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Aspirin, Heparin, and New Antithrombotic Drugs as Adjuncts to Thrombolytic Therapy for Acute Myocaradial Infarction

  • Hans J. Rapold
Part of the Developments in Cardiovascular Medicine book series (DICM, volume 193)

Abstract

Early intravenous thrombolysis has been firmly established as the therapy of choice for acute myocardial infarction. There is room, however, for an important improvement: Between 15% and 50% of coronary thrombi cannot be lysed with the currently available drugs, 10-25% of successfully recanalized vessels reocclude, and 0.5-1% of the treated patients suffer an intracerebral hemorrhage. Dispute over the thrombolytic agent of choice, including pharmacoeconomic aspects, has continued despite megatrials involving over 100,000 patients [1, 2, 3, 4, 5]. While the overall benefit of thrombolysic therapy has been confirmed, questions remain with respect to optimal adjuvant antithrombotic treatment, the validity of surrogate endpoints, and the mechanism through which thrombolysis translates into clinical benefit [6, 7, 8, 9, 10].

Keywords

Acute Myocardial Infarction Thrombolytic Therapy Tissue Factor Pathway Inhibitor Antithrombotic Drug Coronary Thrombolysis 
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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References

  1. 1.
    Gruppo Italiano per lo Studio della Streptokinasi nell Infarto Miocardico (GISSI). Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet 1:397, 1986.Google Scholar
  2. 2.
    IS1S-2 (Second International Study of Infarct Survival) Collaborative Group. Randomized trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 2:349, 1988.Google Scholar
  3. 3.
    The International Study Group. Inhospital mortality and clinical course of 20,891 patients with suspected acute myocardial infarction randomised between alteplase and streptokinase with or without heparin. Lancet 1:71, 1990.Google Scholar
  4. 4.
    Gruppo Italiano per lo Studio della Streptokinasi nell Infarto Miocardico (GISSI). A factorial randomized trial of alteplase versus streptokinase and heparin versus no heparin among 12,490 patients with acute myocardial infarction. Lancet 2:336, 1990.Google Scholar
  5. 5.
    International Study of Infarct Survival. Collaborative Group. ISIS-3: A randomized comparison of streptokinase vs. tissue plasminogen activator vs. anistreplase and of aspirin plus heparin vs. aspirin alone among 41,299 cases of suspected myocardial infarction. Lancet 1:339, 1992.Google Scholar
  6. 6.
    Collen D. Coronary chrombolysis: Streptokinase or recombinant tissue-type plasminogen activator? Ann Intern Med 112:529, 1990.PubMedGoogle Scholar
  7. 7.
    White D. GISSI-2 and the heparin controversy. Lancet 2:297, 1990.Google Scholar
  8. 8.
    Sherry S, Marder V. Streptokinase and recombinant tissue-type plasminogen activator (alteplase) are equally effective in treating acute myocardial infarction. Ann Intern Med 114:417, 1991.PubMedGoogle Scholar
  9. 9.
    Sobel BE, Hirsh J. Principles and practice of coronary thrombolysis and conjunctive treatment. Am J Cardiol 68:382, 1991.PubMedGoogle Scholar
  10. 10.
    Collen D. Thrombolysis: Is there a future for thrombolytic therapy in acute myocardial infarction? Curr Opin Cardiol 6:552, 1991.Google Scholar
  11. 11.
    The TIMI Study Group. The thrombolysis in myocardial infarction (TIMI) trial. Phase I findings. N Engl J Med 312:932, 1985.Google Scholar
  12. 12.
    Verstraete M, Bernard R, Bory M, for the European Co-operative Study Group. Randomized trial of intravenous recombinant tissue-type plasminogen activator versus intravenous streptokinase in acute myocardial infarction. Lancet 1:842, 1985.PubMedGoogle Scholar
  13. 13.
    Lamas GA, Flaker GC, Mitchell G, Smith S, Gersh BJ, Wun CC, Moye L, Rouleau JL, Rutherford JD, Pfeffer, MA, Braunwald E for the SAVE Investigators. Effect of infarct artery patency on prognosis after acute myocardial infarction. Circulation 92:1101, 1995.PubMedGoogle Scholar
  14. 14.
    Ohman EM, Califf RM, Topol EJ, Candela R, Abbottsmith C, Ellis S, Sigmon KN, Kereiakes D, George B, Stack R. Consequences of reocclusion after successful reperfusion therapy in acute myocardial infarction. Circulation 82:781, 1990.PubMedGoogle Scholar
  15. 15.
    Rapold HJ, Kuemmerli H, Weiss M, Baur H, Haeberli A. Monitoring of fibrin generation during thrombolytic therapy of acute myocardial infarction with recombinant tissue-type plasminogen activator. Circulation 79:980, 1989.PubMedGoogle Scholar
  16. 16.
    Rapold HJ. Promotion of thrombin activity by thrombolytic therapy without simultaneous anticoagulation. Lancet 1:481, 1990.Google Scholar
  17. 17.
    Rapold HJ, Lu HR, Wu Z, Nijs H, Collen D. Requirement of heparin for arterial and venous thrombolysis with recombinant tissue-type plasminogen activator. Blood 77:1020, 1991.PubMedGoogle Scholar
  18. 18.
    The GUSTO Investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med 329:673, 1993.Google Scholar
  19. 19.
    Gold HK. Conjunctive antithrombotic and thrombolytic therapy for coronary artery occlusion. N Engl J Med 323:1483, 1990.PubMedCrossRefGoogle Scholar
  20. 20.
    Rapold HJ, Collen D. Conjunctive antithrombotic and thrombolytic therapy for acute myocardial infarction. Fibrinolysis 6:137, 1992.Google Scholar
  21. 21.
    Sobel BE (ed). Conjunctive therapy for thrombolysis. Review in depth. Cor Art Dis 3:987, 1992.Google Scholar
  22. 22.
    International Society and Federation of Cardiology and World Health Organization Task Force on Myocardial Reperfusion. Reperfusion in acute myocardial infarction. Circulation 90:2091, 1994.Google Scholar
  23. 23.
    Folts JD, Criwell EB, Row GG. Platelet aggregation in partially obstructed vessels and its elimination with aspirin. Circulation 54:365, 1976.PubMedGoogle Scholar
  24. 24.
    Golino P, Ashton JH, McNatt J, Glas-Greenwalt P, Yao SK, O’Brien RA, Buja LM, Willerson JT. Simultaneous administration of thromboxane A2 and serotonin S2 receptor antagonists markedly enhances thrombolysis and prevents or delays reocclusion after tissue-type plasminogen activator in a canine model of coronary thrombosis. Circulation 79:911, 1989.PubMedGoogle Scholar
  25. 25.
    Michelson JK, Simpson PJ, Gallas MT, Lucchesi BR. Thromboxane synthase inhibition with CGS13080 improves coronary blood flow after streptokinaseinduce thrombolysis. Am Heart J 113:1345, 1987.Google Scholar
  26. 26.
    Shebuski RJ, Smith JM Jr, Storer BL, Granett JR, Bugelski PJ. Influence of selective endoperoxide/thromboxane A2 receptor antagonism with sulotroban on lysis time and reocclusion rate after tissue plasminogen activator-induced coronary thrombolysis in the drug. J Pharmacol Exp Ther 246:790, 1988.PubMedGoogle Scholar
  27. 27.
