Stomatocytosis (also called hydrocytosis) is defined by the appearance on the peripheral smear of erythrocytes with a mouth-shaped area of central pallor (picture 1) [1,2]. Causes of this condition, which can be either congenital or acquired, will be discussed here.
Stomatocytes are characterized by a decrease in the ratio of surface area-to-volume that can be induced either by a reduction in surface area or an increase in red cell volume. Almost all cases are due to alteration in permeability, leading to an increase in red cell volume. The reduction in surface area/volume ratio leads to trapping in the microvasculature of the spleen and other organs of the monocyte/macrophage system, producing varying degrees of hemolysis.
The red cell volume is increased in most of these disorders with no parallel increase in membrane surface area. As a result, the biconcave disc becomes a uni-concave cup on electron microscopy (picture 2) and a stomatocyte on dried smear (picture 1). In vitro and perhaps in vivo (see below), one can induce stomatocytosis by incubating normal red cells with amphipathic cations which, according the Sheetz-Singer bilayer couples hypothesis, are supposed to intercalate passively into the relatively negative inner half of the membrane phospholipid bilayer, causing an inner bulging — the beginning of the cup; endocytic vacuoles then form at the advancing mouth causing the loss of surface area that completes the transformation (figure 1) [3,4].
Stomatocytes can be found on the peripheral smear of normal subjects. Since this may be due to drying artifact, it is advisable to evaluate several different areas of the smear before making this diagnosis.
- The percentage of stomatocytes among the red cells of normal subjects is usually below 3 percent.
- A higher percentage is seen in the conditions associated with stomatocytosis, eg, up to 40 to 60 percent in patients with hereditary stomatocytosis  and 10 percent or more in some patients with acquired disease such as alcoholism .