Mousa S A, Bozarth J M, Forsythe M S, Slee A
DuPont Pharmaceuticals Co., Wilmington, DE, USA.
Cardiovasc Res. 2000 Sep;47(4):819-26. doi: 10.1016/s0008-6363(00)00150-4.
The present study was undertaken to determine the effects of free ionized calcium influenced by either the anticoagulant used (citrate vs. heparin) or directly varying the calcium levels after treatment of blood with citrate on the antiplatelet efficacy of two classes of GPIIb/IIIa antagonists.
The platelet effects of changes in plasma [Ca(++)] with the different GPIIb/IIIa antagonists were determined using light transmittance aggregometry, direct binding kinetics, and (125)I-fibrinogen binding to activated human platelets.
A significantly higher IC50s was shown with heparin (free ionized calcium=1.1 mM) as compared to that with citrate (free ionized calcium=0.12 mM) with class II GPIIb/IIIa antagonists (P<0.01) such as Orbofiban, and Integrilin. In contrast, class I GPIIb/IIIa antagonists such as Roxifiban and Abciximab showed no significant changes in their IC50s in either citrate or heparin. Similar data were shown with other non-calcium chelating anticoagulant such as PPACK as compared to that with heparin. Additionally, similar data were shown with regard to the [Ca(++)] sensitivity for GPIIb/IIIa antagonists from Class II but not Class I in the changes in IC50 values required for the inhibition of (125)I-fibrinogen binding to activated human gel filtered platelets. Additionally, examples from Class I GPIIb/IIIa antagonists such as (3)H-active form of Roxifiban showed no significant changes in its platelet binding affinity in response to change in [Ca(++)]. In contrast, GPIIb/IIIa antagonists from class II such as (3)H-active form of Orbofiban demonstrated significant changes (P<0.01) in its platelet binding kinetics and antiplatelet efficacy in response to changes in Ca(++) concentrations.
These data suggest the impact of the method of blood collection or changes in plasma calcium levels on the antiplatelet efficacy for class II but not class I GPIIb/IIIa antagonists depending on their platelet binding kinetics.
本研究旨在确定所用抗凝剂（枸橼酸盐与肝素）对游离离子钙的影响，或在用枸橼酸盐处理血液后直接改变钙水平对两类糖蛋白IIb/IIIa拮抗剂抗血小板疗效的影响。
使用透光聚集法、直接结合动力学以及125I-纤维蛋白原与活化的人血小板结合，来确定不同糖蛋白IIb/IIIa拮抗剂引起的血浆[Ca(++)]变化对血小板的影响。
与使用枸橼酸盐（游离离子钙=0.12 mM）相比，使用肝素（游离离子钙=1.1 mM）时，II类糖蛋白IIb/IIIa拮抗剂（如奥布非班和依替巴肽）的IC50显著更高（P<0.01）。相比之下，I类糖蛋白IIb/IIIa拮抗剂（如罗昔非班和阿昔单抗）在枸橼酸盐或肝素中其IC50均无显著变化。与肝素相比，其他非钙螯合抗凝剂（如PPACK）也显示出类似的数据。此外，在抑制125I-纤维蛋白原与活化的人凝胶过滤血小板结合所需的IC50值变化方面，II类而非I类糖蛋白IIb/IIIa拮抗剂对[Ca(++)]的敏感性也显示出类似数据。另外，I类糖蛋白IIb/IIIa拮抗剂（如3H-活性形式的罗昔非班）的例子显示，其血小板结合亲和力不会因[Ca(++)]的变化而有显著改变。相比之下，II类糖蛋白IIb/IIIa拮抗剂（如3H-活性形式的奥布非班）的血小板结合动力学和抗血小板疗效会因Ca(++)浓度的变化而发生显著改变（P<0.01）。
这些数据表明，采血方法或血浆钙水平的变化对II类而非I类糖蛋白IIb/IIIa拮抗剂抗血小板疗效有影响，这取决于它们的血小板结合动力学。
