Hereditary Spherocytosis

Overview

Hereditary spherocytosis is a predominantly autosomal dominant condition leading to spherical-shaped red blood cells (spherocytes). Spherocytes are more fragile than standard red blood cells and are therefore destroyed more easily, resulting in excess splenic red blood cell destruction and splenomegaly. Therefore, hereditary spherocytosis causes extravascular haemolysis. The severity of hereditary spherocytosis varies between different individuals.

A similar condition called hereditary elliptocytosis also exists. This is where the red blood cells are ellipse-shaped.

It may be helpful to look at the chapter on Anaemia: Data Interpretation alongside reading this section to help wrap your head around when to suspect what type of anaemia.

Epidemiology

• Most common in Northern European people
• Most cases are due to autosomal dominant inheritance

Risk Factors

• Family history
• Northern European descent

Example History

An 8-year-old boy has fatigue, pallor, and splenomegaly. He has no other medical conditions and takes no medication. He has a family history of similar symptoms.

Investigations:

Presentation

Features of hereditary spherocytosis are:

• Pallor
• Fatigue
• Dyspnoea
• Failure to thrive in younger children and infants
• Splenomegaly – nearly always palpable in hereditary spherocytosis
  • Due to 
• Jaundice – due to bilirubin release from haemolysis
  • Hereditary spherocytosis can present as prolonged jaundice in neonates
  • Jaundice is more pronounced with more haemolysis
• Dark urine – due to bilirubin release haemolysis
• Gallstones – due to repeated haemolysis and bilirubin release

Differential Diagnoses

G6PD deficiency

• Splenomegaly is not seen in G6PD deficiency
• G6PD deficiency is X-linked recessive, so males are more likely to be affected
• G6PD has Heinz bodies on a blood film

Investigations

Overview

• Full blood count (FBC):
  • Haemoglobin: low but can be normal
  • Mean corpuscular haemoglobin concentration: may be elevated
  • Mean cell volume: usually normal
  • White blood cells: usually normal, but reduced in aplastic crisis
  • Platelets: usually normal, but reduced in aplastic crisis
• Reticulocyte count:
  • Usually elevated, but reduced in aplastic crisis
  • The bone marrow responds by trying to create new, immature red cells 
• Blood film:
  • Presence of spherocytes – these are not 100% specific to hereditary spherocytosis, they are also seen in autoimmune haemolytic anaemia
• Unconjugated bilirubin:
  • Raised on a background of normal LFTs due to haemolysis
• Direct antiglobulin test:
  • Negative, to rule out autoimmune haemolytic anaemia
• Eosin-5-maleimide (EMA) binding test:
  • Not necessary if typical features are present on the blood film and a family history is present
  • Shows reduced intensity of fluorescence and band 3 protein present

Diagnosis

If the presentation is typical, then hereditary spherocytosis can be diagnosed i.e. it can be diagnosed based on the following criteria being met:

• Reticulocytosis with or without anaemia
• Spherocytes seen on the blood film
• Negative direct anti-globulin test, ruling out immune aetiology for haemolysis

If the presentation is not typical (i.e. does not meet the above criteria), then an EMA binding test should be carried out which can help with the diagnosis. 

Management

All patients

• In acute haemolytic crisis: supportive management + transfusions if needed
• Consider splenectomy to reduce the frequency of haemolytic crises. If this is carried out patients need:
  • Antibiotic prophylaxis
  • 5-yearly pneumococcal vaccination
• Consider folate to prevent megaloblastic crises:
  • Megaloblastic crises are where the bone marrow produces megaloblasts – large, abnormal, and immature red blood cells.

Patient Advice

• All patients should have genetic counselling regarding hereditary spherocytosis as it is a genetic condition
• Patients should be safety-netted on when to seek help – worsening pallor, jaundice, and fatigue may be signs of a haemolytic crisis
• Post-splenectomy patients should seek immediate help if they develop a fever due to the increased risk of severe infection

Complications

• Aplastic crises – bone marrow suppression and sudden drop in haemoglobin
  • Most commonly triggered by parvovirus B19
• Gallstones due to increased bilirubin and repeated haemolysis
• Megaloblastic crises
  • The bone marrow produces large, immature, structurally abnormal red blood cells

Prognosis

• Very few patients have severe disease that requires regular blood transfusions