A BLINDED TRIAL OF LOCAL RECOMBINANT TISSUE FACTOR PATHWAY INHIBITOR VERSUS EITHER LOCAL OR SYSTEMIC HEPARIN IN A VEIN BYPASS MODEL

Purpose: Tissue factor pathway inhibitor (TFPI), an endogenous proteas e, is a potent inhibitor of the extrinsic pathway of coagulation. To d etermine whether TFPI could be used as an alternative to systemic hepa rin and dextran in vein bypass grafting procedures, we compared the ef ficacy of these agents in a blinded trial using a pig model of lower e xtremity vein bypass grafting. Methods: Yorkshire pigs (60 to 75 kg) w ere divided into four groups of five each: systemic heparin (5 ml 10(3 ) U heparin, 50 ml intravenous dextran, and 10 U heparin/ml flush), lo cal heparin (5 mi saline solution, 50 mi intravenous dextran, and 10 U heparin/ml hush), recombinant TFPI (rTFPI) (5 ml saline solution, 50 ml intravenous saline, and rTFPI 90 mu g/ml flush), and control (5 ml and 50 ml intravenous saline and intravenous phosphate-buffered saline solution flush). The pigs were anesthetized and the lesser saphenous vein was harvested and reversed to construct a bypass from tile common femoral artery to the saphenous artery at the hock. Each pig received two intravenous infusions before cross-clamping, and the artery and v ein were flushed locally according to the protocol for each treatment group. Coagulation parameters were drawn 30 minutes after cross-clampi ng. The surgical team was blinded as to the pigs' treatment group thro ughout the protocol. Results: The time from initial infusion until byp ass completion averaged 80 minutes. Conduit patency rates at 7 days we re as follows: four of five in the rTFPI group, three of Rye in the sy stemic heparin group, one of five in the local heparin group, and zero of five in the control group. The activated partial thromboplastin ti me was elevated (50.1 +/- 13.8 seconds) with systemic heparin but not in the other groups. Conclusions: Local administration of TFPI prevent s thrombosis as effectively as systemic heparin and dex th an and is s uperior to local heparin flush plus dextran (p = 0.02). Thus local TFP I offers an excellent alternative to systemic heparin plus dextran and avoids the risks of systemic anticoagulation.