Antithrombotic properties of a truncated recombinant tissue factor pathway inhibitor in an experimental venous thrombosis model.
The aim of this study was to investigate whether a truncated recombinant tissue factor pathway inhibitor (rTFPI1-161) had an antithrombotic effect comparable to low-molecular-weight (LMW) heparin. A randomized double-dummy study was conducted with 40 rabbits in 6 groups. An experimental thrombosis was induced in the jugular veins by a combination of destroyed endothelium and restricted blood flow. Group 1 was given placebo; group 2, LMW heparin 60 anti-factor Xa units/kg; group 3, rTFPI1-161 0.1 mg/kg; group 4, rTFPI1-161 1.0 mg/kg and group 5, rTFPI1-161 10.0 mg/kg. rTFPI1-161 reduced the thrombus weights in all treated groups, with a significant effect in doses between 1.0 and 10.0 mg/kg compared to placebo. The frequency of thrombosis was significantly reduced in all treated groups. No hemorrhagic side effects were noted. In conclusion, rTFPI1-161 (1.0-10.0 mg/kg) has an antithrombotic effect comparable to that of LMW heparin.
Department of Surgery and Experimental Research, Malmö General Hospital, University of Lund, Sweden.
J
J
Holst
B
B
Lindblad
D
D
Bergqvist
O
O
Nordfang
P B
PB
Ostergaard
J L
JL
Petersen
G
G
Nielsen
U
U
Hedner
D000818:Animals; D001760:Bleeding Time; D004311:Double-Blind Method; D004353:Drug Evaluation, Preclinical; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D007601:Jugular Veins; D008074:Lipoproteins / Q000627:therapeutic use*; D008297:Male; D010446:Peptide Fragments / Q000627:therapeutic use*; D011817:Rabbits; D011897:Random Allocation; D011994:Recombinant Proteins / Q000627:therapeutic use; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*; D015912:Thrombolytic Therapy; D013927:Thrombosis / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control
D005343:Fibrinolytic Agents; D008074:Lipoproteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D015842:Serine Proteinase Inhibitors; C051928:lipoprotein-associated coagulation inhibitor; C081249:tissue factor pathway inhibitor (1-161)