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Platelet Monitoring and Interaction of Glycoprotein IIb/IIIa Antagonists with Other Antiplatelet Agents

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Platelet Glycoprotein IIb/IIIa Inhibitors in Cardiovascular Disease

Part of the book series: Contemporary Cardiology ((CONCARD))

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Abstract

Unlike other available antiplatelet agents, a clear dose-effect relationship for the platelet glycoprotein (GP) IIb/IIIa antagonists was well established in animal models prior to study in humans. Based on these early studies, a specific level of blockade of platelet GPIIb/IIIa receptors was identified as that necessary to prevent intraarterial thrombus formation, and this target level was carried forward into clinical trials. Subsequently, the efficacy of these agents in preventing thrombotic events has been confirmed in placebocontrolled trials involving nearly 50,000 patients (1,2). Despite these overall positive findings with GPIIb/IIIa receptor-blocker therapy, several large individual studies, in specific patient populations or with suboptimal dosing regimens, have found a lack of effect in preventing thrombotic complications (3,4). These results raise the question as to whether a specific dose of a GPIIb/IIIa antagonist, adjusted only by patient weight, can provide the same level of platelet inhibition across all clinical syndromes and across all individuals. If there is interindividual variability in response to standard dosing of GPIIb/IIIa antagonists, monitoring of platelet inhibition would allow for individualization of therapy and might improve the efficacy and safety of these agents.

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References

  1. The GUSTO V Investigators. Reperfusion therapy for acute myocardial infarction with fibrinolytic therapy or combination reduced fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition: the GUSTO V randomised trial. Lancet 2001;357:1905–1914.

    Article  Google Scholar 

  2. Lincoff AM, Califf R, Topol EJ. Platelet glycoprotein IIb/IIIa receptor blockade in coronary artery disease. J Am Coll Cardiol 2000;35:1103–1115.

    Article  PubMed  CAS  Google Scholar 

  3. The IMPACT-II Investigators. Randomised placebo-controlled trial of effect of eptifibatide on complications of percutaneous coronary intervention: IMPACT-II. Lancet 1997;349:1422–1428.

    Article  Google Scholar 

  4. The GUSTO IV-ACS Investigators. Effect of glycoprotein IIb/IIIa receptor blocker abcximab on outcome in patients with acute coronary syndromes without early coronary revascularization: the GUSTO IV-ACS randomised trial. Lancet 2001;357:1915–1924.

    Article  Google Scholar 

  5. Gold HK, Coller BS, Yasuda T, et al. Rapid and sustained coronary artery recanalization with combined bolus injection of recombinant tissue-type plasminogen activator and monoclonal anti-platelet GPIIb/ Ina antibody in a dog model. Circulation 1988;77:670–677.

    Article  PubMed  CAS  Google Scholar 

  6. Coller BS, Folts JD, Smith SR, Scudder LE, Jordan R. 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.

    Article  PubMed  CAS  Google Scholar 

  7. 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.

    Article  PubMed  CAS  Google Scholar 

  8. 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.

    Article  PubMed  CAS  Google Scholar 

  9. 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 angio-plasty. J Am Coll Cardiol 1996;27:536–542.

    Article  PubMed  CAS  Google Scholar 

  10. Coller BS, Scudder LE, Beer J, et al. Monoclonal antibodies to platelet GPIIb/IIIa as antithrombotic agents. Ann NY Acad Sci 1991;614:193–213.

    Article  PubMed  CAS  Google Scholar 

  11. The EPIC Investigators. Use of a monoclonal antibody directed against the glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. N Engl J Med 1994;330:956–961.

    Article  Google Scholar 

  12. Topol EJ, Ferguson JJ, Weisman HF, et al., for the EPIC Investigator Group. Long-term protection from myocardial ischemic events in a randomized trial of brief integrin β3 blockade with percutaneous coronary intervention. JAMA 1997;278:479–484.

    Article  PubMed  CAS  Google Scholar 

  13. 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.

    Article  PubMed  CAS  Google Scholar 

  14. Gilchrist I, O’Shea J, Kosoglou T, et al. Pharmacodynamics and pharmacokinetics of higher-dose, double-bolus eptifibatide in percutaneous coronary intervention. Circulation 2001;104:406–411.

    Article  PubMed  CAS  Google Scholar 

  15. The PARAGON Investigators. International, randomized, controlled trial of lamifiban (a platelet glycoprotein IIb/IIIa inhibitor), heparin, or both in unstable angina. Circulation 1998;97:2386–2395.