    Kopia GA, Kopaciewicz LJ, Ohlstein EH, Horohonich S, Storer BL, Shebuski RJ. Combination of the thromboxane receptor antagonist, sulotroban, with streptokinase: Demonstration of thrombolytic synergy. J Pharmacol Exp Ther 250:887, 1989.PubMedGoogle Scholar
  28. 28.
    Golino P, Rosolowsky M, Sheng-Kun Yao, Buja LM, Willerson JT. Blockade of TxB2, synthase enhances thrombolysis and prevents reocclusion more efficiently than either intervention alone. Circulation 80:(Suppl II):II113, 1989.Google Scholar
  29. 29.
    Jang IK, Gold HK, Ziskind AA, Leinbach RC, Fallon JT, Collen D. Prevention of platelet-rich arterial thrombosis by selective thrombin inhibition. Circulation 81:219, 1990.PubMedGoogle Scholar
  30. 30.
    Haskel EJ, Prager NA, Sobel BE, Abendschein DR. Relative efficacy of antithrombin compared with antiplatelet agents in accelerating coronary thrombolysis and preventing early reocdusion. Circulation 83:1048, 1991.PubMedGoogle Scholar
  31. 31.
    Lam JYT, Chesebro JH, Badimon L, Fuster V. Serotonin and thromboxane A2 receptor blockade decreases vasoconstriction but not platelet deposition after deep arterial injury (abstr). Circulation 74(SuppI. II):1197, 1986.Google Scholar
  32. 32.
    Chesebro JH, Badimon L, Fuster V. Importance of antithrombin therapy during coronary angioplasty. J Am Coll Cardiol 17:96B, 1991.PubMedGoogle Scholar
  33. 33.
    Heras M, Chesebro JH, Penny WJ, Bailey KR, Badimon L, Fuster V. Effects of thrombin inhibition on the development of acute platelet-thrombus deposition during angioplasty in pigs: Heparin versus recombinant hirudin, a specific thrombin inhibitor. Circulation 79:657, 1989.PubMedGoogle Scholar
  34. 34.
    Bettelheim FR. The clotting of fibrinogen: II. Fractionation of peptide material liberated. Biochim Biophys Acta 19:121, 1956.PubMedGoogle Scholar
  35. 35.
    Bar-Shavit R, Benezra M, Sabbah V, Bode W, Vlodovsky I. Thrombin as a multifunctional protein: Induction of cell adhesion and proliferation. Am J Respir Cell Mol Biol 6:123, 1992.PubMedGoogle Scholar
  36. 36.
    Chesebro JH, Fuster V. Dynamic thrombosis and thrombolysis. Role of antithrombins. Circulation 83:1815, 1991.PubMedGoogle Scholar
  37. 37.
    Stassen JM, Juhan-Vague I, Alessi MC, De Cock F, Collen D. Potentiation by heparin fragments of thrombolysis induced with human tissue-type plasminogen activator. Thromb Haemost 58:947, 1987.PubMedGoogle Scholar
  38. 38.
    Cercek B, Lew AS, Hod H, Yano J, Reddy NK, Ganz W. Enhancement of thrombolysis with tissue-type plasminogen activator by pretreatment with heparin. Circulation 74:583, 1986.PubMedGoogle Scholar
  39. 39.
    Agnelli G, Pasucci C, Cosmi B, Nena G. Effects of therapeutic doses of heparin on thrombolysis with tissue-type plasminogen activator in rabbits. Blood 76:2030, 1990.PubMedGoogle Scholar
  40. 40.
    Stassen JM, Rapold HJ, Valinthout I, Collen D. Comparative effects of Enoxaparin and Heparin on arterial and venous clot lysis with alteplase in dogs. Thromb Haemost 69:454, 1993.PubMedGoogle Scholar
  41. 41.
    Rudd MA, George D, Johnstone MT, Moore RT, Collins L, Robbiani LE, Loscalzo J. Effect of thrombin inhibition on the dynamics of thrombolysis and on platelet function during thrombolytic therapy. Circ Res 70:829, 1992.PubMedGoogle Scholar
  42. 42.
    Klement P, Borm A, Hirsh J, Maraganore J, Wilson G, Weitz J. The effect of thrombin inhibitors on tissue plasminogen activator induced thrombolysis in a rat model. Thromb Heamost 68:64, 1992.Google Scholar
  43. 43.
    Stassen JM, Nystrom A, Hoylaerts M, Collen D. Antithrombotic effects of thrombolytic agents in a platelet-rich femoral vein thrombosis model in the hamster. Circulation 91:1330, 1995.PubMedGoogle Scholar
  44. 44.
    Badimon L, Lassila R, Badimon J, Vallabhajosula S, Chesebro JH, Fuster V. Residual thrombus is more thrombogenic than severely damaged vessel wall (abstr). Circulation 78(Suppl. II):II119, 1988.Google Scholar
  45. 45.
    Weitz JI, Hudoba M, Massel D, Maraganore J, Hirsh J. Clot-bound thrombin is protected from inhibition by heparin-antithrombin III but is susceptible to inactivation by antithrombin III-independent inhibitors. J Clin Invest 86:385, 1990.PubMedCrossRefGoogle Scholar
  46. 46.
    Gold HK, Coller BS, Yasada T, Saito T, Fallon JT, Guerrero JL, Leinbach RC, Ziskind AA, Collen D. Rapid and sustained coronary artery recanalization with combined bolus injection of recombinant tissue-type plasminogen activator and monoclonal antiplatelet GPIIb/IIIa antibody in a canine preparation. Circulation 77:670, 1988.PubMedGoogle Scholar
  47. 47.
    Yasuda T, Gold HK, Fallon JT, Leinbach RC, Guerrero JL, Scudder LE, Kanke M, Shealy D, Ross MJ, Collen D, Coller BS. Monoclonal antibody against the platelet glycoprotein (GP) IIb/IIIa receptor prevents coronary artery reocclusion after reperfusion with recombinant tissue-type plasminogen activator in dogs. J Clin Invest 81:1284, 1988.PubMedGoogle Scholar
  48. 48.
    Mickelson J, Simpson PJ, Cronin M, Homeister JW, Laywel E, Kitzen J, Lucchesi BR. Antiplatelet antibody 7E3 F(ab’)2 prevents rethrombosis after alteplase induced coronary artery thrombolysis in a canine model. Circulation 81:617, 1990.PubMedGoogle Scholar
  49. 49.
    Spriggs D, Gold HK, Hashimoto Y, Vanhoutte E, Bermylen J, Collen D. Absence of potentiation with murine antiplatelet GPIIb/IIIa antibody of thrombolysis with recombinant tissue-type plasminogen activator (alteplase) in a canine venous thrombosis model. Thromb Hemost 61:93, 1989.Google Scholar
  50. 50.
    Shebuski RJ, Stabilito IJ, Sitko GR, Polokoff MH. Acceleration of recombinant tissue-type plasminogen activator-induced thrombolysis and prevention of reocclusion by the combination of heparin and the Arg-Gly-Asp-containing peptide Bitistatin in a canine model of coronary thrombosis. Circulation 82:169, 1990.PubMedGoogle Scholar
  51. 51.
