Topical tissue factor pathway inhibitor improves free-flap survival in a model simulating free-flap errors

Free flap failure is frequently due to tension, twisting, kinking, or compression of the vascular pedicle after the anastomosis is completed. A rabbit model simulating these errors was used to evaluate the capacity of topically-applied tissue factor pathway inhibitor (TFPI) to prevent microvascular thrombosis. The rabbit ear was isolated on the central artery and vein. The artery was transected, shortened, repaired, and twisted 360 degrees around the vein. Immediately following the anastomosis. TFPI in concentrations of 1, 4, 10, or 40 micrograms/ml was irrigated across the lumen. Topically-applied control buffer and heparin (50 U/ml) were compared to TFPI. Treatment with control buffer resulted in a 20 percent survival rate. Topically-applied heparin improved the survival rate to 60 percent (p < 0.05). In contrast, TFPI in concentrations of 4, 10, and 40 micrograms/ml yielded survival rates of 89, 100, and 97 percent, respectively. This was significantly greater than the heparin-treated ears (p < 0.05). TFPI in a concentration of 40 micrograms/ml was effective in preventing arterial thrombosis when applied for as little as 30 sec; 4 micrograms/ml was effective in preventing thrombosis when applied for 10 min. These results support the use of TFPI as a topical irrigation solution to help prevent microvascular arterial thrombosis in free-flap surgery.