Skip to main content
SpringerLink
Log in

Achieving optimal reperfusion without adjunctive antithrombotic therapy: Novel thrombolytic dosing strategies

  • Published:
Journal of Thrombosis and Thrombolysis Aims and scope Submit manuscript

Abstract

There is firm evidence that reperfusion therapy, to be effective must establish and maintain coronary arterial blood flow at a level sufficient to allow myocardial perfusion. However, current thrombolytic regimens have clear limitations, including a relatively low capacity to achieve TIMI Grade 3 blood flow and an unacceptable incidence of coronary reocclusion. Although it has been assumed that the key to achieving optimal reperfusion lies with adjunctive antithrombotic therapy, it may be that novel thrombolytics and dosing strategies can address the problem adequately. This possibility is attractive and requires careful consideration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. The GUSTO Angiographic Investigators. The effects of tissue plasminogen activator, streptokinase, or both on coronary-artery patency, ventricular function, and survival after acute myocardial infarction.N Engl J Med 1993;329: 1615–1622.

    Google Scholar 

  2. The GUSTO Investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction.N Engl J Med 1993;329:673–682.

    Google Scholar 

  3. Karagounis L, Sorensen SG, Menlove RL, Moreno F, Anderson JL for the TEAM 2 Investigators. Does thrombolysis in myocardial infarction (TIMI) perfusion grade 2 represent a mostly patent artery or a mostly occluded artery? Enzyme and electrocardiographic evidence from the TEAM-2 study.J Am Coll Cardiol 1992;19:l-10.

    Google Scholar 

  4. Vogt A, Von Essen R, Tebbe U, Feuerer W, Appel KF, Neuhaus KL. Impact of early perfusion status of the infarct-related artery on short-term mortality after thrombolysis for acute myocardial infarction: Retrospective analysis of four German multicenter studies.J Am Coll Cardiol 1993;21:1391–1395.

    PubMed  Google Scholar 

  5. Falk E. Unstable angina with fatal outcome: Dynamic coronary thrombosis leading to infarction and/or sudden death: Autopsy evidence of recurrent mural thrombosis with peripheral embolization culminating in total vascular occlusion.Circulation 1985;71:699–708.

    PubMed  Google Scholar 

  6. Falk E. Plaque rupture with severe pre-existing stenosis precipitating coronary thrombosis: Characteristics of coronary atherosclerotic plaques underlying fatal occlusive thrombi.Br Heart J 1983;50:127–134.

    PubMed  Google Scholar 

  7. Davies MJ, Thomas AC. Plaque fissuring-the cause of acute myocardial infarction, sudden ischemic death, and crescendo angina.Br Heart J 1985;53:363–373.

    PubMed  Google Scholar 

  8. Lyford CL, Connor WE, Hoak JC, Warner ED. The coagulant and thrombogenic properties of human atheroma.Circulation 1967;35:284–293.

    Google Scholar 

  9. Fernandez-Ortiz A, Badimon JJ, Falk E, et al. Characterization of the relative thrombogenicity of atherosclerotic plaque components: Implications for consequences of plaque rupture.J Am Coll Cardiol, 1994.

  10. Zwaginga JJ, Boer HC, Ijsseldijk MJW, et al. Thrombogenicity of vascular cells. Comparison between endothelial cells isolated from different sources and smooth muscle cells and fibroblasts.Arteriosclerosis 1990;10:437–448.

    PubMed  Google Scholar 

  11. Grabowski EF, Zuckerman DB, Nemerson Y. The functional expression of tissue factor by flbroblasts and endothelial cells under flow conditions.Blood 1993;81: 3265–3270.

    PubMed  Google Scholar 

  12. Wilcox JN, Smith KM, Schwartz SM, Gordon D. Localization of tissue factor in the normal vessel wall in the atherosclerotic plaque.Proc Natl Acad Sci USA 1989;86: 2839–2843.

    PubMed  Google Scholar 

  13. Bar-Shavit R, Eldor A, Vlodavsky I. Binding of thrombin to subendothelial extracellular matrix. Protection and expression of function properties.J Clin Invest 1989;84: 1096–1104.

    PubMed  Google Scholar 

  14. Turitto T, Weiss HJ, Baumgartner HR. The effect of shear rate on platelet interaction with subendothelium exposed to citrated human blood.Microvase Res 1980;19:352–365.

    Google Scholar 

  15. Lassila R, Badimon JJ, Vallabhajosula S, Badimon L. Dynamic monitoring of platelet deposition on severely damaged vessel wall in flowing blood. Effects of different stenosis in thrombus growth.Arteriosclerosis 1990;10:306–315.