    Yasuda T, Gold HK, Leinbach RC, Yaoita H, Fallon JT, Guerrero L, Napier M, Bunting S, Collen D. Kistrin, a polypeptide platelet GPIIb/IIIa receptor antagonist enhances and sustains coronary arterial thrombolysis with recombinant tissue-type plasminogen activator in a canine preparation. Circulation 83:1038, 1991.PubMedGoogle Scholar
  52. 52.
    Haskel EJ, Adams SP, Feigen LP, Saffitz JE, Gorczynski RJ, Sobel BE, Abenschein DR. Prevention of reoccluding platelet-rich thrombi in canine femoral arteries with a novel peptide antagonist ot platelet glycoprotein IIb/IIIa receptors. Circulation 80:1775, 1989.PubMedGoogle Scholar
  53. 53.
    Nichols A, Vasko J, Koster P, Smith J, Barone F, Nelson A, Stadel J, Powers D, Rhodes G, Miller-Stein C, Boppana V, Bennet D, Berry D, Romoff T, Calvo R, Ah F, Sorenson E, Samanen J. SK&F 106760, a novel GPIIb/IIIa antagonist: Antithrombotic activity and potentiation of streptokinase-mediated thrombolysis. Eur J Pharmacol 183:2019, 1990.Google Scholar
  54. 54.
    Lu Hr, Gold HK, Wu Z, Yasuda T, Pauwels P, Rapold HJ, Napier M, Bunting S, Collen D. G4120, a Arg-Gly-Asp containing pentapeptide, enhances arterial eversion graft recanalization with recombinant tissue-type plasminogen activator in dogs. Thromb Haemost 6:686, 1992.Google Scholar
  55. 55.
    Rapold HJ, Gold HK, Wu Z, Napier M, Bunting S, Collen D. Effects of G4120, a ARG-GLY-ASP containing synthetic platelet glycoprotein IIb/IIIa receptor antagonist, on arterial and venous thrombolysis with recombinant tissue-type plasminogen activator in dogs. Fibrinolysis 7:248, 1993.Google Scholar
  56. 56.
    Roux S, Tschopp T, Kuhn H, Steiner B, Hadvary P. Effects of heparin, aspirin and a synthetic platelet GP IIb/IIIa receptor antagonist (Ro 43-5054) on coronary artery reperfusion and reocclusion after thrombolysis with alteplase in the dog. J Pharm Exp Ther 264:501, 1993.Google Scholar
  57. 57.
    Yasuda T, Gold H, Leinbach R, Fellon J, Guerrero L, Yaoita H, Collen D. Effect of reduced heparin on alteplase thrombolysis during platelet IIb/IIIa receptor blockade (abstr). Circulation 81(Suppl. III):III276, 1990.Google Scholar
  58. 58.
    Nossel HL, Yudelman I, Canfield RE, Butler VP Jr, Spanondis K, Wilner GD, Quereshi GD. Measurement of fibrinopeptide A in human blood. J Clin Invest 54:43, 1974.PubMedGoogle Scholar
  59. 59.
    Hofmann V, Straub PA. A radioimmunoassay for rapid measurement of human fibrinopeptide A. Thromb Res 11:171, 1977.PubMedGoogle Scholar
  60. 60.
    Pelzer H, Schwarz A, Heimburger N. Determination of human thrombin-antithrombin-III-complex in plasma with an enzyme-linked immunosorbent assay. Thromb Hemostas 59:101, 1988.Google Scholar
  61. 61.
    Yudelman I, Nossel HL, Kaplan KL, Hirsch J. Fibrinopeptide A levels in symptomatic thromboembolism. Blood 51:1189, 1978.PubMedGoogle Scholar
  62. 62.
    Gallino A, Häberli A, Baur HR, Straub PW. Fibrin formation and platelet aggregation in patients with severe coronary artery disease: Relationship with the degree of myocardial ischemia. Circulation 72:27, 1985.PubMedGoogle Scholar
  63. 63.
    Théroux P, Latour JG, Légier-Gauthier C, De Lara J. Fibrinopeptide A and platelet factor levels in unstable angina pectoris. Circulation 75:156, 1987.PubMedGoogle Scholar
  64. 64.
    Johnsson H, Orinius E, Paul C. Fibrinopeptide A in patients with acute myocardial infarction. Thromb Res 16:255, 1979.PubMedGoogle Scholar
  65. 65.
    Mombelli G, Imhof V, Häberli A, Straub PW. Effect of heparin on plasma fibrinopeptide A in patients with acute myocardial infarction. Circulation 69:684, 1984.PubMedGoogle Scholar
  66. 66.
    Eisenberg PR, Sobel BE, Jaffe AS. Activation of prothrombin accompanying thrombolysis with alteplase. J Am Coll Cardiol 19:1065, 1992.PubMedGoogle Scholar
  67. 67.
    Theroux P, Waters D, Lam J, Juneau M, McCans J. Reactivation of unstable angina after discontinuation of heparin. N Engl J Med 327:141, 1992.PubMedCrossRefGoogle Scholar
  68. 68.
    Granger CB, Miller JM, Bivill EG, Gruber A, Tracy RP, Krucoff MW, Green C, Berrios E, Harrington RA, Ohman M, Califf RM. Rebound increase in thrombin generation and activity after cessation of intravenous heparin in patients with acute coronary syndromes. Circulation 91:1929, 1995.PubMedGoogle Scholar
  69. 69.
    Rapold HJ, de Bono D, Arnold AER, de Cock F, Arnout J, Collen D and Verstraete M, for the European Co-operative Study Group. Plasma fibrinopeptide A levels in patients with acute myocardial infarction treated with alteplase: correlation with concomitant heparin, coronary artery patency, and recurrent ischemia. Circulation 85:928, 1992.PubMedGoogle Scholar
  70. 70.
    Arnout J, Simoons M, de Bono D, Rapold HJ, Collen D, Verstraete M. Correlation between level of heparin and patency of the infarct-related coronary artery after treatment of acute myocardial infarction with alteplase (alteplase). J Am Coll Cardiol 20:513, 1992.PubMedGoogle Scholar
  71. 71.
    Eisenberg PR, Sherman LA, Jaffe AS. Paradoxic elevation of fibrinopeptide A after streptokinase: Evidence of continued thrombosis despite intense fibrinolysis. J Am Coll Cardiol 10:527, 1987.PubMedGoogle Scholar
  72. 72.
    Kruithof EKO. Plasminogen activator inhibitor type 1: Biochemical, biological and clinical aspects. Fibrinolysis Suppl 2:59, 1988.Google Scholar
  73. 73.
    Rapold HJ, Grimaudo V, Declerck PJ, Kruithof EKO, Bachmann F. Plasma levels of plasminogen activator inhibitor type I, betathromboglobulin and fibrinopeptide A before, during and following treatment of acute myocardial infarction with tissue-type plasminogen activator. Blood 6:1490, 1991.Google Scholar
  74. 74.
    Lee CD, Mann KG. Activation and inactivation of human factor V by plasmin. Blood 73:185, 1989.PubMedGoogle Scholar
  75. 75.