    Article  Google Scholar 

  16. Steiner B, Wittke B, Harrington RA, Bhapkar MV, Armstrong PW, Moliterno DJ. Plasma level of lamifiban and platelet receptor occupancy best predict clinical outcome in patients with unstable angina: results from PARAGON A (abstract). Circulation 1998;98J-561.

    Google Scholar 

  17. The PARAGON-B Investigators. Randomized, placebo-controlled trial of titrated lamifiban for acute coronary syndromes. Circulation 2002;105:316–321.

    Article  Google Scholar 

  18. Dyke C, Mahaffey KW, Berdan LG, et al. Optimal dosing of a glycoprotein IIb/IIIa antagonist with a simplifiede renal-based algorithm: pharmacodynamic and clinical findings from PARAGON-B (abstract). J Am Coll Cardiol 2001:343A.

    Google Scholar 

  19. Roth U, Hoffman J, Nehmiz G, et al. Level of inhibition of platelet aggregation predicts outcome of patients treated with the oral glycoprotein IIb/IIIa receptor antagonist lefradafiban: results from the Fibrinogen Receptor Occupancy STudy (FROST) (abstract). Eur Heart J 2000;21:625.

    Article  Google Scholar 

  20. Steinhubl S, Talley J, Braden G, et al. Point-of-care measured platelet inhibition correlates with a reduced risk of an adverse cardiac event following percutaneous coronary intervention. Results of the GOLD (AU-Assessing Ultegra) multicenter study. Circulation 2001;103:1403–1409.

    Article  PubMed  CAS  Google Scholar 

  21. George J, Caen JP, Nurden A. Glanzmann’s thrombasthenia: the spectrum of clinical disease. Blood 1990;175:1383–1395.

    Google Scholar 

  22. 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. Lancet 1998;352: 87–92.

    Article  Google Scholar 

  23. 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.

    Article  Google Scholar 

  24. The ESPRIT Investigators. Novel dosing regimen of eptifibatide in planned coronary stent implantation (ESPRIT): a randomised, placebo-controlled trial. Lancet 2000;356:2037–2044.

    Article  Google Scholar 

  25. Bernardi MM, Califf RM, Kleiman N, Ellis SG, Topol EJ, for the TAMI Study Group. Lack of usefulness of prolonged bleeding time in predicting hemorrhagic events in patients receiving the 7E3 glycoprotein IIb/IIIa platelet antibody. Am J Cardiol 1993;72:1121–1125.

    Article  PubMed  CAS  Google Scholar 

  26. Tamberella M, Bhatt D, Chew D, Kereiakes D, Topol EJ, Steinhubl SR. Relation of platelet inactivation with intravenous glycoprotein IIb/IIIa antagonists to major bleeding (from the GOLD Study). Am J Cardiol 2002;89:1429–1431.

    Article  PubMed  CAS  Google Scholar 

  27. Storey R, Wilcox R, Heptinstall S. Differential effects of glycoprotein IIb/IIIa antagonists on platelet microaggregrate and macroaggregate formation and effect of anticoagulant on antagonist potency. Implications for assay methology and comparison of different antagonists. Circulation 1998;98:1616–1621.

    Article  PubMed  CAS  Google Scholar 

  28. Thompson N, Scrutton M, Wallis R. Particle volume change associated with light transmittance changes in the platelet aggregometer: dependence upon aggregating agent and effectiveness of stimulus. Thromb Res 1986;41:615–626.

    Article  PubMed  CAS  Google Scholar 

  29. Cardinal DC, Flower RJ. The electronic aggregometer: a novel device of assessing platelet behavior in blood. J Pharmacol Methods 1980;3:1350–1358.

    Article  Google Scholar 

  30. Mascelli MA, Worley S, Veriabo NJ, et al. Rapid assessment of platelet function with a modified wholeblood aggregometer in percutaneous transluminal coronary angioplasty patients receiving anti-GPIIIb/IIIa therapy. Circulation 1997;96:3860–3866.

    Article  PubMed  CAS  Google Scholar 

  31. Michelson AD. Flow cytometry: a clinical test of platelet function. Blood 1996;87:4925–4936.

    PubMed  CAS  Google Scholar 

  32. Michelson AD, Barnard MR, Krueger LA, Frelinger AL, Furman MI. Evaluation of platelet function by flow cytometry. Methods 2000;21:259–270.

