Recombinant human tissue factor pathway inhibitor prevents thrombosis in a venous tuck model

Microvascular free tissue transfer has become a mainstay of reconstruction after resections for head and neck cancer. With current techniques, free flap failure is typically low; however, failure rates have been reported as high as 10%. Most thrombotic failures occur within the first few days postoperatively and tend to involve the venous anastomoses. We evaluated the efficacy of recombinant human tissue factor pathway inhibitor (rhTFPI), an anticoagulant that directly inhibits the extrinsic coagulation pathway, using a rat model of microvenous thrombosis.

Prospective, randomized.

Sprague-Dawley rats were randomly assigned to either rhTFPI or saline groups. We performed a venous tuck procedure in the common femoral vein. Prior to closure, the anastamosis was irrigated with either rhTPFI (20 μg/mL) or normal saline. Survival of the anastomosis was measured via clinical assessment at regular postoperative intervals. After a postoperative period of 48 hours, sites were intraoperatively assessed and the vessels harvested.

There was a significant increase in vessel patency in rats treated topically with rhTFPI compared to controls receiving saline. There was no increase in bleeding complications in the treated group versus controls.

Our data suggests that the use of topical rhTPFI increases venous anastomotic patency rates in vivo. The topical means of administration is attractive, as there seems to be a low percentage of systemic complications as is often seen with anticoagulation therapies. Future studies will investigate the potential efficacy in patients undergoing microvascular free tissue transfer.