    Eisenberg PR, Miletich JP, Sobel BE. Factors responsible for the differential procoagulant effects of diverse plasminogen activators in plasma. Fibrinolysis 5:217, 1991.Google Scholar
  76. 76.
    Niewiarowski S, Senyi AF, Gillies P. Plasmin induced platelet aggregation and platelet release reaction. J Clin Invest 52:1647, 1973.PubMedGoogle Scholar
  77. 77.
    Fitzgerald DJ, Cacella F, Roy L, Fitzgerald GA. Marked platelet activation in vivo after intravenous streptokinase in patients with acute myocardial infarction. Circulation 77:142, 1988.PubMedGoogle Scholar
  78. 78.
    Ohlstein EH, Stover B, Fujita T, Shebuski RJ. Tissue-type plasminogen activator and streptokinase induce platelet hyperaggregability in the rabbit. Thromb Res 46:575, 1987.PubMedGoogle Scholar
  79. 79.
    Gouin I, Lecompte T, Morel MC, Lebrazi J, Modderman PW, Kaplan C, Samama MM. In vitro effects of plasmin on human platelet function in plasma. Circulation 85:935, 1992.PubMedGoogle Scholar
  80. 80.
    Roux S, Christeller S, Lüdin E. Effects of aspirin on coronary reocclusion and recurrent ischemia after thrombolysis: A meta-analysis. J Am Col Cardiol 19:671, 1992.Google Scholar
  81. 81.
    Topol EJ, George BS, Kereiakes DJ, Stump DC, Candela RJ, Abbotsmith CW, Aronson L, Pickel A, Boswick JM, Lee KL, Ellis SG, Califf RM, TAMI Study Group. A randomized controlled trial of intravenous tissue plasminogen activator and early intravenous heparin in acute myocardial infarction. Circulation 79:281, 1989.PubMedGoogle Scholar
  82. 82.
    Hsia J, Hamilton WP, Kleiman N, Roberts R, Chaitman BR, Ross AM. A comparison between heparin and low-dose aspirin as adjunctive therapy with tissue-type plasminogen activator for acute myocardial infarction. N Engl J Med 323:1433, 1990.PubMedCrossRefGoogle Scholar
  83. 83.
    Bleich SD, Nichols TC, Schumacher RR, Cooke DII, Tate DA, Teichman SL. Effect of heparin on coronary arterial patency after thrombolysis with tissue plasminogen activator in acute myocardial infarction. Am J Cardiol 66:1412, 1990.PubMedGoogle Scholar
  84. 84.
    De Bono DP, Simoons ML, Tijssen J, Arnold AER, Betriu A, Burgersdijk C, Baseos LL, Müller F., Pfisterer M, Van de Werf F, Zijlstra F, Verstraete M, for the ESCG. The effect of early intravenous heparin on coronary patency, infarct size and bleeding complications after alteplase thrombolysis: Results of a randomized double blind European Co-operative Study Group trial. Br Heart J 67:122, 1992.PubMedGoogle Scholar
  85. 85.
    Simes RJ, Topol EJ, Holmes DR, White HD, Rutsch WR, Vahanian A, Simoons ML, Morris D, Betriu A, Califf RM, Ross AM for the Gusto-1 investigators. Link between the angiographic substudy and mortality outcomes in a large randomized trial of myocardial reperfusion. Circulation 91:1923, 1995.PubMedGoogle Scholar
  86. 86.
    Granger C, Hirsh J, Califf R, Col J, White H, Betriu A, Woodlief L, Lee K, Bovill E, Simes RJ. Activated partial thromboplastin time and outcome after thrombolytic therapy lor acute myocardial infarction. Results from the GUSTO-I trial. Circulation 93:870, 1996.PubMedGoogle Scholar
  87. 87.
    Johnson EA, Mulloy B. The molecular-weight range of commercial heparin preparations. Carbohydr Res 51:119, 1979.Google Scholar
  88. 88.
    Rosenberg RD, Lam L. Correlation between structure and function of heparin. Proc Natl Acad Sci USA 76:1218, 1979.PubMedGoogle Scholar
  89. 89.
    Lindahl U, Backstrom G, Hook M, Thunberg L, Fransson L-A, Linker A. Structure of the antithrombin-binding site of heparin. Proc Natl Acad Sci USA 76:3198, 1979.PubMedGoogle Scholar
  90. 90.
    Rosenberg RD. The heparin-antithrombin system: A natural anticoagulant mechanism. In Coleman RW, Hirsh J, Marder VJ, Salzman EW (eds). Hemostasis and Thrombosis: Basic Principles and Clinical Practice, 2nd ed. Philadelphia: JB Lippincott, 1987:1373.Google Scholar
  91. 91.
    Chaoy J, Petitou M, Lormeau JC, Sinay P, Casu B, Gatti G. Structure-activity relationship in heparin: A synthetic pentasaccharide with high affinity for antithrombin III and eliciting high anti-factor Xa activity. Biochem Biophys Res Commun 116:492, 1983.CrossRefGoogle Scholar
  92. 92.
    Rosenberg RD, Jordan RE, Favreau LV, Lam LH. High active heparin species with multiple binding sites for antithrombin. Biochem Biophys Res Commun 86:1319, 1979.PubMedGoogle Scholar
  93. 93.
    Bjork I, Lindahl U. Mechanism ol the anticoagulant action of heparin. Mol Cell Biochem 48:161, 1982.PubMedGoogle Scholar
  94. 94.
    Danielsson A, Raub E, Lindahl U, Bjork I. Role of ternary complexes in which heparin binds both antithrombin and proteinase, in the acceleration of the reactions between antithrombin and thrombin or factor Xa. J Biol Chem 261:15467, 1986.PubMedGoogle Scholar
  95. 95.
    Jordan RE, Costa GM, Gardner WT, Rosenberg RD. The kinetics of hemostatic enzyme-antithrombin interactions in the presence of low molecular weight heparin. J Biol Chem 255:10081, 1980.PubMedGoogle Scholar
  96. 96.
    Bar-Shavit R, Eldor A, Vlodavsky I. Binding of thrombin to subendothelial extracellular matrix; protection and expression of functional properties. J Clin Invest 84:1096, 1989.PubMedGoogle Scholar
  97. 97.
    Marciniak E. Factor Xa inactivation by antithrombin III. Evidence for biological stabilization of factor Xa by factor V-phospholipid complex. Br J Haematol 23:391, 1973.Google Scholar
  98. 98.
    Walker FJ, Esmon CT. The effects of phospholipid and factor Va on the inhibition of factor Xa by antithrombin III. Biochem Biophys Res Commun 90:641, 1979.PubMedGoogle Scholar
  99. 99.
    Lane DA, Pejler G, Flynn AM, Thompson EA, Lindahl U. Neutralization of heparin-related saccharides by histidine-rich glycoprotein and platelet factor 4. J Biol Chem 261:3980, 1986.PubMedGoogle Scholar
  100. 100.
    Dawes J, Smith RC, Pepper DS. The release, distribution and clearance of human βthromboglobulin and platelet factor 4. Thromb Res 12:851, 1978.PubMedGoogle Scholar
  101. 101.
