Current Cardiology Reports

, Volume 2, Issue 5, pp 386–394 | Cite as

Antithrombotic therapy in the cardiac catheterization laboratory: Focus on antiplatelet agents

  • Mark I. Furman
  • Andrew L. FrelingerIII
  • Alan D. Michelson


Pharmacologic advances in the use of antithrombotic agents have paralleled the technologic innovations used in patients undergoing coronary interventions. The recognition of the central role of platelets in the development of complications related to coronary interventions led to the investigation and subsequent routine use of several antiplatelet agents as adjuvants to coronary intervention. Thus, the oral agents aspirin and either ticlopidine or clopidogrel are routinely administered after coronary stenting. Intravenous glycoprotein (GP) IIb/IIIa antagonists have been extensively studied and reduce adverse cardiac events in patients undergoing coronary interventions, especially those receiving intracoronary stents. Despite the growing use of GP IIb/IIIa antagonists, much information remains unknown as to the proper dosing and the effects these agents have on other elements of the hemostatic and vascular systems.


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References and Recommended Reading

  1. 1.
    2000 Heart and Stroke Statistical Update. Dallas: American Heart Association; 2000.Google Scholar
  2. 2.
    Ellis SG: Elective coronary angioplasty: technique and complications, In Textbook of Interventional Cardiology. Edited by Topol EJ. Philadelphia: WB Saunders; 1999.Google Scholar
  3. 3.
    Fuster V, Badimon L, Badimon JJ, Chesebro JH: The pathogenesis of coronary artery disease and the acute coronary syndromes. N Engl J Med 1992, 326:242–250.PubMedCrossRefGoogle Scholar
  4. 4.
    Wilentz JR, Sanborn TA, Haudenschild CC, et al.: Platelet accumulation in experimental angioplasty: time course and relation to vascular injury. Circulation 1987, 75:636–642.PubMedGoogle Scholar
  5. 5.
    Gruentzig A: Transluminal dilitation of coronary artery stenosis [letter] Lancet 1978, 1:263.CrossRefGoogle Scholar
  6. 6.
    Awtry EH, Loscalzo J: Aspirin. Circulation 2000, 101:1206–1218.PubMedGoogle Scholar
  7. 7.
    Lefkovits J, Topol E: Role of platelet inhibitor agents in coronary artery disease. In Textbook of Interventional Cardiology, end 3. Edited by Topol E. Philadelphia: WB Saunders; 1999:3–24.Google Scholar
  8. 8.
    Roth GJ, Majerus PW: The mechanism of the effect of aspirin on human platelets. I. Acetylation of a particulate fraction protein. J Clin Invest 1975, 56:624–632.PubMedGoogle Scholar
  9. 9.
    Schwartz L, Bourassa MG, Lesperance J, et al.: Aspirin and dipyridamole in the prevention of restenosis after percutaneous transluminal coronary angioplasty. N Engl J Med 1988, 318:1714–1719.PubMedCrossRefGoogle Scholar
  10. 10.
    Barnathan ES, Schwartz JS, Taylor L, et al.: Aspirin and dipyridamole in the prevention of acute coronary thrombosis complicating coronary angioplasty. Circulation 1987, 76:125–134.PubMedGoogle Scholar
  11. 11.
    Lembo NJ, Black AJ, Roubin GS, et al.: Effect of pretreatment with aspirin versus aspirin plus dipyridamole on frequency and type of acute complications of percutaneous transluminal coronary angioplasty. Am J Cardiol 1990, 65:422–426.PubMedCrossRefGoogle Scholar
  12. 12.
    Popma JJ, Bittl JA, Ohman EM, et al.: Antithrombotic therapy in patients undergoing coronary angioplasty. Chest 2000, in press. Latest Consensus Conference on Antithrombotic Therapy (ACCP 2000) guidelines on the use of antithrombotic agents in patients undergoing coronary interventions.Google Scholar
  13. 13.
    Taylor RR, Gibbons FA, Cope GD, et al.: Effects of low-dose aspirin on restenosis after coronary angioplasty. Am J Cardiol 1991, 68:874–878.PubMedCrossRefGoogle Scholar
  14. 14.
    Quinn MJ, Fitzgerald DJ: Ticlopidine and clopidogrel. Circulation 1999, 100:1667–1672.PubMedGoogle Scholar
  15. 15.
    Gregorini L, Marco J, Fajadet J, et al.: Ticlopidine and aspirin pretreatment reduces coagulation and platelet activation during coronary dilation procedures. J Am Coll Cardiol 1997, 29:13–20.PubMedCrossRefGoogle Scholar
  16. 16.
