Xiao Z, Théroux P, Frojmovic M
The Department of Medicine, University of Montreal, Quebec, Canada.
Thromb Haemost. 1999 Feb;81(2):281-5.
The study investigated how drug inhibition of the GPIIb/IIIa receptor influences the interactions between platelets and leukocytes. These interactions are believed to play an important role in the etiology of the acute coronary syndromes. Thirty patients with unstable angina or non-Q-wave myocardial infarction were studied before the administration of tirofiban or placebo and after 4 h and 72 h. Platelet-leukocyte aggregates were characterized in whole blood using three-colour flow cytometry. The leukocyte population was isolated by a nucleic acid probe (LDS 751) and platelet-neutrophil coaggregates identified as particles binding both anti-CD42a-FITC and anti-CD45-PE. Tirofiban decreased by 25% the density of platelets in circulating platelet-neutrophil coaggregates (p <0.01), and prevented the increase induced by platelet agonist stimulation (p <0.0001). The reduction correlated with inhibition of fibrinogen binding to platelet (p <0.0001) and with inhibition of platelet aggregation (p <0.0001). The percentage of neutrophils with bound platelets following platelet agonist stimulation was, however, increased following GPIIb/IIIa inhibition. Thus, inhibition of GPIIb/IIIa receptor promotes platelet-neutrophil adhesion, but markedly reduces the binding density of platelets in the coaggregates.
该研究调查了药物抑制糖蛋白IIb/IIIa受体如何影响血小板与白细胞之间的相互作用。这些相互作用被认为在急性冠脉综合征的病因学中起重要作用。对30例不稳定型心绞痛或非Q波心肌梗死患者在给予替罗非班或安慰剂之前、之后4小时和72小时进行了研究。使用三色流式细胞术对全血中的血小板-白细胞聚集体进行表征。通过核酸探针（LDS 751）分离白细胞群体，并将血小板-中性粒细胞共聚集体鉴定为同时结合抗CD42a-FITC和抗CD45-PE的颗粒。替罗非班使循环中的血小板-中性粒细胞共聚集体中血小板的密度降低了25%（p<0.01），并阻止了血小板激动剂刺激所诱导的增加（p<0.0001）。这种降低与纤维蛋白原与血小板结合的抑制相关（p<0.0001），也与血小板聚集的抑制相关（p<0.0001）。然而，在糖蛋白IIb/IIIa抑制后，血小板激动剂刺激后与血小板结合的中性粒细胞百分比增加。因此，糖蛋白IIb/IIIa受体的抑制促进了血小板-中性粒细胞的黏附，但显著降低了共聚集体中血小板的结合密度。
