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PubMed1977

Decreased fluidity of red cell membrane lipids in abetalipoproteinemia.

Acanthocytic red cells in patients with abetalipoproteinemia are morphologically similar to the red cells in spur cell anemia. Fluidity of membrane lipids is decreased in spur cells due to their excess cholesterol content. Acanthocyte membranes have an increased content of sphingomyelin and a decreased content of lecithin. To assess the effect of this abnormality of acanthocyte membrane lipid composition on membrane fluidity, we studied red cells from five patients with abetalipoproteinemia and four obligate heterozygote family members. Membrane fluidity was measured in terms of microviscosity ( eta) at 37 degrees C, assessed by means of the fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene. It was increased from 3.2+/-0.1 poise in normals to 4.01-4.14 poise in acanthocytes. This was associated with an increase in the sphingomyelin/lecithin ratio from 0.84+/-0.08 in normals in 1.45-1.61 in acanthocytes. The eta of acanthocyte membranes was not influenced by the degree of vitamin E deficiency. Similar changes in eta were observed in liposomes prepared from red cell lipids. Heterozygotes had normal sphingomyelin/lecithin ratios and normal values for eta. The flow activation energy for viscosity, a measure of the degree of order in the hydrophobic portion of the membrane, was decreased from 8.3 kcal/mole in normal red cells to 7.2 kcal/mole in acanthocytes, indicating that acanthocyte membrane lipids are more ordered. Variations in the sphingomyelin/lecithin mole ratio of liposomes prepared from brain sphingomyelin and egg lecithin with equimolar cholesterol caused similar changes in both eta and activation energy. The deformability of acanthocytes, assessed by means of filtration through 3-mum filters, was decreased. These studies indicate that the increased sphingomyelin/lecithin ratio of acanthocytes is responsible for their decreased membrane fluidity. As in spur cells and in red cells enriched with cholesterol in vitro, this decrease in membrane fluidity occurs coincidentally with an abnormality in cell contour and an impairment in cell deformability.

Abetalipoproteinemia↗
PubMed2000

Scanning electron microscopic studies on morphological abnormalities of erythrocytes in alcoholic liver diseases.

BACKGROUND: We previously reported that morphological abnormalities and the altered deformability of erythrocytes play important roles in disturbances of hepatic microcirculation associated with alcoholic liver disease. METHODS: The subjects of this study were five patients with alcoholic liver cirrhosis, two patients with alcoholic fatty liver, and two healthy volunteers. Concentrating on erythrocyte morphology in the presence of alcoholic liver disease, we observed erythrocytes under a scanning electron microscope and examined their morphological changes in relation to the disease. RESULTS: Among the five patients with alcoholic liver cirrhosis, stomatocytes accounted for about 14% and acanthocytes for about 10% of all erythrocytes. In the fatty liver group (n = 2), acanthocytes were absent, and stomatocytes accounted for 23% in one subject and 56% in the other, of the total. When the two patients with liver cirrhosis were examined over time, one of them was found to have 12% stomatocytes, 21% acanthocytes, and a filtration time of 14.7 sec at admission. Following 1 month of abstinence, this patient had 1% stomatocytes, 6% acanthocytes, and a filtration time of 10.4 sec, which were accompanied by improvements in peripheral blood parameters and liver function. In another patient with liver cirrhosis, there were no acanthocytes, 8% stomatocytes, and a filtration time of 5 sec at admission; this patient had 1% stomatocytes and a filtration time of 7.7 sec after 1 month of abstinence. In one patient with fatty liver who was examined over time, the percentage of stomatocytes was 56%, and the filtration time was 7.7 sec at admission; these parameters were 1% and 5.1 sec, respectively, after 1 month of abstinence. CONCLUSIONS: The present study revealed that stomatocytes and acanthocytes are morphologically abnormal erythrocytes observed in the presence of alcoholic liver disease. These abnormal forms of erythrocytes tended to normalize as peripheral blood parameters and liver function were improved by abstinence, which suggests that erythrocyte morphology is related to the pathophysiology of alcoholic liver disease.

Acanthocytes↗
PubMed2005

Testing for acanthocytosis A prospective reader-blinded study in movement disorder patients.