    Klein LW, Calvin JE: Use of clopidrogel in coronary stenting: what was the question? J Am Coll Cardiol 1999, 34:1895–1898.PubMedCrossRefGoogle Scholar
  17. 17.
    McTavish D, Faulds D, Goa KL: Ticlopidine. An updated review of its pharmacology and therapeutic use in plateletdependent disorders [published erratum appears in Drugs 1990, 40] Drugs 1990, 40:238–259.PubMedGoogle Scholar
  18. 18.
    Gent M, Blakely JA, Easton JD, et al.: The Canadian American Ticlopidine Study (CATS) in thromboembolic stroke. Lancet 1989, 1:1215–1220.PubMedCrossRefGoogle Scholar
  19. 19.
    Bennett CL, Weinberg PD, Rozenberg-Ben-Dror K, et al.: Thrombotic thrombocytopenic purpura associated with ticlopidine. A review of 60 cases. Ann Intern Med 1998, 128:541–544.PubMedGoogle Scholar
  20. 20.
    Bennett C, Connors J, Carwile J, et al.: Thrombotic thrombocytopenia purpura associated with clopidogrel. N Engl J Med 2000, 342:1773–1777.PubMedCrossRefGoogle Scholar
  21. 21.
    Balsano F, Rizzon P, Violi F, et al.: Antiplatelet treatment with ticlopidine in unstable angina. A controlled multicenter clinical trial. The Studio della Ticlopidina nell’Angina Instabile Group. Circulation 1990, 82:17–26.PubMedGoogle Scholar
  22. 22.
    The CAPRIE Steering Committee: A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996, 348:1329–1339.CrossRefGoogle Scholar
  23. 23.
    Rupprecht HJ, Darius H, Borkowski U, et al.: Comparison of antiplatelet effects of aspirin, ticlopidine, or their combination after stent implantation. Circulation 1998, 97:1046–1052.PubMedGoogle Scholar
  24. 24.
    Herbert JM, Dol F, Bernat A, et al.: The anti-aggregating and antithrombotic activity of clopidogrel is potentiated by aspirin in several experimental models in the rabbit. Thromb Haemost 1998, 80:512–518.PubMedGoogle Scholar
  25. 25.
    Brack MJ, Hubner PJ, Gershlick AH: Anticoagulation after intracoronary stent insertion. Br Heart J 1994, 72:294–296.PubMedGoogle Scholar
  26. 26.
    Colombo A, Hall P, Nakamura S, et al.: Intracoronary stenting without anticoagulation accomplished with intravascular ultrasound guidance. Circulation 1995, 91:1676–1688.PubMedGoogle Scholar
  27. 27.
    Karrillon GJ, Morice MC, Benveniste E, et al.: Intracoronary stent implantation without ultrasound guidance and with replacement of conventional anticoagulation by antiplatelet therapy — 30-day clinical outcome of the French Multicenter Registry. Circulation 1996, 94:1519–1527.PubMedGoogle Scholar
  28. 28.
    Schomig A, Neumann FJ, Kastrati A, et al.: A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents. N Engl J Med 1996, 334:1084–1089.PubMedCrossRefGoogle Scholar
  29. 29.
    Leon MB, Baim DS, Popma JJ, et al.: A clinical trial comparing three antithrombotic-drug regimens after coronary-artery stenting. Stent Anticoagulation Restenosis Study Investigators. N Engl J Med 1998, 339:1665–1671. Establishes the combination of aspirin and ticlopidine (over the combination of aspirin and warfarin or aspirin alone) as the antithrombotic regimen of choice after intracoronary stent insertion.PubMedCrossRefGoogle Scholar
  30. 30.
    Bertrand ME, Legrand V, Boland J, et al.: Randomized multicenter comparison of conventional anticoagulation versus antiplatelet therapy in unplanned and elective coronary stenting. The Full Anticoagulation versus Aspirin and Ticlopidine (FANTASTIC) study. Circulation 1998, 98:1597–1603. Establishes the combination of aspirin and ticlopidine over aspirin and conventional anticoagulation as the antithrombotic regimen of choice after intracoronary stent insertion.PubMedGoogle Scholar
  31. 31.
    Urban P, Macaya C, Rupprecht HJ, et al.: Randomized evaluation of anticoagulation versus antiplatelet therapy after coronary stent implantation in high-risk patients: the multicenter aspirin and ticlopidine trial after intracoronary stenting (MATTIS). Circulation 1998, 98:2126–232. In high risk patients, establishes the combination of aspirin and ticlopidine over aspirin and conventional anticoagulation as the antithrombotic regimen of choice after intracoronary stent insertion.PubMedGoogle Scholar
  32. 32.
