In vitro flow evaluation of recombinant tissue factor pathway inhibitor immobilized on collagen impregnated Dacron

Recombinant tissue factor pathway inhibitor (rTFPI) was immobilized on collagen impregnated (CI) knitted Dacron surfaces and its resistance to fibrin deposition evaluated following exposure to nonanticoagulated whole blood. Recombinant TFPI readily adsorbed to the CI Dacron surface and maintained its inhibitory activity. Under static conditions, rTFPI treated CI Dacron showed little fibrin deposition when compared with untreated surfaces. Treated samples exposed to flowing native blood at wall shear rates of 100 or 200 sec(-1) also demonstrated reduced fibrin deposition (up to 56%) compared with untreated samples. To assess the relative roles of the contact and tissue factor pathways in fibrin formation on artificial grafts, flow studies were performed with whole blood containing corn trypsin inhibitor, a potent inhibitor of FXIIa and contact activation. Corn trypsin inhibitor reduced fibrin deposition on untreated CI Dacron by 40%. Immobilized rTFPI alone, or corn trypsin inhibitor in combination with immobilized rTFPI, reduced fibrin deposition by 58% and 61%, respectively. These data suggest that immobilized rTFPI slows fibrin deposition on the vascular graft material by inhibiting both the contact pathway and blood borne tissue factor procoagulant activity arising from either the alternatively spliced form of tissue factor or from tissue factor containing microparticles.