SELECTIVE ANTICOAGULATION WITH ACTIVE-SITE BLOCKED FACTOR IXA IN SYNTHETIC PATCH VASCULAR REPAIR RESULTS IN DECREASED BLOOD-LOSS AND OPERATIVE TIME

Heparin has been the mainstay of anti thrombic therapy in arterial rep air procedures. With increasing use of synthetic patch angioplasty (po lytetrafluoroethylene [PTFE] or Dacron, Medical Products, Flagstaff, A Z) to improve long-term patency and limit aneurysmal dilation, however , the use of heparin has been associated with excessive needle hole bl eeding, resulting in time delay in the operating room to achieve hemos tasis, as well as clinically significant blood loss. Because of the mu ltiple sites of action of heparin in the coagulation cascade, both int ravascular (desired effect) and extravascular (untoward side effect) h emostasis are impaired. The authors therefore tested the hypothesis th at selective inhibition of intravascular coagulation, without signific ant impairment of extravascular hemostasis, would prevent clotting int raluminally while preserving hemostasis at the suture line of the patc h graft. The unique position of factor IX/IXa in the coagulation casca de renders its inhibition an ideal target in this setting. The authors prepared active site blocked factor IXa (IXai) using dansyl-Glu-Gly-A rg chloromethylketone, and tested this hypothesis in a New Zealand rab bit aortotomy model with PTFE patch closure using either heparin (25 I U/kg; n = 16) or IXai (300 mu g/kg; n = 21). The infrarenal aorta was identified and isolated, the anti coagulant infused, aortic cross clam p placed, and aortotomy repaired with a 2 x 6 mm PTFE patch. After cro ss-clamp removal, blood loss was measured and time to hemostasis was r ecorded. Compared with heparin, IXai resulted in significantly reduced blood loss (6.97 +/- 4.4 g vs 2.72 +/- 2.51 g, respectively, p < 0.00 8), and time to hemostasis (2.94 +/- 0.77 min vs 2.0 +/- 0.63 min, res pectively, p < 0.003). To assess long-term patency and thrombosis, 12 rabbits (given heparin; n = 6 and IXai; n = 6) were observed for up to 2 months post-operatively. No differences were observed between rabbi ts treated with heparin or IXai; 100% of the grafts were patent with n o differences in degree of intimal hyperplasia by histologic analysis. Together, these data suggest that use of IXai in PTFE vascular repair will safely allow realization of the benefits of longterm patency and decreased aneurysmal dilatation, while eliminating the intraoperative morbidity of needle hole bleeding.