These protein defects lead to a weakened osmotically fragile cell membrane in the patient’s red blood cells (RBCs). “Conditioning” of RBCs occurs in the spleen where damaged RBCs are trapped and decreased oxygen and limited glucose availability contributes to their demise.

The deficiency leads to a remodeling of the usual biconcave disk into cells which resemble spheres. These abnormal cells have a shortened life span which contributes to anemia.

The spherical shape of patient RBCs results from a reduction in the amount of membrane material available thus producing a reduced surface to volume ratio and increase in cell density. As more membrane is lost, the limit of the RBC membrane stretching is reached and lysis occurs

Prevalence and inheritance:

Patients present with varying degrees of anemia, jaundice (may wax and wane), increased reticulocyte count, variable splenomegaly, and often evidence of gall stones.

The CBC with differential shows spherocytes and a positive osmotic fragility test in conjunction with a family history is confirmatory. Patients red blood cell (RBC) indices are also helpful with the combination of elevated red blood cell distribution width (RDW) and increased mean corpuscular hemoglobin concentration (MCHC) are strongly suggestive of HS.

HS can be classified as mild, moderate and severe based on baseline hemoglobin, degree of reticulocytosis, and resting bilirubin levels. These clinical classifications correlate with degree of osmotic fragility (severe has more fragile RBCs) and spectrin content (mild having near normal spectrin, severe with less than 50 % of normal value).

In mild cases of HS there is a compensated hemolytic anemia with normal or near hemoglobin and mildly increased reticulocyte counts. These patients are asymptomatic at steady state and often only come to light during an illness (such as infectious mononucleosis), pregnancy or physical stress (military training).

Severely affected patients have significant anemia and are transfusion dependent. Peripheral smears in these patients show spherocytes as well as bizarrely shaped cells (poikilocytes). Growth failure, and delayed sexual maturation are common and these patients are at risk for severe aplastic crises (later).