Platelets and Thrombosis in the Development of Atherosclerosis and Its Complications

  • J. F. Mustard
  • M. A. Packham
  • R. L. Kinlough-Rathbone
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 102)


Platelets, blood flow, and endothelial injury are among the factors that determine the sites at which atherosclerosis develops. Smooth muscle cells in the vessel wall proliferate in response to endothelial injury;and in addition, endothelial injury plays a role in the development of mural and occlusive thrombi in major arteries and thereby contributes to the development of clinical complications of atherosclerosis. Factors that cause endothelial injury therefore appear to be involved both in the development of atherosclerosis and in its thromboembolic complications. Platelets appear to have a key role in both processes. In animal experiments, platelets that adhere to the subendothelium release a factor which stimulates smooth muscle cell proliferation. In addition, platelets that interact with the damaged vessel wall release factors that result in further accumulation of platelets at an injury site, and also accelerate the coagulation process. Recently it has been shown that repeated endothelial injury produces a surface on the vessel wall that is more thrombogenic than that produced by a single injury, and also results in the accumulation of proteoglycans in the vessel wall. Proteoglycans may trap lipoproteins and thus promote their accumulation at sites of endothelial injury. Injury itself leads to increased permeability of the vessel wall to plasma proteins.

Our increased understanding of the pathways involved in these processes has made it possible to examine the effects of smoking, diet, and drugs on the process. Smoking and diet may damage the endothelium, thereby influencing the development of atherosclerosis and its thromboembolic complications. There are three possible ways of detecting changes in the endothelium: 1) by measuring platelet survival, because in some animals damage to the endothelium is associated with shortened platelet survival; 2) by assaying materials released from the platelets into the circulation; and 3) by examining the blood for platelets that have undergone a release reaction. The detection of altered platelets could be used as an indicator of vessel injury or thromboembolism.

A number of drugs that modify platelet function are now being tested for their effects on these reactions. In animals, drugs such as aspirin or sulfinpyrazone do not appear to inhibit platelet adherence to the subendothelium or release of constituents from platelets adhering to collagen. Thus, it is not surprising that these drugs seem to have little effect on the proliferative response of the vessel wall to endothelial injury. Nevertheless, other effects of these drugs may be important in modifying the thromboembolic complications of vessel wall damage. The results of clinical trials now underway may indicate whether modifying platelet function can significantly influence the clinical complications of atherosclerosis.


Vessel Wall Endothelial Injury Smooth Muscle Cell Proliferation Platelet Factor Mural Thrombus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Wissler RW: Overview of problems of atherosclerosis. In CEREBROVASCULAR DISEASES, edited by Scheinberg P. New York, Raven Press, 1976, pp. 59–75.Google Scholar
  2. 2.
    Geer JC, Haust MD: Smooth muscle cells in atherosclerosis. In MONOGRAPHS ON ATHEROSCLEROSIS 2, edited by Pollak OJ, Simms HS, Kirk JE. New York, Karger, 1972.Google Scholar
  3. 3.
    Strong JB, McGill HC, Jr: The natural history of coronary atherosclerosis. AM J PATROL 40: 37–49, 1962.Google Scholar
  4. 4.
    Mustard JF, Packham MA: The role of blood and platelets in atherosclerosis and the complications of atherosclerosis. THROMB DIATH HAEMORRH 33: 444–456, 1975.PubMedGoogle Scholar
  5. 5.
    Taylor CB, Hass GM, Ho K-J: The role of repair of arterial injury and degeneration in arteriosclerosis. In LE RÔLE DE LA PAROI ARTÊRIELLE DANS L’ATHEROGÉNESES. Colloques Internationaux du Centre National de la Recherche Scientifique No. 169, 853–872, Paris, 1968.Google Scholar
  6. 6.
    Moore S: Thromboatherosclerosis in normolipemic rabbits. A result of continued endothelial damage. LAB INVEST 29: 478487, 1973.Google Scholar
  7. 7.
    Alonso DR, Starek PK, Minick CR: Studies on the pathogenesis of atheroarteriosclerosis induced in rabbit cardiac allografts by the synergy of graft rejection and hypercholesterolemia. AM J PATHOL 87: 415–442, 1977.PubMedGoogle Scholar
  8. 8.
    Packham MA, Rowsell HC, J$rgensen L, Mustard JF: Localized protein accumulation in the wall of the aorta. EXP MOL PATHOL 7: 214–232, 1967.PubMedCrossRefGoogle Scholar
  9. 9.
