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680 Part VI: The Erythrocyte Chapter 46: Erythrocyte Membrane Disorders 681

infection generally requiring short-lasting transfusion support (Chap. group. Occasionally acanthocytes and/or echinocytes may be pres-
36). Interval ultrasonography to detect gallstones should be per- ent in patients with glycolytic enzyme defects, myelodysplasia, hypo-
153
formed. Patients with significant hemolysis should receive daily folate thyroidism, anorexia nervosa, vitamin E deficiency, and in premature
13
a
supplementation. infants. Individuals with suppressed expression of Lu and Lu , the
b
major antigens of the Lutheran blood group system, may also exhibit
SOUTHEAST ASIAN OVALOCYTOSIS acanthocytes. 13
SAO, also known as Melanesian elliptocytosis or stomatocytic ellipto- The molecular mechanisms whereby acanthocytes are generated
cytosis, is widespread in certain ethnic groups of Malaysia, Papua New have not been fully elucidated. However, alterations in band 3 have
Guinea, the Philippines, and Indonesia, but is also common in the emerged as a pivotal causative factor. The abnormal red cell membrane
123
Cape Coloured population in South Africa. It is characterized by the lipid composition and altered lipid distribution between the inner and
154
presence of large oval red cells, many of which contain one or two trans- outer leaflets of the bilayer are only found in some, but not all, of these
verse ridges or a longitudinal slit (Figs. 46–10C and 46–11E). disorders, implying that they may play a secondary role. 162
SAO erythrocytes are rigid and hyperstable because of a structurally
and functionally abnormal band 3. SAO band 3 binds tightly to ankyrin, ACANTHOCYTOSIS IN SEVERE LIVER DISEASE
forms oligomers, exhibits restricted lateral and rotational mobility 155,156
and is unable to transport anions. The underlying molecular abnor- Definition
157
mality is an in-frame deletion of 27 bp in the band 3 gene resulting in The anemia in patients with liver disease is often called “spur cell ane-
the loss of amino acids 400 to 408 located at the boundary of the cyto- mia” because of the projections on the red cells. Although only a small
plasmic and membrane domains of band 3. The defective SLC4A1 number of patients with end-stage liver disease acquire spur cell ane-
158
allele also carries a linked band 3 Memphis polymorphism, L56E. mia, these individuals typically account for the majority of cases of
SAO is a dominantly inherited trait and homozygosity is postu- acanthocytosis seen in clinical practice.
lated to be lethal during embryonic development. A recent case of Etiology and Pathogenesis
159
homozygous SAO has been described where the fetus was kept alive by The anemia in patients with liver disease is of complex etiology. Com-
two intrauterine transfusions and since birth he has been on a monthly mon causes include blood loss, iron or folate deficiency, hypersplenism,
transfusion program. Distal renal tubular acidosis was diagnosed at and marrow suppression from alcohol, malnutrition, hepatitis infec-
160
3 months as a result of the inability of the SAO band 3 to transport anions. tion, or other factors. Acquired abnormalities of the red cell membrane
A remarkable feature of SAO erythrocytes is their resistance to may contribute to the anemia in some patients. 163
infection by several species of malaria parasites. This has been demon- In vivo acanthocyte formation in spur cell anemia is a two-step
strated by numerous in vitro studies, as well as in vivo evidence indicat- process involving accumulation of free (nonesterified) cholesterol in
ing that SAO provides protection against severe malaria and cerebral the red cell membrane and remodeling of abnormally shaped red cells
malaria. 123,161 Epidemiologic data and the increased prevalence of SAO by the spleen. 13,163 The diseased liver of the patient produces abnormal
in populations challenged by malaria suggest a selective advantage of lipoproteins with excess cholesterol, which is acquired by circulating
the gene. Numerous factors have been implicated in the protective erythrocytes, increasing their cholesterol content. The cholesterol pref-
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effect, but the precise mechanism of malaria resistance of SAO red cells erentially partitions into the outer leaflet, increasing the surface area
has not been fully elucidated. to volume ratio and forming scalloped edges. In the spleen, membrane
Clinically, the presence on the blood film of at least 20 percent fragments are lost and the cells develop the characteristic projections
ovalocytic red cells, some containing a central slit or a transverse ridge, of acanthocytes. Cholesterol interacts with band 3 and changes its
and the notable absence of clinical and laboratory evidence of hemolysis conformation, which may affect the membrane skeleton and reduce
are highly suggestive of SAO. Rapid genetic diagnosis can be made by the deformability of the cell, causing it to be trapped and eventually
162
amplifying the defective region of the band 3 gene and demonstrating destroyed in the narrow sinusoids of the spleen.
heterozygosity for the SAO allele containing the 27 bp deletion.
Clinical Features
ACANTHOCYTOSIS Spur cell anemia is characterized by rapidly progressive hemolytic
Spiculated red cells are classified into two types: acanthocytes and echino- anemia with large numbers of acanthocytes on the blood film. Sple-
cytes. Acanthocytes are contracted, dense cells with irregular projections nomegaly and jaundice become more prominent and are accompanied
from the red cell surface that vary in width and length (Figs. 46–10F and by severe ascites, bleeding diatheses, and hepatic encephalopathy. Spur
46–11G). Echinocytes have small, uniform projections spread evenly over cell anemia is most common in patients with alcoholic liver disease,
the circumference of the red cell (Fig. 46–11B). Diagnostically, the dis- but similar clinical syndromes have been described in association with
tinction is not critical, and disorders of spiculated red cells are generally advanced metastatic liver disease, cardiac cirrhosis, Wilson disease, ful-
classified together. Normal adults may have up to 3 percent spiculated minant hepatitis, and infantile cholestatic liver disease. 13
erythrocytes, but care should be taken when preparing and examining the
blood film, because spiculated cells, particularly echinocytes, are common Laboratory Features
artifacts of blood film preparation and blood storage. Most patients have moderate anemia with a hematocrit of 20 to 30 per-
Acanthocytes/echinocytes are found in various inherited disor- cent, marked indirect hyperbilirubinemia, and laboratory evidence of
ders and acquired conditions. Spiculated cells can occur transiently in severe hepatocellular disease. Blood films reveal significant acanthocy-
several instances, such as after transfusion with stored blood, ingestion tosis and in some patients, echinocytes, target cells and microsphero-
of alcohol and certain drugs, exposure to ionizing radiation or certain cytes, many with very fine spicules, are visible (see Fig. 46–13).
venoms, and during hemodialysis. Spiculated cells are commonly
13
seen on the blood films of patients with functional or actual splenec- Differential Diagnosis
tomy, severe liver disease, severe uremia, abetalipoproteinemia, certain Spur cell hemolytic anemia should be distinguished from other hemo-
inherited neurologic disorders and abnormalities of the Kell blood lytic syndromes associated with liver disease, including congestive

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