Makindo Medical Notes

Related Subjects: |Iron deficiency Anaemia |Haemolytic anaemia |Macrocytic anaemia |Megaloblastic anaemia |Microcytic anaemia |Myelodysplasia |Myelofibrosis

The most frequent cause of hereditary spherocytosis is a mutation in the spectrin gene. Spectrin is a crucial component of the RBC membrane, alongside actin, ankyrin, and protein 4.1. Mutations in these proteins are less common but may also lead to hereditary spherocytosis.

About

• An autosomal dominant condition, though 25% of cases are due to de novo mutations.
• The hallmark of haemolytic anaemia is a reduced red cell half-life, leading to chronic anaemia.
• The most common cause of inherited haemolytic anaemia in Europe.
• Affects more than 1 in 5000 people but often goes undetected due to variable severity.

Aetiology

• There is a deficiency of beta spectrin or ankyrin in the RBC cytoskeleton.
• The resulting RBCs become more rigid and lose their typical flexibility.
• These cells are subsequently removed from circulation, primarily by the spleen.

Clinical Features

• Haemolytic crisis can be triggered by infections.
• Significant variability exists between cases.
• Chronic haemolysis leads to anaemia.
• Megaloblastic crises can occur due to folate deficiency.
• Other common features include splenomegaly, jaundice, leg ulcers, and pigment gallstones.
• Aplastic anaemia can result following infection with Parvovirus B19.

Investigations

• Look for megaloblastic anaemia, often due to folate deficiency.
• MCHC is typically elevated.
• Lab findings include increased LDH, increased reticulocytes, and a negative DAT/Coomb's test.
• Diagnosis is made through a blood film and evidence of increased RBC fragility in hypotonic solutions.
• Flow cytometry can be used to confirm the diagnosis in some cases.

Management

• Oral folate supplementation (5 mg once weekly) and splenectomy are standard treatments.
• Splenectomy is usually performed after childhood (around 6 years old) to reduce RBC breakdown and improve erythrocyte lifespan.
• Following splenectomy, there is an increased risk of pneumococcal infection, requiring long-term penicillin prophylaxis.
• Hereditary elliptocytosis, a similar cytoskeletal defect, is clinically milder and typically does not require treatment.

Post-Splenectomy Considerations

• Thrombocythemia may occur transiently and may require aspirin therapy.
• Patients are at risk for infections with encapsulated organisms.

Prevention of Infection Post-Splenectomy

• Vaccination against Pneumococcus before splenectomy.
• Vaccination against Haemophilus Influenza type b (Hib) before splenectomy.
• Meningococcal vaccines, particularly for individuals traveling to endemic areas.
• Penicillin V (500 mg twice daily), possibly for life, to prevent infection.