The presence of acanthocytosis in peripheral blood smears remains the hallmark of the clinical diagnosis of most neuroacanthocytosis syndromes, such as chorea-acanthocytosis (ChAc) and McLeod syndrome. Genetic analyses and/or specific laboratory tests are available only for a minority of these disorders. Testing for acanthocytosis is hampered by the lack of data on normal amounts of acanthocytes assessed by a standardized method. We report a prospective reader-blinded study designed to establish control values for abnormally shaped erythrocytes in healthy volunteers and patients with movement disorders (MDs) using light microscopic assessment of erythrocyte morphology in standard EDTA and isotonically diluted blood samples. We investigated a total of 100 patients fulfilling clinical criteria of specific MDs, 31 patients with MDs not matching any clinical criteria, and 37 healthy controls. In patients with diagnosed MDs and healthy controls, acanthocytes in dry blood smears were significantly more frequent following isotonic dilution compared with standard EDTA blood. In unfixed wet blood preparations of both EDTA blood and isotonically diluted blood, acanthocyte levels were significantly higher than in standard dry blood smear preparations. There were no statistical differences of acanthocyte levels in all test conditions between diagnosed MDs and healthy volunteers. There was no significant correlation of acanthocyte levels in all blood samples and preparations with age, sex or diagnosis. Thus, normal values were defined as the 99th percentile of combined results of the two groups of volunteers. Diluted blood combined with wet blood preparation showed high specificity (0.98) and the highest sensitivity of all test procedures (all genetically confirmed ChAc patients were detected). The reported method is cheap, readily available, and provides high specificity and sensitivity in respect to clinically relevant acanthocytosis. The use of isotonically diluted blood samples combined with unfixed wet blood preparation with a normal range of <6.3% of total erythrocytes is recommended to search for significant acanthocytosis in movement disorders.

Acanthocytes↗
PubMed1992

[Studies on the erythrocyte membrane skeleton in a patient with chorea-acanthocytosis--theoretical speculation on the mechanism of neurological involvement].

Patients with chorea-acanthocytosis exhibit symptoms of self-biting, choreic movement, and acanthocytosis, but not dementia. The mechanism of choreic movements is still unknown. In order to clarify the etiologic mechanism underlying these movements, we evaluated the erythrocyte membrane in one patient with chorea-acanthocytosis. A 35-year-old female was admitted to Saitama Medical School Hospital because of involuntary movements. She was alert, well-oriented, and had no gross memory defects. She had slurred speech, choreic movements and lip biting. Laboratory examination showed acanthocytes in her peripheral red blood cells, normal serum lipid values, and caudate atrophy on her brain CT scan. In analyzing the acanthocytes, we initially evaluated the size of the acanthocyte population by incubating her red blood cells with plasma. The cell population approximately doubled after 2 hours incubation. Next we examined the protein composition of erythrocyte ghost by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). There was no significant difference between the patient's erythrocyte ghosts and those of a control. Then we investigated morphological changes in the patient's erythrocyte by scanning and transmission electron microscopy (SEM and TEM). SEM showed the typical acanthocyte shape. The quick-freeze, freeze-substitution method confirmed that the routine TEM section was not artifactual, and was in fact in accurate reflection of the actual features of acanthocytes. TEM of the sections prepared from erythrocyte ghosts demonstrated that spectrin tended to be accumulated in the thorn region. Furthermore, TEM of quick-freeze, deep-etched replica of the ghost revealed more clearly a spectrin network densely packed on the inner hydrophilic surface.(ABSTRACT TRUNCATED AT 250 WORDS)

Acanthocytes↗
PubMed1999

Ultrastructural changes of erythrocyte membrane skeletons in chorea-acanthocytosis and McLeod syndrome revealed by the quick-freezing and deep-etching method.

The shapes of acanthocytic erythrocytes have been thought to be related to changes of the organization of the membrane components. In this study, acanthocytes from a patient with chorea-acanthocytosis and a patient with McLeod syndrome were examined. These acanthocytes had a greater tendency to form spikes than normal erythrocytes in an incubation culture system, indicating their weakness against membrane tension. The membrane skeletons of erythrocytes from both patients were examined by our erythrocyte-splitting method followed by the quick-freezing and deep-etching method. The ultrastructural organization of the membrane skeletons was heterogeneous even in individual erythrocytes, indicating regional changes in the compactness of their meshworks. In the process of erythrocyte splitting, some erythrocyte membranes became reversed and protruded into the cytoplasmic side. In these regions, there were fewer filamentous structures. The focal membrane skeletal changes, which are probably one of the factors that induce the phenotype of an acanthocytic erythrocyte, were demonstrated for the first time by this method.

Acanthocytes↗
PubMed2002

[Acanthocyturia is more efficient in to differentiate glomerular from non-glomerular hematuria then dysmorphic erythrocytes].

