Pathogenesis

Two factors operate in hereditary spherocytosis:

• membrane instability
• selective retention and destruction of red cells by the spleen

Red blood cells must be strong and deformable to withstand the stress of circulating in the blood for 120 days and passing through narrow capillaries and splenic cords. In hereditary spherocytosis red cells fragment easily.

The fragility of red cells in HS is attributed to lack or dysfunction of one or more skeletal proteins:

• spectrin - spectrin content is 30-50% that of normal in patients with severe HS, and 75-90% in those with moderate HS
• beta spectrin dysfunction - necessary for the spectrin to bind band 4.1. This defects is found in 10% of HS patients.
• ankyrin deficiency } found infrequently
• band 4.2 deficiency }

Membrane weakness results in repeated fragmentation as the red cell circulates, and a gradual decreases in surface to volume ratio and increased spheroidicity. For reasons yet unknown, such cells are selectively retained by the splenic cords and fragmented further or destroyed. Cells which escape the spleen are vulnerable to recapture and eventual destruction.