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Corn trypsin inhibitor coating attenuates the prothrombotic properties of catheters in vitro and in vivo.

机译:玉米胰蛋白酶抑制剂涂层在体外和体内都会减弱导管的血栓形成特性。

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摘要

Catheters initiate coagulation by activating factor (f) XII, which can lead to catheter thrombosis. Fondaparinux, which only targets activated fX (fXa), is associated with more catheter thrombosis than heparin, which targets fXa and thrombin. To render catheters less thrombogenic and fondaparinux more effective, we examined whether coating catheters with corn trypsin inhibitor (CTI), which blocks fXIIa, attenuates catheter-induced clotting and promotes fondaparinux activity. Compared with unmodified catheters, CTI-coated catheters demonstrated (a) decreased adsorption of fibrinogen and fXII, (b) greater inhibition of fXIIa generated by catheter-induced autoactivation, (c) attenuated fXIIa-mediated activation of fXI and (d) longer plasma clotting times in the absence or presence of fondaparinux. In an accelerated catheter thrombosis model in rabbits, (a) the time to catheter occlusion was longer with CTI-coated catheters than with unmodified catheters and (b) an intravenous dose of fondaparinux that had no effect on the time to occlusion of unmodified catheters extended the time to occlusion of CTI-coated catheters. These findings support the concept that the prothrombotic activity of catheters reflects their capacity to activate fXII and identify CTI immobilization as a novel approach for rendering catheters and other blood-contacting medical devices less thrombogenic.
机译:导管通过激活因子(f)XII引发凝血,这可能导致导管血栓形成。仅针对活化的fX(fXa)的Fondaparinux与针对fXa和凝血酶的肝素的导管血栓形成相关性更高。为了使导管减少血栓形成并提高磺达肝素的有效性,我们检查了是否用玉米胰蛋白酶抑制剂(CTI)涂覆导管来阻断fXIIa,从而减弱导管诱发的凝血并促进磺达肝素活性。与未改良的导管相比,涂有CTI的导管表明(a)纤维蛋白原和fXII的吸附减少,(b)导管诱导的自激活对fXIIa的抑制作用更大,(c)减弱了fXIIa介导的fXI激活,以及(d)血浆更长不存在或存在磺达肝癸钠时的凝血时间。在家兔的加速导管血栓形成模型中,(a)使用CTI涂层的导管比使用未改良导管的导管闭塞时间更长;以及(b)对未修饰导管的闭塞时间没有影响的静脉注射fondaparinux封堵CTI导管的时间。这些发现支持了这样的概念,即导管的血栓形成活性反映了它们激活fXII和识别CTI固定的能力,这是使导管和其他与血液接触的医疗设备的血栓形成更少的新方法。

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