Topical Tissue Factor Pathway Inhibitor Improves Free-Flap Survival in a Model Simulating Free-Flap Errors

Abstract

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.

Seasonal patterns of birth for subjects with bulimia nervosa, binge eating, and purging: Results from the National Women's Study

“…In this study, the patency rate of the group treated with 10 μg/mL of rhTFPI was 100% versus 56% in the control group 2 days after exposure. This difference was statistically significant, and prior studies investigating TFPI have shown this dose to be effective 11, 12. Of control vessels, 56% remained patent.…”

“…Khouri et al and Ozbeck et al have shown significant differences in arterial patency rates with TFPI in hypertraumatic and avulsion models when compared to other agents 13, 14. These results were reproduced when applied to rabbit models simulating technical errors with free tissue transfers 11. Lantieri et al exposed everted and intimectomized rabbit arteries to rhTFPI at concentrations as little as 10 μg/mL and compared this to cohorts exposed to hirudin, heparin, and controls 12.…”

Fusion proteins comprising annexin V and Kunitz protease inhibitors are highly potent thrombogenic site-directed anticoagulants

“…by guest www.bloodjournal.org From without systemic anticoagulation. 54,55 However, many prothrombotic vascular lesions are not easily accessible for topical application. Because ANV and ANV-KPI fusions possess the ability to target the PS-exposed membranes of developing thrombi at sites of vascular lesions, it might be possible to inhibit thrombogenesis in situ by bolus injection or prolonged infusion at very low doses without intense systemic anticoagulation, thus minimizing the risk of bleeding.…”

Gene therapy to promote thromboresistance: Local overexpression of tissue plasminogen activator to prevent arterial thrombosis in an in vivo rabbit model

“…Clinical research has shown that thrombolytic therapy improves survival in acute myocardial-infarction and cerebrovascular-accident patients (3)(4)(5)(6), that heparin improves survival in certain high-risk subpopulations (7), and that chronic low-dose aspirin therapy may decrease the incidence of all such events (8,9). In addition, a number of new antithrombotic modalities, including enhancement of nitric oxide production (10), tissue-factor pathway inhibitors (11), hirudin (7), antibodies to glycoprotein IIb͞IIIa (2,12), and TNK-tissue-type plasminogen activator (tPA; Genentech; ref. 13), have shown great promise in initial studies.…”