Varon D, Lashevski I, Brenner B, Beyar R, Lanir N, Tamarin I, Savion N
National Hemophilia Center and the Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel-Hashomer, Israel.
Am Heart J. 1998 May;135(5 Pt 2 Su):S187-93. doi: 10.1016/s0002-8703(98)70248-0.
Exposure of citrated whole blood samples to polystyrene plates under flow conditions with the cone and plate(let) analyzer (CPA) results in surface immobilization of plasma von Willebrand factor (vWF) followed by platelet deposition. Staining the plates allows measurement of the percentage of surface covered (SC) by the adhered particles and their average size (AS). Both SC and AS parameters depend on platelet count and hematocrit level and reach maximal values after 2 minutes; only AS is shear rate dependent. Under optimal assay conditions (2 minutes at 1800 sec(-1)) normal blood samples yielded an SC of 14.9% +/- 2.5% and an AS of 39.4 +/- 5.2 microm2. Severe von Willebrand disease (eight patients) yielded low SC (5.2% +/- 2.1%), which was restored to normal by testing with vWF precoated surfaces. Glanzmann's thrombasthenia (six patients) samples demonstrated no adhesion of platelet at all. Blocking of the glycoprotein (GP) IIb/IIIa receptor by the chimeric antibody abciximab, and of the GPIb by a recombinant vWF fragment, have yielded a dose-response inhibition demonstrating the crucial role of these receptors in platelet deposition on polystyrene plates in this system. Evaluation of a patient with severe von Willebrand disease receiving replacement vWF factor VIII therapy revealed a comparable response as tested by both the CPA and the Ricof methods. In vitro testing of the GPIIb/IIIa blocking by a nonpeptidic analogue tirofiban and abciximab revealed a good correlation between the CPA test and the routine aggregometry. Eleven patients treated by abciximab after coronary angioplasty were studied by the CPA during the first 24 hours, demonstrating a marked decrease in SC and AS, with some diversity in the responses. We conclude that the CPA test is suitable for evaluation of primary hemostasis and for monitoring of anti-platelet drugs.
在流动条件下，使用锥板式分析仪（CPA）将枸橼酸化全血样本暴露于聚苯乙烯板上，会导致血浆血管性血友病因子（vWF）在表面固定，随后血小板沉积。对板进行染色可测量粘附颗粒覆盖的表面百分比（SC）及其平均大小（AS）。SC和AS参数均取决于血小板计数和血细胞比容水平，并在2分钟后达到最大值；只有AS与剪切速率有关。在最佳检测条件下（1800秒⁻¹下2分钟），正常血液样本的SC为14.9%±2.5%，AS为39.4±5.2平方微米。重度血管性血友病患者（8例）的SC较低（5.2%±2.1%），在用vWF预包被表面进行检测时可恢复正常。血小板无力症患者（6例）的样本完全没有血小板粘附。嵌合抗体阿昔单抗对糖蛋白（GP）IIb/IIIa受体的阻断，以及重组vWF片段对GPIb的阻断，产生了剂量反应抑制，证明了这些受体在该系统中血小板在聚苯乙烯板上沉积中的关键作用。对一名接受vWF因子VIII替代治疗的重度血管性血友病患者的评估显示，通过CPA和Ricof方法检测的反应具有可比性。非肽类类似物替罗非班和阿昔单抗对GPIIb/IIIa阻断的体外检测显示，CPA检测与常规血小板聚集测定之间具有良好的相关性。对11例冠状动脉成形术后接受阿昔单抗治疗的患者在最初24小时内进行了CPA研究，结果显示SC和AS显著降低，反应存在一定差异。我们得出结论，CPA检测适用于原发性止血的评估和抗血小板药物的监测。