    Berger PB, Bell MR, Hasdai D, et al.: Safety and efficacy of ticlopidine for only 2 weeks after successful intracoronary stent placement. Circulation 1999, 99:248–253.PubMedGoogle Scholar
  33. 33.
    Steinhubl SR, Lauer MS, Mukherjee DP, et al.: The duration of pretreatment with ticlopidine prior to stenting is associated with the risk of procedure-related non-Q-wave myocardial infarctions. J Am Coll Cardiol 1998, 32:1366–1370. Suggests that the optimal time of administration of ticlopidine in stented patients is before insertion of the stent.PubMedCrossRefGoogle Scholar
  34. 34.
    Moussa I, Oetgen M, Roubin G, et al.: Effectiveness of clopidogrel and aspirin versus ticlopidine and aspirin in preventing stent thrombosis after coronary stent implantation. Circulation 1999, 99:2364–2366. Suggests that, in combination with aspirin, clopidogrel is as effective as ticlopidine in patients receiving intracoronary stents.PubMedGoogle Scholar
  35. 35.
    Berger PB, Bell MR, Rihal CS, et al.: Clopidogrel versus ticlopidine after intracoronary stent placement. J Am Coll Cardiol 1999, 34:1891–1894. Suggests that, in combination with aspirin, clopidogrel is as effective as ticlopidine in patients receiving intracoronary stents.PubMedCrossRefGoogle Scholar
  36. 36.
    Mishkel GJ, Aguirre FV, Ligon RW, et al.: Clopidogrel as adjunctive antiplatelet therapy during coronary stenting. J Am Coll Cardiol 1999, 34:1884–1890. Suggests that, in combination with aspirin, clopidogrel is as effective as ticlopidine in patients receiving intracoronary stents.PubMedCrossRefGoogle Scholar
  37. 37.
    Muller C, Buttner HJ, Petersen J, Roskamm H: A randomized comparison of clopidogrel and aspirin versus ticlopidine and aspirin after the placement of coronary-artery stents. Circulation 2000, 101:590–593. Suggests that, in combination with aspirin, clopidogrel is as effective as ticlopidine in patients receiving intracoronary stents.PubMedGoogle Scholar
  38. 38.
    Kleiman NS, Graziadei N, Jordan RE, et al.: Ticlopidine enhances the platelet inhibitory capacity of abciximab in vitro. J Thromb Thrombolysis 2000, 9:29–36.PubMedCrossRefGoogle Scholar
  39. 39.
    Fredrickson BJ, Turner NA, Kleiman NS, et al.: Effects of abciximab, ticlopidine, and combined Abciximab/ Ticlopidine therapy on platelet and leukocyte function in patients undergoing coronary angioplasty. Circulation 2000, 101:1122–1129. This study demonstrates that the combination of ticlopidine and abciximab is a more powerful antithrombotic then either agent alone. Moreover, abciximab inhibits the formation of leukocyte platelet aggregates.PubMedGoogle Scholar
  40. 40.
    Harker L, Mann K: Thrombosis and fibrinolysis. In Cardiovascular Thrombosis: Thrombocardiology and Thromboneurology, edn 2. Edited by Verstraete M, Fuster V, Topol E. Philadelphia: Lippincott-Raven; 1998:3–22.Google Scholar
  41. 41.
    Wagner CL, Mascelli MA, Neblock DS, et al.: Analysis of GPIIb/ IIIa receptor number by quantification of 7E3 binding to human platelets. Blood 1996, 88:907–914.PubMedGoogle Scholar
  42. 42.
    Phillips DR, Charo IF, Scarborough RM: GPIIb/IIIa: the responsive integrin. Cell 1991, 65:359–362.PubMedCrossRefGoogle Scholar
  43. 43.
    Lincoff AM, Califf RM, Topol EJ: Platelet glycoprotein IIb/IIIa receptor blockade in coronary artery disease. J Am Coll Cardiol 2000, 35:1103–1115.PubMedCrossRefGoogle Scholar
  44. 44.
    The EPIC Investigators: Use of monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high risk angioplasty. N Engl J Med 1994, 330:956–961.CrossRefGoogle Scholar
  45. 45.
    The EPILOG Investigators: Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization. N Engl J Med 1997, 336:1689–1696.CrossRefGoogle Scholar
  46. 46.