    PubMed  Google Scholar 

  16. Badimon L, Badimon JJ. Mechanism of arterial thrombosis in nonparallel streamlines: Platelet thrombi grow on the apex of stenotic severely injured vessel wall.J Clin Invest 1989;84A:1134–1144.

    Google Scholar 

  17. Swords NA, Mann KG. The assembly of the prothrombinase complex on adherent platelets.Arterioscler Thromb 1993;13:1602–1612.

    PubMed  Google Scholar 

  18. Friedman MF, van der Bovenkamp EJ. Pathogenesis of a coronary thrombus.Am J Pathol 1966;48:19–44.

    PubMed  Google Scholar 

  19. French JE. The fine structure of experimental thrombi. In: Sherry S, Brinkhous KM, Genton E, Stengle JM, eds.Thrombosis. Washington DC: National Academy of Sciences, 1969:300–319.

    Google Scholar 

  20. Frieman DG. The structure of thrombi. In: Colman RW, Hirsh J, Marder VJ, Salzman EW, eds.Hemostasis and Thrombosis;Basic Principles and Clinical Practice, 2nd ed. Philadelphia: J.B. Lippincott, 1987:1123–1135.

    Google Scholar 

  21. Ludmer PL, Selwyn AP, Shook TL, et al. Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries.N Engl J Med 1986;315:1046–1051.

    PubMed  Google Scholar 

  22. Nabel EG, Selwyn AP, Ganz P. Paradoxical narrowing of atherosclerotic coronary arteries induced by increases in heart rate.Circulation 1990;81:850–859.

    PubMed  Google Scholar 

  23. Vita JA, Treasure CB, Ganz P, et al. Control of shear stress in the epicardial coronary arteries of humans: Impairment by atherosclerosis.J Am Coll Cardiol 1989;14: 1193–1199.

    PubMed  Google Scholar 

  24. Coupe MO, Mak JCW, Yacoub M, et al. Autoradiographic mapping of calcitonin gene-related polypeptide receptors in human and guinea pig hearts.Circulation 1990;81:741–747.

    PubMed  Google Scholar 

  25. Yatani A, Yokoyama M, Akita H, Fakuzak H. Endothelium-dependent vasodilating effect of substance P during flow-reducing coronary stenosis in the dog.J Am Coll Cardiol 1990;15:1374–1384.

    PubMed  Google Scholar 

  26. Schwartz JS, Carlyle PF, Cohn JN. Effect of dilation of the distal coronary bed on flow and resistance in severely stenotic coronary arteries in the dog.Am J Cardiol 1979; 43:219–224.

    PubMed  Google Scholar 

  27. Jellke FW, Quillen JE, Brooks LA, Harrison DG. Endothelial modulation of the coronary vasculature in the vessels perfused via mature collaterals.Circulation 1990;81: 1938–1947.

    PubMed  Google Scholar 

  28. Peters KG, Marcus ML, Harrison DG. Vasopressin and the mature coronary collateral circulation.Circulation 1989;79:1324–1331.

    PubMed  Google Scholar 

  29. Kwaawn HC. Possible effects of risk factors on fibrinolysis. In: Chandler AB, ed.Thrombotic Processes in Atherosclerosis. New York: Plenum, 1978:235–300.

    Google Scholar 

  30. Walker ID, Davidson JF, Hutton I, et al. Disordered fibrinolytic potential in coronary heart disease.Thromb Res 1977;10:509–520.

    PubMed  Google Scholar 

  31. Chakrabarti R, Hocking ED. Fibrinolytic activity and coronary heart disease.Lancet 1968;1:987–990.

    PubMed  Google Scholar 

  32. Davies GL, Chjierchia S, Maseri A. Prevention of myocardial infarction by very early treatment with intracoronary streptokinase: Some clinical observations.N Engl J Med 1984;311:1488–1492.

    PubMed  Google Scholar 

  33. Hackett D, Davies G, Chierchia S, Maseri A. Intermittent coronary occlusion in acute myocardial infarction: Value of combined thrombolytic and vasodilator therapy. iVEngl J Med 1987;317:1055–1059.

    Google Scholar 

  34. Dellborg M, Topol EJ, Swedberg K. Dynamic QRS complex and ST segment vectorcardiographic monitoring can identify vessel patency in patients with acute myocardial infarction treated with reperfusion therapy.Am Heart J 1991;122:943–948.

