Journal
ACTA BIOMATERIALIA
Volume 8, Issue 11, Pages 4092-4100Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2012.07.019
Keywords
Corn trypsin inhibitor; Factor XII; Catheter thrombosis; Surface modification; Fondaparinux; Contact activation
Funding
- Canadian Institutes of Health Research [FRN 3992, MOP 102735, FRN 79846]
- Heart and Stroke Foundation of Ontario [T4729, T4730]
- Ontario Research and Development Challenge Fund
- Ontario Graduate Scholarship
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Catheters initiate coagulation by activating factor (f) XII, which can lead to catheter thrombosis. Fondaparinux, which only targets activated IX (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. (C) 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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