Sickle Syndromes

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
    • Precipitatnts 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

Other sickling disorders (sickle cell disease)

  • Compound heterozygosity for HbS and another β chain mutation, for example:
    • HbS/β thalassaemia
    • HbSC disease; milder, but increased risk of thrombosis

Clinical presentation

Clinical features of sickle cell anaemia

  • Vaso-occlusive crises - acute pain in the hands and feet due to vaso-occlusion of the small vessels
  • Acute chest sydrome - caused by infection, fat embolism from necrotic bone marrow in a vaso-occlusive crisis or pulmonary infarction due to sequestration of sickle cells
    • Shortness of breath, chest pain, pyrexia, hypoxia and new chest x-ray changes due to consolidation
  • Pulmonary hypertension
  • Anaemia
    • Splenic sequestration - vaso-occlusion produces an acute painful enlargement of the spleen
    • Bone marrow aplasia - most commonly follows infection with parvovirus B19, which invades proliferating erythroid progenitors

Investigations

  • Bloods - FBC, Hb, red cell indices, blood film
  • High performance liquid chromatography (HPLC) or electophoresis to quantify haemoglobins present
    • Will identify abnormal haemoglobins

Management

Long-term management of sickle cell anaemia

  • Hyposplenism - reduce risk of infection
    • Prophylactic penicillin
    • Vaccination - pneumococcus, meningococcus, haemophilus
  • Folic acid supplementation (increased RBC turnover so increased demand)
  • Hydroxycarbamide can reduce severity of disease by indicing HbD production
  • Regular transfusion to prevent stroke in selected cases

Management of a sickle crisis

  • Opiate analgesia
  • Hydration
  • Rest
  • Oxygen
  • Antibiotics if evidence of infection
  • Red cell exchange transfusion in severe crisis e.g. chest crisis (lung) or brain (stroke)