A phase II trial of intraluminal irrigation with recombinant human tissue factor pathway inhibitor to prevent thrombosis in free flap surgery

A multicenter, multinational, blinded, randomized, parallel-group, phase II study was conducted to investigate the use of recombinant human tissue fac tor pathway inhibitor (rhTFPI; SC-59735) as an antithrombotic additive to t he intraluminal irrigating solution during microvascular anastomosis in fre e flap reconstructive surgery. A total of 622 patients undergoing free flap reconstruction were randomly assigned to thr ee groups. For each group, a different intraluminal irrigating solution was administered at completion o f the microvascular arterial and venous anastomoses and before blood flow t o the flap was reestablished: rhTFPI at a concentration of 0.05 or 0.15 mg/ ml (low-dose or high-dose group, respectively) or heparin at a concentratio n of 100 U/ml (current-standard-of-practice group). There were no other dif ferences in treatment among the groups. Patient characteristics, risk facto rs, and surgical techniques used were similar among all three groups. Flap failure was lower (2 percent) in the low-dose rhTFPI group than in the high -dose rhTFPI (6 percent) and heparin (5 percent) groups, but this differenc e was not statistically significant (p = 0.069). There were no significant differences in the rate of intraoperative revisions of vessel anastomoses ( 11 percent, 12 percent, and 13 percent) or postoperative thrombosis (8 perc ent, 8 percent, and 7 percent) among the low-dose rhTFPI, high-dose rhTFPI, and heparin groups, respectively. The rate of postoperative wound hematoma was significantly lower in the low-dose rhTFPI group (3 percent) than in t he high-dose rhTFPI (8 percent) and heparin (9 percent) groups (p = 0.040). There were no differences in blood chemistry or coagulation values among t he three study groups. Other than hematomas, there were no differences in t he incidence or severity of adverse reactions among the three groups. It is concluded that use of rhTFPI as an intraluminal irrigant during free flap reconstruction is safe, well tolerated, and as efficacious as use of hepari n for preventing thrombotic complications during and after the operation. F urthermore, the lower dose of rhTFPI (0.05 mg/ml) may reduce the occurrence of postoperative hematoma and help prevent flap failure.