Vol. 297, Issue 2, 496-500, May 2001

Occupancy of the Internal and External Pools of Glycoprotein IIb/IIIa following Abciximab Bolus and Infusion

Martin J. Quinn, Ross T. Murphy, Michelle Dooley, J. Brendan Foley and Desmond J. Fitzgerald

The Centre for Cardiovascular Science, The Royal College of Surgeons in Ireland, Dublin, Ireland (M.J.Q., M.D., D.J.F.); and Cardiology Department, St. James's Hospital, Dublin, Ireland (R.T.M., J.B.F.)

The internal pool of GPIIb/IIIa, which is expressed upon platelet activation, may be inaccessible to inhibition by GPIIb/IIIa antagonists. To determine the occupancy of the internal and external pools of GPIIb/IIIa and platelet function following an abciximab bolus and infusion, 15 patients undergoing elective percutaneous transluminal coronary angioplasty were administered abciximab as a bolus and 36-h infusion. GPIIb/IIIa receptor number and occupancy in resting and TRAP-6 (20 µM)-activated samples (to expose the internal pool of GPIIb/IIIa) was quantified using a monoclonal antibody-based assay. Antibody binding was quantified by flow cytometry and platelet inhibition by light transmittance aggregation and by the rapid platelet function analyser (Accumetrics, San Diego, CA). The target of >80% receptor occupancy (range 82-99% occupancy) of the external pool of GPIIb/IIIa was achieved in all patients at 3 min. Receptor occupancy of the combined internal and external pools of GPIIb/IIIa was less, ranging from 75 to 93% and again was maximal at 3 min. Platelet aggregation was markedly inhibited to 20 µM ADP (maximal, 11 ± 2% of baseline), but less so to 5 µM TRAP-6 (maximal, 36 ± 25% of baseline). Following discontinuation of the drug, there was a gradual fall in receptor occupancy over 15 days coinciding with the disappearance of abciximab from the platelet surface. Maximum inhibition of platelet function and receptor occupancy of the external pool of GPIIb/IIIa occurs within 3 min of an abciximab bolus and infusion. However, some internal receptors that are expressed by potent agonists are not occupied, which may explain the incomplete inhibition of platelet aggregation.