Preincubation of Dacron grafts with recombinant tissue factor pathway inhibitor decreases their thrombogenicity in vivo

Background: We have previously shown that preincubation of whole blood clots with recombinant tissue factor pathway inhibitor (rTFPI) attenuates clot-associated procoagulant activity assessed ex vivo. This study was undertaken to determine whether a single local application of rTFPI induces similar attenuation of the procoagulant activity on preclotted Dacron grafts implanted in an artery in vivo. Methods: Dacron grafts (4 mm x 4 cm long) were preclotted in porcine blood and incubated with either rTFPI (5 mg/ml) or arginine-phosphate buffer for 15 minutes. Grafts were implanted end-to-end in the femoral arteries of 10 pigs, with one rTFPI-treated and one buffer- treated graft implanted in each animal. Animals did not undergo anticoagulation either before or after graft implantation. Radiolabeled porcine fibrinogen was injected intravenously, and the grafts underwent perfusion for 1 hour. A subgroup of animals (n = 7) also had infusion of radiolabeled autologous platelets at the time of administration of radiolabeled fibrinogen. Results: Fibrin(ogen) deposition was decreased in rTFPI-treated grafts by 36% ± 7% (mean ± SEM) compared with buffer-treated grafts (p = 0.001). Platelet deposition was also reduced in the rTFPI- treated grafts by 31% ± 15%, although the reduction did not reach statistical significance (p = 0.10). The extent of rTFPI-mediated attenuation of fibrin(ogen) versus platelet deposition varied independently among animals. Conclusions: Clot-directed anticoagulant effects of rTFPI appear to be useful for substantially decreasing the thrombogenicity of Dacron grafts immediately after their implantation. Chronic studies to determine whether the decreases in thrombogenicity result in improved long-term graft patency appear warranted.