    Article  PubMed  CAS  Google Scholar 

  33. Gawaz M, Ruf A, Neumann F-J, et al. Effect of glycoprotein IIb/IIa receptor antagonism on platelet membrane glycoproteins after coronary stent placement. Thromb Haemost 1998;80:994–1001.

    PubMed  CAS  Google Scholar 

  34. Mascelli MA, Lance ET, Damaraju L, Wagner CL, Weisman HF, Jordan RE. 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.

    Article  PubMed  CAS  Google Scholar 

  35. Quinn M, Deering A, Stewart M, Cox D, Foley B, Fitzgerald D. Quantifying GPIIb/IIIa receptor binding using 2 monoclonal antibodies: discriminating abciximab and small molecular weight antagonists. Circulation 1999;99:2231–2238.

    Article  PubMed  CAS  Google Scholar 

  36. Duke W. The relationship of blood platelets to hemorrhagic disease. Description of a method for determining the bleeding time and coagulation time and report of three cases of hemorrhagic disease relieved by transfusions. JAMA 1910;55:1185–1192.

    Article  Google Scholar 

  37. Milian MG. Influence de la peau sur la coagulabilité du sang. CR Soc Biol (Paris) 1901;53:576–578.

    Google Scholar 

  38. Ivy A, Nelson D, Bucher G. The standardization of certain factors in the cutaneous “venostatsis” bleeding time technique. J Lab Clin Med 1941;26:1812–1822.

    Google Scholar 

  39. Channing Rogers RP, Levin J. A critical reappraisal of the bleeding time. Semin Thromb Hemost 1990; 16:1–20.

    Article  Google Scholar 

  40. Smith JW, Steinhubl SR, Lincoff AM, et al. The rapid platelet function assay (RPFA): an automated and quantitative cartridge-based method. Circulation 1999;99:620–625.

    Article  PubMed  CAS  Google Scholar 

  41. Wheeler G. Braden G, Steinhubl S, et al. The Accumetrics Ultegra RPFA: a study of equivalence to standard platelet function assays in patients undergoing percutaneous coronary intervention with abciximab therapy. Am Heart J 2002;143:602–611.

    Article  PubMed  CAS  Google Scholar 

  42. Steinhubl SR, Kottke-Marchant K, Molitemo DJ, et al. Attainment and maintenance of platelet inhibition by standard dosing of abciximab in diabetic and nondiabetic patients undergoing percutaneous coronary intervention. Circulation 1999:100:1977–1982.

    Article  PubMed  CAS  Google Scholar 

  43. Kereiakes DJ, Mueller M, Howard W, et al. Efficacy of abciximab induced platelet blockade using a rapid point of care assay. J Thromb Thrombolysis 1999;7:265–275.

    Article  PubMed  CAS  Google Scholar 

  44. Gum P, Kottke-Marchant K, Poggio ED, et al. Profile and prevalence of aspirin resistance in patients with cardiovascular disease. Am J Cardiol 2001;88:230–235.

    Article  PubMed  CAS  Google Scholar 

  45. Madan M, Berkowitz SD, Christie DJ, et al. Rapid assessment of glycoprotein IIb/IIIa blockade with the platelet function analyzer (PFA-100) during percutaneous coronary intervention. Am Heart J 2001; 141:226–233.

    Article  PubMed  CAS  Google Scholar 

  46. Shenkman B, Savion N, Dardik R, Tamarin I, Varon D. Testing of platelet deposition on polystyrene surface under flow conditions by the cone and plate(let) analyzer: role of platelet activation, fibrinogen and von Willebrand factor. Thromb Res 2000:99:353–361.

    Article  PubMed  CAS  Google Scholar 

  47. Osende JI, Fuster V, Lev EI, et al. Testing platelet activation with a shear-dependent platelet function test versus aggregation-based tests. Relevance for monitoring long-term glycoprotein IIb/IIIa inhibition. Circulation 2001;103:1488–1491.

    Article  PubMed  CAS  Google Scholar 

  48. Salooja N, Perry DJ. Thromboelastography. Blood Coagul Fibrinolysis 2001;12:327–337.

    Article  PubMed  CAS  Google Scholar 

  49. Greilich PE, Alving BM, O’Neill KL, Chang AS, Reid TJ. A modified thromboelastographic method of monitoring c7E3 Fab in heparinized patients. Anesth Anal 1997;84:31–38.

