Hereditary Spherocytosis (HS)

This is a collection of inherited disorders which manifest as spherical-shaped erythrocytes (spherocytes) on the peripheral blood smear.¹ Clinical severity varies (depending on the mutation), from asymptomatic to a life-threatening haemolytic anaemia, but all mutations alter the cell membrane causing loss of membrane surface area and reduced deformability of the cell. These abnormal red cells are then selectively retained and destroyed in the spleen which reduces red cell life and produces the haemolytic anaemia.

Affects about 1 in 2000 in Europe and North America.¹ Both dominant and recessive forms exist, and a significant number may be new mutations without prior family history. Defects in several membrane proteins may be involved (e.g. alpha-spectrin, beta-spectrin, ankyrin, protein 4.2).

The commonest defect in an European population is a combined spectrin and ankyrin deficiency, found in 40–65% of patients (usually autosomal dominant). Isolated beta-spectrin defects account for about 15–30%, are usually only mild or moderately severe, autosomal dominant and do not to require transfusion.^1,2 Isolated alpha-spectrin defects occur in 5% and usually severe and display autosomal recessive inheritance, and other mutations producing defects in other membrane proteins (e.g. protein 4.2) can occur (more common in Japan).

20-30% of patients have mild disease with an increased red cell turnover compensated with adequate replacement. They are not symptomatic nor anaemic, but may have mild splenomegaly, slight reticulocytosis, and minimal spherocytes visible.

60-70% of patients have moderate disease and half of these present in childhood with anaemia.
Patients may present however at any age with haemolytic anaemia, jaundice (either from haemolysis or gallstones), splenomegaly; and spherocytes and reticulocytosis on peripheral blood film. Film may also show an increased number of hyperdense cells, raised MCHC (mean corpuscular haemoglobin concentration) and increased red cell distribution width. Always ask about any family history of anaemia.

Neonates with severe hereditary disease do not always present at birth with anaemia, but haemoglobin may fall dramatically over the first few weeks of life and may be severe enough to require exchange transfusion.³

• FBC, red cell morphology and blood film including reticulocyte count
• Liver function tests (for jaundice)
• Direct antiglobulin test - autoimmune haemolytic anaemia should be excluded, and osmotic fragility tests may be needed if no family history available

Monitor mild cases with regular FBC tests, they usually do not require folate supplements nor splenectomy.
More severely affected individuals are usually given folate supplementation, and may benefit from splenectomy (usually performed after age 6).³ There needs to be a full discussion on the dangers and benefits of splenectomy, and such patients will need lifelong prophylaxis post splenectomy (see Splenectomy, Hyposplenism and Asplenia).

• Gallstones and gall bladder disease. Co-existent Gilberts Syndrome increases the risk of gallstones by four times. The increased risk of gallstones is abolished by splenectomy.
• Haemolytic, aplastic and megaloblastic crises. Rapid haemolysis can be triggered by viral infections and produce jaundice, anaemia and occasionally abdominal pain and tender splenomegaly. Supportive treatment is usually all that is needed.
  Aplastic crises (aplastic anaemia) can follow viral bone marrow suppression and can be life threatening. They are most commonly caused by Parvoviral infection (B19) and usually last 10-14 days.¹
  Megaloblastic crises are rare and due to folate deficiency.

3-5% of patients have severe hereditary disease requiring regular transfusions.

Genetic testing and family tracing is available. Relatives who are carriers of the gene may show a persistent reticulocytosis. The incubated osmotic fragility test is the most sensitive way of identifying them.