    PubMed  Google Scholar 

  35. Kwon KI, Freedman B, Wilxos I, Allman K, Madden A, Carter GS, Harris PJ: The unstable ST segment early after thrombolysis for acute infarction and its usefulness as a marker of recurrent coronary occlusion.Am J Cardiol 1991;67:109–115.

    PubMed  Google Scholar 

  36. Grines CL, Topol EJ, Bates ER, Juni JE, Walton JA, O'Neill WW. Infarct vessel status after intravenous tissue plasminogen activator and acute coronary angioplasty: Prediction of clinical outcome.Am Heart J 1988;115:1–7.

    PubMed  Google Scholar 

  37. Lim MJ, Gallagher MA, Zladeh M, Buda AJ: Effect of coronary reocclusion after initial reperfusion on ventricular function and infarct size.J Am Coll Cardiol 1991;18: 879–885.

    PubMed  Google Scholar 

  38. Ohman EM, Califf RM, Topol EJ, et al. Consequences of reocclusion after successful reperfusion therapy in acute myocardial infarction.Circulation 1990;82:781–791.

    PubMed  Google Scholar 

  39. Ito H, Tomooka T, Sakai N, et al. Lack of myocardial perfusion immediately after successful thrombolysis: A predictor of poor recovery of left ventricular function in anterior myocardial infarction.Circulation 1992;85:1699–1705.

    PubMed  Google Scholar 

  40. Granger CB, Califf RM, Topol EJ. Thrombolytic therapy for acute myocardial infarction. A review.Drugs 1992;44: 293–325.

    PubMed  Google Scholar 

  41. Greenberg JP, Packham MA, Guccione MA, et al. The effect of pretreatment of human or rabbit platelets with chymotrypsin on their response to human fibrinogen and aggregation agents.Blood 1979;54:753–765.

    PubMed  Google Scholar 

  42. Guccione MA, Kinlough-Rathbone RL, Packham MA, et al. Effect of plasmin on rabbit platelets.Thromb Haemost 1985;53:8–14.

    PubMed  Google Scholar 

  43. Schafer AI, Mars AK, Ware JA, Honson PC, Rittenhouse SE, Salzman EW. Platelet protein phosphorylation, elevation of cytosolic calcium, and inositol phospholipid breakdown in platelet activation induced by plasmin.J Clin Invest 1986;78:73–79.

    PubMed  Google Scholar 

  44. Kowalski E, Budzynski AZ, Kopee N, Catallo ZS, Lipinski B, Wegrzynowicz Z. Studies on the molecular pathology and pathogenesis of bleeding in severe fibrinolytic states in dogs.Thromb Death Haemorrh 1964;12:69–86.

    Google Scholar 

  45. Rao AK, Mintz PD, Lavine SJ, Bove AA, McDonough MT, Spann TP, Walsh PN. Coagulant activities of platelets in coronary artery disease.Circulation 1984;69:15–21.

    PubMed  Google Scholar 

  46. Griffin JT, Cochran LHG. Recent advances in the understanding of contact activation reactions.Semin Thrormb Hemost 1979;5:254–273.

    Google Scholar 

  47. Weitz JI, Cruickshank MK, Thong B, et al. Human tissue type plasminogen activator releases fibrinopeptides A and B from fibrinogen.J Clin Invest 1988;82:1700–1707.

    PubMed  Google Scholar 

  48. Rapold JH, 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 1989;79:980–989.

    PubMed  Google Scholar 

  49. Kruithof EK, Tran-Thang C, Bachmann F. Studies on the release of plasminogen activator inhibitor from human platelets.Thromb Haemost 1986;55:201–205.

    PubMed  Google Scholar 

  50. Plow EF, Collen D. The presence and release of α-antiplasmin from human platelets.Blood 1981;58:1069–1074.

    PubMed  Google Scholar 

  51. Erickson LA, Ginsberg MH, Loskutoff DJ. Detection and partial characterization of an inhibitor of plasminogen activator in human platelets.J Clin Invest 1984;74:1465–1472.

    PubMed  Google Scholar 

  52. Lucore CL, Fujii S, Won TC, Billardello JJ, Sobel BE. Regulation of the expression of Type I plasminogen activator inhibitor in Hep G2 cells by epidermal growth factor.J Biol Chem 1988;263:15845–15848.

    PubMed  Google Scholar 

  53. Fujii S, Lucore CL, Hopkins WE, Billardello JJ, Sobel BE. Potential attenuation of fibrinolysis by growth factors released from platelets and their pharmacologic implications.Am J Cordial 1989;63:1505–1511.

