abnormal lipoprotein in cholestasis

1
68 6 Correspondence Department of Clinical Haematology and Medical Oncology, Royal Melbourne Hospital, Grattan Street, Parkville 3050, Victoria, Australia M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030. U.S.A. JOHN F. SEYMOUR M. J. KEATING REFERENCES Fain, O., El M’Selmi. A., Dosquet. C., Meseure. D.. Lejeune. F., Garel, J.-M. & Thomas, M. (1994) Hypercalcaemia in B-cell chronic lymphocyticleukaemia. British JournalofHuematology, 87,856-858. ABNORMAL LIPOPROTEIN IN CHOLESTASIS The case history described in the Short Report ‘Red cell lipid abnormalities in acquired acanthocytosis are extended to platelets’ (Ulibarrena et al, 1994) is that of a typical case of spur cell anaemia, the only atypical feature being an increase of phosphatidylcholine (PC) whereas the other phospholipids were normal. This pattern of selective accumulation of PC (combined with an equimolar increase of cholesterol resulting in a normal cholesterol/phospholipid ratio) causes the increase in red cell surface area of leptocytes which can be seen in any patient with cholestasis of some duration (Werre et al, 1970;Verkley et al, 1976). Target cells as exaggerated forms of leptocytes show the same pattern. We have shown that this pattern is caused by the adhesion and subsequent fusion of an abnormal lipoprotein (LP-X) which circulates in the plasma of patients with cholestasis. This lipoprotein contains equimolar quantities of PC and cholesterol and from electromicroscopicobservations we know that is consists of vesicular structures. For these reasons, LP-X closely resembles the cholesterol/PC-micelles in bile. In variance with Cooper’s statements (Cooper,1980), our results suggest that there is an equilibrium between fusion of LP-X vesicles with the erythrocytes and efflux of cholesterol and PC by molecular exchange with normal lipoproteins. So when LP-X ceases to circulate in the plasma, cholesterol and PC quickly normalize in the red cell membrane. It seems reasonable to assume that the same mechanism occurred in the platelet membranes of this patient. Pandian. M.R., Morgan, C.H.. Carlton, E. & Segre, G.V. (1992) Modified immunoradiometric assay of parathyroid hormone- related protein: clinical application in the differential diagnosis of hypercalcemia. Clinical Chemistry, 38, 282-288. Seymour, J.P. & Gagel, R.F. (1993) Calcitriol: the major humoral mediator of hypercalcemia in Hodgkin’s disease and non- Hodgkin‘s lymphomas. Blood, 82, 1383-1394. Seymour, J.F., Kouri. I.F., Champlin, R.E. & Keating. M.J. (1994) Refractory chronic lymphocytic leukemia complicated by hyper- calcemia treated by allogeneic bone marrow transplantation: case report and review. American Journal of Clinical Oncology. 17, 360-368. Keywords: pathogenesis, CLL, hypercalcaemia. R.C. Blood Bank, 22 Velperweg, 6824 BH Arnhem Department of Biochemistry of Membranes, University oj Utrecht, Transitorium Ill, 8 Padualaan, 3584 CH Utrecht, The Netherlands J. M. WERRE J. DE GIER REFERENCES Cooper, R.A. (1980) Hemolytic syndromes and red cell membrane abnormalities in liver disease. Seminars in Hematolog$, 17, 103- 112. Ulibarrena, C.. Vecino, A. & Cesar. J.M. (1994) Red cell lipid abnormalities in acquired acanthocytosis are extended to platelets. British Journal of Haematology. 87, 614-616. Verkley, A.J., Nauta, J.L.D., Werre, J.M., Mandersloot, J.G..Reinders, B., Ververgaert. P.H.J.Th. & de Gier, J. (1976) The fusion of abnormal plasma lipoprotein (LP-X) and the erythrocyte membrane in patients with cholestasis studied by electron microscopy. Biochimica et Biophysica Acta, 436, 366-376. Werre, J.M.. Helleman, P.W., Verloop, M.C. & de Gier, J. (1970) Causes of macroplania of erythrocytes in diseases of the liver and biliary tract with special reference to leptocytosis. British Journal of Haernatology, 19, 22 3-23 5. Keywords: red cell lipid abnormalities. RELATION BETWEEN SPICULATED RED CELLS AND PLATELETS IN URAEMIC PATIENTS It has recently been reported in the journai by Ulibarrena et a1 (1 994) that patients with alcoholic cirrhosis developed acanthocytosis associated with morphological and biochem- ical abnormalities of platelets similar to those of red cells. Spiculated red cells with five to 10 irregular spicules on their surface are called acanthocytes, whereas spiculated red cells with 10-30 regular and uniform spicules are called echinocytes. the echinocytes are considered as precursors of

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Page 1: ABNORMAL LIPOPROTEIN IN CHOLESTASIS

68 6 Correspondence Department of Clinical Haematology

and Medical Oncology, Royal Melbourne Hospital, Grattan Street, Parkville 3050, Victoria, Australia M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030. U.S.A.

