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Figure 12.23 Diagrammatic representation of pathogenesis of hereditary spherocytosis. A, Normal red cell with biconcave surface and normal CHAPTER 12
size. B, Red cell membrane as seen in cross section in hereditary spherocytosis. Mutations in membrane proteins—α-spectrin, β-spectrin and
ankyrin, result in defect in anchoring of lipid bilayer of the membrane to the underlying cytoskeleton. C, This results in spherical contour and small
size so as to contain the given volume of haemoglobin in the deformed red cell. D, During passage through the spleen, these rigid spherical cells
lose their cell membrane further. This produces a circulating subpopulation of hyperspheroidal spherocytes while splenic macrophages in large
numbers phagocytose defective red cells causing splenomegaly.

Spectrin deficiency correlates with the severity of anaemia. LABORATORY FINDINGS. The usual haematological
Mutation in spectrin by recessive inheritance called α−spectrin and biochemical findings are as under:
causes more severe form of anaemia, while mutation by 1. Anaemia of mild to moderate degree.
dominant inheritance forming β-spectrin results in mild form 2. Reticulocytosis, usually 5-20%.
of the disease. 3. Blood film shows the characteristic abnormality of
2. Ankyrin abnormality.About half the cases of hereditary erythrocytes in the form of microspherocytes (Fig.12.24).
spherocytosis have defect in ankyrin, protein that binds
protein 3 and spectrin. Homozygous state with recessive 4. MCV is usually normal or slightly decreased but MCHC
is increased.
inheritance pattern has severe anaemia while heterozygotes 5. Osmotic fragility test is helpful in testing the spheroidal
with more common dominant inheritance pattern have nature of red cells which lyse more readily in solutions of
milder anaemia.
Inherited mutation in spectrin or ankyrin causes defect low salt concentration i.e. osmotic fragility is increased
in anchoring of lipid bilayer cell membrane. Red cells with (Fig.12.25).
such unstable membrane but with normal volume, when 6. Autohaemolysis test is similar to osmotic fragility test after
released in circulation, lose their membrane further, till they incubation and shows increased spontaneous Introduction to Haematopoietic System and Disorders of Erythroid Series
can accommodate the given volume. This results in formation autohaemolysis (10-15% red cells) as compared to normal
of spheroidal contour and smaller size of red blood cells, red cells (less than 4%). Autohaemolysis is correctable by
termed microspherocytes. These deformed red cells are not addition of glucose.
flexible, unlike normal biconcave red cells. These rigid cells 7. Direct Coombs’ (antiglobulin) test is negative so as to
are unable to pass through the spleen, and in the process distinguish this condition from acquired spherocytosis of
they lose their surface membrane further. This produces a AIHA in which case it is positive.
subpopulation of hyperspheroidal red cells in the peripheral Spherocytes may also be seen in blood film in acquired
blood which are subsequently destroyed in the spleen. immune haemolytic anaemia and following red cell
transfusion.
CLINICAL FEATURES. The disorder may be clinically
apparent at any age from infancy to old age and has equal Hereditary Elliptocytosis (Hereditary Ovalocytosis)
sex incidence. The family history may be present. The major Hereditary elliptocytosis or hereditary ovalocytosis is another
clinical features are as under: autosomal dominant disorder involving red cell membrane
1. Anaemia is usually mild to moderate. protein spectrin. Some patients have an inherited defect in
2. Splenomegaly is a constant feature. erythrocyte membrane protein 4.1 that interconnects spectrin
3. Jaundice occurs due to increased concentration of with actin in the cytoskeleton. The disorder is similar in all
unconjugated (indirect) bilirubin in the plasma (also termed respects to hereditary spherocytosis except that the blood
congenital haemolytic jaundice). film shows oval or elliptical red cells and is clinically a milder
4. Pigment gallstones are frequent due to increased bile disorder than hereditary spherocytosis.
pigment production. Splenectomy offers the only reliable Acquired causes of elliptocytosis include iron deficiency
mode of treatment. and myeloproliferative disorders.