Hereditary spherocytosis (HS) is a common congenital hemolytic anemia, particularly in northern European ancestry. The inheritance pattern is autosomal dominant in 75% of cases, while 25% are sporadic or occur due to autosomal recessive inheritance.
The basic defect in HS is loss of RBC membrane surface area due to defects in several RBC structural proteins that mediate vertical interactions with the lipid bilayer. HS is associated with spectrin deficiency which occurs most commonly due to mutations in the ankyrin gene.
Structural protein deficiency results in the spontaneous release of spectrin from the membrane and leads to formation of spherocytes. The rigidity of spherocytes leads to trapping of erythrocytes in the spleen, where the RBCs lose additional membrane and become microspherocytes. Ultimately, after many trips through the splenic circulation, microspherocytes are trapped and destroyed. The anemia may be compensated by an increase in the production of new RBCs.
Clinical manifestations are variable, reflecting the heterogeneity of the molecular defects that underlie the disease. They range from no anemia to severe transfusion – dependent anemia. Members of a given kindred will often exhibit a similar pattern.
Clinical presentation may include: (a) No clinical signs or symptoms. (b) Jaundice, often with concomitant viral infection. (c) Formation of pigment gallstones (from the high turnover of heme); complications of gallstones include cholecystitis, biliary obstruction, and cholangitis. (d) Mild to moderate splenomegaly. (e) Leg ulcers (in patients with severe HS).
Most RBC destruction occurs in the spleen, so splenectomy will either cure or ameliorate anemia. Splenectomy is recommended only for patients with symptomatic anemia. After splenectomy, spherocytes are present on the peripheral blood smear, but RBC survival is markedly improved.