    The CAPTURE Study Investigators: Randomised placebocontrolled trial of abciximab before and during coronary intervention in refractory unstable angina: the CAPTURE Study. Lancet 1997, 349:1429–1435.CrossRefGoogle Scholar
  47. 47.
    The EPISTENT Investigators: Randomised placebo-controlled and balloon-angioplasty-controlled trial to assess safety of coronary stenting with use of platelet glycoprotein- IIb/IIIa blockade. Evaluation of Platelet IIb/IIIa Inhibitor for Stenting. Lancet 1998, 352:87–92. The landmark study demonstrating the superiority of the combination of stenting and abciximab over either therapy alone in reducing complications after PCI.CrossRefGoogle Scholar
  48. 48.
    Brener SJ, Barr LA, Burchenal JE, et al.: Randomized, placebocontrolled trial of platelet glycoprotein IIb/IIIa blockade with primary angioplasty for acute myocardial infarction. ReoPro and Primary PTCA Organization and Randomized Trial (RAPPORT) Investigators. Circulation 1998, 98:734–741.PubMedGoogle Scholar
  49. 49.
    Topol EJ, Ferguson JJ, Weisman HF, et al.: Long-term protection from myocardial ischemic events in a randomized trial of brief integrin beta3 blockade with percutaneous coronary intervention. EPIC Investigator Group. Evaluation of Platelet IIb/IIIa Inhibition for Prevention of Ischemic Complication. JAMA 1997, 278:479–484.PubMedCrossRefGoogle Scholar
  50. 50.
    Lincoff AM, Tcheng JE, Califf RM, et al.: Sustained suppression of ischemic complications of coronary intervention by platelet GP IIb/IIIa blockade with abciximab: one-year outcome in the EPILOG trial. Evaluation in PTCA to Improve Long-term Outcome with abciximab GP IIb/IIIa blockade. Circulation 1999, 99:1951–1958.PubMedGoogle Scholar
  51. 51.
    Topol EJ, Mark DB, Lincoff AM, for the EPISTENT Investigators: Outcomes at 1 year and economic implications of platelet glycoprotein IIb/IIIa blockade in patients undergoing coronary stenting: results from a multicentre randomised trial. Lancet 1999, 354:2019–2024. One-year data in EPISTENT demonstrates sustained reduction in mortality at 1 year with the combination of abciximab and stenting.PubMedCrossRefGoogle Scholar
  52. 52.
    IMPACT-II Investigators: Randomised placebo-controlled trial of effect of eptifibatide on complications of percutaneous coronary intervention: IMPACT-II. Integrilin to Minimise Platelet Aggregation and Coronary Thrombosis-II. Lancet 1997, 349:1422–1428.CrossRefGoogle Scholar
  53. 53.
    Phillips DR, Teng W, Arfsten A, et al.: Effect of Ca2+ on GP IIb/IIIa interactions with integrilin: enhanced GP IIb/IIIa binding and inhibition of platelet aggregation by reductions in the concentration of ionized calcium in plasma anticoagulated with citrate. Circulation 1997, 96:1488–1494.PubMedGoogle Scholar
  54. 54.
    The PURSUIT Trial Investigators: Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes. The PURSUIT Trial Investigators. Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy. N Engl J Med 1998, 339:436–443.CrossRefGoogle Scholar
  55. 55.
    Tcheng JE, Madan M, Cohen EA, et al.: Enhanced suppression of the platelet receptor using integrilin (eptifibatide) therapy. 49th Scientific Session of the American College of Cardiology Meeting, Late-Breaking Clinical Trials Session. Anaheim, CA: March 12–15, 2000.Google Scholar
  56. 56.
    The RESTORE Investigators: Effects of platelet glycoprotein IIb/IIIa blockade with tirofiban on adverse cardiac events in patients with unstable angina or acute myocardial infarction undergoing coronary angioplasty. Randomized Efficacy Study of Tirofiban for Outcomes and REstenosis. Circulation 1997, 96:1445–1453.Google Scholar
  57. 57.
    Mathew V, Grill DE, Scott CG, et al.: The influence of abciximab use on clinical outcome after aortocoronary vein graft interventions. J Am Coll Cardiol 1999, 34:1163–1169.PubMedCrossRefGoogle Scholar
  58. 58.
    Coller BS, Folts JD, Smith SR, et al.: Abolition of in vivo platelet thrombus formation in primates with monoclonal antibodies to the platelet GPIIb/IIIa receptor. Correlation with bleeding time, platelet aggregation, and blockade of GPIIb/IIIa receptors. Circulation 1989, 80:1766–1774.PubMedGoogle Scholar
  59. 59.