    Mahadoo J, Hiebert L, Jaques LB. Vascular sequestration of heparin. Thromb Res 12:79, 1977.Google Scholar
  102. 102.
    Glimelius B, Busch C, Hook M. Binding of heparin on the surface of cultured human endothelial cells. Thromb Res 12:773, 1978.PubMedGoogle Scholar
  103. 103.
    Lindahl U, Hook M. Glycosaminoglycans and their binding to biological macromolecules. Ann Rev Biochem 46:385, 1978.Google Scholar
  104. 104.
    Ofosu FA, Barrowcliffe TW. Mechanisms of action of lower molecular weight heparins and heparinoids. In Hirsch J (ed). Antithrombiotic Therapy, Baillere’s Clinical Haematology. London: Baillere Tindal, 1990:505.Google Scholar
  105. 105.
    Lane DA, Denton J, Flynn AM, Thunberg L, Lindahl U. Anticoagulant activities of heparin oligosaccharides and their neutralization by platelet factor 4. Biochem J 218:725, 1984.PubMedGoogle Scholar
  106. 106.
    Beguin S, Lindhout T, Hemker HC. The mode of action of heparin in plasma. Thromb Haemost 60:457, 1989.Google Scholar
  107. 107.
    Handeland GF, Abildgaard U, Holm U, Arnesen K-E. Dose adjusted heparin treatment of deep venous thrombosis: A comparison of unfractionated and low molecular weight heparin. Eur J Clin Pharmacol 39:107, 1990.PubMedGoogle Scholar
  108. 108.
    Baru T, Molho P, Tobelem G, Petitou M, Caen JP. Binding of heparin and lower molecular weight heparin fragments to human vascular endothelial cells in culture. Nouv Rev Fr Haematol 26:243, 1984.Google Scholar
  109. 109.
    Kakkar VV, Murray WJG. Efficacy and safety of low molecular weight heparin (CY216) in preventing post-operative venous thromboembolism. Br J Surg 72:786, 1985.PubMedGoogle Scholar
  110. 110.
    Caen JP. A randomised double-blind study between a low molecular weight heparin Kabi 2165 and standard heparin in the prevention of deep vein thrombosis in general surgery. Thromb Haemost 59:216, 1988.PubMedGoogle Scholar
  111. 111.
    Hartle P, Brucke P, Dienstl E, Vinazzer H. Prophylaxis of thromboembolism in general surgery: Comparison between standard heparin and fragmin. Thromb Res 57:577, 1990.Google Scholar
  112. 112.
    Leizorovicz A, Picolet H, Peyrieux JC, Borssel JP. Prevention of perioperarive deep vein Thrombosis in general surgery: A multicentre double-blind study comparing two doses of logiparin and standard heparin. Br J Surg 78:412, 1991.Google Scholar
  113. 113.
    Planes A, Bochelle N, Mazas F, Mansat C, Zucman J, Landais A, et al. Prevention of postoperative venous thrombosis: A randomized trial comparing unfractionated heparin with low molecular weight heparin in patients undergoing total hip replacement. Thromb Haemost 60:407, 1988.PubMedGoogle Scholar
  114. 114.
    Estoppey D, Hochretter J, Breyer HG, Jakubek H, Leyvraz PF, Haas S, et al. ORG 10172 (Lomoparin) versus heparin-DHE in prevention of thromboembolism in total hip replacement: A multicentre trial (abstr). Thromb Haemost 61(Suppl.):356, 1989.Google Scholar
  115. 115.
    Levine MN, Hirsh J, Gent M, Turpie AGG, LeClerc J, Powers PJ, et al. Prevention of deep vein thrombosis after elective hip surgery: A randomized trial comparing low molecular weight heparin with standard unfractionated heparin. Ann Intern Med 114:545, 1991.PubMedGoogle Scholar
  116. 116.
    Kontny F, Abildgaard U, Pedersen T for the FRAMI Study Group. Low molecular weight Heparin (Fragmin) in acute myocardial infacrion (abstr). J Am Coll Cardiol 27:(Suppl A):166A, 1996.Google Scholar
  117. 117.
    Markwardt F, Nowak G, Stürzebecher J, Griessbach U, Walsmann P, Vogel G. Pharmacokinetics and anticoagulant effect of hirudin in man. Thromb Haemost 52:160, 1984.PubMedGoogle Scholar
  118. 118.
    Stone SR, Hofsteenge J. Kinetics of the inhibition of thrombin by hirudin. Biochemistry 25:4622, 1986.PubMedGoogle Scholar
  119. 119.
    Inauen W, Baumgartner HR, Bombeli T, Haeberli A, Straub PW. Dose and shear rate-dependent effects of heparin on thrombogenesis induced by rabbit aorta subendothelium exposed to flowing human blood. Arteriosclerosis 10:607, 1990.PubMedGoogle Scholar
  120. 120.
    Heras M, Chesebro JH, Webster MWI, Mruk JS, Grill DE, Penny WJ. Hirudin, heparin and placebo during deep arterial injury in the pig. The in vivo role of thrombin in platelet-mediated thrombosis. Circulation 82:1476, 1990.PubMedGoogle Scholar
  121. 121.
    Maraganore JM, Chao B, Joseph ML, Jablonski J, Ramachandran KL. Anticoagulant activity of synthetic hirudin peptides. J Biol Chem 264:8692, 1989.PubMedGoogle Scholar
  122. 122.
    Jakubowski JA, Maraganore JM. Inhibition of coagulation and thrombin-induced platelet activation by a synthetic dodecapeptide modeled on the carbox-terminus of hirudin. Blood 75:399, 1990.PubMedGoogle Scholar
  123. 123.
    Maraganore JM, Buordon P, Jablonski J, Ramachandran KL, Fenton JW II. Design and characterization of hirulogs: A novel class of bivalent peptide inhibitors of thrombin. Biochemistry 29:7095, 1990.PubMedGoogle Scholar
  124. 124.
    Collen D, Matsuo O, Stassen JM, Kettner C, Shaw E. In vivo studies of a synthetic inhibitor of thrombin. J Lab Clin Med 99:76, 1982.PubMedGoogle Scholar
  125. 125.
    Kettner C, Mersinger L, Knabb R. The selective inhibition of thrombin by peptides of boroarginine. J Biol Chem 265:18289, 1990.PubMedGoogle Scholar
  126. 126.
    Knabb RM, Kettner CA, Timmermans PB, Reilly TM. In vivo characterization of a new synthetic thrombin inhibitor. Thromb Haemost 67:56, 1992.PubMedGoogle Scholar
  127. 127.
    Claeson G, Philipp M, Agner E, Sully M, Metternich R, Kakkar V, Desoyza T, Niu L. Benzyloxy-carbonyl-D-phe-pro-methoxyprophyl-boroglycine: A novel inhibitor of thrombin with high selectivity containing a neutral side chain at the P1 position. Biochem J 290:309, 1993.PubMedGoogle Scholar
  128. 128.
    Jang I, Gold HK, Leinbach RC, Fallon JT, Collen D. In vivo thrombin inhibition enhances and sustains arterial recanalization with recombinant tissue-type plasminogen activator. Circ Res 67:1552, 1990.PubMedGoogle Scholar
  129. 129.
