Prevention of thrombosis by topical application of tissue factor pathway inhibitor in a rabbit model of vascular trauma.

Abstract

The extrinsic pathway of coagulation is initiated when tissue factor complexes with factor VII. A naturally occurring protein inhibitor of this complex, tissue factor pathway inhibitor (TFPI), has recently been isolated and the cDNA coding for this protein cloned. We used a rabbit ear artery model of crush/avulsion injury and microvascular repair to investigate the efficacy of TFPI as a topically applied antithrombotic agent. Traumatized arteries treated through lumenal irrigation with normal saline vehicle (controls) achieved patency rates of 8% and 0% at 1 and 7 postoperative days, respectively. Heparin irrigation (10 U/ml) resulted in patencies of 40% at both evaluation times. In contrast, TFPI at a dose of 20 micrograms/ml (0.2 ml total volume; 10 minute exposure) yielded a 91% patency rate at 1 day and 73% at 7 days postoperatively (p < 0.0005 vs controls). Prothrombin time and activated partial thromboplastin time values were not altered after topical treatment with TFPI. Scanning electron microscopy revealed dramatically inhibited thrombogenesis upon the injured surfaces of TFPI-treated vessels. These results suggest that TFPI used as a topically applied antithrombotic agent is effective for the prevention of thrombosis in microvascular anastomoses.

• Authors: R K Khouri, B Koudsi, F Kaiding, R L Ornberg, T C Wun
• Journal: Annals of plastic surgery (Ann Plast Surg) Vol. 30 Issue 5 Pg. 398-402; discussion 402-4 (May 1993) ISSN: 0148-7043 [Print] United States
• PMID: 8342923 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Fibrinolytic Agents
• Lipoproteins
• lipoprotein-associated coagulation inhibitor
• Heparin

Topics

• Administration, Topical
• Anastomosis, Surgical (methods)
• Animals
• Arteries (injuries)
• Disease Models, Animal
• Ear, External (blood supply)
• Fibrinolytic Agents (administration & dosage, therapeutic use)
• Heparin (administration & dosage, therapeutic use)
• Lipoproteins (administration & dosage, therapeutic use)
• Microscopy, Electron, Scanning
• Postoperative Complications (prevention & control)
• Rabbits
• Thrombosis (prevention & control)
• Vascular Patency (physiology)