal recessive disorder due to a point mutation in the HBB gene encoding beta-globin.
  • Sickle cell trait (HbAS): heterozygous state, usually asymptomatic but can cause complications in extreme conditions.
  • Sickle cell disease (HbSS): homozygous mutation, leading to severe clinical manifestations.

Pathophysiology

  • Under hypoxic conditions, HbS polymerises, causing red cells to become rigid and sickle shaped.
  • Sickled cells have reduced deformability, leading to vaso-occlusion and microvascular ischaemia.
  • Chronic haemolysis results in anaemia, increased bilirubin, and gallstone formation.
  • Repeated vaso occlusive episodes lead to progressive organ damage (stroke, pulmonary hypertension, renal impairment).

Risk Factors

  • African, Caribbean, Middle Eastern, and Indian ancestry.
  • Positive family history of sickle cell disease.
  • Exposure to hypoxia, dehydration, or infections, which can trigger sickling crises.

Signs and Symptoms

  • Chronic anaemia: fatigue, pallor, jaundice.
  • Vaso occlusive crisis: severe bone pain (commonly in long bones, chest, and back).
  • Dactylitis: painful swelling of hands and feet (common in children).
  • Avascular necrosis: hip or shoulder joint pain due to bone infarction.
  • Stroke: common in children and young adults with SCD.
  • Acute chest syndrome: fever, cough, hypoxia, and lung infiltrates on imaging.
  • Splenic sequestration crisis: sudden splenomegaly with severe anaemia (more common in children).

Investigations

  • Full blood count (FBC): normocytic anaemia, reticulocytosis.
  • Blood film: sickle cells, Howell Jolly bodies (if splenic dysfunction present).
  • Haemoglobin electrophoresis: confirms presence of HbS and distinguishes sickle cell disease from trait.
  • Bilirubin and LDH: elevated due to haemolysis.
  • Transcranial Doppler ultrasound: used for stroke risk assessment in children.
  • Renal function tests: assess for sickle nephropathy.

Management

1. Acute Crisis Management:

  • Analgesia (opioids for severe pain, NSAIDs for mild to moderate pain).
  • IV fluids to prevent dehydration-induced sickling.
  • Oxygen therapy if hypoxic.
  • Empirical antibiotics if infection suspected.
  • Exchange transfusion in severe vaso-occlusive crisis or acute chest syndrome.

2. Long-Term Management:

  • Hydroxycarbamide to reduce frequency of crises and increase HbF levels.
  • Penicillin prophylaxis (lifelong) and pneumococcal vaccination due to functional asplenia.
  • Folic acid supplementation.
  • Regular monitoring for complications (stroke, nephropathy, pulmonary hypertension).

3. Curative Treatment:

  • Allogeneic stem cell transplantation in selected cases.

4. Referral:

  • Haematology: for long term disease management.
  • Paediatrics: for stroke screening in children.
  • Respiratory: if pulmonary hypertension or recurrent acute chest syndrome.
  • Orthopaedics: for avascular necrosis requiring surgical intervention.
HaematologymypanotesSickle cell disease