    Yasuda T, Gold HK, Yaoita H, Leinbach RC, Guerrero JL, Jang I. Comparative effects of aspirin, a synthetic thrombin inhibitor and a monoclonal antiplatelet glycoprotein Ilb/IIIa antibody on coronary artery reperfusion, reocclusion and bleeding with recombinant tissue-type plasminogen activator in a canine preparation. J Am Coll Cardiol 16:714, 1990.PubMedGoogle Scholar
  130. 130.
    The GUSTO 2A investigators. Randomized trial of intravenous heparin versus recombinant hirudin for acute coronary syndromes. Circulation 90:632, 1994.Google Scholar
  131. 131.
    Antman EM for the TIMI 9a investigators. Hirudin in acute myocardial infarction — safety report from the thrombolysis and thrombin inhibition in myocardial infarction (TIMI) 9A trial. Circulation 90:1624, 1994.Google Scholar
  132. 132.
    Neuhaus KL, v. Essen R, Tebbe U, Jessel A, Heinrichs H. Safety observations from the pilot phase of the randomized r-Hirudin for Improvement of Thrombolysis (HIT 3) study. Circulation 90:1638, 1994.PubMedGoogle Scholar
  133. 133.
    Topol EJ. Global Use of Strategies To Open occluded arteries (GUSTO). The preliminary results of GUSTO 2b in patients undergoing thrombolysis for acute myocardial infarction. Presentation at the American Heart Association, Anaheim, CA, November 12th, 1995.Google Scholar
  134. 134.
    Elliot EM. Heparin Versus hirudin as adjunctive therapy for thrombolysis in acute myocardial infarction. The preliminary results of TIMI 9b. Presentation at the American Heart Association, Anaheim, CA, November 12th, 1995.Google Scholar
  135. 135.
    Van de Werf F. Global Use of Strategies To Open coronary arteries (GUSTO). The preliminary results of GUSTO 2b in patients with acute coronary syndromes. Presentation at the American College of Cardiology, Orlando, FL, March 26th, 1996.Google Scholar
  136. 136.
    Serruys PW, Herrman JP, Simon R, Rutsch W, Bode C, Laarman GJ, Van Dijk R, Van denBos AA, Uhmans VA, Fox KA, Close P, Deckers JW for the HELVETICA investigators. A comparison of hirudin with heparin in the prevention of restenosis after coronary angioplasty. N Engl J Med 333:757, 1995.PubMedGoogle Scholar
  137. 137.
    Bittl JA, Strony J, Brinker JA, Ahmed WH, Meckel CR, Chaitman BR, Maraganore J, Deutsch E, Adelman B for the Hirulog Angioplasty Study investigators. Treatment with Bivalirudin (hirulog) as compared with heparin during coronary angioplasty for unstable or postinfarction angina. N Engl J Med 333:764, 1995.PubMedGoogle Scholar
  138. 138.
    Gold HK, Torres FW, Garabedian HD, Werner W, Jang I, Khan A, Hagstrom J, Yasuda T, Leinbach R, Newell J. Evidence for a rebound coagulation phenomenon after cessation of a 4-hour infusion of a specific thrombin inhibitor in patients with unstable angina pectoris. J Am Coll Cardiol 21:1039, 1993.PubMedGoogle Scholar
  139. 139.
    Marmur JD, Rossikhina M, Guha A, Fyfe B, Friedrich V, Mendlowiu M, Nemerson Y, Taubman MB. Tissue factor is rapidly induced in arterial smooth muscle after balloon injury. J Clin Invest 91:2253, 1993.PubMedCrossRefGoogle Scholar
  140. 140.
    Wilcox JN, Smith KM, Schwartz SM, Gordon D. Localization of tissue factor in normal vessel wall and in the atherosclerotic plaque. Proc Natl Acad Sci USA 86:2839, 1989.PubMedGoogle Scholar
  141. 141.
    Haskel EJ, Torr SR, Day KC, Palmier M, Wun TC, Sobel BF., Prevention of arterial reocclusion after thrombolysis with lipoprotein associated coagulation inhibitor (LAC1). Circularion 84:821, 1991.Google Scholar
  142. 142.
    Creasy AA, Chang AC, Feigen L, Wun TC, Taylor FB, Hinshaw LB. Tissue factor pathway inhibitor reduces mortality from Escberichia coli septic shock. J Clin Invest 91:2850, 1993.CrossRefGoogle Scholar
  143. 143.
    Mueller Berghaus G. Pathophysiologic and biochemical events in disseminated intravascular coagulation: Dysregulation of procoagulant and anticoagulant pathways. Semin Thromb Hemost 15:58, 1989.Google Scholar
  144. 144.
    Giercksky KE, Bjorklid E, Prydz H, Renck H. Circulating tissue thromboplastin during hip surgery. Eur Surg Res 11:296, 1979.PubMedGoogle Scholar
  145. 145.
    Carson SD, Haire WD, Broze GJ, Novotny WF Pirrucello SJ, Duggan MJ. Lipoprotein associated coagulation inhibitor, factor VII, antithrombin III and monocyte tissue factor following surgery, Thromb Haemost 66:534, 1991.PubMedGoogle Scholar
  146. 146.
    Girard TJ, Macphail LA, Likert KM, Novotny WF, Miletich JP, Broze GJ. Inhibition of factor VVLA-tissue factor coagulation activity by a hybrid protein. Science 248:1421, 1990.PubMedGoogle Scholar
  147. 147.
    Ruf W, Edgington TS. An anti-tissue factor monoclonal antibody which inhibits TF. VIIa complex is a potent anticoagulant in plasma. Thromb Haemost 66:529, 1991.PubMedGoogle Scholar
  148. 148.
    Broze GJ, Girard TJ, Novotny WF, et al. Regulation of coagulation by a multivalent Kunitz-type inhibitor. Biochemistry 29:7539, 1990.PubMedGoogle Scholar
  149. 149.
    Novotny WF, Palmier M, Wun TC, et al. Purification and properties of heparin-releasable lipoproteinassociated coagulation inhibitor. Blood 78:394, 1991.PubMedGoogle Scholar
  150. 150.
    Diaz-Collier JA, Palmier MO, Kretzmer KK. Refold and characterization of recombinant tissue factor pathway inhibitor expressed in Escbenchia colt. Thromb Haemost 71:1, 1994.Google Scholar
  151. 151.
    Gustafson ME, Junger KD, Wun TC, et al. Renaturation and purification of human tissue factor pathway inhibitor expressed in recombinant E. colt. Protein Expr Purif, in press.Google Scholar
  152. 152.
    Speidel CM, Eisenberg PR, Ruf W, Edgington TS, Abendschein DR. Tissue factor mediated prolonged procoagulant activity on the luminal surface of balloon-injured aortas in rabbits. Circulation 92:3323, 1995.PubMedGoogle Scholar
  153. 153.
    Yang L, St. Pierre J, Kam G, Thornton D, Eisenberg P, Abendschein D. Tissue factor pathway inhibitor attenuates prothrombinase complex formation on balloon-injured arteries in pigs (abstr). J Am Coll Cardiol 27(Suppl. A):14A, 1996.Google Scholar
  154. 154.