    Phillips DR, Scarborough RM: Clinical pharmacology of eptifibatide. Am J Cardiol 1997, 80:B11-B20.CrossRefGoogle Scholar
  60. 60.
    Kereiakes DJ, Broderick TM, Roth EM, et al.: Time course, magnitude, and consistency of platelet inhibition by abciximab, tirofiban, or eptifibatide in patients with unstable angina pectoris undergoing percutaneous coronary intervention. Am J Cardiol 1999, 84:391–395. Demonstrates that at current FDA-recommended doses, there is significant variability among the GPIIb/IIIa antagonists in inhibiting platelet aggregation.PubMedCrossRefGoogle Scholar
  61. 61.
    Steinhubl S, Talley D, Kereiakes DJ, et al.: A prospective multicenter study to determine the optimal level of platelet inhibition with GPIIb/IIIa inhibitiors inpatients undergoing coronary intervention [abstract]. J Am Coll Cardiol 2000, 35:4A.Google Scholar
  62. 62.
    Steinhubl SR, Kottke-Marchant K, Moliterno DJ, et al.: Attainment and maintenance of platelet inhibition through standard dosing of abciximab in diabetic and nondiabetic patients undergoing percutaneous coronary intervention. Circulation 1999, 100:1977–1982.PubMedGoogle Scholar
  63. 63.
    Kleiman NS, Raizner AE, Jordan R, et al.: Differential inhibition of platelet aggregation induced by adenosine diphosphate or a thrombin receptor-activating peptide in patients treated with bolus chimeric 7E3 Fab: Implications for inhibition of the internal pool of GPIIb/IIIa receptors. J Am Coll Cardiol 1995, 26:1665–1671.PubMedCrossRefGoogle Scholar
  64. 64.
    Bihour C, Durrieu-Jais C, Macchi L, et al.: Expression of markers of platelet activation and the interpatient variation in response to abciximab. Arterioscler Thromb Vasc Biol 1999, 19:212–219.PubMedGoogle Scholar
  65. 65.
    Tcheng JE, Harrington RA, Kottke-Marchant K, et al.: Multicenter, randomized, double-blind, placebo-controlled trial of the platelet integrin glycoprotein IIb/IIIa blocker integrelin in elective coronary intervention. Circulation 1995, 91:2151–2157.PubMedGoogle Scholar
  66. 66.
    Smith JW, Steinhubl SR, Lincoff AM, et al.: Rapid plateletfunction assay: an automated and quantitative cartridge- based method. Circulation 1999, 99:620–625.PubMedGoogle Scholar
  67. 67.
    Coller BS: Potential non-glycoprotein IIb/IIIa effects of abciximab. Am Heart J 1999, 138:S1-S5. An excellent discussion about the pharmacologic differences between the GP IIb/IIIa antagonists.PubMedCrossRefGoogle Scholar
  68. 68.
    Scarborough RM, Kleiman NS, Phillips DR: Platelet glycoprotein IIb/IIIa antagonists. What are the relevant issues concerning their pharmacology and clinical use? Circulation 1999, 100:437–444. An excellent discussion about the pharmacologic differences between the GP IIb/IIIa antagonists.PubMedGoogle Scholar
  69. 69.
    Kereiakes DJ, Runyon JP, Broderick TM, Shimshak TM: IIb’s are not IIb’s. Am J Cardiol 2000, 85:23–31.CrossRefGoogle Scholar
  70. 70.
    Tam SH, Sassoli PM, Jordan RE, Nakada MT: Abciximab (ReoPro, chimeric 7E3 Fab) demonstrates equivalent affinity and functional blockade of glycoprotein IIb/IIIa and alpha(v)beta3 integrins. Circulation 1998, 98:1085–1091. Demonstrates that abciximab binds with equal affinity to avb3 and GP IIb/IIIa.PubMedGoogle Scholar
  71. 71.
    Byzova TV, Rabbani R, D’Souza SE, Plow EF: Role of integrin alpha(v)beta3 in vascular biology. Thromb Haemost 1998, 80:726–734.PubMedGoogle Scholar
  72. 72.
    Stouffer GA, Hu Z, Sajid M, et al.: Beta3 integrins are upregulated after vascular injury and modulate thrombospondin- and thrombin-induced proliferation of cultured smooth muscle cells. Circulation 1998, 97:907–915.PubMedGoogle Scholar
  73. 73.
