Hereditary Spherocytosis (HS)

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

🔬 The most frequent cause of hereditary spherocytosis is a mutation in the spectrin gene. Spectrin is a crucial RBC membrane protein (with actin, ankyrin, protein 4.1). Defects weaken the cytoskeleton → fragile, spherical RBCs removed by the spleen.

📖 About

• Autosomal dominant in most cases (25% de novo mutations) 🧬.
• The hallmark is reduced RBC survival → chronic haemolytic anaemia 🩸.
• The most common inherited haemolytic anaemia in Europe 🌍.
• Prevalence: >1 in 5,000, often underdiagnosed due to variable severity.

🧬 Aetiology

• Deficiency of cytoskeletal proteins (β-spectrin, ankyrin, band 3, protein 4.2).
• RBCs lose biconcave shape → become rigid spheres ⚪.
• Rigid RBCs trapped and destroyed in the spleen → extravascular haemolysis.

⚡ Clinical Features

• Variable severity: asymptomatic → severe anaemia.
• Chronic haemolysis → anaemia, jaundice 🟡, splenomegaly.
• Haemolytic crises after infections 😷.
• Megaloblastic crises if folate deficient 🌿.
• Aplastic crisis may occur after Parvovirus B19 🦠.
• Leg ulcers and pigment gallstones 🪨 are common complications.

🔬 Investigations

• Blood film: Spherocytes (small, dense RBCs lacking central pallor).
• MCHC: Typically elevated 📈.
• Labs: ↑ LDH, ↑ reticulocytes, negative DAT (excludes immune haemolysis).
• Osmotic fragility test: Increased fragility in hypotonic saline.
• Flow cytometry: Eosin-5-maleimide (EMA) binding test is now the diagnostic standard ✅.

🩺 Management

• Folate supplementation: 5 mg once weekly to prevent deficiency 🌿.
• Splenectomy: Recommended in severe disease (usually >age 6) to reduce haemolysis and anaemia.
• HS is more severe than hereditary elliptocytosis (HE), which usually needs no treatment.

⚠️ Post-Splenectomy Considerations

• ↑ Risk of infection with encapsulated organisms (pneumococcus, Hib, meningococcus) 🦠.
• Thrombocytosis may occur transiently; aspirin may be required 💊.

💉 Prevention of Infection Post-Splenectomy

• Vaccination: Pneumococcus, Hib, Meningococcus (A, C, W, Y ± B) before surgery.
• Penicillin V prophylaxis 500 mg bd, often lifelong in UK practice 💊.
• Education: Patients should seek urgent care for febrile illness 🚑.

Cases - Hereditary Spherocytosis (HS)

• Case 1 - Mild Disease, Incidental Finding: A 20-year-old woman is found to have mild anaemia on routine bloods (Hb 11.5 g/dL). She feels well but reports intermittent jaundice. Blood film shows numerous spherocytes; reticulocytes slightly elevated. Splenomegaly on exam. Family history: father required splenectomy in his 30s. Diagnosis: Mild HS.
• Case 2 - Severe Childhood Presentation: An 8-year-old boy presents with pallor, jaundice, and splenomegaly. Hb 7.8 g/dL, reticulocytes markedly raised, unconjugated bilirubin elevated. Blood film shows spherocytes; osmotic fragility test positive. He has had previous gallstones. Diagnosis: Severe HS with haemolytic anaemia and gallstone complications.
• Case 3 - Aplastic Crisis: A 15-year-old boy with known HS presents with sudden pallor and lethargy following a febrile illness. Hb 4.9 g/dL, reticulocyte count very low. Parvovirus B19 IgM positive. Diagnosis: Transient aplastic crisis in HS triggered by parvovirus infection.

Teaching Commentary 🩸

Hereditary Spherocytosis is an autosomal dominant red cell membrane defect (spectrin, ankyrin, band 3, or protein 4.2). Defective membrane scaffolding produces less deformable spherocytes, leading to splenic sequestration and haemolysis. Clinical features vary: mild (asymptomatic, detected incidentally), moderate (anaemia, jaundice, splenomegaly), or severe (transfusion dependence, gallstones, aplastic crises). Lab clues: raised MCHC, reticulocytosis, unconjugated hyperbilirubinaemia, and spherocytes on blood film. Confirmed by osmotic fragility or EMA binding test. Management includes folate supplementation, supportive transfusions, and splenectomy in severe disease (often after age 6 to reduce sepsis risk, with vaccination against encapsulated organisms).