Local application of recombinant active-site inhibited human clotting factor VIIa reduces thrombus weight and improves patency in a rabbit venous thrombosis model

Research output: Contribution to journalArticle

Abstract

Objective: To study whether locally administered recombinant inactivated human coagulation factor VIIa (FFR-rFVIIa) would reduce the thrombus formation and improve patency in an experimental venous thrombosis model without inducing systematic changes in the coagulation. Design: Experimental double-dummy randomised study. Materials: In 20 healthy New Zealand White rabbits both juguIar veins were exposed under general anaesthesia. Methods: The thrombi were induced in a 10 mm long jugular vein segment with a combination of chemical destruction of the intima and a restriction of the bloodflow. Each segment was treated with either FFR-rFVIIa or placebo injected directly into the vein. Results: 1.5 mg topically applied FFR-rFVIIa significantly reduced the thrombus weight (p < 0.001). The 30 and the 120 min patency tests were significantly improved (p < 0.05 and p < 0.001, respectively). Plasma analyses (APTT, dilute-TF time, FVII protein) were evaluated as baseline, 3 min after declamping and at sacrifice. No prolongation of the clotting times were seen. FFR-rFVIIa protein was detected in minute amounts (ng/ml); however, this was not enough to prolong the dilute-TF time. Conclusions: Local application of recombinant active-site inhibited human FVIIa reduced both thrombus weight and improved patency significantly in an experimental venous thrombosis model without affecting the systematic clotting times.

Details

Authors
  • J. Holst
  • A. T. Kristensen
  • H. I. Kristensen
  • M. Ezban
  • U. Hedner
External organisations
  • Helsingborg Hospital
  • Novo Nordisk A/S
  • Skåne University Hospital
Research areas and keywords

Keywords

  • FVIIa, Inactivated FVIIa, Patency, TF, TF-FVII-dependent coagulation, Venous thrombosis
Original languageEnglish
Pages (from-to)515-520
JournalEuropean Journal of Vascular and Endovascular Surgery
Volume15
Issue number6
Publication statusPublished - 1998
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes