Investigation of the PADA as a Method for Monitoring GPIIb/IIIa Inhibitors and Other Antiplatelet Agents

ABSTRACT

Treatment with glycoprotein (GP) IIb/IIIa inhibitors in combination with aspirin and clopidogrel have become essential therapeutic strategies during invasive procedures and coronary events. However, the ideal monitoring test for the effects of these treatments is still missing. Therefore, we investigated the new Platelet Adhesion Assay (PADA) for its sensitivity in characterizing antiplatelet therapy.

Five healthy volunteers were studied before and after a single dose of aspirin (500 mg). Samples were spiked in vitro with increasing doses of abciximab (0, 0.25, 1, 3 μg/mL), eptifibatide (0, 0.25, 1, 2 μg/mL), and AR-C 69931MX (1 μg/mL) in citrated and hirudinized whole blood. The adhesion index (AI), as the characteristic parameter of the PADA test, decreased in a dose-dependent fashion for abciximab and eptifibatide. Variable effects between the different anticoagulants were shown for eptifibatide. Aspirin showed no additional effect, while inhibition by AR-C 69931MX was demonstrated in hirudinized blood only. We concluded that different levels of GPIIb/IIIa inhibitors and adenosine diphosphate-receptor inhibition could be assessed with the PADA test, although different anticoagulants led to different results. The suitability of this test for daily use will have to be elucidated in further patient studies.

Platelet function assay - GPIIb/IIIa inhibitor - P2Y₁₂ inhibitor - aspirin - monitoring

REFERENCES

• 1 McKenzie M E, Gurbel P A, Levine D J, Serebruany V L. Clinical utility of available methods for determining platelet function.  Cardiology. 1999;  92 240-247
• 2 Harder S, Klinkhardt U, Graff J et al.. In vitro dose response to different GPIIb/IIIa antagonists: inter-laboratory comparison of various platelet function tests.  Thromb Res. 2001;  102 39-48
• 3 [No authors listed.] Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization. The EPILOG Investigators.  N Engl J Med. 1997;  336 1689-1696
• 4 Michelson A D. Flow cytometric analysis of platelets.  Vox Sang. 2000;  78 137-142
• 5 Kereiakes D J, Mueller M, Howard W et al.. Efficacy of abciximab induced platelet blockade using a rapid point of care assay.  J Thromb Thrombolysis. 1999;  7 265-276
• 6 Steinhubl S R. Assessing the optimal level of platelet inhibition with GPIIb/IIIa inhibitors in patients undergoing coronary intervention. Rationale and design of the GOLD study.  J Thromb Thrombolysis. 2000;  9 199-205
• 7 Harrington R A, Kleiman N S, 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
• 8 Storey R F, Newby L J, Heptinstall S. Effects of P2Y(1) and P2Y(12) receptor antagonists on platelet aggregation induced by different agonists in human whole blood.  Platelets. 2001;  12 443-447
• 9 Marciniak Jr S J, Jordan R E, Mascelli M A. Effect of Ca2+ chelation on the platelet inhibitory ability of the GPIIb/IIIa antagonists abciximab, eptifibatide and tirofiban.  Thromb Haemost. 2001;  85 539-543
• 10 Phillips D R, 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