    McGill HC, Geer JC, Holman RL: Sites of vascular vulnerability in dogs demonstrated by Evans blue. ARCH PATROL 64: 303–311, 1957.Google Scholar
  10. 10.
    J$rgensen L, Packham MA, Rowsell HC, Buchanan MR, Mustard JF: Focal aortic injury caused by cannulation: Increased plasma protein accumulation and thrombosis. ACTA PATROL MICROBIOL SCAND [A] 82: 637–647, 1974.Google Scholar
  11. 11.
    Baumgartner HR, Muggli R, Tschopp TB, Turitto VT: Platelet adhesion, release and aggregation in flowing blood: Effects of surface properties and platelet function. THRONE HAEMOSTAS 35: 124–138, 1976.Google Scholar
  12. 12.
    Rutherford RB, Ross R: Platelet factors stimulate fibroblasts and smooth muscle cells quiescent in plasma serum to proliferate. J CELL BIOL 69: 196–203, 1976.PubMedCrossRefGoogle Scholar
  13. 13.
    Ihnatowycz IO, Cazenave J-P, Moore S, Mustard JF: Platelet-derived growth factor production during the platelet release reaction independent of the arachidonate pathway. THROMB HAEMOSTAS 38: 229, 1977.Google Scholar
  14. 14.
    Stemerman MB, Ross R: Experimental arteriosclerosis. I. Fibrous plaque formation in primates, an electron microscope study. J EXP MED 136: 769–789, 1972.PubMedCrossRefGoogle Scholar
  15. 15.
    Ross R, Glomset JA: Atherosclerosis and the arterial smooth muscle cell. Proliferation of smooth muscle is a key event in the genesis of the lesions of atherosclerosis. SCIENCE 180: 1332–1339, 1973.PubMedCrossRefGoogle Scholar
  16. 16.
    Moore S, Friedman RJ, Singal DP, Gauldie J, Blajchman MA, Roberts RS: Inhibition of injury-induced thromboatherosclerotic lesions by anti-platelet serum in rabbits. THROMB HAEMOSTAS 35: 70–81, 1976.Google Scholar
  17. 17.
    Friedman RJ, Stemerman MB, Wenz B, Moore S, Gauldie J, Gent M, Tiell ML, Spaet TH: The effect of thrombocytopenia on experimental arteriosclerotic lesion formation in rabbits: I. Smooth muscle cell proliferation and re-endothelialization. J CLIN INVEST 60: 1191–1201, 1977.PubMedCrossRefGoogle Scholar
  18. 18.
    Ross R: Personal communication.Google Scholar
  19. 20.
    Baumgartner HR, Muggii R: Adhesion and aggregation: Morphological demonstration and quantitation in vivo and in vitro. In PLATELETS IN BIOLOGY AND PATHOLOGY, edited by Gordon JL, Elsevier/North Holland Biomedical Press, 1976, pp. 23–60.Google Scholar
  20. 20.
    Groves HM, Kinlough-Rathbone RL, Richardson M, Mustard JF: Platelet survival and interaction with damaged rabbit aorta. BLOOD 50 (Suppl 1): 241, 1977.Google Scholar
  21. 21.
    Friedman RJ: Personal communication.Google Scholar
  22. 22.
    Stemerman MB: Thrombogenesis of the rabbit arterial plaque. AM J PATHOL 73: 7–26, 1973.PubMedGoogle Scholar
  23. 23.
    Ross R, Harker L: Hyperlipidemia and atherosclerosis. Chronic hyperlipidemia initiates and maintains lesions by endothelial cell desquamation and lipid accumulation. SCIENCE 193: 1094 1100, 1976.Google Scholar
  24. 24.
    Meuleman DG, Buchanan MR, Giles AR, Hirsh J: Normalization of platelet survival in an experimental model after platelet exposure to thrombin in vitro or to ADP in vivo. THRONE HAEMOSTAS 38: 124, 1977.Google Scholar
  25. 25.
    Somer JB, Schwartz CJ: Focal 3H-cholesterol uptake in the pig aorta. ATHEROSCLEROSIS 13: 293–304, 1971.PubMedCrossRefGoogle Scholar
  26. 26.
    Ross R, Glomset JA: The pathogenesis of atherosclerosis. N ENGL J MED 7: 369–377, 1976.CrossRefGoogle Scholar
  27. 27.
