- It is an inherited (intrinsic) defect in the red cell membrane that renders the cells spheroidal, less deformable, and vulnerable to splenic sequestration and destruction.

It is transmitted most as an autosomal dominant trait; approximately 25% of patients have a more severe autosomal recessive form of the disease. 

- The primary abnormality resides in one of a group of proteins that form a mesh-like supportive skeleton on the intracellular face of the red cell membrane. 

The major protein in this skeleton is spectrin, a long, flexible structure that is linked to the membrane. 

Vertical spectrin and Horizontal spectrin intrinsic membrane proteins work together to hold the membrane and are responsible for the normal shape, strength and flexibility of red blood cells. 

- The spleen plays a major role in the destruction of spherocytes. Red cells must undergo extreme degrees of deformation to leave the cords of Billroth and enter the splenic sinusoids. 

The discoid shape of normal red cells allows considerable freedom for changes in cell shape. 

On the contrary, due to their spherical shape and limited deformability, spherocytes are sequestered in the splenic cords and eventually destroyed by a large number of macrophages 

- The countless beneficial effects of splenectomy illustrate the key role of the spleen. 

Although red blood cell defects and spheroid cells persisted, the anemia was corrected. 

- On the smear, the red blood cells lack a pale central area due to their spherical shape. 

- Spherocytosis, though distinctive, is not diagnostic; it is seen in other conditions, such as immune hemolytic anemias, in which there is a loss of cell membrane relative to cell volume. 

- Due to their spheroidal shape, HS red cells show increased osmotic fragility when placed in hypotonic salt solutions, a characteristic that is helpful for diagnosis. 

 

- The excessive red cell destruction and resultant anemia lead to compensatory hyperplasia of marrow red cell progenitors and an increase in red cell production, which is marked by peripheral blood reticulocytosis. 

- Autohemolysis test in HS: There is increased hemolysis in the patient in comparison with the control. Glucose has given a partial correction. 

- Splenomegaly is more likely to occur in HS than other forms of hemolytic anemia. 

The splenic weight is usually between 500 and 1000 gm and can be even greater. 

The enlargement results from marked congestion of the cords of Billroth and increased numbers of mononuclear phagocytes. 

Phagocytosed red cells are frequently seen within macrophages lining the sinusoids and within the cords. 

- In long-standing cases, there is obvious systemic hemosiderosis. 

The other general features of hemolytic anemias described earlier are also present, pigmented gall stone, which occurs in up to 50% of HS patients. 

The clinical features are anemia, splenomegaly, and jaundice. 

The severity of the anemia is highly variable; most commonly it is of moderate degree. The clinical course is often stable but maybe punctuated by aplastic crises. 

Such episodes are often triggered by the infection of bone marrow erythroblasts by parvovirus B19, which causes a transient cessation of red cell production. 

Because HS red cells have a shortened life span, the failure of erythropoiesis for even a few days results in a rapid worsening of the anemia. 

- The main form of treatment is splenectomy, although unless there are clinical indications, splenectomy should not be performed because of the risk of sepsis after splenectomy, especially in early childhood. 

- Folic acid is given in severe cases.