Download PDF
Thromb Haemost 1998; 80(06): 994-1001
DOI: 10.1055/s-0037-1615400
Letters to the Editor
Schattauer GmbH

Effect of Glycoprotein IIb-IIIa Receptor Antagonism on Platelet Membrane Glycoproteins after Coronary Stent Placement

Meinrad Gawaz
1   From the 1. Medizinische Klinik, Klinikum rechts der Isar and Deutsches Herzzentrum, Technische Universität München, Germany, Zentrum für Labormedizin, Mikrobiologie und Transfusionsmedizin, Klinikum Karlsruhe, Germany
,
Andreas Ruf
1   From the 1. Medizinische Klinik, Klinikum rechts der Isar and Deutsches Herzzentrum, Technische Universität München, Germany, Zentrum für Labormedizin, Mikrobiologie und Transfusionsmedizin, Klinikum Karlsruhe, Germany
,
Franz-Josef Neumann
1   From the 1. Medizinische Klinik, Klinikum rechts der Isar and Deutsches Herzzentrum, Technische Universität München, Germany, Zentrum für Labormedizin, Mikrobiologie und Transfusionsmedizin, Klinikum Karlsruhe, Germany
,
Gisela Pogátsa-Murray
1   From the 1. Medizinische Klinik, Klinikum rechts der Isar and Deutsches Herzzentrum, Technische Universität München, Germany, Zentrum für Labormedizin, Mikrobiologie und Transfusionsmedizin, Klinikum Karlsruhe, Germany
,
Timm Dickfeld
1   From the 1. Medizinische Klinik, Klinikum rechts der Isar and Deutsches Herzzentrum, Technische Universität München, Germany, Zentrum für Labormedizin, Mikrobiologie und Transfusionsmedizin, Klinikum Karlsruhe, Germany
,
Dietlind Zohlnhöfer
1   From the 1. Medizinische Klinik, Klinikum rechts der Isar and Deutsches Herzzentrum, Technische Universität München, Germany, Zentrum für Labormedizin, Mikrobiologie und Transfusionsmedizin, Klinikum Karlsruhe, Germany
,
Albert Schömig
1   From the 1. Medizinische Klinik, Klinikum rechts der Isar and Deutsches Herzzentrum, Technische Universität München, Germany, Zentrum für Labormedizin, Mikrobiologie und Transfusionsmedizin, Klinikum Karlsruhe, Germany
› Author Affiliations
Further Information

Publication History

Received 23 February 1998

Accepted after revision 19 May 1998

Publication Date:
07 December 2017 (online)

Also available at
    Permissions and Reprints

Summary

Platelet membrane glycoproteins play a crucial role in ischemic complications after coronary stenting. Glycoprotein IIb-IIIa blockade reduces adverse clinical events after angioplasty but is associated with rare but profound thrombocytopenia that might increase hemorrhagic complications.

Changes in platelet membrane glycoproteins of patients with angina who underwent coronary stenting and were treated with the GPIIb-IIIa antagonist abciximab (n = 20) or with heparin (n = 23) were studied. GPIIb-IIIa receptor blockade and membrane glycoproteins were evaluated with immunological markers in venous blood samples taken before, 10, 24, 48, 72, and 96 h after initial treatment with either abciximab or heparin.

Patients receiving abciximab therapy showed a rapid inhibition of binding of fluorochrome-conjugated mAb CD41 and c7E3 concomitant with a reduction in platelet aggregation which was restored in part in the days after termination of abciximab infusion. Induction of ligand-induced binding sites on GPIIb-IIIa was increased in patients receiving abciximab. The expression of ligand-induced binding sites correlated inversely with platelet count. No significant change in platelet membrane markers were found in the heparin group. In vitro studies showed that abciximab induces ligand-induced binding sites on isolated platelets and on nuclear cells bearing recombinant GPIIb-IIIa.

Abciximab rapidly achieves GPIIb-IIIa receptor blockade after coronary stent placement that might be beneficial in high-risk settings to bridge the delayed action of ticlopidine. Significant alterations of platelet membrane glycoproteins during GPIIb-IIIa antagonism might contribute to development of acute profound thrombocytopenia.