    Slepian MJ, Massia SP, Dehdashti B, et al.: Beta3-integrins rather than beta1-integrins dominate integrin-matrix interactions involved in postinjury smooth muscle cell migration. Circulation 1998, 97:1818–1827.PubMedGoogle Scholar
  74. 74.
    Marso SP, Lincoff AM, Ellis SG, et al.: Optimizing the percutaneous interventional outcomes for patients with diabetes mellitus: results of the EPISTENT (Evaluation of platelet IIb/IIIa inhibitor for stenting trial) diabetic substudy. Circulation 1999, 100:2477–2484.PubMedGoogle Scholar
  75. 75.
    The ERASER Investigators: Acute platelet inhibition with abciximab does not reduce in-stent restenosis (ERASER study). Circulation 1999, 100:799–806.Google Scholar
  76. 76.
    Munro JM, Cotran RS: The pathogenesis of atherosclerosis: atherogenesis and inflammation. Lab Invest 1988, 58:249–261.PubMedGoogle Scholar
  77. 77.
    Mattsson E, Clowes AW: Current concepts in restenosis following balloon angioplasty. Trends in Cardiovascular Medicine 1995, 5:200–204.CrossRefGoogle Scholar
  78. 78.
    Mickelson JK, Lakkis NM, Villarreallevy G, et al.: Leukocyte activation with platelet adhesion after coronary angioplasty: A mechanism for recurrent disease? J Am Coll Cardiol 1996, 28:345–353.PubMedCrossRefGoogle Scholar
  79. 79.
    Altieri DC, Edginton TS: A monoclonal antibody reacting with distinct adhesion molecules defines a transition in the functional state of the receptor CD11b/CD18 (Mac-1). J Immunol 1988, 141:2656–2660.PubMedGoogle Scholar
  80. 80.
    Simon DI, Xu H, Ortlepp S, et al.: 7E3 monoclonal antibody directed against the platelet glycoprotein IIb/IIIa cross-reacts with the leukocyte integrin Mac-1 and blocks adhesion to fibrinogen and ICAM-1. Arterioscler Thromb Vasc Biol 1997, 17:528–535.PubMedGoogle Scholar
  81. 81.
    Rogers C, Edelman ER, Simon DI: A mAb to the beta(2)- leukocyte integrin Mac-1 (CD11b/CD18) reduces intimal thickening after angioplasty or stent implantation in rabbits. Proc Natl Acad Sci U S A 1998, 95:10134–10139.PubMedCrossRefGoogle Scholar
  82. 82.
    Cerletti C, Evangelista V, de Gaetano G: P-selectin-beta 2-integrin cross-talk: a molecular mechanism for polymorphonuclear leukocyte recruitment at the site of vascular damage. Thromb Haemost 1999, 82:787–793.PubMedGoogle Scholar
  83. 83.
    Simon DI, Chen Z, Xu H, et al.: Platelet glycoprotein Iba is a counter-receptor of the leukocyte integrin Mac-1 (CD11b/ CD18). J Exper Med 2000, in press.Google Scholar
  84. 84.
    Weyrich AS, Elstad MR, McEver RP, et al.: Activated platelets signal chemokine synthesis by human monocytes. J Clin Invest 1996, 97:1525–1534.PubMedCrossRefGoogle Scholar
  85. 85.
    Siminiak T, Flores NA, Sheridan DJ: Neutrophil interactions with endothelium and platelets: possible role in the development of cardiovascular injury. Eur Heart J 1995, 16:160–170.PubMedGoogle Scholar
  86. 86.
    Lefer A, Campbell B, Scalia R, Lefer DJ: Synergism between platelets and neutrophils in provoking cardiac dysfunction after ischemia and reperfusion. Role of selectins. Circulation 1998, 98:1322–1328. Demonstrates the role of both platelets and neutrophils in reperfusion injury.PubMedGoogle Scholar
  87. 87.
    Lefer DJ, Shandelya SM, Serrano CV Jr, et al.: Cardioprotective actions of a monoclonal antibody against CD-18 in myocardial ischemia-reperfusion injury. Circulation 1993, 88:1779–1787.PubMedGoogle Scholar
  88. 88.
    Simpson PJ, Todd RF, Fantone JC, et al.: Reduction of experimental canine myocardial reperfusion injury by a monoclonal antibody (anti-Mo1, anti-CD11b) that inhibits leukocyte adhesion. J Clin Invest 1988, 81:624–629.PubMedGoogle Scholar
  89. 89.
    Furman MI, Benoit SE, Barnard MR, et al.: Increased platelet reactivity and circulating monocyte-platelet aggregates in patients with stable coronary artery disease. J Am Coll Cardiol 1998, 31:352–358.PubMedCrossRefGoogle Scholar
  90. 90.