    CAS  Google Scholar 

  50. Mousa SA, Khurana S, Forsythe MS. Comparative in vitro efficacy of different platelet glycoprotein IIb/ IIIa antagonists on platelet-mediated clot strength induced by tissue factor with use of thromboelastography. Differentiation among glycoprotein IIb/Illa antagonists. Arterioscler Thromb Vasc Biol 2000; 20:1162–1167.

    Article  PubMed  CAS  Google Scholar 

  51. Lakkis NM, George S, Thomas E, Ali M, Guyer K, Carville D. Use of ICHOR-platelet works to assess platelet function in patients treated with GP IIb/IIIa inhibitors. Cathet Cardiovasc Intervent 2001; 53:346–351.

    Article  CAS  Google Scholar 

  52. Nicholson NS, Panzer-Knodle SG, Haas NF, et al. Assessment of platelet function assays. Am Heart J 1998;135:S170–S178.

    Article  PubMed  CAS  Google Scholar 

  53. Li CKN, Hoffman TJ, Hsieh P-Y, Malik S, Watson WC. The Xylum Clot Signature Analyzer: a dynamic flow system that simulates vascular injury. Thromb Res 1998;92:S67–577.

    Article  PubMed  CAS  Google Scholar 

  54. Simon DI, Liu CB, Ganz P, et al. A comparative study of light transmission aggregometry and automated bedside platelet function assays in patients undergoing percutaneous coronary intervention and receiving abciximab, eptifibatide, or tirofiban. Cathet Cardiovasc Intervent 2001;52:425–432.

    Article  CAS  Google Scholar 

  55. 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.

    Article  PubMed  CAS  Google Scholar 

  56. 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.

    Article  PubMed  CAS  Google Scholar 

  57. Kleiman NS, Graziadei N, Maresh K, et al. Abciximab, ticlopidine, and comcomitant abciximab-ticlopidine therapy: ex vivo platelet aggregation inhibition profiles in patients undergoing percutaneous coronary interventions. Am Heart J 2000;140:492–501.

    Article  PubMed  CAS  Google Scholar 

  58. Klinkhardt U, Kirchmaier CM, Westrup D, et al. Ex vivo-in vitro interaction between aspirin, clopidogrel, and the glycoprotein IIb/IIIa inhibitors abciximab and SR121566A. Clin Pharmacol Ther 2000;67: 305–313.

    Article  PubMed  CAS  Google Scholar 

  59. Marciniak SJ Jr, Jordan RE, Mascelli MA. Effect of Ca2+ chelation on the platelet inhibitory ability of the GPIIb/IIIa antagonists abciximab, eptifibatide and tirofiban. Thromb Haemost 2001;85:539–543.

    PubMed  CAS  Google Scholar 

  60. Braunwald E, Antman E, Beasley J, et al. ACC/AHA guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients with Unstable Angina). Available at: http://www.acc.org/clinical/guidelines/ unstable/unstable.pdf, 2002.

    Google Scholar 

  61. Second SYMPHONY Investigators. Randomized trial of aspirin, sibrafiban, or both for secondary prevention after acute coronary syndromes. Circulation 2001;103:1727–1733.

    Google Scholar 

  62. Steinhubl SR, Ellis SG, Wolski K, Lincoff AM, Topol EJ. Ticlopidine pretreatment before coronary stenting is associated with sustained decrease in adverse cardiac events: data from the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT) Trial. Circulation 2001;103:1403–1409.

    Article  PubMed  CAS  Google Scholar 

  63. 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.

    Article  PubMed  CAS  Google Scholar 

  64. Topol EJ, Moliterno DJ, Herrmann HC, et al., for the Target Investigators. Comparison of two platelet glycoprotein IIb/IIIa inhibitors, tirofiban and abciximab, for the prevention of ischemic events with percutaneous coronary revascularization. N Engl J Med 2001;344:1888–1894.

    Article  PubMed  CAS  Google Scholar 

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  1. Steven R. Steinhubl MD
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Editors and Affiliations

  1. Department of Cardiovascular Medicine, The Cleveland Clinic Foundation, Cleveland, OH, USA

    A. Michael Lincoff MD

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Steinhubl, S.R. (2003). Platelet Monitoring and Interaction of Glycoprotein IIb/IIIa Antagonists with Other Antiplatelet Agents. In: Lincoff, A.M. (eds) Platelet Glycoprotein IIb/IIIa Inhibitors in Cardiovascular Disease. Contemporary Cardiology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-376-7_15

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  • DOI: https://doi.org/10.1007/978-1-59259-376-7_15

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-408-1

  • Online ISBN: 978-1-59259-376-7

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