Thromb Haemost 2001; 85(02): 309-313
DOI: 10.1055/s-0037-1615685
Review Article
Schattauer GmbH

Time and Dose Dependent Augmentation of Inhibitory Effects of Abciximab by Aspirin

David J. Schneider
1   University of Vermont, Burlington, VT, USA
,
Patricia Q. Baumann
1   University of Vermont, Burlington, VT, USA
,
Michael B. Holmes
1   University of Vermont, Burlington, VT, USA
,
Douglas Taatjes
*   Departments of Medicine and Pathology, University of Vermont, Burlington, VT, USA
,
Burton E. Sobel
1   University of Vermont, Burlington, VT, USA
› Author Affiliations
Further Information

Publication History

Received 30 May 2000

Accepted after resubmission 31 August 2000

Publication Date:
08 December 2017 (online)

Summary

Aspirin and abciximab independently decrease the incidence of cardiac events. To identify potential interactions, antiplatelet effects of abciximab were characterized in blood from healthy subjects given aspirin. Platelet activation was determined in whole blood with and without abciximab (2 μg/ml) added in vitro. Flow cytometry was used to quantify fibrinogen binding (glycoprotein IIb-IIIa activation). Binding of fluorochrome-labeled and 125I-labeled abciximab was determined before and after exposure to aspirin. In blood from subjects given aspirin for 5 days, abciximab-induced inhibition of the capacity to bind fibrinogen in response to 1 μM ADP was greater when the daily dose had been 325 mg compared with 81 mg (% inhibition: no aspirin 53 ± 6; 81 mg daily 62 ± 5; 325 mg daily 69 ± 6). The effect of 5 daily doses of aspirin was greater than that of one. Larger single doses elicited larger effects (% inhibition 2 h after 325 mg 59 ± 6; 2 h after 650 mg 78 ± 5). Neither salicylsalicylic acid nor naproxen sodium potentiated the effect of abciximab. Exposure of platelets to 14Cacetylsalicylic acid led to acetylation of glycoprotein IIb and IIIa. Binding of 125I-abciximab to platelets was increased after 30 and 60 min. Acetylation of glycoprotein IIb-IIIa by aspirin augments inhibitory effects of abciximab in a dose- and time-dependent manner by increasing binding of abciximab to platelets.