    Ott I, Neumann FJ, Gawaz M, et al.: Increased neutrophilplatelet adhesion in patients with unstable angina. Circulation 1996, 94:1239–1246.PubMedGoogle Scholar
  91. 91.
    Neumann FJ, Marx N, Gawaz M, et al.: Induction of cytokine expression in leukocytes by binding of thrombin-stimulated platelets. Circulation 1997, 95:2387–2394.PubMedGoogle Scholar
  92. 92.
    Furman MI, Krueger LA, Frelinger AL, et al.: Tirofiban and eptifibatide, but not abciximab, induce leukocyte-platelet aggregation. Circulation 1999, 100:I-681.Google Scholar
  93. 93.
    Tcheng JE, Ellis SG, George BS, et al.: Pharmacodynamics of chimeric glycoprotein IIb/IIIa integrin antiplatelet antibody fab 7E3 in high-risk coronary angioplasty. Circulation 1994, 90:1757–1764.PubMedGoogle Scholar
  94. 94.
    Mascelli MA, Lance ET, Damaraju L, et al.: Pharmacodynamic profile of short-term abciximab treatment demonstrates prolonged platelet inhibition with gradual recovery from GP IIb/IIIa receptor blockade. Circulation 1998, 97:1680–1688. These results are consistent with continuous re-equilibration of abciximab among circulating platelets and may explain the gradual recovery of platelet function seen in patients treated with abciximab.PubMedGoogle Scholar
  95. 95.
    Harrington RA, Kleiman NS, Kottke-Marchant K, et al.: Immediate and reversible platelet inhibition after intravenous administration of a peptide glycoprotein IIb/IIIa inhibitor during percutaneous coronary intervention. Am J Cardiol 1995, 76:1222–1227.PubMedCrossRefGoogle Scholar
  96. 96.
    Kereiakes DJ, Kleiman NS, Ambrose J, et al.: Randomized, double-blind, placebo-controlled dose-ranging study of tirofiban (MK-383) platelet IIb/IIIa blockade in high risk patients undergoing coronary angioplasty. J Am Coll Cardiol 1996, 27:536–542.PubMedCrossRefGoogle Scholar
  97. 97.
    Alig L, Edenhofer A, Hadvary P, et al.: Low molecular weight, non-peptide fibrinogen receptor antagonists. J Med Chem 1992, 35:4393–4407.PubMedCrossRefGoogle Scholar
  98. 98.
    Hillegass WB, Newman AR, Raco DL: Economic issues in glycoprotein IIb/IIIa receptor therapy. Am Heart J 1999, 138:S24-S32.PubMedCrossRefGoogle Scholar
  99. 99.
    Du XP, Plow EF, Frelinger AL, et al.: Ligands "activate" integrin alpha IIb beta 3 (platelet GPIIb/IIIa). Cell 1991, 65:409–416.PubMedCrossRefGoogle Scholar
  100. 100.
    Frelinger AL, Du XP, Plow EF, Ginsberg MH: Monoclonal antibodies to ligand-occupied conformers of integrin alpha IIb beta 3 (glycoprotein IIb/IIIa) alter receptor affinity, specificity, and function. J Biol Chem 1991, 266:17106–17111.PubMedGoogle Scholar
  101. 101.
    Peter K, Schwarz M, Ylanne J, et al.: Induction of fibrinogen binding and platelet aggregation as a potential intrinsic property of various glycoprotein IIb/IIIa (alphaIIbbeta3) inhibitors. Blood 1998, 92:3240–3249. This study suggests that abciximab may paradoxically enhance fibrinogen binding to platelets.PubMedGoogle Scholar
  102. 102.
    Holmes MB, Sobel BE, Cannon CP, Schneider DJ: Increased platelet reactivity in patients given orbofiban after an acute coronary syndrome: an OPUS-TIMI 16 substudy. Orbofiban in Patients with Unstable coronary syndromes. Thrombolysis In Myocardial Infarction [abstract]. Am J Cardiol 2000, 85:491–493.PubMedCrossRefGoogle Scholar
  103. 103.
    Larsen E, Celi A, Gilbert GE, et al.: PADGEM protein: a receptor that mediates the interaction of activated platelets with neutrophils and monocytes. Cell 1989, 59:305–312.PubMedCrossRefGoogle Scholar
  104. 104.