JOHN F. SEYMOUR

M. J. KEATING

REFERENCES

Fain, O., El M’Selmi. A., Dosquet. C., Meseure. D.. Lejeune. F., Garel, J.-M. & Thomas, M. (1994) Hypercalcaemia in B-cell chronic lymphocytic leukaemia. British JournalofHuematology, 87,856-858.

ABNORMAL LIPOPROTEIN IN CHOLESTASIS

The case history described in the Short Report ‘Red cell lipid abnormalities in acquired acanthocytosis are extended to platelets’ (Ulibarrena et al, 1994) is that of a typical case of spur cell anaemia, the only atypical feature being an increase of phosphatidylcholine (PC) whereas the other phospholipids were normal. This pattern of selective accumulation of PC (combined with an equimolar increase of cholesterol resulting in a normal cholesterol/phospholipid ratio) causes the increase in red cell surface area of leptocytes which can be seen in any patient with cholestasis of some duration (Werre et al, 1970; Verkley et al, 1976). Target cells as exaggerated forms of leptocytes show the same pattern.

We have shown that this pattern is caused by the adhesion and subsequent fusion of an abnormal lipoprotein (LP-X) which circulates in the plasma of patients with cholestasis. This lipoprotein contains equimolar quantities of PC and cholesterol and from electromicroscopic observations we know that is consists of vesicular structures. For these reasons, LP-X closely resembles the cholesterol/PC-micelles in bile. In variance with Cooper’s statements (Cooper, 1980), our results suggest that there is an equilibrium between fusion of LP-X vesicles with the erythrocytes and efflux of cholesterol and PC by molecular exchange with normal lipoproteins. So when LP-X ceases to circulate in the plasma, cholesterol and PC quickly normalize in the red cell membrane. It seems reasonable to assume that the same mechanism occurred in the platelet membranes of this patient.

Pandian. M.R., Morgan, C.H.. Carlton, E. & Segre, G.V. (1992) Modified immunoradiometric assay of parathyroid hormone- related protein: clinical application in the differential diagnosis of hypercalcemia. Clinical Chemistry, 38, 282-288.

Seymour, J.P. & Gagel, R.F. (1993) Calcitriol: the major humoral mediator of hypercalcemia in Hodgkin’s disease and non- Hodgkin‘s lymphomas. Blood, 82, 1383-1394.

Seymour, J.F., Kouri. I.F., Champlin, R.E. & Keating. M.J. (1994) Refractory chronic lymphocytic leukemia complicated by hyper- calcemia treated by allogeneic bone marrow transplantation: case report and review. American Journal of Clinical Oncology. 17, 360-368.

Keywords: pathogenesis, CLL, hypercalcaemia.

R.C. Blood Bank, 22 Velperweg, 6824 BH Arnhem Department of Biochemistry of Membranes, University o j Utrecht, Transitorium I l l , 8 Padualaan, 3584 CH Utrecht, The Netherlands

J . M. WERRE

J. DE GIER

REFERENCES

Cooper, R.A. (1980) Hemolytic syndromes and red cell membrane abnormalities in liver disease. Seminars in Hematolog$, 17, 103- 112.

Ulibarrena, C.. Vecino, A. & Cesar. J.M. (1994) Red cell lipid abnormalities in acquired acanthocytosis are extended to platelets. British Journal of Haematology. 87, 614-616.

Verkley, A.J., Nauta, J.L.D., Werre, J.M., Mandersloot, J.G.. Reinders, B., Ververgaert. P.H.J.Th. & de Gier, J. (1976) The fusion of abnormal plasma lipoprotein (LP-X) and the erythrocyte membrane in patients with cholestasis studied by electron microscopy. Biochimica et Biophysica Acta, 436, 366-376.

Werre, J.M.. Helleman, P.W., Verloop, M.C. & de Gier, J. (1970) Causes of macroplania of erythrocytes in diseases of the liver and biliary tract with special reference to leptocytosis. British Journal of Haernatology, 19, 22 3-23 5.

Keywords: red cell lipid abnormalities.

RELATION BETWEEN SPICULATED RED CELLS AND PLATELETS IN URAEMIC PATIENTS

It has recently been reported in the journai by Ulibarrena et a1 (1 994) that patients with alcoholic cirrhosis developed acanthocytosis associated with morphological and biochem- ical abnormalities of platelets similar to those of red cells.

Spiculated red cells with five to 10 irregular spicules on their surface are called acanthocytes, whereas spiculated red cells with 10-30 regular and uniform spicules are called echinocytes. the echinocytes are considered as precursors of