    Google Scholar 

  54. Verstaete M, Arnold AE, Brower RW, et al. Acute coronary thrombolysis with recombinant human tissue type plasminogen activator: Initial patency and influence of maintained infusion on reocclusion rate.Am J Cardiol 1987;60:231–237.

    PubMed  Google Scholar 

  55. Gold HK, Leibach RC, Garabedian HD, et al. Acute coronary reocclusion after thrombolysis with recombinant human tissue type plasminogen activator: Prevention by a maintenance infusion.Circulation 1986;73:347–352.

    PubMed  Google Scholar 

  56. Williams DO, Borer J, Braunwald E, et al. Intravenous recombinant tissue type plasminogen activator in acute myocardial infarction: A report from the NHLBI Thrombolysis in Myocardial Infarction (TIMI) trial.Circulation 1986;73:338.

    PubMed  Google Scholar 

  57. Chesebro JH and TIMI Investigators. Thrombolysis in Myocardial Infarction (TIMI) trial, phase I. A comparison between intravenous tissue plasminogen activator and intravenous streptokinase: Clinical findings through hospital discharge.Circulation 1987;76:142–154.

    PubMed  Google Scholar 

  58. Mueller HS and TIMI Investigators. Thrombolysis in Myocardial Infarction (TIMI): Comparative studies of coronary reperfusion and systemic fibrinogenolysis for two forms of recombinant tissue type plasminogen activator.J Am Coll Cardiol 1987;10:479–490.

    PubMed  Google Scholar 

  59. Simoons ML, Arnold AE, Betriu A, et al. Thrombolysis with tissue plasminogen activator in acute myocardial infarction: No additional benefit from immediate percutaneous coronary angioplasty.Lancet 1988;1:197–203.

    PubMed  Google Scholar 

  60. Topol EJ, Morris DC, Smalling RW, et al. A multicenter, randomized, placebo-controlled trial of a new form of intravenous recombinant tissue type plasminogen activator (Activase) in acute myocardial infarction.J Am Coll Cardiol 1987;9:205–213.

    Google Scholar 

  61. Bates ER, Califf RM, Stack RS, et al. Thrombolysis and Angioplasty in Myocardial Infarction (TAMI-1) trial. Influence of infarct location on arterial patency, left ventricular function and mortality.J Am Coll Cardiol 1989;13: 12–18.

    PubMed  Google Scholar 

  62. Topol EJ, George BS, Kereiakes DJ, et al. A randomized controlled trial of intravenous heparin in acute myocardial infarction.Circulation 1989;79:281–286.

    PubMed  Google Scholar 

  63. Topol EJ, Califf RM, George BS, et al. A randomized trial of immediate versus delayed elective angioplasty after intravenous tissue plasminogen activator in acute myocardial infarction.N Engl J Med 1987;317:581–588.

    PubMed  Google Scholar 

  64. Ny T, Elgh F, Lung B. The structure of human tissue type plasminogen activator gene: Correlation of intron and eutron structure to functional and structural domains.Proc Natl Acad Sci USA 1984;231:146–152.

    Google Scholar 

  65. Collen D, Strassen JM, Marafino BJ, et al. Biologic properties of human tissue type plasminogen activator obtained by expression of recombinant DNA in mammalian cells.J Pharm Exp Res 1984;231:146–152.

    Google Scholar 

  66. Garabedian HD, Gold HK, Leinbach RC, et al. Comparative properties of two clinical preparations of recombinant tissue type plasminogen activator in patients with acute myocardial infarction.J Am Coll Cardiol 1987;9:599–607.

    PubMed  Google Scholar 

  67. Agnelli G, Buchanon MR, Fernandez F, Hirsh J. The thrombolytic and hemorrhagic effects of tPA: Influence on dosage regimens in rabbits.Thromb Res 1985;40:769–777.

    PubMed  Google Scholar 

  68. Kanamasa K, Watanabe I, Cercek B, Yano J, Fishbein MC, Ganz W. Selective decrease in a lysis or old thrombi after rapid administration of t-tPA.J Am Coll Cardiol 1989;14:1359–1364.

    PubMed  Google Scholar 

  69. Clozel J-P, Tschopp T, Luedin E, Holvoet P. Time course of thrombolysis induced by IV bolus or infusion of tPA in a rabbit. Jugular vein thrombosis model.Circulation 1989;79:125–133.