    Goldstein JL, Brown MS: Lipoprotein receptors, cholesterol metabolism and atherosclerosis. ARCH PATHOL 99: 181–184, 1975.PubMedGoogle Scholar
  28. 28.
    Goldstein JL, Anderson RGW, Buja LM, Basu SK, Brown MS: Overloading human aortic smooth muscle cells with low density lipoprotein-cholesteryl esters reproduces features of atherosclerosis in vitro. J CLIN INVEST 59: 1196–1202, 1977.PubMedCrossRefGoogle Scholar
  29. 29.
    Iverius P-H: Possible role of glycosaminoglycans in the genesis of atherosclerosis. In ATHEROGENESIS: INITIATING FACTORS. Ciba Foundation Symposium No. 12 ( New Series). Amsterdam and New York, Associated Scientific Publishers, 1973, pp. 185–196.Google Scholar
  30. 30.
    Minick CR, Alonso DR, Litrenta M, Silane MF, Stemerman MB: Regenerated endothelium and intimal proteoglycan accumulation. CIRCULATION 56: 27, 1977.Google Scholar
  31. 31.
    Smith EB: The relationship between plasma and tissue lipids in human atherosclerosis. ADV LIPID RES 12: 1–49, 1974.PubMedGoogle Scholar
  32. 32.
    Caplan BA, Gerrity RG, Schwartz CJ: Endothelial cell morphology in focal areas of in vivo Evans blue uptake in the young pig aorta. I. Quantitative light microscopic findings. EXP MOL PATHOL 21: 102–117, 1974.PubMedCrossRefGoogle Scholar
  33. 33.
    Gutstein WH, Farrell GA, Armellini C: Blood flow disturbance and endothelial cell injury in preatherosclerotic swine. LAB INVEST 29: 134–149, 1973.PubMedGoogle Scholar
  34. 34.
    J$rgensen L, Packham MA, Rowsell HC, Mustard JF: Deposition of formed elements of blood on the intima and signs of intimai injury in the aorta of rabbit, pig and man. LAB INVEST 27: 341–350, 1972.Google Scholar
  35. 35.
    Wright HP: Mitosis patterns in aortic endothelium. ATHEROSCLEROSIS 15: 93–100, 1972.PubMedCrossRefGoogle Scholar
  36. 36.
    Caplan BA, Schwartz CJ: Increased endothelial cell turnover in areas of in vivo Evans blue uptake in the pig aorta. ATHEROSCLEROSIS 17: 401–417, 1973.PubMedCrossRefGoogle Scholar
  37. 37.
    Stary HC, McMillan GC: Kinetics of cellular proliferation in experimental atherosclerosis. Radioautography with grain counts in cholesterol-fed rabbits. ARCH PATHOL 89:173–183, 19 70.Google Scholar
  38. 38.
    Fry DL: Response of the arterial wall to certain physical factors. In ATHEROGENESIS: INITIATING FACTORS Ciba Foundation Symposium 12 ( New Series). Amsterdam and New York, Associated Scientific Publishers, 1973, pp. 93–125.Google Scholar
  39. 39.
    Nerem RM: Vibration-induced arterial shear stresses. LANCET 1: 78, 1971.PubMedCrossRefGoogle Scholar
  40. 40.
    Mustard JF, Moore S, Packham MA, Kinlough-Rathbone RL: Platelets, thrombosis and atherosclerosis. In PROCEEDINGS OF THE FIRST INTERNATIONAL ATHEROSCLEROSIS CONFERENCE. Prog Biochem Pharmacol.Basel, Karger (In Press).Google Scholar
  41. 41.
    Kniker WT, Cochrane CG: The localization of circulating immune complexes in experimental serum sickness. The role of vaso-active amines and hydrodynamic forces. J EXP MED 127: 119–135, 1968.PubMedCrossRefGoogle Scholar
  42. 42.
    Friedman RJ, Moore S, Singal DP: Repeated endothelial injury and induction of atherosclerosis in normolipemic rabbits by human serum. LAB INVEST 30: 404–415, 1975.Google Scholar
  43. 43.
    Moore S, Ihnatowycz IO: Vessel injury and atherosclerosis. In THROMBOSIS: ANIMAL AND HUMAN MODELS, edited by Day HJ, Molony BA, Nishizawa EE, Rynbrandt RH. New York, Plenum Publishing Corp., 1978, pp. 145–163.Google Scholar
  44. 44.
