AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

INTRODUCTION

Section 2 of 10  

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• Clinical
• Differentials
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• Follow-up
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Background

Spur cells or acanthocytes are large erythrocytes covered with spikelike projections that vary in width, length, and distribution. Acanthocytes can be encountered in acquired or inherited disorders. Historically, spur cell anemia has been described with advanced alcoholic liver cirrhosis, but it also can be observed in other severe liver diseases. The inherited disorders associated with significant acanthocytosis are characterized by an association with neuromuscular disorders. These diseases are presented together in this article because of the common hematologic feature of peripheral blood acanthocytosis.

Pathophysiology

The red cell membrane is composed of a lipid bilayer and proteins assembled in a complex manner, which allows the erythrocyte to function as an interface between the cell and its environment, protecting the red cell integrity and allowing a bidirectional flux of electrolytes, energy, and information. To preserve the red cell shape and regulate its deformability and mechanical stability, the plasma membrane is tethered to a filamentous network of proteins known as the membrane skeleton.

The lipid bilayer contains nearly equal quantities (molar ratio 0.9-1) of unesterified cholesterol and phospholipids that are asymmetrically distributed between the outer and inner leaflets. Phosphatidylcholine (30% of phospholipids) and sphingomyelin (30%) are found mainly in the outer layer, while phosphatidylethanolamine (28%) and phosphatidylserine (14%) reside in the inner layer. While the cholesterol contents of the membrane are in equilibrium with the plasma-free cholesterol, the uneven distribution of phospholipids is maintained by both passive and active processes. Most acanthocytic disorders are associated with acquired abnormalities of the outer leaflet of the lipid bilayer. However, some rare conditions have normal lipids and abnormal membrane proteins.

In severe liver disease, free cholesterol in red cells equilibrates with abnormal lipoproteins containing a high free cholesterol-to-phospholipid ratio, resulting in the preferential expansion of the outer leaflet and the development of the spur cell shape. A decrease occurs in polyunsaturated versus saturated and monounsaturated fatty acid content in red cells of patients with cirrhosis. This abnormality is more pronounced in patients with spur cell anemia, resulting in the alteration of the red cell shape and a decrease of their fluidity. An increase in the proteolytic activity of the erythrocyte membrane also is reported in spur cell anemia. The significance and role of this abnormality in changing the shape of the red cell shape and in hemolysis are unknown.

The plasma of some of these patients exhibits decreased activity of lecithin cholesterol acyltransferase, resulting in increased free cholesterol in the outer layer of the red cell membrane as a direct consequence of its increased concentration in the plasma. After acquiring these abnormalities in the plasma, the red cells undergo a remodeling process in the spleen, which gives them the spheroidal shape with longer and more irregular projections. Spur cells are characterized by diminished deformability, which is responsible for their entrapment and destruction in the spleen.

In abetalipoproteinemia B-apoprotein–containing lipoproteins (chylomicrons, very low-density lipoproteins, low-density lipoproteins) are nearly absent in the plasma. Plasma cholesterol and phospholipids are decreased, with a relative increase of sphingomyelin at the expanse of lecithin. At equilibrium, the sphingomyelin concentration in the outer leaflet increases, resulting in its expansion and acanthocytosis.

The expression of the Kell antigen (the product of a single gene on band 7q23) on red cells, white cells, and monocytes is under the control of the Kx antigen encoded for by XK gene on band Xp21. Both antigens are transmembrane proteins bound by a single disulfide bond. In the McLeod phenotype, the XK gene is deleted and the Kell antigen cannot be expressed, while in the Kell null phenotype, the Kell antigen is missing and the Kx antigen is present at a normal level. The Kell null phenotype is not associated with hematologic disorders.

The close proximity on the short arm of band Xp21 of the genes responsible for chronic granulomatous disease (CGD) of childhood, retinitis pigmentosa (RP), and Duchenne muscular dystrophy (DMD) explains the variable association of the McLeod phenotype with these diseases. Red cells from patients with chorea-acanthocytosis syndrome and McLeod phenotype do not show measurable abnormalities of the lipid bilayer. Focal membrane skeleton heterogeneity has been described as characterized by decreased compactness of the filamentous meshwork in the areas underlying the spikes. This focal weakness allows limited detachment of the lipid bilayer that does not result in membrane loss. The nature of the membrane skeleton abnormality is not known.

