Spherocytosis, Hereditary

Key Features

• Disorder of RBC membrane, leading to chronic hemolytic anemia

• Autosomal dominant disease of variable severity

• Membrane defect is in spectrin or actin, RBC skeleton proteins, resulting in decreased surface–volume ratio and a spherical RBC shape, which is less deformable

• Hemolysis occurs because of trapping of RBCs within the spleen and their premature removal by splenic macrophages

Clinical Findings

• Often diagnosed in childhood, but milder cases discovered incidentally late in life. Family history often positive

• Anemia may or may not be present because bone marrow may be able to compensate for shortened RBC survival

• Severe anemia (aplastic crisis) may occur with folic acid deficiency or infection

• Chronic hemolysis causes

  • Jaundice

  • Pigment (calcium bilirubinate) gallstones, leading to attacks of cholecystitis

  • Medial malleolar skin ulcers

• Palpable spleen

Diagnosis

• Hyperchromic red blood cells (elevated mean corpuscular hemoglobin concentration [MCHC])

• Anemia of variable severity; hematocrit may be normal

• Increased MCHC, often > 36 g/dL

• Reticulocytosis present

• Peripheral blood smear shows small percentage of spherocytes, small cells that have lost their central pallor

• Indirect bilirubin often increased

• Coombs test negative

• Increased osmotic fragility (abnormally vulnerable to swelling induced by hypotonic media) can be demonstrated by ektacytometry

• EMA (eosin-5 maleimide) binding by flow cytometry is another diagnostic tool

Treatment

• Folic acid, 1 mg orally once daily

• Splenectomy

  • Eliminates site of hemolysis

  • May not be necessary in mild cases discovered late in adult life