    Abendschein DR, Meng YY, Torr-Brown S, Sobel BE. Maintenance of coronary patency after fibrinolysis with tissue factor pathway inhibitor. Circulation 92:944, 1995.PubMedGoogle Scholar
  155. 155.
    Koudsi B, Ferguson EW, Yu CD, Miller GA, Merkel KD, Wun TC, Money SR, Kraemer BA. The effects of tissue factor pathway inhibitor on myocardial infarct size (abstr). J Am Coll Cardiol 27(Suppl. A):81A, 1996.Google Scholar
  156. 156.
    Carr C, Bild GS, Chang AC, et al. Recombinant E. coli-derived tissue factor pathway inhibitor reduced coagulopathic and lethal effects in the baboon gram-negative model of septic shock. Circ Shock 44:126, 1995.Google Scholar
  157. 157.
    Benedict CR, Ryan J, Wolitzky B, Ramos R, Gerlach M, Tijburg P, et al. Active site-blocked factor Ixa prevents intravascular thrombus formation in the coronary vasculature without inhibiting extravascular coagulation in a canine thrombosis model. J Clin Invest 88:1760, 1991.PubMedGoogle Scholar
  158. 158.
    Marlar RA, Kleiss AJ, Griffin JH, Mechanism of action of human activated protein C, a thrombindependent anticoagulant enzyme. Blood 59:1067, 1982.PubMedGoogle Scholar
  159. 159.
    Gruber A, Hanson SR, Kelly AB, Yan BS, Bang N, Griffin JH. Inhibition of thrombus formation by activated recombinant protein C in a primate model of arterial thrombosis. Circulation 82:578, 1990.PubMedGoogle Scholar
  160. 160.
    Waxman L, Smith DE, Arcuri KE, Vlasuk GP. Tick anticoagulant peptide (TAP) is a novel inhibitor of blood coagulation factor Xa. Science 248:593, 1990.PubMedGoogle Scholar
  161. 161.
    Schaffer LW, Davidson JT, Vlasuk GP, Siegl PKS. Annthrombotic efficacy of recombinant tick anticoagulant peptide. A potent inhibitor of coagulation factor Xa in a primate model of arterial thrombosis. Circulation 84:1741, 1991.PubMedGoogle Scholar
  162. 162.
    Nawroth PP, Kisiel W, Stern DM. Anticoagulant and antithrombotic properties of a gamma-carboxyglutamic acid-rich peptide derived from the light chain of blood coagulation factor X. Thromb Res 44:625, 1986.PubMedGoogle Scholar
  163. 163.
    Gruber A, Harker LA, Hanson SR, Kelly AB, Griffin JH. Antithrombotic effects of combining activated protein C and urokinase in non-human primates. Circulation 84:2454, 1991.PubMedGoogle Scholar
  164. 164.
    Sitko GR, Ramjit DR, Stabilito H, Lehman D, Lynch JJ, Vlasuk GP. Conjunctive enhancement of enzymatic thrombolysis and prevention of thrombotic reocclusion with the selective factor Xa inhibitor, tick anticoagulant peptide. Circulation 85:805, 1992.PubMedGoogle Scholar
  165. 165.
    Richardson SG, Allen DC, Morton P, Murtagh JG, Scott ME, O’Keefe DB. Pathological changes after intravenous streptokinase treatment in eight patients with acute myocardial infarction. Br Heart J 61:390, 1989.PubMedGoogle Scholar
  166. 166.
    Jang IK, Gold HK, Ziskind AA, Fallon JT, Holt RE, Leinbach RC, et al. Differential sensitivity of erythrocyte-rich and platelet-rich arterial thrombi to lysis with recombinant tissue-type plasminogen activator. A possible explanation for resistance to coronary thrombolysis. Circulation 79:920, 1989.PubMedGoogle Scholar
  167. 167.
    Fitzgerald DJ, Wright F, Fitzgerald GA. Increased thromboxane biosynthesis during coronary thrombolysis. Evidence that platelet activation and thromboxane A2 modulate the response to tissue-type plasminogen activator in vivo. Circ Res 65:83, 1989.PubMedGoogle Scholar
  168. 168.
    Bertele V, Certletti C, Schieppati A, Di Minno G, DeGaetano G. Inhibition of thromboxane synthase does not necessarily prevent platelet aggregation. Lancet 1:1057, 1981.Google Scholar
  169. 169.
    Shebuski RJ, Storer BL, Fujita T. Effect of thromboxane synthase inhibition on the thrombolytic action of tissue-type plasminogen activator, in a rabbit model of peripheral arterial thrombosis. Thromb Res 52:382, 1988.Google Scholar
  170. 170.
    Grover GJ, Parham CS, Schumacher WA. The combined antiischemic effects of the thromboxane receptor antagonist SQ 30741 and tissue type plasminogen activator. Am Heart J 121:426, 1991.PubMedGoogle Scholar
  171. 171.
    Golino P, Rosolowsky M, Sheng-Kun Yao, Buja LM, Willerson JT. Blockade of TXA, receptors and inhibition of TXA2 synthase enhances thrombolysis and prevents reocclusion more efficiently than either intervention alone (abstr). Circulation 80(Suppl. II) III13, 1989.Google Scholar
  172. 172.
    Van De Water A, Xhonneux R, De Clerck F, Willerson JT. Heparin enhances the synergism between platelet TXA2 synthase inhibition/receptor blockade (ridogrel) and tissue plasminogen activator in lysing canine coronary thrombi (abstr). J Am Coll Cardiol 17:52, 1991.Google Scholar
  173. 173.
    Rapold HJ, Van de Werf F, De Geest H, Arnout J, Sangtawesin W, Vercammen E, De Clerck F, Weber C, Collen D. Pilot study of combined administration of ridogrel and alteplase in patients with acute myocardial infarction. Cor Art Dis 2:455, 1991.Google Scholar
  174. 174.
    Tranchesi B, Caramelli B, Gebara O, Bellotti G, Pileggi F, and Van de Werf F, et al. Efficacy and safety of ridogrel versus aspirin in coronary thrombolysis with alteplase for myocardial infarction (abstr). J Am Coll Cardiol 19:92A, 1992.Google Scholar
  175. 175.
    Golino P, Buja LM, Ashton JH, Kulkarni P, Taylor A, Willerson JT. Effect of thromboxane and serotonin receptor antagonists on intracoronary platelet deposition in dogs with experimentally stenosed coronary-arteries. Circulation 78:701, 1988.PubMedGoogle Scholar
  176. 176.
    Golino P, Ashton JH, Glas-Greenwalt P, McNatt J, Buja LM, Willerson JT. Mediation of reocclusion by thromboxane A2 and serotonin after thrombolysis with tissue-type plasminogen activator in a canine preparation of coronary thrombosis. Circulation 77:678, 1988.PubMedGoogle Scholar
  177. 177.
    Schumacher WA, Lee EC, Lucchesi BR. Augmentation of streptokinase-induced thrombolysis by heparin and prostacyclin. J Cardiovasc Pharmacol 7:739, 1985.PubMedGoogle Scholar
  178. 178.
    Nicolini FA, Mehta JL, Nichols WW, Saldeen TGP, Grant M. Prostacyclin analogue iloprost decreases thrombolytic potential of tissue-type plasminogen activator in canine coronary thrombosis. Circulation 81:1115, 1990.PubMedGoogle Scholar
  179. 179.