    PubMed  Google Scholar 

  70. Neuhaus KL, Feuerer W, Tebbe SJ, Niederer W, Vogt A, Tebbe U. Improved thrombolysis with a modified dose regimen of recombinant tissue type plasminogen activator.J Am Coll Cardiol 1989;14:1566–1569.

    PubMed  Google Scholar 

  71. Smalling RW, Schumacher R, Morris D, et al. Improved infarct related arterial patency after high dose, weight adjusted, rapid infusion of tissue type plasminogen activator in myocardial infarction. Results of a multicenter randomized trial of two dosage regimens.J Am Coll Cardiol 1990; 15:915–921.

    PubMed  Google Scholar 

  72. McKendall GR, Attubato MJ, Drew TM, et al. Safety and efficacy of a new regimen of intravenous recombinant tissue type plasminogen activator potentially suitable for either prehospital or in hospital administration.J Am Coll Cardiol 1991;18:1774–1778.

    PubMed  Google Scholar 

  73. Nuehaus KL, von Essen R, Tebbe U, et al. Improved thrombolysis in acute myocardial infarction with front loaded administration of alteplase: Results of the rt-PA-APSAC patency study (TAPS).J Am Coll Cardiol 1992;19: 885–891.

    PubMed  Google Scholar 

  74. Carney RJ, Murphy GA, Brandt TR, et al. Randomized angiographic trial of recombinant tissue type plasminogen activator (Alteplase) in myocardial infarction.J Am Coll Cardiol 1992;20:17–23.

    PubMed  Google Scholar 

  75. Tebbe U, Tanswell P, Seifried E, Feuerer W, Scholz KH, Herrmann KS. Single bolus injection of recombinant tissue type plasminogen activator in acute myocardial infarction.Am J Cardiol 1989;64:448–453.

    PubMed  Google Scholar 

  76. Tranchesi B, Chamone DF, Cobbaert C, Van de Werf F, Vanhove P, Verstraete M. Coronary recanalization rate after intravenous bolus of alteplase in acute myocardial infarction.Am J Cardiol 1991;68:161–165.

    PubMed  Google Scholar 

  77. Gemmill JD, Hogg KJ, MacIntyre PD, Booth N, Rae AP, Dunn FG, Hills WS. A pilot study of the efficacy and safety of bolus administration of alteplase in acute myocardial infarction.Br Heart J 1991;66:134–138.

    PubMed  Google Scholar 

  78. Purvis JA, McNeill AJ, Siddiqui RA, et al Efficacy of 100 mg of double bolus alteplase in achieving complete perfusion in the treatment of acute myocardial infarction.J Am Coll Cardiol 1994;23:6–10.

    PubMed  Google Scholar 

  79. Gottlich CM, Cooper B, Schumacher JR, Hillis LD. Do Different doses of intravenous streptokinase alter the frequency of coronary reperfusion in acute myocardial infarction?Am J Cardiol 1988;62:843–846.

    PubMed  Google Scholar 

  80. Six AJ, Louwerenburg HW, Braams R, et al. A double blind randomized multicenter dose ranging trial of intravenous streptokinase in acute myocardial infarction.Am J Cardiol 1990;65:119–123.

    PubMed  Google Scholar 

  81. Taylor GJ, Moses HW, Koester K, et al. A difference between front loaded streptokinase and standard dose recombinant tissue type plasminogen activator in preserving left ventricular function after acute myocardial infarction (The Central Illinois Thrombolytic Study).Am J Cardiol 1993; 72:1010–1014.

    PubMed  Google Scholar 

  82. Torr SR, Nachowiak DA, Fujii S, Sobel BE. “Plasminogen steal” and clot lysis.J Am Coll Cardiol 1992;19:1085–1090.

    PubMed  Google Scholar 

  83. Andrew M, Brooker L, Beaker M, Paes B, Weitz J. Fibrin clot lysis by thrombolytic agents is impaired in newborns due to a low plasminogen concentration.Thromb Haemost 1992;68:325–330.

    PubMed  Google Scholar 

  84. Lucore CL, Fujii S, Sobel BE. Dependence of fibrinolytic activity on the concentration of free rather than total tissue type plasminogen activator in plasma after pharmacologic administration.Circulation 1989;79:1204–1213.

    PubMed  Google Scholar 

  85. Tanswell P, Tebbe U, Neuhaus KL, Glasle L, Wojcik J, Seifried E. Pharmacokinetics and fibrin specificity of alteplase during accelerated infusions in acute myocardial infarction.J Am Coll Cardiol 1992;19:1071–1075.

