The spherocytic haemolytic anaemias


In Packman's excellent historical review of the spherocytic haemolytic anaemias (Packman, 2001) several uncommon entities are included in which the abnormal cells may not be truly spherocytic, specifically Zieve's syndrome and Wilson's disease. It is important to distinguish spherocytes, which, as Packman records, were recognized by Vanlair and Masius in 1871 as being ‘parfaitement spherique’ with completely smooth contours, from irregularly contracted cells. The latter resemble spherocytes in having a reduced diameter and appearing hyperchromatic but differ in that the outlines are irregular. Sometimes there are small protrusions from the surface of the cell that represent Heinz bodies. These cells were described by Sir John Dacie as ‘spherocyte-like cells’. ‘Hemighosts’ and erythrocytes with the haemoglobin ‘puddled’ to one or two edges of the cell can be regarded as variants of irregularly contracted cells. Because the differential diagnosis of haemolytic anaemia with predominant spherocytes differs from that of haemolytic anaemia with predominant irregularly contracted cells, this distinction is of some clinical importance.

Zieve (1958) described a syndrome of haemolytic anaemia and hyperlipidaemia associated with alcoholic fatty liver and cirrhosis. Although he stated that the red cells were spherocytic, the accompanying photograph showed predominantly irregularly contracted cells and my own observations (unpublished) confirm this. Similarly, spherocytosis is not a feature of acute haemolytic anaemia associated with Wilson's disease. In this instance, the irregularly contracted cells reflect a Heinz-body haemolytic anaemia resulting from the oxidant effects of copper (Bain, 1999). The important causes of these two types of hyperchromatic cell are summarized in Table I. In addition, small numbers of spherocytes may be present in hyposplenism and are seen in microangiopathic haemolytic anaemia.

Table I.  The important causes of spherocytes and irregularly contracted cells.
Causes of spherocytesCauses of irregularly contracted cells
Autoimmune haemolytic anaemia, including
warm autoimmune haemolytic anaemia,
cold autoimmune haemolytic anaemia
and acute paroxysmal cold haemoglobinuria
Acute haemolysis in glucose-6-phosphate dehydrogenase deficiency
Allo-immune haemolytic anaemia including
neonatal allo-immune haemolytic anaemia
(particularly ABO but to a lesser extent Rh),
delayed transfusion reactions, administration of
ABO-incompatible plasma or immunoglobulin
and stem cell transplantation across an ABO barrier
Severe oxidant stress from drugs or chemicals
Drug-induced immune haemolytic anaemiaHereditary xerocytosis (dehydrated variant of hereditary stomatocytosis)
Clostridium welchii sepsisUnstable haemoglobins
Some snake bites and some insect bitesOther haemoglobinopathies, particularly haemoglobin C disease but, to a
lesser extent, compound heterozygosity for haemoglobin S and
haemoglobin C, haemoglobin E heterozygosity and homozygosity
and some cases of β thalassaemia heterozygosity
Severe burnsSickle cell anaemia, during severe hypoxia