Differential antiplatelet efficacy for various GPIIb/IIIa antagonists: Role of plasma calcium levels

Objectives: The present study was undertaken to determine the effects of fr ee ionized calcium influenced by either the anticoaqulant used (citrate vs. heparin) or directly varying the calcium levels after treatment of blood w ith citrate on the antiplatelet efficacy of two classes of GPIIb/IIIa antag onists. Methods: The platelet effects of changes in plasma [Ca++] with the different GPIIb/IIIa antagonists were determined using light transmittance aggregometry, direct binding kinetics, and I-125-fibrinogen binding to acti vated human platelets. Results: A significantly higher IC50s was shown with heparin (free ionized calcium=1.1 mM) as compared to that with citrate (fr ee ionized calcium=0.12 mM) with class II GPIIb/IIIa antagonists (P<0.01) s uch as Orbofiban, and Integrilin. In contrast, class I GPIIb/IIIa antagonis ts such as Roxifiban and Abciximab showed no significant changes in their I C50s in either citrate or heparin. Similar data were shown with other non-c alcium chelating anticoagulant such as PPACK as compared to that with hepar in. Additionally, similar data were shown with regard to the [Ca++] sensiti vity for GPIIb/IIIa antagonists from Class II but not Class I in the change s in IC50 values required for the inhibition of I-125-fibrinogen binding to activated human gel filtered platelets. Additionally, examples from Class I GPIIb/IIIa antagonists such as H-3-active form of Roxifiban showed no sig nificant changes in its platelet binding affinity in response to change in [Ca++]. In contrast, GPIIb/IIIa antagonists from class II. such as H-3-acti ve form of Orbofiban demonstrated significant changes (P<0.01) in its plate let binding kinetics and antiplatelet efficacy in response to changes in Ca ++ concentrations. Conclusions: These data suggest the impact of the method of blood collection or changes in plasma calcium levels on the antiplatele t efficacy for class II but not class I GPIIb/IIIa antagonists depending on their platelet binding kinetics. (C) 2000 DuPont Pharmaceuticals Company. Published by Elsevier Science B.V. All rights reserved.