Palmerini Tullio, Coller Barry S, Cervi Vittorio, Tomasi Luciana, Marzocchi Antonio, Marrozzini Cinzia, Leone Ornella, Piccioli Milena, Branzi Angelo
Istituto di Cardiologia, Policlinico S. Orsola, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy.
J Am Coll Cardiol. 2004 Oct 19;44(8):1570-7. doi: 10.1016/j.jacc.2004.07.028.
This study evaluated the role of circulating tissue factor (TF) in mediating thrombus formation on stents in an in vitro model of stent perfusion.
The traditional view of coagulation has recently been challenged by the demonstration that TF is present in circulating blood. The potential contribution of this intravascular pool of TF to thrombus formation on stents is not known.
Coronary stents were placed in parallel silicone tubes connected to a roller pump that was set to pump blood at a flow rate of 10 ml/min. Stents were then exposed to heparinized blood from healthy volunteers for 120 min.
The presence of the stent in the circuit caused a significant increase in monocyte TF expression, but only monocytes with attached platelets stained positive for TF. Thrombi formed on stents and the thrombi stained positive for TF. Pretreatment of blood with a monoclonal antibody against TF (cH36) caused a 56% reduction in (125)I-fibrin(ogen) deposition on stents compared with controls (p = 0.002). Monocyte depletion of blood reduced (125)I-fibrin(ogen) deposition by 45% (p = 0.01) and TF staining in the thrombus by 83% (p = 0.01). Pretreatment of blood with a monoclonal antibody against P-selectin reduced (125)I-fibrin(ogen) deposition by 24% (p = 0.04). Perfusion of stents with leukocyte-reduced platelet-rich plasma (PRP) produced small thrombi and treatment of PRP with cH36 reduced (125)I-fibrin(ogen) deposition by 43% (p = 0.01).
Circulating TF plays a pivotal role in thrombus formation on stents. Monocytes appear to be the main, but not only, source of TF depositing in the thrombus.
本研究在支架灌注体外模型中评估循环组织因子(TF)在介导支架上血栓形成中的作用。
凝血的传统观点最近受到了TF存在于循环血液中的证明的挑战。这种血管内TF池对支架上血栓形成的潜在贡献尚不清楚。
将冠状动脉支架置于连接到滚轴泵的平行硅胶管中,滚轴泵设置为以10 ml/min的流速泵血。然后将支架暴露于健康志愿者的肝素化血液中120分钟。
回路中支架的存在导致单核细胞TF表达显著增加,但只有附着血小板的单核细胞TF染色呈阳性。支架上形成血栓,且血栓TF染色呈阳性。用抗TF单克隆抗体(cH36)预处理血液,与对照组相比,支架上(125)I-纤维蛋白(原)沉积减少56%(p = 0.002)。血液单核细胞清除使(125)I-纤维蛋白(原)沉积减少45%(p = 0.01),血栓中TF染色减少83%(p = 0.01)。用抗P-选择素单克隆抗体预处理血液使(125)I-纤维蛋白(原)沉积减少24%(p = 0.04)。用白细胞减少的富血小板血浆(PRP)灌注支架产生小血栓,用cH36处理PRP使(125)I-纤维蛋白(原)沉积减少43%(p = 0.01)。
循环TF在支架上血栓形成中起关键作用。单核细胞似乎是血栓中TF沉积的主要但非唯一来源。