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Antithrombotic effect of recombinant truncated tissue factor pathway inhibitor (TFPI1-161) in experimental venous thrombosis : A comparison with low molecular weight heparin

Holst, J. LU ; Lindblad, B. LU ; Bergqvist, D.; Nordfang, O.; Ostergaard, P. B.; Petersen, J. G.L.; Nielsen, G. and Hedner, U. LU (1994) In Thrombosis and Haemostasis 71(2). p.214-219
Abstract

The aim was to investigate whether a truncated recombinant Tissue Factor Pathway Inhibitor (TFPI1-161) which lacked the third Kunitz-type domain and the basic c-terminal region, had an antithrombotic effect comparable to LMWH in a randomised double-dummy study. The experimental thrombosis was induced in jugular veins, in a total of 40 rabbits by a combination of destruction of the endothelium and restricted blood flow. Group 1: placebo, gr 2- LMWH 60 anti-FXa IU/kg, gr 3-5: 0.1, 1.0 and 10.0 mg/kg TFPI1-161. TFPI1-161 reduced the thrombus weights in all treated groups, significantly in doses of 1.0 and 10.0 mg/kg compared to placebo. The frequency of thrombosis and occlusive thrombosis were also... (More)

The aim was to investigate whether a truncated recombinant Tissue Factor Pathway Inhibitor (TFPI1-161) which lacked the third Kunitz-type domain and the basic c-terminal region, had an antithrombotic effect comparable to LMWH in a randomised double-dummy study. The experimental thrombosis was induced in jugular veins, in a total of 40 rabbits by a combination of destruction of the endothelium and restricted blood flow. Group 1: placebo, gr 2- LMWH 60 anti-FXa IU/kg, gr 3-5: 0.1, 1.0 and 10.0 mg/kg TFPI1-161. TFPI1-161 reduced the thrombus weights in all treated groups, significantly in doses of 1.0 and 10.0 mg/kg compared to placebo. The frequency of thrombosis and occlusive thrombosis were also significantly reduced in those doses. The antithrombotic properties of TFPI1-161 (1.0-10.0 mg/ kg) measured as thrombus weight, frequency of thrombosis and frequency of occlusive thrombosis was equivalent to the antithrombotic properties of LMWH. In the anti-FXa, APTT and PT-assays TFPI1-161 displayed a dose dependent increase of activity. Recombinant-TFPI1-161 did not influence the anti-FIIa-assay. No haemorrhagic side effects were noted.

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Contribution to journal
publication status
published
subject
in
Thrombosis and Haemostasis
volume
71
issue
2
pages
214 - 219
publisher
F K Schattauer Verlag Gmbh
external identifiers
  • scopus:0028082448
ISSN
0340-6245
language
English
LU publication?
yes
id
667c1511-2d85-42f0-aca8-976dab719f92
date added to LUP
2018-04-06 13:48:43
date last changed
2018-11-21 21:39:07
@article{667c1511-2d85-42f0-aca8-976dab719f92,
  abstract     = {<p>The aim was to investigate whether a truncated recombinant Tissue Factor Pathway Inhibitor (TFPI<sub>1-161</sub>) which lacked the third Kunitz-type domain and the basic c-terminal region, had an antithrombotic effect comparable to LMWH in a randomised double-dummy study. The experimental thrombosis was induced in jugular veins, in a total of 40 rabbits by a combination of destruction of the endothelium and restricted blood flow. Group 1: placebo, gr 2- LMWH 60 anti-FXa IU/kg, gr 3-5: 0.1, 1.0 and 10.0 mg/kg TFPI<sub>1-161</sub>. TFPI<sub>1-161</sub> reduced the thrombus weights in all treated groups, significantly in doses of 1.0 and 10.0 mg/kg compared to placebo. The frequency of thrombosis and occlusive thrombosis were also significantly reduced in those doses. The antithrombotic properties of TFPI<sub>1-161</sub> (1.0-10.0 mg/ kg) measured as thrombus weight, frequency of thrombosis and frequency of occlusive thrombosis was equivalent to the antithrombotic properties of LMWH. In the anti-FXa, APTT and PT-assays TFPI<sub>1-161</sub> displayed a dose dependent increase of activity. Recombinant-TFPI<sub>1-161</sub> did not influence the anti-FIIa-assay. No haemorrhagic side effects were noted.</p>},
  author       = {Holst, J. and Lindblad, B. and Bergqvist, D. and Nordfang, O. and Ostergaard, P. B. and Petersen, J. G.L. and Nielsen, G. and Hedner, U.},
  issn         = {0340-6245},
  language     = {eng},
  number       = {2},
  pages        = {214--219},
  publisher    = {F K Schattauer Verlag Gmbh},
  series       = {Thrombosis and Haemostasis},
  title        = {Antithrombotic effect of recombinant truncated tissue factor pathway inhibitor (TFPI<sub>1-161</sub>) in experimental venous thrombosis : A comparison with low molecular weight heparin},
  volume       = {71},
  year         = {1994},
}