Frequency

United States

Five percent of all patients with severe hepatocellular disease develop spur cell anemia. Abetalipoproteinemia is an uncommon disorder. Chorea-acanthocytosis syndrome and McLeod phenotypes are rare; only a few dozen cases have been published in the literature.

Age

• Acanthocytosis in abetalipoproteinemia is an autosomal-recessive disease that manifests in the first months of life.
• Neurologic symptoms appear in patients aged 5-10 years and may progress to death in the second or third decade of life.
• In chorea-acanthocytosis syndrome, the median age at onset of symptoms is 32 years.

CLINICAL

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• Clinical
• Differentials
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History

The symptoms of spur cell anemia are related to the anemia and to the underlying disease.

• Spur cell anemia in severe liver disease
• • In spur cell anemia, the hemoglobin level usually falls to less than 10 g/dL and, occasionally, to levels as low as 5 g/dL. This fall may be associated with severe jaundice and rapid deterioration of liver function, coagulopathy, and hepatic encephalopathy.
  • In its chronic presentation, the anemia accompanying the alcoholic cirrhosis is mild, while in the acute presentation, the anemia develops weeks to months before death and as liver function deteriorates.
  • The course of the disease correlates with liver function. Cases of reversal of the hemolytic anemia have been reported after improvement of liver disease.
  • Spur cell anemia has been reported in cases of pediatric cholestatic liver disease. In most cases, the condition is transient and resolves with the improvement of underlying liver disease.
  • Hemosiderosis is reported in 20% of patients undergoing orthotopic liver transplantation for alcoholic liver disease. Spur cell hemolytic anemia is present in 75% of these patients. In the absence of the C282Y/HFE hemochromatosis gene mutation, spur cell hemolytic anemia is postulated to be responsible for the hemosiderosis related to repeated blood transfusions and increasing intestinal iron absorption.
• Acanthocytosis in abetalipoproteinemia
• • Clinical presentation includes ataxia, retinitis pigmentosa that may lead to blindness, and fat malabsorption.
  • Symptoms related to deficiency of lipid-soluble vitamins (ie, A, K, E, D) may be seen.
  • Spur cells (50-90%) are present on the peripheral smear, and the hemolysis and anemia are mild.
  • This is an autosomal-recessive disease that manifests in the first months of life, with steatorrhea, abdominal distension, and growth retardation. Neurologic symptoms appear in patients aged 5-10 years and may progress to death in the second or third decade.
• Chorea-acanthocytosis syndrome
• • The median age at onset of symptoms is 32 years. Median survival is 8-14 years.
  • Limb chorea is the initial symptom in many cases, but, because it may be mild, patients may be able to suppress it for long periods before the other symptoms are evident.
  • Orofacial tics, buccolingual dyskinesia, and tongue biting causing major problems with eating and swallowing occur early in the disease course.
  • Neurogenic muscle hypotonia, atrophy, and areflexia are common.
  • Dysarthria develops during the course of the disease and, occasionally, may be the presenting feature.
  • Dementia and seizures are relatively common.
  • Organic personality changes with impulsive, easily distracted behavior occur. Apathy and loss of insight are the most consistent symptoms.
  • Other psychiatric symptoms that are encountered include depression, anxiety, paranoid delusions, and obsessive-compulsive features.
  • The percentage of acanthocytes in the peripheral blood varies from 20-50%. Patients do not have anemia.
• McLeod phenotype
• • This condition is characterized by a mild compensated hemolytic anemia and, occasionally, late-onset myopathy or chorea.
  • The acanthocyte number varies between 25% and 85%, and serum creatine kinase is elevated. This disorder also is described in association with CGD, RP, and DMD. The deletion of band Xp21 affects all or some of the genetic loci of these disorders because of their close proximity on the short arm of chromosome X.

Physical

Signs are related to the associated disease entity.