    PubMed  Google Scholar 

  86. LATE Study Group. Late Assessment of Thrombolytic Efficacy (LATE) study with alteplase 6–24 hours after onset of acute myocardial infarction.Lancet 1993;342:759–766.

    Google Scholar 

  87. Eisenberg PR, Abdenschein DR, Becker RC, Loscalzo J, Sobel BE, and the TIMI V Investigators. Lack of suppression of thrombin activity in vivo: A determinant of failure of recanalization.J Am Coll Cardiol 1993;21:464A.

    Google Scholar 

  88. Scharfstein JS, George D, Rurchenal JEB, et al. for the TIMI 5 investigators. Hemostatic markers predict clinical events in patients treated with rt-PA and adjunctive antithrombotic therapy.J Am Coll Cardiol 1994;1A–48AA.

  89. Loscalzo J, Abdenschein D, Eisenberg P, et al., for the TIMI 5 investigators. Comparative effects of heparin and hirudin on fibrinolytic and thrombotic activities during tissue type plasminogen activator therapy.Circulation 1993; 88(Suppl I):I-200.

    Google Scholar 

  90. Cannon CP, McCabel CH, Henry TD, et al. for the TIMI 5 investigators. Recombinant disulfate hirudin compared to heparin in conjunction with alteplase and aspirin for acute myocardial infarction: Results of the TIMI 5 trial.J Am Coll Cardiol 1994;23:993–1003.

    PubMed  Google Scholar 

  91. Ohman EM, Califf RM, Topol EJ, et al. and the TAMI study group. Consequences of reocclusion after successful reperfusion therapy in acute myocardial infarction.Circulation 1990;82:781–791.

    PubMed  Google Scholar 

  92. Reiner JS, Lundergan CF, Dekan J, et al. for the GUSTO Investigators. Late infarct related coronary artery opening after initially failed thrombolysis is common and improves left ventricular function.J Am Coll Cardiol 1994;(Suppl A):14A.

    Google Scholar 

  93. Lerman A, Edwards BS, Hallett JW, Heublein DM, Sandberg SM, Burnett JC. Circulating and tissue endothelial immunoreactivity in advanced atherosclerosis.N Engl J Med 1991;325:997–1001.

    PubMed  Google Scholar 

  94. Chin JH, Azhar S, Hoffman BB. Inactivation of endothelial derived relaxing factor by oxidized lipoproteins.J Clin Invest 1992;89:10–18.

    PubMed  Google Scholar 

  95. Wilson BD, Pitas RE, Rodgers GM. Regulation of endothelial cell protein C activation by native and oxidized low density lipoprotein.Thromb Hemost 1992;18:11–17.

    Google Scholar 

  96. Snow TR, Deal MT, Dickey DT, Esmon CT. Protein C activation following coronary artery occlusion in the in situ porcine heart.Circulation 1991;84:293–299.

    PubMed  Google Scholar 

  97. Gruber A, Harker LA, Hanson SR, Kelly AB, Griffin JH. Antithrombotic effects of combining activated protein C and urokinase in nonhuman primates.Circulation 1991;84: 2454–2462.

    PubMed  Google Scholar 

  98. Soifer SJ, O'Keefe J, Vu TKH, Charo IF, Coughlin SR. Thrombin receptor expression in normal and atherosclerotic human arteries.J Clin Invest 1992;90:1614–1612.

    PubMed  Google Scholar 

  99. Haskel EJ, Torr SR, Day KD, et al. Prevention of arterial reocclusion after thrombolysis with recombinant lipoprotein-associated coagulation inhibitor.Circulation 1991;84: 821–827.

    PubMed  Google Scholar 

  100. van der Wal AC, Becker AE, van der Loos CM, Das PK. Site of intimai rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology.Circulation 1994;89:36–44.

    PubMed  Google Scholar 

  101. Moliterno DJ, Lange RA, Meidell RS, et al. Relation of plasma lipoprotein (a) to infarct artery patency in survivors of myocardial infarction.Circulation 1993;88:935–940.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Thrombosis Research Center, University of Massachusetts Medical School, Worcester, Massachusetts

    Richard C. Becker

Authors
  1. Richard C. Becker
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Becker, R.C. Achieving optimal reperfusion without adjunctive antithrombotic therapy: Novel thrombolytic dosing strategies. J Thromb Thrombol 1, 269–277 (1995). https://doi.org/10.1007/BF01060736

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01060736

Key words

Search

Navigation