Hereditary Spherocytosis

What happens in hereditary spherocytosis

Normal red blood cells are flexible discs that squeeze through tiny blood vessels and the narrow spaces of the spleen. Their membrane is supported by a scaffold of proteins, including ankyrin, spectrin, band 3 and protein 4.2. In HS, a gene change affects one of these proteins. The cell gradually loses pieces of membrane, becoming a small sphere that is less flexible. The spleen filters out and destroys these spherocytes, shortening red cell lifespan from about 120 days to as little as 10 to 30 days.

The bone marrow increases production to compensate. When it cannot keep up, hemolytic anemia results. Breakdown of red cells raises bilirubin, causing jaundice and gallstones.

Severity

Symptoms

• jaundice or yellow eyes, which may come and go, often worse with infections
• pale skin and fatigue
• an enlarged spleen (splenomegaly), felt as fullness in the upper left belly
• gallstones, sometimes in childhood
• dark urine during episodes of increased red cell breakdown
• in newborns, jaundice that may need phototherapy or exchange transfusion

Crises

• Aplastic crisis: infection with parvovirus B19 (the cause of fifth disease) temporarily stops red cell production. Hemoglobin falls sharply over days. Transfusion may be needed. See aplastic crisis.
• Hemolytic crisis: increased red cell destruction during infections, with worsening jaundice and anemia.
• Megaloblastic crisis: folate deficiency in people with high red cell turnover, especially in pregnancy.

Diagnosis

• Family history of anemia, jaundice, gallstones at a young age or splenectomy
• Complete blood count: anemia, high reticulocyte count, raised MCHC (mean corpuscular hemoglobin concentration)
• Blood smear: spherocytes
• Bilirubin (unconjugated) and LDH raised
• Direct antiglobulin (Coombs) test: negative, which distinguishes HS from autoimmune hemolytic anemia
• EMA binding test by flow cytometry: the preferred confirmatory test
• Osmotic fragility test: older test, still used in some places
• Genetic testing in unclear cases

Treatment

General care

• Folic acid supplements for moderate to severe HS to support red cell production
• Blood transfusions for severe anemia, aplastic crises and in infancy
• Monitoring of growth, hemoglobin and spleen size
• Ultrasound of the gallbladder periodically, especially before planned splenectomy

Splenectomy

Removing the spleen stops most red cell destruction and corrects anemia. It is considered for severe HS and often for moderate HS. It is usually delayed until after age 6, if possible, to reduce infection risk. Partial splenectomy is an option in young children. Keyhole surgery is standard. The gallbladder may be removed at the same time if gallstones are present.

After splenectomy, there is a lifelong increased risk of severe infections, especially from pneumococcus, meningococcus and Haemophilus influenzae. Precautions include:

• vaccines against these bacteria, ideally before surgery, plus yearly flu vaccine
• daily preventive antibiotics, at least in childhood and the first years after surgery
• seeking urgent care for any fever
• a medical alert bracelet

Gallstones

Gallbladder removal (cholecystectomy) for symptomatic gallstones.

Outlook

Most people with HS lead normal lives. People with mild disease may need no treatment beyond monitoring. Splenectomy cures the anemia in most moderate and severe cases, though it carries an infection risk. Genetic counseling is helpful for families.

Frequently asked questions

What is hereditary spherocytosis?

Hereditary spherocytosis is an inherited red blood cell disorder in which a membrane protein defect makes red cells small and round. The spleen destroys them early, causing anemia, jaundice, an enlarged spleen and gallstones. Severity varies widely between people.

What are the symptoms of hereditary spherocytosis?

Symptoms include fatigue, pale skin, jaundice or yellow eyes that may worsen with infections, an enlarged spleen and gallstones, sometimes in childhood. Newborns may have significant jaundice. Mild cases can cause few or no symptoms.

How is hereditary spherocytosis inherited?

About 75% of cases are autosomal dominant, so a parent with HS has a 50% chance of passing it to each child. The rest are recessive or arise from new gene changes. Family members of someone with HS may be offered a blood test.

Is splenectomy necessary for hereditary spherocytosis?

Not always. Mild HS usually needs no surgery. Splenectomy is considered for severe disease and often for moderate disease with significant anemia, poor growth or frequent transfusions. It is usually delayed until after age 6 because of infection risk.

What is an aplastic crisis in spherocytosis?

An aplastic crisis is a temporary shutdown of red blood cell production, usually caused by parvovirus B19, the virus behind fifth disease. Because red cells already have a short lifespan in HS, hemoglobin drops quickly. It often needs a transfusion and resolves in 1 to 2 weeks.