Abnormal Platelet Functions in a Patient with Abetalipoproteinemia

Summary Studies with isolated lipoproteins and washed platelets suggest that lipoproteins may affect platelet functions. We investigated platelet-rich plasma (PRP) from a patient with abetalipoproteinemia (ABL), whose plasma lacks apo-B containing lipoproteins (VLDL, LDL and chylomicrons). ABL-PRP aggregated poorly with different agonists and failed to respond to arachidonate. Thromboxane. B2 (T×B2) formation was severely impaired. After gel-filtration most of the aggregation defects persisted in agreement with reduced metabolism of endogenous arachidonate. However, arachidonate-induced aggregation and T×B2 production partially normalized. Normal platelets suspended in ABL plasma showed similar defects in aggregation and T×B2 production but arachidonate-induced aggregation was much lower than expected on the basis of T×B2. We conclude that the abnormal platelet functions in ABL-PRP are caused by (i) an intrinsic platelet abnormality due to reduced arachidonate mobilization and (ii) a property in ABL plasma that inhibits aggregation partially by trapping the arachidonate and partially by an unidentified mechanism. The latter properties may be the result of the abnormal lipid composition of ABl-plasma.

[1]  J. Akkerman,et al.  PAF-acetylhydrolase, predominantly present in LDL in healthy subjects, is associated with HDL in a patient with LDL deficiency. , 1991, Journal of lipid mediators.

[2]  K. Bruckdorfer.  The effects of plasma lipoproteins on platelet responsiveness and on platelet and vascular prostanoid synthesis. , 1989, Prostaglandins, leukotrienes, and essential fatty acids.

[3]  W. Vetter,et al.  Low density lipoprotein causes general cellular activation with increased phosphatidylinositol turnover and lipoprotein catabolism. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[4]  M. Aviram,et al.  Platelet activation by plasma lipoproteins. , 1987, Progress in cardiovascular diseases.

[5]  V. Skinner,et al.  Intracellular mechanisms in the activation of human platelets by low-density lipoproteins. , 1987, The Biochemical journal.

[6]  Y. Marcel,et al.  Epitopes of apolipoprotein B-100 and B-48 in both liver and intestine. Expression and evidence for local synthesis in recessive abetalipoproteinemia. , 1986, The Journal of clinical investigation.

[7]  R. Deckelbaum,et al.  Platelet function in a case with abetalipoproteinemia. , 1985, Atherosclerosis.

[8]  M. Aviram,et al.  Native and modified low-density-lipoprotein interaction with human platelets in normal and homozygous familial-hypercholesterolaemic subjects. , 1984, The Biochemical journal.

[9]  A. Verhoeven,et al.  Quantification of energy consumption in platelets during thrombin-induced aggregation and secretion. Tight coupling between platelet responses and the increment in energy consumption. , 1984, The Biochemical journal.

[10]  Y. Nozawa,et al.  Alterations in erythrocyte membrane lipids in abetalipoproteinemia: phospholipid and fatty acyl composition. , 1984, Biochemical medicine.

[11]  L. Curtiss,et al.  Interaction of plasma lipoproteins with human platelets. , 1984, Blood.

[12]  J. S. Owen,et al.  The aggregation of isolated human platelets in the presence of lipoproteins and prostacyclin. , 1983, The Biochemical journal.

[13]  M. Frojmovic,et al.  Microscopic measurements of platelet aggregation reveal a low ADP-dependent process distinct from turbidometrically measured aggregation. , 1983, The Journal of laboratory and clinical medicine.

[14]  M. Aviram,et al.  Platelet interaction with high and low density lipoproteins. , 1983, Atherosclerosis.

[15]  M. Aviram,et al.  The effect of blood constituents on platelet function: role of blood cells and plasma lipoproteins. , 1983, Artery.

[16]  M. Aviram,et al.  Characterization of the effect of plasma lipoproteins on platelet function in vitro. , 1983, Haemostasis.

[17]  C. Blum,et al.  Abnormal high density lipoproteins of abetalipoproteinemia: relevance to normal HDL metabolism. , 1982, Journal of lipid research.

[18]  D. Goodman,et al.  Studies on the mechanism of the inhibition of platelet aggregation and release induced by high levels of arachidonate. , 1982, Blood.

[19]  E. Koller,et al.  Specific binding sites on human blood platelets for plasma lipoproteins. , 1982, Hoppe-Seyler's Zeitschrift fur physiologische Chemie.

[20]  V. Smirnov,et al.  Study of low density lipoprotein interaction with platelets by flow cytofluorimetry , 1982, FEBS letters.

[21]  R. Lees,et al.  Low density lipoprotein binding to human platelets: role of charge and of specific amino acids. , 1981, Biochemical and biophysical research communications.

[22]  A. Nordøy,et al.  Platelet Function and Serum High Density Lipoproteins , 1979, Thrombosis and Haemostasis.

[23]  G. Béréziat,et al.  Turnover of phospholipid linoleic and arachidonic acids in human platelets from plasma lecithins. , 1978, Journal of lipid research.

[24]  J. Lubowsky,et al.  The lumi-aggregometer: a new instrument for simultaneous measurement of secretion and aggregation by platelets. , 1977, The Journal of laboratory and clinical medicine.

[25]  L. Levine,et al.  Inhibition of arachidonic acid release from cells as the biochemical action of anti-inflammatory corticosteroids. , 1976, Proceedings of the National Academy of Sciences of the United States of America.

[26]  J. White,et al.  An improved method for the extraction of endogenous platelet serotonin. , 1976, The Journal of laboratory and clinical medicine.

[27]  W. D. Mcelroy,et al.  Kinetics of the firefly luciferase catalyzed reactions. , 1974, Biochemistry.

[28]  H. Kayden.  Abetalipoproteinemia. , 2020, Annual review of medicine.

[29]  H. Weiss,et al.  Further evidence for a deficient storage pool of adenine nucleotides in platelets from some patients with thrombocytopathia--"storage pool disease". , 1972, Blood.

[30]  W. J. Dyer,et al.  A rapid method of total lipid extraction and purification. , 1959, Canadian journal of biochemistry and physiology.

[31]  F A BASSEN,et al.  Malformation of the erythrocytes in a case of atypical retinitis pigmentosa. , 1950, Blood.