Red cell membrane abnormalities in two cases with a special type of a hereditary megaloblastoid hemolytic anemia
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Summary
Case reports are presented of two related patients suffering from a hereditary megaloblastoid hemolytic anemia which at the moment cannot be categorized into one of the well-known entities. The main characteristics of the disease consisted of constant jaundice, macrocytic normochromic anemia, marked hemolysis without a substantial decrease in osmotic resistance, increased iron turnover and hepatic hemosiderosis at a relatively young age. One patient had to undergo splenectomy due to hemolytic crises, the other one cholecystectomy due to gallstones.
In contrast to their uncharacteristic morphology in smear, red cells displayed highly variable forms (“lumpy”, “Y”, “U”, drumstick forms) when examined in transmission and scanning electron microscopes. These changes corresponded well with reduced filtrability and aggregability of erythrocytes. The apparent relative blood viscosity was unchanged. The protein pattern of ghosts in SDS gel-electrophoresis revealed neither defects nor additional bands. Changes in the lipid composition of the membrane were indirectly deduced from electron spin-resonance studies, which showed an additional signal at g=2.192. Similarly, the lipid related membrane mobility agent A2C failed to exert the usual stabilizing effect against osmotic stress. The negative surface potential, estimated by free flow electrophoresis, was only altered in the splenectomized patient.
It is concluded that the primary abnormal physical properties of the enlarged red cell contribute at least in part to the marked hemolysis. The similar findings in the two related patients and the fact that the disorder was obviously congenital suggest a special subtype of a megaloblastoid hemolytic anemia.
Key words
Dyserythropoiesis Scanning electron microscopy Electron spin resonance FiltrabilityPreview
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References
- 1.Allen DW, Cadman S (1979) Calcium-induced erythrocyte membrane changes. The role of adsorption of cytosol proteins and proteases. Biochim Biophys Acta 551: 1–9Google Scholar
- 2.Curtis ASG, Chandler C, Picton N (1975) Cell surface lipids and adhesion. III. The effects on cell adhesion of changes in plasma — lemmal lipids. J Cell Sci 18: 475–478Google Scholar
- 3.David G, van Dorpe A (1977) Aberrant congenital dyserythropoietic anaemias. In: Lewis SM, Verwilghen RL (eds) Dyserythropoiesis. Academic Press, London New York San Francisco, pp 93–100Google Scholar
- 4.Fairbanks G, Steck ThL, Wallach DFH (1971) Electrophoretic analysis of the major polypeptides of the human erythrocyte membrane. Biochemistry 10: 2606–2617Google Scholar
- 5.Folch J, Less M, Sloane Stanley GH (1957) A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 226: 497Google Scholar
- 6.Frisch B, Lewis SM, Swan M (1976) Intercellular contacts between erythroid precursors in the bone marrow in dyserythropoiesis. Br J Haematol 33: 469–475Google Scholar
- 7.Frisch B, Broeckaert-Van Orshoven A (1977) Ultrastructure of normal and abnormal erythropoiesis. In: Lewis SM, Verwilghen RL (eds) Dyserythropoiesis. Academic Press, London New York San Francisco, pp 271–314Google Scholar
- 8.Haase G, Dunkley WL (1969) Ascorbic acid and linoleate oxydation. J Lipid Res 10: 555–567Google Scholar
- 9.Hannig K (1978) Continuous free-flow electrophoresis as an analytical and preparative method in biology. J Chromatogr 159: 183–191Google Scholar
- 10.Heimpel H, Wendt F (1968) Congenital dyserythropoietic anemia with Karyorrhexis and multinuclearity of erythroblasts. Helv Med Acta 34: 103–115Google Scholar
- 11.Heimpel H (1977) Congenital dyserythropoietic anaemia, type I. In: Lewis SM, Verwilghen RL (eds) Dyserythropoiesis. Academic Press, London New York San Francisco, pp 55–70Google Scholar
- 12.Johnsson R (1978) Red cell membrane proteins and lipids in spherocytosis. Scand J Haematol 20: 349–350Google Scholar
- 13.Kosower NS, Zipser Y, Kosower EM (1980) Membrane mobility agents: alteration of human red blood cell membrane properties. Arch Biochem Biophys 203: 325–331Google Scholar
- 14.Kosower NS, Faltin Z, Kosower EM (1981) Cell-membrane receptor classed delimited through cap formation either with diamide or with membrane mobility agent, A2C. J Immunol Methods 41: 215–223Google Scholar
- 15.Lewis SM, Lambertenghi G, Ferrone S, Sirchia G (1971) Electron microscope study of PNH red cells and AET-treated normal red cells (PNH-like cells). J Clin Pathol 24: 677–684Google Scholar
- 16.Lewis SM, Verwilghen RL (1977) Dyserythropoiesis: definition, diagnosis and assessment. In: Lewis SM, Verwilghen RL (eds) Dyserythropoiesis. Academic Press, London New York San Francisco, pp 3–20Google Scholar
- 17.Linderkamp O, Meiselman HJ, Miller FC, Wu PYK (1981) Mechanical properties of neonatal and adult red cells. Pediatr Res 15: 1209Google Scholar
- 18.Lohmann W, Schreiber J, Greulich W (1979) On the possible involvement of ascorbic acid and copper proteins in leukemia. IV. ESR investigation on the interaction between ascorbic acid and some copper proteins. Z Naturforsch 34c: 550–554Google Scholar
- 19.Lohmann W, Schreiber J, Greulich W, Strobelt W, Müller E, Löffler H, Pralle H, Feustel H, Schwemmle K, Filler RD (1981) ESR investigations on tissue growth. Collect Phenom 3: 245–258Google Scholar
- 20.Oakley BR, Kirsch DR, Morris NR (1980) A simplified ultrasensitive silver stain for detecting proteins in polyacrylamide gels. Anal Biochem 105: 361–363Google Scholar
- 21.Reid HL, Barnes AJ, Lock JA, Dormandy JA (1976) A simple method for measuring erythrocyte deformability. J Clin Pathol 29: 855–859Google Scholar
- 22.De Sandre G, Cortesi S, Corrocher R, Falezza G, Perona G (1970) On the mechanism of the in vitro production of ham-positive red cells by sulphhydryl compounds: role of pH and free-SH groups. Br J Haematol 18: 551–566Google Scholar
- 23.Schmid-Schönbein H, Weiss J, Ludwig H (1973a) A simple method for measuring red cell deformability in models of microcirculation. Blut 26: 369–379Google Scholar
- 24.Schmid-Schönbein H, von Gosen H, Heinrich L, Klose HJ, Volger E (1973b) A counter-rotating “rheoscope chamber” for the study of the microrheology of blood cell aggregation by microscopic observation and microphotometry. Microvasc Res 6: 366–376Google Scholar
- 25.Sebahoun G, Bayle J, Muratore R, Carcassonne Y (1980) Acquired dyserythropoiesis with abnormal intercellular contacts between erythroblasts. Scand J Haematol 25: 318–322Google Scholar
- 26.Zwaal RFA (1981) Structure and function of red blood cell membranes. Pediatr Res 15: 1143–1149Google Scholar