Selective anticoagulation with active site blocked factor IXa in synthetic patch vascular repair results in decreased blood loss and operative time

Talia B. Spanier, Mehmet C. Oz, John D. Madigan, Eric A. Rose, David Stern, Roman Nowygrod, Ann Marie Schmidt

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Heparin has been the mainstay of anti thrombic therapy in arterial repair procedures. With increasing use of synthetic patch angioplasty (polytetrafluoroethylene [PTFE] or Dacron, Medical Products, Flagstaff, AZ) to improve long-term patency and limit aneurysmal dilation, however, the use of heparin has been associated with excessive needle hole bleeding, resulting in time delay in the operating room to achieve hemostasis, as well as clinically significant blood loss. Because of the multiple sites of action of heparin in the coagulation cascade, both intravascular (desired effect) and extravascular (untoward side effect) hemostasis are impaired. The authors therefore tested the hypothesis that selective inhibition of intravascular coagulation, without significant impairment of extravascular hemostasis, would prevent clotting intraluminally while preserving hemostasis at the suture line of the patch graft. The unique position of factor IX/IXa in the coagulation cascade renders its inhibition an ideal target in this setting. The authors prepared active site blocked factor IXa (IXai) using dansyl-Glu- Gly-Arg chloromethylketone, and tested this hypothesis in a New Zealand rabbit aortotomy model with PTFE patch closure using either heparin (25 IU/kg; n = 16) or IXai (300 μg/kg; n = 21). The infrarenal aorta was identified and isolated, the anti coagulant infused, aortic cross clamp placed, and aortotomy repaired with a 2 x 6 mm PTFE patch. After cross-clamp removal, blood loss was measured and time to hemostasis was recorded. Compared with heparin, IXai resulted in significantly reduced blood loss (6.97 ± 4.4 g vs 2.72 ± 2.51 g, respectively, p < 0.008), and time to hemostasis (2,94 ± 0.77 min vs 2.0 ± 0.63 min, respectively, 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 rabbits treated with heparin or IXai; 100% of the grafts were patent with no 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 long-term patency and decreased aneurysmal dilatation, while eliminating the intraoperative morbidity of needle hole bleeding.

Original languageEnglish (US)
JournalASAIO Journal
Volume43
Issue number5
StatePublished - Sep 1 1997
Externally publishedYes

Fingerprint

Factor IXa
Operative Time
Blood Vessels
Heparin
Hemostasis
Catalytic Domain
Repair
Blood
Polytetrafluoroethylene
Polytetrafluoroethylenes
Coagulation
Clamping devices
Rabbits
Grafts
Needles
Dilatation
Tunica Intima
Hemorrhage
Transplants
Operating rooms

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Biophysics
  • Medicine(all)
  • Biomaterials
  • Biomedical Engineering

Cite this

Selective anticoagulation with active site blocked factor IXa in synthetic patch vascular repair results in decreased blood loss and operative time. / Spanier, Talia B.; Oz, Mehmet C.; Madigan, John D.; Rose, Eric A.; Stern, David; Nowygrod, Roman; Schmidt, Ann Marie.

In: ASAIO Journal, Vol. 43, No. 5, 01.09.1997.

Research output: Contribution to journalArticle

Spanier, Talia B. ; Oz, Mehmet C. ; Madigan, John D. ; Rose, Eric A. ; Stern, David ; Nowygrod, Roman ; Schmidt, Ann Marie. / Selective anticoagulation with active site blocked factor IXa in synthetic patch vascular repair results in decreased blood loss and operative time. In: ASAIO Journal. 1997 ; Vol. 43, No. 5.
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AU - Rose, Eric A.

AU - Stern, David

AU - Nowygrod, Roman

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