    Minick CR, Stemerman MB, Insull W, Jr.: Effect of regenerated endothelium on lipid accumulation in the arterial wall. PROC NATL ACAD SCI USA 74: 1724–1728, 1977.Google Scholar
  45. 45.
    Bjorkerud S, Bondjers G: Repair responses and tissue lipid after experimental injury to the artery. ANN NY ACAD SCI 275: 180–198, 1976.PubMedCrossRefGoogle Scholar
  46. 46.
    Nam SC, Lee WM, Jarmolych J, Lee KT, Thomas WA: Rapid production of advanced atherosclerosis in swine by a combination of endothelial injury and cholesterol feeding. EXP MOL PATHOL 18: 369–379, 1973.PubMedCrossRefGoogle Scholar
  47. 47.
    Clowes AW, Ryan GB, Breslow JL, Karnovsky MJ: Absence of enhanced intimal thickening in the response of the carotid artery wall to endothelial injury in hypercholesterolemic rats. LAB INVEST 35: 6–17, 1976.PubMedGoogle Scholar
  48. 48.
    Minick CR, Murphy GE: Experimental induction of atheroarteriosclerosis by the synergy of allergic injury to arteries and lipid-rich diet. AM J PATHOL 73: 265–300, 1973.PubMedGoogle Scholar
  49. 49.
    Mustard JF: Function of blood platelets and their role in thrombosis. TRANS AM CLIN CLIMATOL ASSOC 87: 104–127, 1976.PubMedGoogle Scholar
  50. 50.
    Leonard EF, Grabowski EF, Turitto VT: The role of convection and diffusion on platelet adhesion and aggregation. ANN NY ACAD SCI 201: 329–342, 1972.PubMedCrossRefGoogle Scholar
  51. 51.
    Holmsen H: Biochemistry of the platelet release reaction. In BIOCHEMISTRY AND PHARMACOLOGY OF PLATELETS, Ciba Foundation Symposium 35 (New Series). New York, Elsevier–Excerpta Medica–North Holland, 1975, pp. 175–205.Google Scholar
  52. 52.
    Baumgartner HR: Platelet interaction with collagen fibrils in flowing blood. I. Reaction of human platelets with a chymotrypsin-digested subendothelium. THROMB HAEMOSTAS 37: 1–16, 1977.Google Scholar
  53. 53.
    Smith JB, Ingerman CM, Kocsis J, Silver MJ: Formation of an intermediate in prostaglandin biosynthesis and its association with the platelet release reaction. J CLIN INVEST 53: 1468 1472, 1974.Google Scholar
  54. 54.
    Smith JB, Ingerman CM, Silver NJ: Effects of arachidonic acid and some of its metabolites on platelets. In PROSTAGLANDINS IN HEMATOLOGY, edited by Silver NJ, Smith JB, Kocsis JJ. New York, Spectrum Publications Inc., 1977, pp. 277–292.Google Scholar
  55. 55.
    Svensson J, Hamberg M, Samuelsson B: On the formation and effects of thromboxane A2 in human platelets. ACTA PHYSIOL SCAND 98: 285–294, 1976.PubMedCrossRefGoogle Scholar
  56. 56.
    Niewiarowski S, Stuart RK, Thomas DP: Activation of intra-vascular coagulation by collagen. PROC SOC EXP BIOL MED 123: 196–200, 1966.PubMedGoogle Scholar
  57. 57.
    Nemerson Y, Pitlick FA: The tissue factor pathway of blood coagulation. In PROGRESS IN HEMOSTASIS AND THROMBOSIS Vol. 1, edited by Spaet TH, New York, Grune and Stratton, Inc., 1972, pp. 1–37.Google Scholar
  58. 58.
    Walsh PN: The role of platelets in the contact phase of blood coagulation. BR J HAEMATOL 22: 237–254, 1972.PubMedCrossRefGoogle Scholar
  59. 59.
    Joist JH, Dolezel G, Lloyd JV, Kinlough-Rathbone RL, Mustard JF: Platelet factor-3 availability and the platelet release reaction. J LAB CLIN MED 84: 474–482, 1974.Google Scholar
  60. 60.
    Kinlough-Rathbone RL, Packham MA, Reimers H-J, Cazenave J-P, Mustard JF: Mechanisms of platelet shape change, aggregation and release induced by collagen, thrombin or A23,187. J LAB CLIN MED 90: 707–719, 1977.PubMedGoogle Scholar
  61. 61.
