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 protease, is a potent inhibitor of the extrinsic pathway of coagulation. To determine whether TFPI could be used as an alternative to systemic heparin and dextran in vein bypass grafting procedures, we compared the efficacy of these agents in a blinded trial using a pig model of lower extremity vein bypass grafting.

METHODS

Yorkshire pigs (60 to 75 kg) were 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), local heparin (5 ml saline solution, 50 ml intravenous dextran, and 10 U heparin/ml flush), recombinant TFPI (rTFPI) (5 ml saline solution, 50 ml intravenous saline, and rTFPI 90 micrograms/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 the common femoral artery to the saphenous artery at the hock. Each pig received two intravenous infusions before cross-clamping, and the artery and vein were flushed locally according to the protocol for each treatment group. Coagulation parameters were drawn 30 minutes after cross-clamping. The surgical team was blinded as to the pigs' treatment group throughout the protocol.

RESULTS

The time from initial infusion until bypass completion averaged 80 minutes. Conduit patency rates at 7 days were as follows: four of five in the rTFPI group, three of five in the systemic heparin group, one of five in the local heparin group, and zero of five in the control group. The activated partial thromboplastin time was elevated (50.1 +/- 13.8 seconds) with systemic heparin but not in the other groups.

CONCLUSIONS

Local administration of TFPI prevents thrombosis as effectively as systemic heparin and dextran and is superior to local heparin flush plus dextran (p = 0.02). Thus local TFPI offers an excellent alternative to systemic heparin plus dextran and avoids the risks of systemic anticoagulation.