 

  • References

  • 1 Gawaz M, Neumann FJ, Ott I, May A, Rüdiger S, Schömig A. Role of activation-dependent platelet membrane glycoproteins in development of subacute occlusive coronary stent thrombosis. Coron Art Dis 1997; 8: 121-8.
    CrossrefPubMedGoogle Scholar
  • 2 Neumann FJ, Gawaz M, Ott I, May A, Mössmer G, Schömig A. Prospective evaluation of hemostatic predictors of subacute stent thrombosis after coronary Palmaz-Schatz stenting. J Am Coll Cardiol 1996; 27: 15-21.
    PubMedGoogle Scholar
  • 3 Schömig A, Neumann FJ, Kastrati A, Schühlen H, Blasini R, Hadamitzki M, Walter H, Zitzmann-Roth EM, Richard G, Alt E, Schmitt C, Ulm K. A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary stents. N Engl J Med 1996; 334: 1084-9.
    CrossrefPubMedGoogle Scholar
  • 4 Leon MB, Baim DS, Gordon P. Clinical and angiographic results from the stent anticoagulation regimen study (STARS) [abstract]. Circulation 1996; 94: I-685.
    PubMedGoogle Scholar
  • 5 The EPIC Investigators.. Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. The EPIC investigation. N Engl J Med 1994; 330: 956-61.
    CrossrefPubMedGoogle Scholar
  • 6 The CAPTURE Investigators.. Randomized placebo-controlled trial of abciximab before and during coronary intervention in refractory unstable angina: the CAPTURE study. Lancet 1997; 349: 1429-35.
    CrossrefPubMedGoogle Scholar
  • 7 IMPACT-II Investigators.. Effects of competitive platelet glycoprotein IIb/IIIa inhibition with velofibatide (integrilin) in reducing complications of percutaneous coronary intervention: results of the randomized clinical trial IMPACT-II. Lancet 1997; 349: 1422-8.
    CrossrefPubMedGoogle Scholar
  • 8 The EPILOG Investigators.. Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization. N Engl J Med 1997; 336: 1689-96.
    CrossrefPubMedGoogle Scholar
  • 9 The RESTORE Investigators.. Effects of platelet glycoprotein IIb/IIIa blockade with tirofiban on adverse cardiac events in patients with unstable angina in acute myocardial infarction undergoing coronary angioplasty. Circulation 1997; 96: 1445-53.
    CrossrefPubMedGoogle Scholar
  • 10 Berkowitz SD, Harrington RA, Rund MM, Tcheng JE. Acute profound thrombocytopenia after c7E3 Fab (abciximab) therapy. Circulation 1997; 95: 809-13.
    CrossrefPubMedGoogle Scholar
  • 11 Ruf A, Pick M, Deutsch V, Patscheke H, Goldfarb A, Rachmilewitz EA, Guillin MC, Eldor A. The procoagulant activity of red cells from patients with β-thalassemia major correlates with in-vivo platelet activation. Brit J Haematol 1997; 98: 51-6.
    CrossrefPubMedGoogle Scholar
  • 12 Shattil SJ, Cunningham M, Hoxie JA. Detection of activated platelets in whole blood using activation-dependent monoclonal antibodies and flow cytometry. Blood 1987; 70: 307-15.
    PubMedGoogle Scholar
  • 13 Born GVR, Cross GP. Effect of inorganic ions and of plasma proteins on the aggregation of blood platelets by adenosine diphosphate. J Physiol 1964; 170: 397-414.
    CrossrefPubMedGoogle Scholar
  • 14 Jin Y, Dietz HC, Nurden A, Bray PF. Single-strand conformation polymorphism analysis is a rapid and effective method for the identification of mutations and polymorphisms in the gene for glycoprotein IIIa. Blood 1993; 82: 2281-8.
    PubMedGoogle Scholar
  • 15 O’Toole TE, Loftus JC, Du X, Glass AA, Ruggeri ZM, Shattil SJ, Plow EF, Ginsberg MH. Affinity modulation of the aIIbb3 integrin (platelet GPIIb-IIIa) is an intrinsic property of the receptor. Cell Regulation 1990; 1: 883-93.
    CrossrefPubMedGoogle Scholar
  • 16 Gawaz M, Loftus JC, Bajt ML, Frojmovic MM, Plow EF, Ginsberg MH. Ligand bridging mediates integrin alpha IIb beta 3 (platelet GPIIb-IIIa) dependent homotypic and heterotypic cell-cell interactions. J Clin Invest 1991; 88: 1128-34.
    CrossrefPubMedGoogle Scholar
  • 17 Gawaz M, Mayinger P, Neumann FJ. Effects of adenosine-5’-triphosphate (ATP) on ligand recognition of platelet fibrinogen receptor on GPIIb-IIIa. Am J Physiol 1994; 267: H1098-H1106.
