Molecular insights into the anticoagulant-induced spontaneous activation of platelets in whole blood - Various anticoagulants are not equal
Molecular insights into the anticoagulant-induced spontaneous activation of platelets in whole blood - Various anticoagulants are not equal
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DOI：
10.1016/0049-3848(96)00129-6
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发表时间：
1996-08-01
影响因子：
7.5
通讯作者：
Watala, C
中科院分区：
文献类型：
--
作者：
Golanski, J;Pietrucha, T;Watala, C
体外自发的抗凝依赖性血小板活化可能会干扰止血参数的测定。使用流式细胞术监测各种血液抗凝剂对血小板活化的影响。无论使用何种血液抗凝剂（EDTAK（2）、肝素、柠檬酸盐或PPACK），血小板活化在抽血后立即开始，并且在EDTAK（2）抗凝血液样本中最为明显。 GMP 140 抗原的表达进展伴随着血小板膜整合素 α(IIb)β(3) 亚基 β(3) 丰度的增加，而整合素 α(IIb)β(3) 复合体形式的荧光没有平行变化。 GMP-140 表达的增加与用EDTAK(2) 或肝素抗凝的样品中血小板凝集增强以及抽取到柠檬酸盐中的血液中凸起的血小板微粒并行。酪氨酸激酶抑制剂 2,5-二羟基肉桂酸甲酯可显着降低 EDTAK(2) 诱导的血小板活化。 EDTA 二钠对血小板膜动力学的影响与纤维蛋白原与血小板 GPIIb-IIIa 相互作用引起的变化非常相似。因此，EDTAK(2)诱导的血小板活化可能是由于血小板膜蛋白结构和构象的干扰造成的，并且可能与信号转导途径的“非特异性”触发有关。总体而言，EDTAK(2) 和肝素似乎是最不合适的抗凝剂，特别是在 GMP-140 抗原的表达方面。未能认识到自发抗凝剂诱导的血小板活化的重要性可能会导致凝血参数监测过程中的误诊。
The spontaneous anticoagulant-dependent platelet activation in vitro may potentially interfere with the determination of haemostatic parameters. The effects of various blood anticoagulants on platelet activation were monitored using flow cytometry. Regardless of a blood anticoagulant used (EDTAK(2), heparin, citrate or PPACK), platelet activation began immediately after blood withdrawal and was most pronounced in the EDTAK(2)-anticoagulated blood samples. The progressing expression of GMP 140 antigen was accompanied by the enhanced abundance of the subunit beta(3) of the platelet membrane integrin alpha(IIb)beta(3) without parallel changes in the fluorescence attributed to the complex form of the integrin alpha(IIb)beta(3). The increased expression of GMP-140 was paralleled by the enhanced platelet clumping in the samples anticoagulated with either EDTAK(2) or heparin, and the raised platelet microparticles in blood withdrawn into citrate. The EDTAK(2)-induced platelet activation was markedly reduced by methyl 2,5-dihydroxycinnamate, tyrosine kinase inhibitor. The influence of disodium EDTA on platelet membrane dynamics closely mimicked the alterations induced upon the interaction of fibrinogen with platelet GPIIb-IIIa. Thus, the EDTAK(2)-induced platelet activation might result from an interference with platelet membrane protein structure and conformation and possibly relate to an ''unspecific'' trigerring of a signal transduction pathway. Overall, EDTAK(2) and heparin appeared the least suitable anticoagulants, particularly with the regard to the expression of GMP-140 antigen. The failure to recognize the importance of a spontaneous anticoagulant-induced platelet activation may result in misdiagnoses during the monitoring of coagulation parameters.