    Bills TK, Smith JB, Silver MJ: Selective release of arachidonic acid from the phospholipids of human platelets in response to thrombin. J CLIN INVEST 60: 1–6, 1977.PubMedCrossRefGoogle Scholar
  62. 62.
    Niewiarowski S, Regoeczi E, Stewart GJ, Senyi A, Mustard JF: Platelet interaction with polymerizing fibrin. J CLIN INVEST 51: 685–700, 1972.PubMedCrossRefGoogle Scholar
  63. 63.
    Mustard JF, Rowsell HC, Murphy EA: Platelet economy (platelet survival and turnover). BR J HAEMATOL 12: 1–24, 1966.PubMedCrossRefGoogle Scholar
  64. 64.
    Reimers H-J, Cazenave J-P, Senyi AF, Hirsh J, Kinlough-Rathbone RL, Packham MA, Mustard JF: In vitro and in vivo functions of thrombin-treated platelets. THROMB HAEMOSTAS 35: 151–166, 1976.Google Scholar
  65. 65.
    Turner SR, Tainer JA, Lynn WS: Biogenesis of chemotactic molecules by the arachidonate lipoxygenase system of platelets. NATURE 257: 680–681, 1975.PubMedCrossRefGoogle Scholar
  66. 66.
    Weksler BB, Coupai CE: Platelet-dependent generation of chemotactic activity in serum. J EXP MED 137: 1419–1430, 1973.PubMedCrossRefGoogle Scholar
  67. 67.
    Nilsson IM, Pandolfi M: Fibrinolytic response of the vascular wall. THROMB DIATH HAEMORRH (Suppl) 40: 231–242, 1970.Google Scholar
  68. 68.
    Kaplan AP, Meier HL, Mandle R, Jr.: The Hageman factor dependent pathways of coagulation, fibrinolysis, and kiningeneration. SEMIN THROMB HEMOSTAS 3: 1–26, 1976.Google Scholar
  69. 69.
    Yecies LD, Kaplan AP: The activation of plasminogen by the Hageman factor dependent plasminogen activator. FED PROC 35: 731, 1976.Google Scholar
  70. 70.
    Stein PD, Sabbah HN: Measured turbulence and its effect on thrombus formation. CIRC RES 35: 608–614, 1974.PubMedCrossRefGoogle Scholar
  71. 71.
    Murphy EA, Rowsell HC, Downie HG, Robinson GA, Mustard JF: Encrustation and atherosclerosis: The analogy between early in vivo lesions and deposits which occur in extracorporeal circulations. CAN MED ASSOC J 87: 259–274, 1962.PubMedGoogle Scholar
  72. 72.
    Goldsmith HL: The flow of model particles and blood cells and its relation to thrombogenesis. In PROGRESS IN HEMOSTASIS AND THROMBOSIS, Vol. 1, edited by Spaet TH. New York, Grune and Stratton, 1972, pp. 97–139.Google Scholar
  73. 73.
    Goldsmith HL: Bloow flow and thrombosis. THROMB DIATH HAEMORRH 32: 35–48, 1974.PubMedGoogle Scholar
  74. 74.
    Fulton GP, Akers RP, Lutz BR: White thrombo-embolism and vascular fragility in hamster cheek pouch after anticoagulants. BLOOD 8: 140–152, 1953.PubMedGoogle Scholar
  75. 75.
    Baumgartner HR: The role of blood flow in platelet adhesion, fibrin deposition, and formation of mural thrombi. MICROVASC RES 5: 167–179, 1973.PubMedCrossRefGoogle Scholar
  76. 76.
    Niewiarowski S, Lowery CT, Hawiger J, Millman M, Timmons S: Immunoassay of human platelet factor 4 (PF4, antiheparin factor) by radial immunodiffusion. J LAB CLIN MED 87: 720–733, 1976.PubMedGoogle Scholar
  77. 77.
    Kaplan KL, Drillings M, Nossel HL, Lesnik G: Radioimmunoassay of S-thromboglobulin (BTG) and platelet factor 4 (PF4). In THE SIGNIFICANCE OF PLATELET FUNCTION TESTS IN THE EVALUATION OF HEMOSTATIC AND THROMBOTIC TENDENCIES, WORKSHOP ON PLATELETS Philadelphia, 1976, edited by Day HJ, Zucker MB, Holmsen H. US Govt. Printing Office (In Press).Google Scholar
  78. 78.
