A. Hereditary spherocytosis – Explanation
hereditary spherocytosis.
Hereditary Spherocytosis
Hereditary Spherocytosis is the most common inherited RBC membrane defect
characterized by variable degrees of haemolysis, spherocytic RBCs with increased
osmotic fragility.
Approximately 75% of cases display an autosomal dominant pattern of inheritance; the
rest are recessive forms and de novo mutations.
Clinical features
• Patients may present at any age with haemolytic anaemia, jaundice (either from
haemolysis or gallstones) and splenomegaly
• 20-30% of patients have mild disease with an increased red cell turnover
compensated with adequate replacement. They are neither 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.
• 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.
• Occasional aplastic crises occur, e.g. with parvovirus B19 infection.
Diagnosis
(These are the 3 most important test that you need to know in the exam for Hereditary
Spherocytosis)
• Blood film shows spherocytes and increased reticulocytes
• MCHC would be elevated
• Osmotic fragility test → confirms presence of spherocytes but does not permit
hereditary spherocytosis to be distinguished from other spherocytic haemolytic
disorders such as autoimmune haemolytic anaemia. This is not reliable until six
months of age.
Some authors mention that osmotic fragility test is unreliable and is no longer
recommended. However, it is still considered the gold standard despite missing up to
20% of cases. In the PLAB exam, osmotic fragility test may be given as a choice for a
diagnostic test for Hereditary Spherocytosis. Pick it if it is.
Note:
Spherocytosis almost always refers to hereditary spherocytosis but note that
spherocytes are found in hereditary spherocytosis and also autoimmune haemolytic
anaemias. The test to distinguish the two would be a direct Coombs test. Hereditary
spherocytosis has a negative direct Coombs test but autoimmune haemolytic anaemias
have a positive direct Coombs test
Management
Steroid therapy
• effective in augmenting haemoglobin levels during haemolytic crises in patients with
moderate disease
Folate supplementation
Splenectomy
• eliminates anaemia and hyperbilirubinaemia and lowers the high reticulocyte number
to nearly normal levels
• Splenectomy is curative in most patients but increased recognition of the long-term
risks of splenectomy has led to re-evaluation of the role of splenectomy.
Mild cases do not usually require folate supplements or splenectomy
Complications
• 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). They are most commonly caused by infection with
parvovirus B19 and usually last 10-14 days. This can be life-threatening.
When you see parvovirus B19 in the exam, immediately think of sickle cell anaemia or
hereditary spherocytosis
Parvovirus and anaemia
Although most patients have a decrease of erythropoiesis (production of red blood cells)
during parvovirus infection, it is most dangerous in patients with sickle cell anaemia or
hereditary spherocytosis, as they are heavily dependent on erythropoiesis due to the
reduced lifespan of the red cells.