    Sharma B, Wyeth RP, Gimenez HJ, Franciosa JA. Intracoronary prostaglandin E1 plus streptokinase in acute myocardial infarction. Am J Cardiol 58:1161, 1986.PubMedGoogle Scholar
  180. 180.
    Topol EJ, Ellis SG, Califf RM, George BS, Stump DC, Bates ER, et al. Combined tissue-type plasminogen activator and prostacyclin therapy for acute myocardial infarction. J Am Coll Cardiol 14:877, 1989.PubMedCrossRefGoogle Scholar
  181. 181.
    Coller BS. Platelets in cardiovascular thormbosis and thrombolysis. In Fozzard HA, Haber E, Jennings RB, Katz AM, and Morgan HE (eds). The Heart and Cardiovascular Systems, 2nd ed. New York: Raven Press, 1991:219.Google Scholar
  182. 182.
    Coller BS, Peerschke EI, Scudder LE, Sullivan CA. A murine monoclonal antibody that completely blocks the binding of fibrinogen to platelets produces a thrombasthenic-like state in normal platelet and binds to glycoproteins IIb and/or IIIa. Clin Invest 72:325, 1983.Google Scholar
  183. 183.
    Fitzgerald DJ, Wright F, FitzGerald GA. Increased thromboxane biosynthesis during coronary thrombolysis. Circ Res 65:83, 1989.PubMedGoogle Scholar
  184. 184.
    Fitzgerald DJ, Hanson M, FitzGerald GA. Systemic lysis protects against the effects of platelet activation during coronary thrombolysis. J Clin Invest 88:1589, 1991.PubMedGoogle Scholar
  185. 185.
    Rote WE, Walsh DG, Bates E.R, Mu DX, Nedelman MA, Lucchesi BR. Comparison of 7E3 F(ab’), antibody with hirudin after alteplase induced thrombolysis in a chronic model of coronary thrombosis. FASEB J 6:A1877, 1992.Google Scholar
  186. 186.
    Yasuda T, Gold HK, Leinbach RC, Saito T, Guerrero JL, Jang I-K. Lysis of plasminogen activator-resistant platelet-rich coronary artery thrombus with combined bolus injection of recombinant tissue-type plasminogen activator and antiplatelet GPIIb/IIIa antibody. J Am Coll Cardiol 7:1728, 1990.Google Scholar
  187. 187.
    Lu HR, Gold HK, Wu Z, De Cock F, Jang IK, Pauwels P. Acceleration and persistence of recombinant tissue plasminogen activator induced arterial eversion graft recanalization with a single bolus injeccion of F(ab’), fragments of the antiplatelet GPIIb/ IIIa antibody 7E3. Cor Art Dis 2:1039, 1991.Google Scholar
  188. 188.
    Holahan MA, Mellott MJ, Garsky VM, Shebuski RJ. Prevention of reocclusion following tissue-type plasminogen activator-induced thrombolysis by the RGD-containing peptide, echistatin, in a canine model of coronary thrombosis. Pharmacology 42:340, 1991.PubMedGoogle Scholar
  189. 189.
    Scarborough RM, Rose JW, Hsu MA, Phillips DR, Fried VA, Campbell AM. Barbourin: A GPIIb/IIIa specific integrin antagonist from the venom of Sistrurus M barbouri. J Biol Chem 266:9359, 1991.PubMedGoogle Scholar
  190. 190.
    Alig L, Edenhofer A, Hadvary P, Hiirzeler M, Knopp D, Müller M, Steiner B, Trzeciak A, Weller T. Low molecular weight, non-peptide fibrinogen receptor antagonists. J Med Chem 35:4393, 1992.PubMedGoogle Scholar
  191. 191.
    The EPIC investigators. Use of a monoclonal antibody directed against the platelet glycoprotein IIb/ IIIa receptor in high-risk coronary angioplasty. N Engl J Med 330:956, 1994.Google Scholar
  192. 192.
    Topol EJ, Califf RM, Weisman HF, Anderson K, Wang A, Willerson JT. Randomized trial of coronary intervention with antibody against platelet IIb/IIIa integrin for reduction of clinical restenosis: Results at six months. The EPIC investigators. Lancet 343:881, 1994.PubMedGoogle Scholar
  193. 193.
    Lincoff AM. Use of the monoclonal antibody against GP IIb/IIIa 7E3-F(ab’)2 (ReoPro) in percutaneous coronary interventions. The preliminary results of the EPILOG trial (1500 patients). Presentation at the American College of Cardiology, Orlando, FL, March 27th, 1996.Google Scholar
  194. 194.
    Simoons M. Use of the monoclonal antibody against GP IIb/IIIa 7E3-F(ab’)2 (ReoPro) in high risk patients undergoing PTCA. The preliminary results of the CAPTURE trial (2000 patients). Presentation at the American College of Cardiology, Orlando, FL, March 27th, 1996.Google Scholar
  195. 195.
    Horrigan MC, Tscheng JE, Califf RM, Kitt M, Lorenz T, Sigmon K, Lincoff AM, Topol EJ. Maximal benefit of Integrelin Platelet IIb/IIIa blockade 6-24 hours after therapy: Results of the IMPACT-2 trial (abstr). J Am Coll Cardiol 27(Suppl. A):55, 1996.Google Scholar
  196. 196.
    King S. Administration of Tirofiban (MK 383) will reduce the incidence of adverse cardiac outcome following PTCA/PTA. The preliminary results of the RESTORE trial. Presentation at the American College of Cardiology, Orlando, FL, March 27th, 1996.Google Scholar
  197. 197.
    Theroux P, Kouz S, Nasmith J, Knudtson M, Kells C, Bokslag M, Rapold HJ. Platelet membrane receptor GP IIb/IIIa antagonism in unstable angina. The Canadian Lamifiban study. Circulation 94:899, 1996.PubMedGoogle Scholar
  198. 198.
    Kleiman NS, Ohman EM, Keriakes DJ, Ellis SG, Weisman HF, Topol EJ. Profound platelet inactivation with 7E3 shortly after thrombolytic therapy for acute myocardial infarction: Preliminary results of the TAMI 8 trial (abstr). Circulation 84(Suppl. II):II522, 1991.Google Scholar
  199. 199.
    Ohman EM, Kleiman NS, Gacioch G, et al. For the IMPACT-AMI group. Simultaneous platelet glycoprotein IIb/IIIa integrin blockade and front-loaded tissue plasminogen activator in acute myocardial infarction: Results from a randomized trial (abstr). J Am Coll Cardiol 27(Suppl. A):167, 1996.Google Scholar
  200. 200.
    Moliterno DJ, Harrington RA, Rapold HJ, Califf RM, Topol EJ. Randomized, placebo-controlled study of lamifiban with thrombolytic therapy for the treatment of acute myocardial infarction: Rationale and design for the Platelet Aggregation Receptor Antagonist Dose Investigation and reperfusion Gain in Myocardial infarction (PARADIGM) study. J Thrombos Thromboly 2:16, 1995.Google Scholar

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© Kluwer Academic Publishers 1997

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  • Hans J. Rapold

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