title: Corn trypsin inhibitor coating attenuates the prothrombotic properties of catheters in vitro and in vivo.
abstract: 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.
authors: School of Biomedical Engineering, McMaster University, Hamilton, Ontario, Canada.
authors: Jonathan W
authors: JW
authors: Yau
authors: Alan R
authors: AR
authors: Stafford
authors: Peng
authors: P
authors: Liao
authors: James C
authors: JC
authors: Fredenburgh
authors: Robin
authors: R
authors: Roberts
authors: John L
authors: JL
authors: Brash
authors: Jeffrey I
authors: JI
authors: Weitz
mesh_terms: D000327:Adsorption; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D057785:Catheters / Q000009:adverse effects*; D020099:Coated Materials, Biocompatible / Q000494:pharmacology*; D005174:Factor XII / Q000378:metabolism; D000077425:Fondaparinux; D006801:Humans; D062645:Percutaneous Coronary Intervention; D056951:Photoelectron Spectroscopy; D010940:Plant Proteins / Q000494:pharmacology*; D011134:Polysaccharides / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D011817:Rabbits; D013499:Surface Properties / Q000187:drug effects; D013927:Thrombosis / Q000517:prevention & control*; D014867:Water / Q000737:chemistry
chemical_list: D020099:Coated Materials, Biocompatible; D010940:Plant Proteins; D011134:Polysaccharides; C052160:trypsin inhibitor, Zea mays; D014867:Water; D005174:Factor XII; D000077425:Fondaparinux