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

Holst, J. (author): Lund University,Lunds universitet,Vaskulära sjukdomar - kliniska studier,Forskargrupper vid Lunds universitet,Vascular Diseases - Clinical Research,Lund University Research Groups,Helsingborg Hospital

Lindblad, B. (author)

Bergqvist, D. (author)

Nordfang, O. (author)

Ostergaard, P. B. (author)

Petersen, J. G.L. (author)

Nielsen, G. (author)

Hedner, U. (author)

(creator_code:org_t)

Abstract Subject headings

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.

By the author/editor: Holst, J.; Lindblad, B.; Bergqvist, D.; Nordfang, O.; Ostergaard, P. B ...; Petersen, J. G.L ...; show more...; Nielsen, G.; Hedner, U.; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cardiac and Card ...

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