    Ludlam CA, Cash JD: Studies on the liberation of S-thromboglobulin from human platelets in vitro. BR J HAEMATOL 33: 239247, 1976.Google Scholar
  79. 79.
    Cieslar P, Greenberg JP, Packham MA, Kinlough-Rathbone RL, Mustard JF: Separation of degranulated platelets from normal platelets. THROMB. HAEMOSTAS 38: 122, 1977.Google Scholar
  80. 80.
    Zahavi J, Marder VJ: Acquired “storage pool disease” of platelets associated with circulating anti-platelet antibodies. AM J MED 56: 883–890, 1974.PubMedCrossRefGoogle Scholar
  81. 81.
    Duguid JB: Thrombosis as a factor in the pathogenesis of aortic atherosclerosis. J PATH BACT 60: 57–61, 1948.PubMedCrossRefGoogle Scholar
  82. 82.
    Hand RA, Chandler AB: Atherosclerotic metamorphosis of autologous pulmonary thromboemboli in the rabbit. AM J PATHOL 40: 469–486, 1962.PubMedGoogle Scholar
  83. 83.
    Woolf N, Bradley JWP, Crawford T, Carstairs KC: Experimental mural thrombi in the pig aorta. The early natural history. BR J EXP PATHOL 49: 257–264, 1968.PubMedGoogle Scholar
  84. 84.
    Mitchell JRA, Schwartz CJ: The relationship between myocardial lesions and coronary artery disease. II. A selected group of patients with massive cardiac necrosis or scarring. BR HEART J 25: 1–24, 1963.PubMedCrossRefGoogle Scholar
  85. 85.
    Chandler AB, Chapman I, Erhardt LR, Roberts WC, Schwartz CJ, Sinapius D, Spain DM, Sherry S, Ness PM, Simon TL: Coronary thrombosis in myocardial infarction. Report of a workshop on the role of coronary thrombosis in the pathogenesis of acute myocardial infarction. AM J CARDIOL 34: 823–833, 1974.PubMedCrossRefGoogle Scholar
  86. 86.
    Erhardt LR, Lundman T, Mellstedt H: Incorporation of 125I-labelled fibrinogen into coronary arterial thrombi in acute myocardial infarction in man. LANCET 1: 387–390, 1973.PubMedCrossRefGoogle Scholar
  87. 87.
    Cade JF, Hirsh J, Regoeczi E, Gent M, Buchanan MR, Hynes DM: Resolution of experimental pulmonary emboli with heparin and streptokinase in different dosage regimens. J CLIN INVEST 54: 782–791, 1974.PubMedCrossRefGoogle Scholar
  88. 88.
    Coleman RE, Harwig SSL, Harwig JF, Siegel BA, Welch MJ: Fibrinogen uptake by thrombi: Effect of thrombus age. J NUCL MED 16: 370–373, 1975.PubMedGoogle Scholar
  89. 89.
    Moore S, Belbeck LW, Evans G: Myocardial lesions associated with partial, compared to complete, thrombotic occlusion of a coronary artery. CIRCULATION 54 (Suppl II): 202, 1976.Google Scholar
  90. 90.
    Haerem JW: Myocardial lesions in sudden, unexpected coronary death. AM HEART J 90: 562–568, 1975.PubMedCrossRefGoogle Scholar
  91. 91.
    Haerem JW: Platelet aggregates in intramyocardial vessels of patients dying suddenly and unexpectedly of coronary artery disease. ATHEROSCLEROSIS 15: 199–213, 1972.PubMedCrossRefGoogle Scholar
  92. 92.
    Haerem JW: Mural platelet microthrombi and major acute lesions of main epicardial arteries in sudden coronary death. ATHEROSCLEROSIS 19: 529–541, 1974.PubMedCrossRefGoogle Scholar
  93. 93.
    Renaud S, Kinlough-Rathbone RL, Mustard JF: Relationship be- tween platelet aggregation and the thrombotic tendency in rats fed hyperlipemic diets. LAB INVEST 22: 339–343, 1970.PubMedGoogle Scholar
  94. 94.
    Hornstra G: Dietary fats and arterial thrombosis. HAEMOSTASIS 2: 21–52, 1973–74.Google Scholar
  95. 95.
    Hornstra G, Chait A, Karvonen MJ, Lewis B, Turpeinen 0, Vergroesen AJ: Influence of dietary fat on platelet function in men. LANCET 1: 1155–1157, 1973.PubMedCrossRefGoogle Scholar
  96. 96.
