Bertram Ulf, Moser Martin, Peter Karlheinz, Kuecherer Helmut F, Bekeredjian Raffi, Straub Andreas, Nordt Thomas K, Bode Christoph, Ruef Johannes
Department of Cardiology, University of Heidelberg, Germany.
J Thromb Thrombolysis. 2002 Dec;14(3):197-203. doi: 10.1023/a:1025044625487.
Due to considerably high rates of reocclusion under standard thrombolytic therapy GP IIb/IIIa inhibitors have been combined with thrombolytics to improve therapeutic outcomes. Potential reasons for arterial reocclusion may be increased platelet activation, interaction of platelets with other cell types such as leukocytes and inadequate drug dosing due to lack of ideal platelet monitoring. We compared combination therapy regimens consisting of GP IIb/IIIa inhibitors and thrombolytics with respect to platelet inhibition and platelet-leukocyte interactions.
From the GUSTO V trial (standard rPA vs. reduced dose rPA and abciximab) and the FASTER trial (standard TNK-tPA vs. reduced dose TNK-tPA and tirofiban) 15 patients were monitored by platelet aggregometry, rapid platelet function assay (RPFA) and flow cytometry (FC). rPA alone (n = 5) caused initial increases in platelet aggregation. However, platelet aggregation was significantly (p < 0.05) and sufficiently (>80%) inhibited by abciximab/rPA (n = 5) and tirofiban/TNK-tPA (n = 5). The platelet inhibitory effect of tirofiban/TNK-tPA was more pronounced compared to abciximab/rPA with a significant difference after 2 h (p < 0.05). Tirofiban/TNK-tPA and abciximab/rPA caused decreases in platelet-leukocyte aggregates as well as in binding of specific antibodies to the platelet vitronectin receptor and P-selectin (p < 0.05, respect.). No differences among the treatment groups were seen with respect to antibody binding to MAC-1 and CD154/CD40 ligand.
Taken together, GP IIb/IIIa inhibitors overcome the platelet activating effect of thrombolytics resulting in sufficient platelet inhibition. RPFA is a suitable monitoring tool to accurately assess platelet inhibition. Within the given combination treatment regimen tirofiban appears to be more effective compared to abciximab and to exert effects beyond the inhibition of GP IIb/IIIa.
由于在标准溶栓治疗下再闭塞率相当高，因此已将糖蛋白IIb/IIIa抑制剂与溶栓剂联合使用以改善治疗效果。动脉再闭塞的潜在原因可能是血小板活化增加、血小板与其他细胞类型（如白细胞）相互作用以及由于缺乏理想的血小板监测导致药物剂量不足。我们比较了由糖蛋白IIb/IIIa抑制剂和溶栓剂组成的联合治疗方案在血小板抑制和血小板-白细胞相互作用方面的情况。
从GUSTO V试验（标准剂量重组纤溶酶原激活剂[rPA]与低剂量rPA及阿昔单抗）和FASTER试验（标准剂量替奈普酶[tPA]与低剂量替奈普酶及替罗非班）中选取15例患者，通过血小板聚集试验、快速血小板功能测定（RPFA）和流式细胞术（FC）进行监测。单独使用rPA（n = 5）会导致血小板聚集最初增加。然而，阿昔单抗/rPA（n = 5）和替罗非班/替奈普酶（n = 5）可显著（p < 0.05）且充分（>80%）抑制血小板聚集。与阿昔单抗/rPA相比，替罗非班/替奈普酶的血小板抑制作用更显著，在2小时后有显著差异（p < 0.05）。替罗非班/替奈普酶和阿昔单抗/rPA可使血小板-白细胞聚集体以及特异性抗体与血小板玻连蛋白受体和P-选择素的结合减少（分别为p < 0.05）。各治疗组在抗体与巨噬细胞-1（MAC-1）和CD154/CD40配体的结合方面未见差异。
总体而言，糖蛋白IIb/IIIa抑制剂克服了溶栓剂的血小板激活作用，从而实现充分的血小板抑制。RPFA是准确评估血小板抑制的合适监测工具。在给定的联合治疗方案中，替罗非班似乎比阿昔单抗更有效，且其作用超出了对糖蛋白IIb/IIIa的抑制。
