Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty Mannheim, University of Heidelberg, Germany.
Platelets. 2010;21(3):176-82. doi: 10.3109/09537100903518260.
Previous investigations revealed that AB0 blood groups are associated with divergent concentrations of several coagulation factors. Concentrations of von Willebrand factor (vWF) and factor VIII are lower in individuals with blood group 0 compared to subjects with blood group A, B or AB, which might in turn result in a reduced inhibition of platelet aggregation in individuals with blood group 0. The aim of the present in vitro investigation was to elucidate the impact of AB0 blood group-dependent vWF concentrations on eptifibatide and abciximab mediated inhibition of GPIIb/IIIa function. Platelet function was measured with the platelet function analyzer PFA-100(R) at baseline and at increasing concentrations of eptifibatide and abciximab. It was stratified for blood group 0 vs A. If measured with the collagen/ADP cartridge, blood group 0 was associated with a prolonged mean baseline closure time in comparison with blood group A (94.3 +/- 14.6 s vs. 74.6 +/- 9.9 s, p = 0.007) which was paralleled by reduced concentrations of vWF and factor VIII. In contrast, no statistically significant differences in closure times (167.4 +/- 83.9 s vs. 140.1 +/- 99.0 s, p = 0.562) could be found in the presence of eptifibatide (0.1 microg/ml). Higher concentrations of abciximab (1 microg/ml) than those of eptifibatide were needed to increase the closure times in both cartridges of the PFA-100, but at this concentration of abciximab differences in closure times could not be detected most probably due to higher variability at these drug concentrations. The PFA-100(R) is not suitable for monitoring abciximab or eptifibatide within the therapeutic concentration range because the highest concentrations where the PFA-100(R) had measurable closure times of below 300 s is much too low to lead to the necessary platelet inhibition and, consequently, does not resemble the in vivo situation.
先前的研究表明,AB0 血型与几种凝血因子的浓度存在差异。与血型为 A、B 或 AB 的个体相比,血型为 0 的个体中血管性血友病因子(vWF)和因子 VIII 的浓度较低,这可能导致血型为 0 的个体血小板聚集抑制作用降低。本体外研究的目的是阐明 AB0 血型依赖性 vWF 浓度对依替巴肽和阿昔单抗介导的 GPIIb/IIIa 功能抑制的影响。使用血小板功能分析仪 PFA-100(R)在基线和依替巴肽和阿昔单抗浓度增加时测量血小板功能。根据血型分为 0 组与 A 组。如果使用胶原/ADP 检测管进行测量,与血型 A 相比,血型 0 的平均基线闭合时间延长(94.3 +/- 14.6 s 与 74.6 +/- 9.9 s,p = 0.007),同时 vWF 和因子 VIII 的浓度降低。相比之下,在依替巴肽(0.1 μg/ml)存在的情况下,闭合时间无统计学差异(167.4 +/- 83.9 s 与 140.1 +/- 99.0 s,p = 0.562)。需要更高浓度的阿昔单抗(1 μg/ml)来增加 PFA-100 两种检测管的闭合时间,但在这种阿昔单抗浓度下,由于药物浓度较高的变异性,无法检测到闭合时间的差异。PFA-100(R)不适合监测依替巴肽或阿昔单抗在治疗浓度范围内的情况,因为 PFA-100(R)具有可测量的闭合时间低于 300 s 的最高浓度太低,无法导致必要的血小板抑制,因此与体内情况不符。