OBJECTIVE: Our purpose was to determine which was the most reliable method for differentiating glomerular from non-glomerular (lower urinary tract) hematuria by microscopic examination of urinary red blood cells: dysmorphic red cell count or acanthocyte count. The latter is a special type of dysmorphic red cell specific to glomerular hematuria. METHODS: Urine samples of 170 patients with hematuria [73 had renal and 97 non-renal (urological) pathology] were analyzed. Urinary sediment phase-contrast microscopy was performed to determine the percentage of dysmorphic red cells and acanthocytes in each patient. Data were correlated with the diagnosis. RESULTS: Glomerular hematuria defined as dysmorphic red cell count > 35% showed a sensitivity and specificity of 69% and 100%, respectively. Glomerular hematuria defined as acanthocytes > 5% showed a sensitivity and specificity of 88% and 100%, respectively. CONCLUSIONS: Phase-contrast microscopy urinary sediment acanthocyte count is more effective than dysmorphic red cell count in the diagnosis of glomerular hematuria.

Acanthocytes↗
PubMed2003

[Evaluation of a new method for diagnosing the origin of urinary bleeding by the morphological characteristics of urinary red blood cells].

In this study, we attempted to develop a new method for diagnosing the origin of urinary bleeding by the morphological characteristics of urinary red blood cells (RBC). Seventy-five samples were divided into five types by individual features using phase-contrast microscopy. It was revealed that the ratios of type III, namely acanthocytes, and IV, namely donut-shaped RBC, were significantly higher in patients with glomerular bleeding than those with non-glomerular bleeding. Acanthocytes seemed to be specific to glomerular bleeding, but some urinary samples from patients with glomerular bleeding did not show acanthocytes. Therefore, we suggest that the detection of a combination of acanthocytes and donut-shaped RBC in a urine sample is useful for the diagnosis of glomerular bleeding.

Acanthocytes↗
PubMed1993

Qualitative evaluation of irregularly spiculated red blood cells in the dog.

Irregularly speculated red blood cells (IS-RBC) were quantified on fresh blood fixed in glutaraldehyde and were compared to RBC shape changes observed on Wright's-stained blood smears, RBC histograms, and RBC distribution widths (RDW). IS-RBC were infrequently found in healthy control dogs. Twenty dogs with increased IS-RBC were evaluated. The most common clinical diagnoses were lymphosarcoma (seven cases), glomerulonephritis (two cases), hemangiosarcoma (two cases), and chronic liver disease (two cases). Five cases had evidence of disseminated intravascular coagulopathy. In 12 of the 20 cases, keratocytes, schizocytes, and/or acanthocytes were detected in the monolayer area of blood smears. In the other seven cases, keratocytes, schizocytes, and/or acanthocytes were found only in thick areas of the smears. Acanthocytes were the most frequent cell type seen, while schizocytes were absent or present only in low numbers. RBC histograms had a shoulder on the left side of the tracing in six of the 20 cases, suggesting the presence of RBC fragments; however, cases with evidence of platelet aggregation had similar shoulders in RBC histograms. Red cell distribution widths were increased in 12 of the 20 cases with IS-RBC; however, the increase in RDW did not correlate with the presence of schizocytes and was most likely the result of reticulocytosis. This study suggests that quantitative evaluation of RBC shape is a more sensitive method for detection of mild RBC fragmentation when compared to blood smear evaluation, RBC histograms, or RDW. Additionally, acanthocyte-type cells were the most frequent shape change seen in dogs with evidence of RBC fragmentation.

Journal Article↗
PubMed1984

Mechanism of red blood cell acanthocytosis and echinocytosis in vivo.

Patients with abetalipoproteinemia have an inborn absence of the major apoprotein of low density plasma lipoproteins, an abnormal serum and red cell lipid profile, and spiny erythrocytes, called acanthocytes. We now show that these deformed cells are reversibly converted to a normal shape, that of a biconcave disk, by incubation with 3 to 10 X 10(-5) M chlorpromazine. We suppose that chlorpromazine acts by expanding the cytoplasmic leaflet of the bilayer, thus promoting inward curvature. Ghosts isolated from the acanthocytes are themselves spiny but are also converted to normal, concave disks by chlorpromazine or merely by a brief incubation at 37 degrees C in low ionic strength buffer. We attribute the latter to a redistribution of lipids between the two leaflets of the membrane bilayer. Similar observations were made with red cells and ghosts from a patient with benign echinocytosis. These observations suggest that the morphological abnormality in acanthocytes and echinocytes can be ascribed to the same mechanism as crenation in vitro; that is, a bilayer couple effect in which an excess of surface area in the outer leaflet over the inner leaflet of the membrane bilayer drives outward curvature. It is striking that cells which were chronically abnormal in shape in vivo contain the information to become biconcave disks immediately upon simple chemical treatment in vitro.

Abetalipoproteinemia↗