    Fleischman AI, Justice D, Bierenbaum ML, Stier A, Sullivan A: Beneficial effect of increased dietary linoleate upon in vivo platelet function in man. J NUTR 105: 1286–1290, 1975.PubMedGoogle Scholar
  97. 97.
    Seyberth HW, Oelz 0, Kennedy T, Sweetman BJ, Danon A, Frölich JC, Heimberg M, Oates JA: Increased arachidonate in lipids after administration to man: Effects on prostaglandin biosynthesis. CLIN PHARMACOL THER 18: 521–529, 1975.PubMedGoogle Scholar
  98. 98.
    Kernoff PBA, Davies JA, McNicol GP, Willis AL, Stone KJ: The antithrombotic potential of dihomo-y-linolenic acid. THROMB HAEMOSTAS 38: 194, 1977.Google Scholar
  99. 99.
    Mustard JF, Murphy EA: Effect of different dietary fats on blood coagulation, platelet economy, and blood lipids. BR MED J 1: 1651–1655, 1962.PubMedCrossRefGoogle Scholar
  100. 100.
    Jonker JJ, Veen MR, Schopman W, den Ottolander GJG: Platelet survival time in angina pectoris and hyperlipoproteinemia. THRONE RES 4 (Suppl 1): 65–67, 1974.CrossRefGoogle Scholar
  101. 101.
    Kim WM, Merskey C, Deming QB, Adel HN, Wolinsky H, Clarkson TB, Lofland HB: Hyperlipidemia, hypercoagulability and accelerated thrombosis: Studies in congenitally hyperlipidemic rats and in rats and monkeys with induced hyperlipidemia. BLOOD 47: 275–286, 1976.PubMedGoogle Scholar
  102. 102.
    Florentin RA, Nam SC, Lee KT, Thomas WA: Increased 3H-thymidine incorporation into endothelial cells of swine fed cholesterol for 3 days. EXP MOL PATROL 10: 250–255, 1969.CrossRefGoogle Scholar
  103. 103.
    Reimers HJ, Packham MA, Kinlough-Rathbone RL, Mustard JF: Effect of repeated treatment of rabbit platelets with low concentrations of thrombin on their function, metabolism and survival. BR J HARMATOL 25: 675–689, 1973.CrossRefGoogle Scholar
  104. 104.
    Dougherty JH, Jr., Levy DE, Weksler BB: Platelet activation in acute cerebral ischaemia. LANCET 1: 821–824, 1977.PubMedCrossRefGoogle Scholar
  105. 105.
    Wu KK, Hoak JC: Spontaneous platelet aggregation in arterial insufficiency: Mechanisms and implications. THROMB HAEMOSTAS 35: 702–711, 1976.Google Scholar
  106. 106.
    Hornstra G, ten Hoor F: The filtragometer: A new device for measuring platelet aggregation in venous blood of man. THROMB DIATH HAEMORRH 34: 531–544, 1975.PubMedGoogle Scholar
  107. 107.
    Packham MA, Mustard JF: Methods for detection of hypersensitive platelets. Working Party VIth Cong. of Int. Soc. on Thromb. and Haemostas. Philadelphia, June 1977. THROMB HAEMOSTAS (In preparation).Google Scholar
  108. 108.
    Packham MA, Mustard JF: Platelet aggregation, relevance to thrombotic tendencies. In THROMBOSIS: ANIMAL AND HUMAN MODELS, edited by Day HJ, Molony BA, Nishizawa EE, Rynbrandt RH. New York, Plenum Publishing Corp., 1978, pp. 51–72.Google Scholar
  109. 109.
    Greenberg JP, Rand ML, Packham MA: Relation of platelet age to platelet sialic acid. FED PROC 36: 453, 1977.Google Scholar
  110. 110.
    Mustard JF, Murphy EA: Effect of smoking on blood coagulation and platelet survival in man. BR MED J 1: 846–849, 1963.PubMedCrossRefGoogle Scholar
  111. 111.
    Mustard JF, Packham MA, Kinlough-Rathbone RL: Platelet survival. In THE SIGNIFICANCE OF PLATELET FUNCTION TESTS IN THE EVALUATION OF HEMOSTATIC AND THROMBOTIC TENDENCIES, WORKSHOP ON PLATELETS, Philadelphia, 1976, edited by Day HJ, Zucker MB, Holmsen H. US Govt. Printing Office (In Press).Google Scholar
  112. 112.