    Matzdorff AC, Kuhnel G, Kemkes-Matthes B, et al.: Effect of glycoprotein IIb/IIIa inhibitors on CD62p expression, platelet aggregates, and microparticles in vitro. J Lab Clin Med 2000, 135:247–255.PubMedCrossRefGoogle Scholar
  105. 105.
    Mann KG: Prothrombin and thrombin. In Hemostasis and Thrombosis. Basic Principles and Clinical Practice. Edited by Colman RW, Hirsh J, Marder, VJ, Salzman EW. Philadelphia: JB Lippincott; 1994:184–200.Google Scholar
  106. 106.
    Ammar T, Scudder LE, Coller BS: In vitro effects of the platelet glycoprotein IIb/IIIa receptor antagonist c7E3 Fab on the activated clotting time. Circulation 1997, 95:614–617.PubMedGoogle Scholar
  107. 107.
    Moliterno DJ, Califf RM, Aguirre FV, et al.: Effect of platelet glycoprotein IIb/IIIa integrin blockade on activated clotting time during percutaneous transluminal coronary angioplasty or directional atherectomy (the EPIC trial). Am J Cardiol 1995, 75:559–562.PubMedCrossRefGoogle Scholar
  108. 108.
    Dangas G, Badimon JJ, Coller BS, et al.: Administration of abciximab during percutaneous coronary intervention reduces both ex vivo platelet thrombus formation and fibrin deposition: implications for a potential anticoagulant effect of abciximab. Arterioscler Thromb Vasc Biol 1998, 18:1342–1349.PubMedGoogle Scholar
  109. 109.
    Reverter JC, Beguin S, Kessels H, et al.: Inhibition of plateletmediated, tissue factor-induced thrombin generation by the mouse/human chimeric 7E3 antibody. Potential implications for the effect of c7E3 Fab treatment on acute thrombosis and "clinical restenosis". J Clin Invest 1996, 98:863–874.PubMedGoogle Scholar
  110. 110.
    Pedicord DL, Thomas BE, Mousa SA, Dicker IB: Glycoprotein IIb/IIIa receptor antagonists inhibit the development of platelet procoagulant activity. Thromb Res 1998, 90:247–258.PubMedCrossRefGoogle Scholar
  111. 111.
    Gemmell CH, Sefton MV, Yeo EL: Platelet-derived microparticle formation involves glycoprotein IIb-IIIa. Inhibition by RGDS and a Glanzmann’s thrombasthenia defect. J Biol Chem 1993, 268:14586–14589.PubMedGoogle Scholar
  112. 112.
    Keularts IM, Beguin S, de Zwaan C, Hemker HC: Treatment with a GPIIb/IIIa antagonist inhibits thrombin generation in platelet rich plasma from patients. Thromb Haemost 1998, 80:370–371.PubMedGoogle Scholar
  113. 113.
    Byzova TV, Plow EF: Networking in the hemostatic system. Integrin alphaIIbbeta3 binds prothrombin and influences its activation. J Biol Chem 1997, 272:27183–27188.PubMedCrossRefGoogle Scholar
  114. 114.
    Furman MI, Krueger LA, Frelinger AL, et al.: GPIIb/IIIa antagonist-induced reduction in platelet surface factor V/Va binding and phosphatidylserine expression in whole blood. Thromb Haemost 2000, in press. GP IIb/IIIa antagonists exert an anticoagulant effect by inhibiting Factor V/Va binding to the platelet surface and inhibit the formation of an anionic phospholipid surface.Google Scholar
  115. 115.
    Sobel M, Adelman B: Characterization of platelet binding of heparins and other glycosaminoglycans. Thromb Res 1988, 50:815–826.PubMedCrossRefGoogle Scholar
  116. 116.
    Xiao Z, Theroux P: Platelet activation with unfractionated heparin at therapeutic concentrations and comparisons with a low-molecular-weight heparin and with a direct thrombin inhibitor. Circulation 1998, 97:251–256.PubMedGoogle Scholar
  117. 117.
    Mascelli MA, Kleiman NS, Marciniak SJ Jr, et al.: Therapeutic heparin concentrations augment platelet reactivity: implications for the pharmacologic assessment of the glycoprotein IIb/IIIa antagonist abciximab. Am Heart J 2000, 139:696–703.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc 2000

Authors and Affiliations

  • Mark I. Furman
    • 1
  • Andrew L. FrelingerIII
    • 2
  • Alan D. Michelson
    • 2
  1. 1.Division of Cardiovascular MedicineUniversity of Massachusetts Medical SchoolWorcesterUSA
  2. 2.Center for Platelet Function StudiesUniversity of Massachusetts Medical SchoolWorcesterUSA

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