* University of Vermont, Burlington, VT, USA


 
  • References

  • 1 Theroux P, Waters D, Qiu S, McCans J, de Guise P, Juneau M. Aspirin versus heparin to prevent myocardial infarction during the acute phase of unstable angina. Circulation 1993; 88: 2045-8.
  • 2 Theroux P, Ouimet H, McCans J, Latour J-G, Joly P, Levy G, Pelletier E, Juneau M, Stasiak J, de Guise P. Aspirin, heparin, or both to treat acute unstable angina. N Engl J Med 1988; 319: 1105-1111.
  • 3 Lewis HD, Davis JW, Archibald DG, Steinke WE, Smitherman TC, Doherty JE, Schnaper HW, LeWinter MM, Linares E, Pouget JM, Sabharwal SC, Chesler E, DeMots H.. Protective Effects of Aspirin Against Acute Myocar-dial Infarction and Death in Men with Unstable Angina. N Engl J Med 1983; 309: 396-403.
  • 4 Holdright D, Patel D, Cunningham D, Thomas R, Hubbard W, Hendry G, Sutton G, Fox K. Comparison of the effect of heparin and aspirin versus aspirin alone on transient myocardial ischemia and in-hospital prognosis in patients with unstable angina. J Am Coll Cardiol 1994; 24: 39-45.
  • 5 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: 624-9.
  • 6 Holmes MB, Howard DB, Sobel BE, Schneider DJ. Differences between activation thresholds for platelet P-selectin and glycoprotein IIb-IIIa expression and their clinical implications. Thromb Res 1999; 95: 75-82.
  • 7 Farrell TP, Hayes KB, Sobel BE, Schneider DJ. The lack of augmentation by aspirin of inhibition of platelet reactivity by ticlopidine. Am J Cardiol 1999; 83: 770-4.
  • 8 Rinder CS, Student LA, Bonan JL, Rinder HM, Smith BR. Aspirin does not inhibit adenosine diphosphate-induced platelet -granule release. Blood 1993; 82: 505-512.
  • 9 Chronos NAF, Wilson DJ, Janes SL, Hutton RA, Buller NP, Goodal AH. Aspirin does not affect the flow cytometric detection of fibrinogen binding to, or release of α-granules or lysosomes from human platelets. Clinical Science 1994; 87: 575-580.
  • 10 Califf RM, Lincoff AM, Tcheng JE, and Topol EJ. An overview of the results of the EPIC trial.. Eur Heart J 1995; 16 (Suppl. L) 43-49.
  • 11 The EPILOG Investigators.. Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous revascularization. N Engl J Med 1997; 336: 1689-96.
  • 12 The CAPTURE Study Group.. Randomised placebo-controlled trial of abciximab before and during coronary intervention in refractory unstable angina: the CAPTURE study. Lancet 1997; 349: 1429-35.
  • 13 Antman EM, Giugliano RP, Gibson CM, McCabe CH, Coussement P, Kleiman NS, Vahanian A, Adgey AA, Menown I, Rupprecht HJ, Van der Wieken R, Ducas J, Sherer J, Anderson K, Van der Werf F, Braunwald E. Abciximab facilitates the rate and extent of thrombolysis: results of the thrombolysis in myocardial infarction (TIMI) 14 trial. Circulation 1999; 99: 2720-32.
  • 14 Rand MD, Lock JB, Veer CV, Gaffney DP, Mann KG. Blood clotting in minimally altered whole blood. Blood 1996; 88: 3432-45.
  • 15 Schneider DJ, Tracy PB, Mann KG, Sobel BE. Differential effects of anticoagulants on the activation of platelets ex vivo. Circulation 1997; 96: 2877-83.
  • 16 Xia V, Wong T, Liu Q, Kasirer-Friede A, Brown E, Frojmovic MM. Optimally functional fluorescein isothiocyanate-labeled fibrinogen for quantitative studies of binding to activated platelets and platelet aggregation. Br J Haematol 1996; 93: 204-14.
  • 17 Schneider DJ, Holmes MB, Taatjes DJ, Sobel BE. Dose and duration dependence of aspirin-induced augmentation of inhibition of fibrinogen binding by ReoPro. Circulation 1999; 100: I-430.
  • 18 Klinkhardt U, Kirchmaier CM, Westrup D, Graff J, Mahnel R, Breddin HK, Harder S. Ex vivo—in vitro interaction between aspirin, clopidogrel, and the glycoprotein IIb/IIIa inhibitors abciximab and SR121566A. Clin Pharmacol Ther 2000; 67: 305-13.
  • 19 Schneider DJ, Taatjes DJ, Sobel BE. Paradoxical inhibition of fibrinogen binding and potentiation of -granule release by specific types of inhibitors of glycoprotein IIb-IIIa. Cardiovasc Res, 1999; 45: 437-46.
  • 20 Weksler BB, Kent JL, Rudolph D, Scherer PB, Levy DE. Effects of low dose aspirin on platelet function in patients with recent cerebral ischemia. Stroke 1985; 16: 5-9.
  • 21 Tohgi H, Konno S, Tamura K, Kimura B, Kawano K. Effects of lowto-high doses of aspirin on platelet aggregability and metabolites of thromboxane A2 and prostacyclin. Stroke 1992; 23: 1400-3.
  • 22 Coller BS. A new murine monoclonal antibody reports activation-dependent change in the conformation and/or microenvironment of the platelet glycoprotein IIb/IIIa complex. J Clin Invest 1985; 76: 101-8.
  • 23 Morris DC. Results from late-breaking clinical trials session at ACCIS ‘99 and ACC ‘99. American College of Cardiology. J Am Coll Cardiol 1999; 34: 1-8.
  • 24 Peter K, Schwartz M, Ylanne J, Kihler B, Moer M, Nordt T, Salbach P, Kubler W, Bode C. Inductin of fibringogen binding and platelet aggregation as a potential intrinsic property of various glycoprotein IIb-IIIa inhibitors. Blood 1998; 92: 3240-9.
  • 25 Frelinger A, Du X, Plow EF, Ginsburg MH. Monoclonal antibodies to ligand-occupied conformers of glycoprotein IIb/IIIa alter receptor affinity, specificity, and function. J Biol Chem 1991; 266: 17106-11.