    PubMedGoogle Scholar
  • 18 Frelinger AL, Cohen I, Plow EF, Smith MA, Roberts J, Lam SCT, Ginsberg MH. Selective inhibition of integrin function by antibodies specific for ligand-occupied receptor conformers. J Biol Chem 1990; 260: 6346-52.
    PubMedGoogle Scholar
  • 19 Woods VL, Wolff LE, Keller DM. Resting platelets contain a substantial centrally located pool of glycoprotein IIb-IIIa complexes which may be accessible to some but not other extracellular proteins. J Biol Chem 1986; 261: 15242-51.
    PubMedGoogle Scholar
  • 20 Ginsberg MH, Frelinger AL, Lam SCT, Forsyth J, McMillan R, Plow EF, Shattil SJ. Analysis of platelet aggregation disorders based on flow cytometric analysis of platelet membrane glycoprotein IIb-IIIa with conformation specific monoclonal antibodies. Blood 1990; 76: 2017-23.
    PubMedGoogle Scholar
  • 21 Kereiakes DJ, Lincoff AM, Simoons ML, deBoer MJ, Tcheng JE, Vahanian A, Anderson KM, Weisman HF, Califf RA, Topol EJ. Complementarity of stenting and abciximab for percutaneous coronary interventions. JACC 1998; 31: 54A.
    CrossrefPubMedGoogle Scholar
  • 22 Harker A, Bruno JJ. Ticlopidine’s mechanism of action on human platelets. In: Hass Easton JD, eds. Ticlopidine, Platelets and Vascular Disease. New York, NY: Springer-Verlag; 1993: 99-116.
    Google Scholar
  • 23 McFarland JG. Platelet immunology and alloimmunization. In: E Rossi, TL Simon, GS Mors, Gould SA eds. Principles of transfusion medicine. Baltimore: Williams & Wilkins; Second edition 1996
    Google Scholar
  • 24 Kereiakes DJ, Essell JH, Abbottsmith CW, Broderick TM, Runyon JP. Abciximab-associated profound thrombocytopenia: therapy with immunoglobulin and platelet transfusion. Am J Cardiol 1996; 78: 1161-6.
    CrossrefPubMedGoogle Scholar
  • 25 Christopoulos CG, Machin SJ. A new type of pseudothrombocytopenia: EDTA-mediated agglutination of platelets bearing Fab fragments of a chimaeric antibody. Br J Haematol 1994; 87: 650-2.
    CrossrefPubMedGoogle Scholar
  • 26 Bednar B, Bednar RA, Cook JJ, Booag DM, Chang CT, Gaul SL, McQueney PA, Egbertson MS, Hartman GD, Holahan MA. Drug-dependent antibodies against GPIIb-IIIa induce thrombocytopenia. Circulation 1996; 94: I-99.
    PubMedGoogle Scholar
  • 27 Du X, Plow EF, Frelinger AL, O’Toole TE, Loftus JC, Ginsberg MH. Ligands “activate” integrin aIIbb3 (platelet GPIIb-IIIa). Cell 1991; 65: 409-16.
    CrossrefPubMedGoogle Scholar
  • 28 Du X, Ginsberg MH. Integrin aIIbb3 and platelet function. Thromb Haemost 1997; 78: 96-100.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 29 Ginsberg MH. Integrins: dynamic regulation of ligand binding. Biochem Soc Trans 1995; 23: 439-46.
    CrossrefPubMedGoogle Scholar
  • 30 Plow EF, D’Souza SE, Ginsberg MH. Consequences of the interaction of platelet membrane glycoprotein GPIIb-IIIa and its ligands. J Lab Clin Med 1992; 120: 198-204.
    PubMedGoogle Scholar
  • 31 Shattil SJ, Ginsberg MH. Integrin signaling in vascular biology. J Clin Invest 1997; 100: 1-5.
    CrossrefPubMedGoogle Scholar
  • 32 Shattil SJ, Ginsberg MH, Brugge JS. Adhesive signaling in blood platelets. Curr Opin Cell Biol 1994; 6: 695-704.
    CrossrefPubMedGoogle Scholar
  • 33 Richardson A, Parsons JT. Signal transduction through integrins: a central role for focal adhesion kinase. BioEssays 1995; 17: 229-36.
    CrossrefPubMedGoogle Scholar
  • 34 Nurden AT. Polymorphisms of human platelet membrane glycoproteins: structure and clinical significance. Thromb Haemost 1995; 74: 345-51.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 35 Newman PJ. Platelet GPIIb-IIIa: molecular variations and alloantigens. Thromb Haemost 1991; 66: 111-8.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 36 Weiss EJ, Bray PF, Tayback M, Schulman SP, Kickler TS, Becker LC, Weiss JL, Gerstenblith G, Goldschmidt-Clermont PF. A polymorphism of a platelet glycoprotein receptor as an inherited risk factor for coronary thrombosis. N Engl J Med 1996; 334: 1090-4.
    CrossrefPubMedGoogle Scholar