HEREDITARY

SPHEROCYTOSIS
This is the most common type of

hereditary hemolytic anemia in North

Europeans. Hereditary spherocytosis (HS)

is characterized by an inherited defect in

the red cell cytoskeleton leading to the

formation of spherocytes. Normally, the

lipid bilayer is anchored to the underlying

cytoskeleton by interactions of (i)

 spectrin, protein 4.1, actin, and

glycophorin C, and (ii) spectrin, ankyrin,

and band 3. In most cases of HS, there is

a deficiency of ankyrin so that membrane

becomes unstable with fragmentation of

part of membrane, loss of surface area,

and spherocyte formation. Spherocytic

red cells are rigid, less deformable than

normal red cells, and are destroyed

prematurely in spleen. Mode of

 transmission is usually autosomal

dominant. Usual clinical manifestations

are presentation in childhood with mild

to moderate anemia, intermittent

jaundice, and splenomegaly. Pigment

gallstones are frequent. Similar history is

obtained in a close relative. Clinical

presentation, however, is markedly

variable
 Fig. 27.10: Blood smear in hereditary

spherocytosis showing spherocytes, a

polychromatic cell, and a nucleated red

cell
 Anemia, reticulocytosis, and

microspherocytes on blood

smear are the usual findings .

Microspherocytes are small and

dense red cells lacking central

area of pallor. (They are also

observed in autoimmune

hemolytic anemia, ABO

hemolytic disease of newborn,

burns, microangiopathic
hemolytic anemia, and hemolytic

transfusion reaction). The usual

screening test for HS is osmotic

fragility (OF) test . This test

assesses the ability of the red

cells to withstand osmotic stress

when they are suspended in

decreasing concentrations of

hypotonic saline solutions.

Spherocytes have reduced

 surface area to volume ratio and

are osmotically fragile. Incubated

variant of OF test is more

sensitive. Autohemolysis test

shows markedly increased

hemolysis that is partially

corrected by addition of glucose.

Osmotic Fragility Test In this test, red

cells are suspended in decreasing

 concentrations of hypotonic saline

solutions to determine the ability of the

red cells to withstand osmotic stress. In

hypotonic solutions, water enters red

cells causing cellular swelling, and at one

point, cell lysis occurs. Normal red cells

are biconcave and disc-shaped, have high

surface area to volume ratio, and

therefore can increase their volume upto

70% before they are lysed. Spherocytes

 have decreased surface area to volume

ratio and therefore they can take up less

water than normal red cells and lyse

earlier (i.e. at relatively higher saline

concentration than normal red cells).

With normal red cells, hemolysis usually

starts at saline concentration of 0.5

gm/dl and is complete at 0.30gm/dl

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