• In advanced liver disease, jaundice, hepatosplenomegaly, ascites, altered mental status, and bleeding diathesis may be present.
• In abetalipoproteinemia, ataxia and decreased visual acuity are the main findings.
• Chorea-acanthocytosis syndrome is characterized by limb chorea, orofacial dyskinesia, muscle atonia, and atrophy.

Causes

• Acquired acanthocytosis is associated with advanced liver disease regardless of the primary cause, anorexia nervosa, hypothyroidism, and myelodysplasia.
• Inherited disorders are regrouped under the name of neuroacanthocytosis. They include autosomal-recessive disorders, abetalipoproteinemia/aprebetalipoproteinemia (chromosome 2), chorea-acanthocytosis syndrome (band 9q21), and the X-linked McLeod phenotype.

DIFFERENTIALS

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Other Problems to be Considered

Echinocytes and keratocytes should be considered in the differential. Echinocytes or burr cells are spiculated red cells with uniform narrow spikelike surface projections. Spur cells have fewer spicules, and the spicules vary more in size than echinocytes. Keratocytes are acanthocytelike cells with bizarre shapes and horny projections.

Other causes of hemolytic anemia in severe liver disease include the following:
Zieve syndrome
Hemolytic anemia with echinocytes
Severe hypophosphatemia
Splenomegaly-related hemolytic anemia with spherocytosis

WORKUP

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• Differentials
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• Follow-up
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Lab Studies

• Complete blood count
• • Test findings reveal variable degrees of anemia, with the hematocrit commonly between 15% and 20%.
  • White blood cell and platelet counts may be normal. However, due to the severe and advanced liver disease, they are decreased in most cases.
• Reticulocyte count
• • An increase depends on the degree of anemia but usually is greater than 5%.
  • In certain cases, the reticulocyte count may be decreased as a result of concomitant folate deficiency.
• Peripheral blood film
• • This study is the mainstay for diagnosis. It reveals the presence of red cells with thornlike surface projections, which are variable in size.
  • Characteristically, a high percentage of acanthocytes is present, equal to or greater than 20% of the erythrocytes observed. In cases of liver disease, target cells also may be seen, particularly if obstructive jaundice is present.
• Liver function tests
• • Hyperbilirubinemia, predominantly indirect bilirubin, is present and its increase parallels the hemolysis.
  • Synthetic liver function is decreased, as attested by low levels of albumin and fibrinogen and prolongation of the prothrombin time and activated partial thromboplastin time.
• Plasma lipids
• • This study is helpful in screening suspected cases of abetalipoproteinemia.
  • Serum cholesterol, phospholipid, and triglyceride levels are very low.
  • Lipoprotein electrophoresis reveals the absence of beta-lipoproteins.
• Blood typing: Kell antisera react poorly with red cells, white cells, or both in the McLeod phenotype.
• Serum creatine kinase: In McLeod syndrome, levels are increased.

Procedures

• Intestinal biopsy in abetalipoproteinemia: This procedure reveals the presence of fat droplets within the mucosal cells.

TREATMENT

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• Clinical
• Differentials
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• Medication
• Follow-up
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Medical Care

Treatment is directed at the underlying disease.

• Anemia can be corrected by red cell transfusion. However, the transfused cells become acanthocytic, with shortened life span in the circulation.
• Supportive care for patients with reversible liver disease is the mainstay of treatment. Abstinence from alcohol use may result in the nearly complete disappearance of acanthocytes in the peripheral blood in patients with mild-to-moderate alcoholic liver cirrhosis.
• Patients with abetalipoproteinemia may benefit from dietary measures that include triglyceride restriction and lipid-soluble vitamin supplementation.

Surgical Care

The poor general status of these patients limits the use of surgical care.

• Three cases of spontaneous resolution of spur cell anemia following orthotopic liver transplantation have been reported.
• Splenectomy may improve the hemolytic anemia. However, these patients are severely ill and, in most cases, cannot undergo surgery.

Consultations

Genetic counseling is offered to families of patients with abetalipoproteinemia and chorea-acanthocytosis syndromes.

Diet

• Because patients with abetalipoproteinemia cannot absorb triglycerides, a diet restricted in these nutrients may result in significant improvement of symptoms. Supplementation of the diet with lipid-soluble vitamins A, K, E, and D results in further improvement of neurologic and retinal symptoms.
• Patients should abstain from alcohol use.

