In vitro effects of the glycoprotein IIb/IIIa receptor antagonists abciximab and eptifibatide on platelet aggregation in healthy cats

Aliya N. Magee Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907.

Search for other papers by Aliya N. Magee in
Current site
Google Scholar
PubMed
Close
 DVM
,
Daniel F. Hogan Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907.

Search for other papers by Daniel F. Hogan in
Current site
Google Scholar
PubMed
Close
 DVM
,
Kimberly A. Sederquist Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907.

Search for other papers by Kimberly A. Sederquist in
Current site
Google Scholar
PubMed
Close
 BS
, and
Jaylyn A. Durham Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907.

Search for other papers by Jaylyn A. Durham in
Current site
Google Scholar
PubMed
Close
 DVM

Abstract

Objective—To determine effects of the glycoprotein IIb/IIIa receptor antagonists abciximab and eptifibatide on in vitro inhibition of cat platelets.

Sample—Venous blood samples from 10 healthy cats.

Procedures—Blood samples were anticoagulated with hirudin. Aliquots of whole blood from each cat were allocated to 5 treatments (baseline, 50 μg of abciximab/mL, abciximab volumetric control treatment, 4μM eptifibatide, and eptifibatide volumetric control treatment). Impedance platelet aggregometry was performed with 6.5μM ADP or 32μM thrombin receptor activator peptide (TRAP). Magnitude of platelet aggregation was determined by measuring the area under the curve 15 minutes after addition of ADP or TRAP.

Results—Eptifibatide caused a significant reduction in platelet aggregation, compared with baseline values, for aggregometry with both ADP (median, 50.0; range, 8 to 122 [baseline median, 306.0; baseline range, 130 to 664]) and TRAP (median, 75.5; range, 3 to 148 [baseline median, 219.0; baseline range, 97 to 578]). There was no significant difference in platelet aggregation with abciximab, the abciximab volumetric control treatment, or the eptifibatide volumetric control treatment for aggregometry with ADP or TRAP.

Conclusions and Clinical Relevance—Eptifibatide caused a significant reduction in platelet aggregation in vitro, but there was no identifiable antiplatelet effect for abciximab. Eptifibatide and abciximab have different binding and inhibitory actions; therefore, it can be hypothesized that abciximab would be ineffective in cats because of a lack of receptor binding, reduced binding kinetics, or lack of downstream signaling. Eptifibatide may be useful in identifying hyperreactive platelets in cats in an in vitro platelet inhibitory assay.

Abstract

Objective—To determine effects of the glycoprotein IIb/IIIa receptor antagonists abciximab and eptifibatide on in vitro inhibition of cat platelets.

Sample—Venous blood samples from 10 healthy cats.

Procedures—Blood samples were anticoagulated with hirudin. Aliquots of whole blood from each cat were allocated to 5 treatments (baseline, 50 μg of abciximab/mL, abciximab volumetric control treatment, 4μM eptifibatide, and eptifibatide volumetric control treatment). Impedance platelet aggregometry was performed with 6.5μM ADP or 32μM thrombin receptor activator peptide (TRAP). Magnitude of platelet aggregation was determined by measuring the area under the curve 15 minutes after addition of ADP or TRAP.

Results—Eptifibatide caused a significant reduction in platelet aggregation, compared with baseline values, for aggregometry with both ADP (median, 50.0; range, 8 to 122 [baseline median, 306.0; baseline range, 130 to 664]) and TRAP (median, 75.5; range, 3 to 148 [baseline median, 219.0; baseline range, 97 to 578]). There was no significant difference in platelet aggregation with abciximab, the abciximab volumetric control treatment, or the eptifibatide volumetric control treatment for aggregometry with ADP or TRAP.

Conclusions and Clinical Relevance—Eptifibatide caused a significant reduction in platelet aggregation in vitro, but there was no identifiable antiplatelet effect for abciximab. Eptifibatide and abciximab have different binding and inhibitory actions; therefore, it can be hypothesized that abciximab would be ineffective in cats because of a lack of receptor binding, reduced binding kinetics, or lack of downstream signaling. Eptifibatide may be useful in identifying hyperreactive platelets in cats in an in vitro platelet inhibitory assay.

Contributor Notes

Dr. Durham's present address is Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

Presented as a poster at the American College of Veterinary Internal Medicine Forum, Seattle, June 2013.

The authors thank Dr. George Moore for statistical assistance.

Address correspondence to Dr. Hogan (hogandf@purdue.edu).
  • 1. Hogan DF. Arterial thromboembolic disease. In: Ettinger SJ, Feldman EC, eds. Textbook of veterinary internal medicine. 7th ed. St Louis: Saunders Elsevier, 2010; 13811386.