    Steele PP, Weily HS, Davies H, Genton E: Platelet function studies in coronary artery disease. CIRCULATION 48: 1194–1200, 1973.PubMedCrossRefGoogle Scholar
  113. 113.
    Harker LA, Slichter SJ: Arterial and venous thromboembolism: Kinetic characterization and evaluation of therapy. THROMB DIATH HAEMORRH 31: 188–203, 1974.PubMedGoogle Scholar
  114. 114.
    Greenberg J, Packham MA, Cazenave J-P, Reimers H-J, Mustard JF: Effects on platelet function of removal of platelet sialic acid by neuraminidase. LAB INVEST 32: 476–484, 1975.PubMedGoogle Scholar
  115. 115.
    Scott S, Reimers H-J, Chernesky MA, Greenberg JP, KinloughRathbone RL, Packham MA, Mustard JF: The effect of viruses on platelet aggregation and platelet survival in rabbits. (Submitted for publication)Google Scholar
  116. 116.
    Roth GJ, Majerus PW: The mechanism of the effect of aspirin on human platelets. I. Acetylation of a particulate fraction protein. J CLIN INVEST 56: 624–632, 1975.PubMedCrossRefGoogle Scholar
  117. 117.
    Cazenave J-P, Packham MA, Kinlough-Rathbone RL, Mustard JF: Platelet adherence to the vessel wall and to collagen-coated surfaces. In THROMBOSIS: ANIMAL AND HUMAN MODELS, edited by Day HJ, Molony BA, Nishizawa EE, Rynbrandt RH. New York, Plenum Publishing Corp., 1978, pp. 31–49.Google Scholar
  118. 118.
    Baumgartner HR, Studer A: Platelet factors and the proliferation of vascular smooth muscle cells. Workshop on Thrombosis and Atherosclerosis IVth International Symposium on Atherosclerosis, Tokyo, 1976.Google Scholar
  119. 119.
    Harker LA, Slichter SJ: Platelet and fibrinogen consumption in man. N ENGL J MED 287: 999–1005, 1972.PubMedCrossRefGoogle Scholar
  120. 120.
    Ali M, Mcdonald JWD: Effects of sulfinpyrazone on platelet prostaglandin synthesis and platelet release of serotonin. J LAB CLIN MED 89: 868–875, 1977.PubMedGoogle Scholar
  121. 121.
    Smythe HA, Ogryzlo MA, Murphy EA, Mustard JF: The effect of sulfinpyrazone (Anturan) on platelet economy and blood coagulation in man. CAN MED ASSOC J 92: 818–821, 1965.PubMedGoogle Scholar
  122. 122.
    Steele P, Battock D, Genton E: Effects of clofibrate and sulfinpyrazone on platelet survival time in coronary artery disease. CIRCULATION 52: 473–476, 1975.PubMedCrossRefGoogle Scholar
  123. 123.
    Turpie AGG, Chernesky MA, Larke RPB, Moore S, Regoeczi E, Mustard JF: Thrombocytopenia and vasculitis induced in rabbits by Newcastle disease virus. Proc. III Congr. Int. Soc. Thromb. Haemostas., Washington, 1972, p. 344 (Abstract).Google Scholar
  124. 124.
    Mustard JF, Packham MA: Platelets, thrombosis and drugs. DRUGS 9: 19–76, 1975.PubMedCrossRefGoogle Scholar
  125. 125.
    Harker LA, Ross R, Slichter SJ, Scott CR: Homocystine-induced arteriosclerosis. The role of endothelial cell injury and platelet response in its genesis. J CLIN INVEST 58: 731–741, 1976.PubMedCrossRefGoogle Scholar
  126. 126.
    Fields WS, Lemak NA, Frankowski RF, Hardy RJ: Controlled trial of aspirin in cerebral ischaemia. STROKE 8: 301–316, 1977.PubMedCrossRefGoogle Scholar
  127. 127.
    Sullivan JM, Harken DE, Gorlin R: Pharmacologie control of thromboembolic complications of cardiac-valve replacement. N ENGL J MED 284: 1391–1394, 1971.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1978

Authors and Affiliations

  • J. F. Mustard
    • 1
    • 2
  • M. A. Packham
    • 1
    • 2
  • R. L. Kinlough-Rathbone
    • 1
    • 2
  1. 1.Department of PathologyMcMaster UniversityHamiltonCanada
  2. 2.Department of BiochemistryUniversity of TorontoTorontoCanada

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