Hereditary Spherocytosis: Pathogenesis, Morphology, Clinical Features, and Treatment

What is hereditary spherocytosis?

     Hereditary means it is an inherited condition, and spherocytosis means RBCs become sphere-shaped, and increase in number. Hereditary spherocytosis is a type of hemolytic anemia, that can be inherited from parents to the offspring. 

     It is caused by an Intrinsic defect in the RBC membrane skeleton. The defect occurs mostly due to mutations in alpha-spectrin, beta-spectrin, ankyrin, band-4.2, and band-3.

Why the shape of the RBC is biconcave?

     Normally, RBCs are of biconcave shape, pale from the center just because of the skeleton of different proteins linkage with lipid bilayer membrane. The spectrin protein chain is of two types, named alpha and beta. Both are intervened and forming a helical structure. The head region of spectrin forms a self-associated tetramer while the tail region is associated with the actin protein chain.

     Spectrin-actin skeleton connects to the membrane via two interactions, both are given below:

1. First: This involves protein Ankyrin and band 4.2, which binds spectrin to the transmembrane protein named Band-3.
2. Second: This interaction involves protein 4.1, which binds spectrin to another protein in the membrane called Glycophorin-A (GPA).

     These all proteins and chains interacting with the membrane give RBC a biconcave shape, that is deformable and pale from the center. The deformability helps RBCs to squeeze from the spleen. 

Pathogenesis of Hereditary Spherocytosis

     If a mutation occurs in any of the linkages present in the skeletal system of RBC, it leads to the defect in membrane integrity that leads to the leakage of cytoplasm outside. It then causes a change of shape forming a spheroid structure.

     These diverse mutations lead to the insufficiency of membrane skeletal components, results in a decrease of RBCs life span from normal (120 days) to abnormal (4-5 days). These spherocytes are less deformable so while passing through the spleen, these are trapped there and results in splenomegaly.

Morphology

     When a patient with hereditary spherocytosis is examined, its peripheral blood smear contains a large number of spherocytes, with dark red color in the centers. Spleen become enlarged as the spherocytes are trapped in the spleen. Marrow erythroid hyperplasia can occur, also hemosiderosis, reticulocytosis, and pigmented gall stones (Cholelithiasis).

Clinical features

     Hereditary spherocytosis is diagnosed by family history. They have increase Mean cell hemoglobin concentration. Following are the clinical features of Hereditary spherocytosis:

1. Anemia: As Hereditary spherocytosis is a type of hemolytic anemia, where the destruction of blood cells occurs, so Anemia can occur.
2. Jaundice: Due to hemolysis of RBCs, the level of bilirubin can increase very much, so leads to Jaundice.
3. Abdominal Pain: The pigmented gall stones are formed in it, they may cause pain in the abdomen.
4. Splenomegaly: As the spherocytes trap in the spleen, they lead to the enlargement of the spleen.

Treatment

     There is no such treatment of Hereditary spherocytosis, but if hereditary spherocytosis occurs in children, then partial splenectomy is the treatment because complete splenectomy leads to the impairment of the immune system. But if it occurs in the adult, then complete splenectomy is done. When splenectomy is done, the spherocytosis is still present but anemia is recovered.

Conclusion

     Hereditary spherocytosis is an inherited hemolytic anemic disorder that is caused by mutations that occur in the linkages of membrane skeletal complex, presented with anemia, jaundice, splenomegaly, and abdominal pain. The treatment is only by removing the partial spleen in child, while complete in adults.