MEDICATION

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The goals of pharmacotherapy are to reduce morbidity, correct vitamin deficiencies, and prevent complications.

Drug Category: Vitamins

Organic substances essential to normal metabolism.

FOLLOW-UP

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• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Deterrence/Prevention:

• The best preventive treatment of spur cell anemia is abstinence from alcohol.

Prognosis:

• The prognosis of spur cell hemolytic anemia of advanced liver disease is poor because frequently the condition precedes death by a few weeks to months. Most patients die of gastrointestinal bleeding, hepatic encephalopathy, or sepsis.
• Patients with abetalipoproteinemia develop functional deterioration early in life and do not survive beyond the third decade.
• Chorea-acanthocytosis syndrome is an irreversible entity with a slow unrelenting progression of symptoms to death over 8-14 years.

Patient Education:

• For excellent patient education resources, visit eMedicine's Liver, Gallbladder, and Pancreas Center; Cholesterol Center; and Statins Center. Also, see eMedicine's patient education articles Cirrhosis, High Cholesterol, Cholesterol FAQs, and Atorvastatin (Lipitor).

MULTIMEDIA

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• Multimedia
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Media file 1:  Spur cell anemia - Acanthocytes with target cells in advanced liver disease
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Media type:  Image

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

• Arienti G, Carlini E, Scionti L. Liver alcoholic cirrhosis and spur-cell (acanthocytic) anaemia. A study of erythrocyte ghost composition and fluidity. Scand J Gastroenterol. Dec 1995;30(12):1204-9. [Medline].
• Bohlega S, Riley W, Powe J. Neuroacanthocytosis and aprebetalipoproteinemia. Neurology. Jun 1998;50(6):1912-4. [Medline].
• Chitale AA, Sterling RK, Post AB. Resolution of spur cell anemia with liver transplantation: a case report and review of the literature. Transplantation. Apr 15 1998;65(7):993-5. [Medline].
• Cooper RA. Hemolytic syndromes and red cell membrane abnormalities in liver disease. Semin Hematol. Apr 1980;17(2):103-12. [Medline].
• Cynamon HA, Isenberg JN, Gustavson LP. Erythrocyte lipid alterations in pediatric cholestatic liver disease: spur cell anemia of infancy. J Pediatr Gastroenterol Nutr. Aug 1985;4(4):542-9. [Medline].
• Doll DC, Doll NJ. Spur cell anemia. South Med J. Oct 1982;75(10):1205-10. [Medline].
• Hardie RJ, Pullon HW, Harding AE. Neuroacanthocytosis. A clinical, haematological and pathological study of 19 cases. Brain. Feb 1991;114 ( Pt 1A):13-49. [Medline].
• Olivieri O, Guarini P, Negri M. Increased proteolytic activity of erythrocyte membrane in spur cell anaemia. Br J Haematol. Dec 1988;70(4):483-9. [Medline].
• Pascoe A, Kerlin P, Steadman C. Spur cell anaemia and hepatic iron stores in patients with alcoholic liver disease undergoing orthotopic liver transplantation. Gut. Aug 1999;45(2):301-5. [Medline].
• Redman CM, Russo D, Lee S. Kell, Kx and the McLeod syndrome. Baillieres Best Pract Res Clin Haematol. Dec 1999;12(4):621-35. [Medline].
• Rubio JP, Danek A, Stone C. Chorea-acanthocytosis: genetic linkage to chromosome 9q21. Am J Hum Genet. Oct 1997;61(4):899-908. [Medline].
• Shohet SB, Ness PM. Hemolytic anemias. Failure of the red cell membrane. Med Clin North Am. Sep 1976;60(5):913-32. [Medline].
• Terada N, Fujii Y, Ueda H. Ultrastructural changes of erythrocyte membrane skeletons in chorea- acanthocytosis and McLeod syndrome revealed by the quick-freezing and deep-etching method. Acta Haematol. Mar 1999;101(1):25-31. [Medline].

Article Last Updated: Aug 25, 2006