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.

• References

• 1 Basen FA, Kornzweig AL. Malformation of the erythrocytes in a case of a typical retinitis pigmentosa. Blood 1950; 5: 381-387
• 2 Kayden HJ. Abetalipoproteinemia. Annu Rev Med 1972; 23: 285-296
• 3 Herbert PN, Gotto Jr AM, Frederickson DS. Familial lipoprotein deficiency (abetalipoproteinemia and Thngier disease). In: The Metabolic Base of Inherited Disease Stanbury JB, Wyngaarden JB, Frederickson DS, Goldstein JL, Brown MS. ed McGraw-Hill Inc; New York: 1982: 553-565
• 4 Dullaart RPS, Speelberg B, Schuurman HJ, Milne RW, Havekes LM, Marcel YL, Geuze HJ, Hulshof MM, Erkelens Dw. Epitopes of apolipoprotein 8-100 and B-48 in both liver and intestine: expression and evidence for local synthesis in recessive abetalipoproteinemia. J Clin Invest 1986; 78: 1397-1404
• 5 Deckelbaum RJ, Eisenberg s, oschry y, cooper M, Blum c. Abnormal high density lipoproteins of abetalipoproteinemia: relevance to normal HDL metabolism. J Lipid Res 1982; 23: 1274-1282
• 6 Aviram M, Brook JG. Characterization of the effect of plasma lipoprotein on platelet function in vitro. Haemostasis 1983; 13: 344-350
• 7 Aviraffi M, Brook JG. The effect of blood constituents on platelet function: Role of blood cells and plasma lipoproteins. Artery 1983; 11: 297-305
• 8 Aviram M, Brook JG. Selective release from platelet granules by plasma lipoproteins. Biochem Med 1984; 32: 304
• 9 Hassal DG, Owen JS, Bruckdorfer KR. The aggregation of isolated platelets in the presence of lipoproteins and prostacyclin. Biochem J 1983; 216: 43-49
• 10 Andrews HE, Aitken JW, Hassall DG, Skinner VO, Bruckdorfer KR. Intracellular mechanisms in the activation of human platelets by low density lipoproteins. Biochem J 1987; 242: 559-564
• 11 Block LH, Knorr M, Vogt E, Locher R, Vetter W, Groscurth p, eiao BX, Pometta D, James R, Rigenass M, pletscher A. Low density lipoproteins cause general cellular activation with increased phosphatidylinositol turnover and lipoprotein catabolism. Proc Natl Acad Sci USA 1988; 85: 885-899
• 12 Knorr M, Locher R, vogt E, vetter W, Block LH, Rerracin R, Lefkovits FI, Pletscher A. Rapid activation of human platelets by low concentration of LDL via phosphatidylinositol cycle. Eur J Biochem 1988; 172: 753-759
• 13 Nordoy A, Refsum N, Thelle D, Jaeger S. Platelet function and serum high density lipoproteins. Thromb Haemostas 1979; 42: 1181-1186
• 14 Desai K, Bruckdorfer R, Hutton RA, Owen JS. Binding of apo E rich high density lipoprotein particles by saturable sites on human blood platelets inhibits agonist-induced platelet aggregation. J Lipid Res 1989; 30: 831-840
• 15 Curtiss LK, Plow EE. Interaction of plasma lipoproteins with human platelets. Blood 1984; 64: 365-374
• 16 Koller E, Koller E, Doleschel W. Specific binding sites of human blood platelets for plasma lipoproteins. Hoppe-Seyler’s Z Physiol Chem 1982; 363: 395-405
• 17 Aviram M, Brook JG, Lees AM, Lees RS. Low density lipoprotein binding to human platelets: Role of charge and of specific amino acids. Biochem Biophys Res Comm 1981; 99: 308-318
• 18 Mazurov AV, Preobrazhensky SN, Leytin VL, Repin VS, Smirnov VN. Study of low density lipoprotein interaction with platelets by flow cytofluorimetry. FEBS Lett 1982; 137: 319-322
• 19 Shmulewitz A, Brook JG, Aviram M. Native and modified low density lipoprotein interaction with human platelets in normal and homozygous familial hypercholesterolemic subjects. Biochem J 1984; 224: 13-20
• 20 Holmsen H, Weiss HJ. Further evidence for a deficient storage pool of adenine nucleotides in platelets from some patients with thrombocytopathia-storage pool disease. Blood 1972; 39: 197-209
• 21 Rao GHR, white JG, Jachimowics AA, witkop CJ. An improved method for the extraction of endogenous platelet serotonin. J Lab Clin Med 1976; 87: 129-137
• 22 Surya II, Mommersteeg M, Erkelens DW, Akkerman JWN. pAFacetylhydrolase, predominantly present in LDL in healthy subjects, is associated with HDL in a patient with LDL deficiency. J Lipid Med 1991; 3: 27-38
• 23 Froimovic MM, Milton JG, Duchastel A. Microscopic measurements of platelet aggregation reveal a low ADP-dependent process distinct from tubridometrically measured aggregation. J Lab Clin Med 1983; 101: 964-976
• 24 Yerhoeven AJM, Mommersteeg ME, Akkerman JWN. Quantification of energy consumption in platelets during thrombin induced aggregation and secretion. Tight coupling between platelet responses and the increment in energy consumption. Biochem J 1984; 221: 777-787
• 25 Feinrnan RD, Lubowsky J, Charo IR, Zabinsky MP. The lumiaggregometer. A new instrument for simultaneous measurement of secretion and aggregation. J Lab Clin Med 1977 90. 125-129
• 26 DeLuca M, McElroy WD. Kinetics of the firefly luciferase catalyzed reaction. Biochemistry 1974; 13: 921-925
• 27 Bligtr EG, Dyer WJ. A rapid method of total lipid extraction and purification. Can J Biochem Physiol 1959; 37: 911-918
• 28 Hong SCL, Levine L. Inhibition of arachidonic acid release from cells as the biochemical action of anti-inflammatory corticosteroids. Proc Natl Acad Sci USA 1976; 73: 1730-1734
• 29 Lindrer L, Goodman DS. Studies of the mechanism of the inhibition of platelet aggregation and release induced by high levels of arachidonate. Blood 1982; 60: 436-445
• 30 Aviretm M, Deckelbaum RI, Brook JG. Platelet function in a case with abetalipoproteinemia. Atherosclerosis 1985; 57: 313-323
• 31 Iida T, Thkashima Y, Maedo S, Sekiya T, Kawade M, Kawamura M, Okano Y, Nozawa Y. Alterations in erythrocyte membrane lipids in abetalipoproteinemia: Phospholipid and fatty acid composition. Biochem Med 1984; 32: 79-87
• 32 Chambaz J, Wolf C, Pepitr D, Bereziat G. Phospholipid and fatty acid exchange between human platelets and plasma. Biol Cellulaire 1980; 37: 223-240
• 33 Bereziat G, Chambaz J, Tiugnan G, Pepin D, Polonovski J. Turnover of phospholipid linoleic and arachidonic acids in human platelets from plasma lecithins. J Lipid Res 1978; 19: 495-500
• 34 Aviram M, Brook JG. Platelet interaction with high and low density lipoproteins. Atherosclerosis 1983; 46: 259-268
• 35 Bruckdorfer KR. The effects of plasma lipoproteins on platelet responsiveness and on platelet and vascular prostanoid synthesis. Prostaglandins Leukotrienes and Essential Fatty Acids Reviews 1989; 38: 247-254
• 36 Aviram M, Brook JG. Platelet activation by plasma lipoproteins. Prog Cardiovasc Dis 1987; XXX 61-72