    • Search Google Scholar
    • Export Citation
  • 2. Atkins CE, Gallo AM, Kurzman ID, et al. Risk factors, clinical signs, and survival in cats with a clinical diagnosis of idiopathic hypertrophic cardiomyopathy: 74 cases (1985–1989). J Am Vet Med Assoc 1992; 201: 613618.

    • Search Google Scholar
    • Export Citation
  • 3. Rush JE, Freeman LM, Fenollosa NK, et al. Population and survival characteristics of cats with hypertrophic cardiomyopathy: 260 cases (1990–1999). J Am Vet Med Assoc 2002; 220: 202207.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4. Stokol T, Brooks M, Rush JE, et al. Hypercoagulability in cats with cardiomyopathy (Erratum published in J Vet Intern Med 2009; 23:224). J Vet Intern Med 2008; 22: 546552.

    • Search Google Scholar
    • Export Citation
  • 5. Luis Fuentes V. Arterial thromboembolism: risks, realities and a rational first-line approach. J Feline Med Surg 2012; 14: 459470.

  • 6. Smith SA, Tobias AH, Jacob KA, et al. Arterial thromboembolism in cats: acute crisis in 127 cats (1992–2001) and long-term management with low-dose aspirin in 24 cases. J Vet Intern Med 2003; 17: 7383.

    • Search Google Scholar
    • Export Citation
  • 7. Hogan DF, Andrews DA, Green HW, et al. Antiplatelet effects and pharmacodynamics of clopidogrel in cats. J Am Vet Med Assoc 2004; 225: 14061411.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8. Coller BS. Seminars in medicine of the Beth Israel Hospital, Boston: platelets and thrombolytic therapy. N Engl J Med 1990; 322: 3342.

  • 9. Nurden AT, Poujol C, Durrieu-Jais C, et al. Platelet glycoprotein IIb/IIIa inhibitors: basic and clinical aspects. Arterioscler Thromb Vasc Biol 1999; 19: 28352840.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10. Phillips DR, Scarborough RM. Clinical pharmacology of eptifibatide. Am J Cardiol 1997; 80:11B20B.

  • 11. Konopka A, Spychalska J, Piotrowski W, et al. Influence of some cardiovascular risk factors on the expression of platelet glycoprotein IIb/IIIa receptors in patients with myocardial infarction treated with antiplatelet drugs under primary percutaneous coronary intervention. Mol Diagn Ther 2009; 13: 375382.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12. Bright JM, Dowers K, Powers BE. Effects of the glycoprotein IIb/IIIa antagonist abciximab on thrombus formation and platelet function in cats with arterial injury. Vet Ther 2003; 4: 3546.

    • Search Google Scholar
    • Export Citation
  • 13. Gurm HS, Smith DE, Collins JS. The relative safety and efficacy of abciximab and eptifibatide in patients undergoing primary percutaneous coronary intervention: insights from a large regional registry of contemporary percutaneous coronary intervention. J Am Coll Cardiol 2008; 51: 529535.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14. Tcheng JE, Ellis SG, George BS. Pharmacodynamics of chimeric glycoprotein IIb/IIIa integrin antiplatelet antibody Fab 7E3 in high-risk coronary angioplasty. Circulation 1994; 90: 17571764.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15. 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: 17661774.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16. Dickfeld T, Ruf A, Murray GP, et al. Differential antiplatelet effects of various glycoprotein IIb-IIIa antagonists. Thromb Res 2001; 101: 5364.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17. The EPILOG Investigators. Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization. N Engl J Med 1997; 336: 16891696.

    • Search Google Scholar
    • Export Citation
  • 18. Shipley EA, Hogan DF, Fiakpui NN, et al. In vitro effect of pimobendan on platelet aggregation in dogs. Am J Vet Res 2013; 74: 403407.

  • 19. Quinn M, Deering A, Stewart M, et al. Quantifying GPIIb/IIIa receptor binding using 2 monoclonal antibodies: discriminating abciximab and small molecular weight antagonists. Circulation 1999; 99: 22312238.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20. Topol EJ, Califf RM, Weisman HF, et al. Randomised trial of coronary intervention with antibody against platelet IIb/IIIa integrin for reduction of clinical restenosis: results at six months. Lancet 1994; 343: 881886.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21. Bright JM, Dowers K, Hellyer P. In vitro anti-aggregatory effects of the GP IIb/IIIa antagonist eptifibatide on feline platelets (lett). J Vet Intern Med 2002; 16:640.

    • Search Google Scholar
    • Export Citation
  • 22. Scarborough RM, Rose JW, Hsu MA, et al. Barbourin. A GPIIb-IIIa-specific integrin antagonist from the venom of Sistrurus m barbouri. J Biol Chem 1991; 266: 93599362.

    • Crossref
    • Search Google Scholar
    • Export Citation

Advertisement