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

Holst, J. LU ; Kristensen, A. T.; Kristensen, H. I.; Ezban, M. and Hedner, U. LU (1998) In European Journal of Vascular and Endovascular Surgery 15(6). p.515-520
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... (More)

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.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
FVIIa, Inactivated FVIIa, Patency, TF, TF-FVII-dependent coagulation, Venous thrombosis
in
European Journal of Vascular and Endovascular Surgery
volume
15
issue
6
pages
515 - 520
publisher
Elsevier
external identifiers
  • scopus:0031876354
ISSN
1078-5884
DOI
10.1016/S1078-5884(98)80112-3
language
English
LU publication?
no
id
1cfd718a-0acf-4d40-b5cd-f8e684851e2a
date added to LUP
2018-04-05 15:43:49
date last changed
2018-05-29 09:41:29
@article{1cfd718a-0acf-4d40-b5cd-f8e684851e2a,
  abstract     = {<p>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 &lt; 0.001). The 30 and the 120 min patency tests were significantly improved (p &lt; 0.05 and p &lt; 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.</p>},
  author       = {Holst, J. and Kristensen, A. T. and Kristensen, H. I. and Ezban, M. and Hedner, U.},
  issn         = {1078-5884},
  keyword      = {FVIIa,Inactivated FVIIa,Patency,TF,TF-FVII-dependent coagulation,Venous thrombosis},
  language     = {eng},
  number       = {6},
  pages        = {515--520},
  publisher    = {Elsevier},
  series       = {European Journal of Vascular and Endovascular Surgery},
  title        = {Local application of recombinant active-site inhibited human clotting factor VIIa reduces thrombus weight and improves patency in a rabbit venous thrombosis model},
  url          = {http://dx.doi.org/10.1016/S1078-5884(98)80112-3},
  volume       = {15},
  year         = {1998},
}