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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
; ; ; and
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
  • pmid:9659887
  • 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
2024-05-27 09:40:48
@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}},
  keywords     = {{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}},
  doi          = {{10.1016/S1078-5884(98)80112-3}},
  volume       = {{15}},
  year         = {{1998}},
}