Hereditary spherocytosis is the most common hereditary haemolytic anaemia in people of northern European descent.

Pathophysiology

• autosomal dominant mutations affecting proteins that anchor the cytoskeleton to the plasma membrane e.g. spectrin
• the normal biconcave disc shape is replaced by a sphere-shaped red blood cell
• red blood cell survival reduced as destroyed by the spleen
  • spherocytes cannot deform adequately to traverse the splenic cords
  • they become trapped and destroyed by splenic macrophages (extravascular haemolysis)

Presentation

• failure to thrive
• jaundice, gallstones
• splenomegaly
• aplastic crisis precipitated by parvovirus infection
• degree of haemolysis variable
• MCHC elevated (because spherocytes lose membrane surface area relative to volume.)

Diagnosis

• the osmotic fragility test was previously the recommend investigation of choice. However, it is now deemed unreliable and is no longer recommended
• the British Journal of Haematology (BJH) guidelines state that 'patients with a family history of HS, typical clinical features and laboratory investigations (spherocytes, raised mean corpuscular haemoglobin concentration [MCHC], increase in reticulocytes) do not require any additional tests
• if the diagnosis is equivocal the BJH recommend the EMA binding test and the cryohaemolysis test
  • The eosin-5'-maleimide (EMA) binding test is a flow cytometric assay: EMA is a fluorescent dye that covalently binds to band 3 protein and other membrane proteins on red blood cells (RBCs). Defective RBCs → reduced binding → less fluorescence activity. A reduction of >15% from control values is highly suggestive of HS
  • The cryohaemolysis test assesses RBC membrane stability at low temperatures (0–4°C)
• for atypical presentations electrophoresis analysis of erythrocyte membranes is the method of choice

Management

• acute haemolytic crisis:
  • treatment is generally supportive
  • transfusion if necessary
• longer term treatment:
  • folate replacement
  • splenectomy