Efficacy of pentasaccharide on a prethrombosis model based on a calibrated stasis by the increase in up-stream venous pressure.

On a previous model using Wessler's principle in the rat, we have demonstrated that a partial ligature of the inferior vena cava leading to a 40% increase in up-stream venous pressure was thrombogenic only in association with the infusion of low dose of thromboplastin (90 microg/kg). In these thrombogenic conditions, the infusion of pentasaccharide (Arixtra, fondaparinux) should lead to a strong inhibition of thrombus formation. Therefore, we performed on five groups of 10 rats: stasis alone (group S) with a 40% increase in up-stream venous pressure; stasis and thromboplastin (group ST90); and stasis, thromboplastin and pentasaccharide (groups SPT50, SPT100 and SPT250) at three different dosages (50, 100 and 250 microg/kg). The efficacy of pentasaccharide was measured according to the variations in up-stream venous pressure, thrombus weight and thrombin-antithrombin complexes levels. Only 250 microl/kg pentasaccharide significantly reduced the thrombus weight in comparison with group ST90 (5 mg versus 23.8 mg, P = 0.01) but it was not sufficient to induce a return to the basic state (5 mg versus 0.2 mg in group S, P = 0.049). Thrombin-antithrombin complex levels measured at the end of the experiment were significantly reduced in comparison with group ST90 (16.7 versus 57.8 mg, P = 0.01) and were not statistically different from group S (16.1 versus 16.6 mg, P = 0.65). In conclusion, in a very borderline model toward thrombogenesis, pentasaccharide was able to reduce thrombus weight and abolished biological hypercoagulability.
AuthorsP Pottier, B Planchon, F Truchaud, G Leftheriotis, J M Herbert, L Bressollette, N Passuti
JournalBlood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis (Blood Coagul Fibrinolysis) Vol. 14 Issue 6 Pg. 587-91 (Sep 2003) ISSN: 0957-5235 [Print] England
PMID12960613 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Polysaccharides
  • antithrombin III-protease complex
  • Antithrombin III
  • Thromboplastin
  • Peptide Hydrolases
  • fondaparinux
  • Animals
  • Antithrombin III (analysis)
  • Blood Pressure
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Hemostasis
  • Male
  • Peptide Hydrolases (analysis)
  • Polysaccharides (pharmacology, therapeutic use)
  • Rats
  • Rats, Sprague-Dawley
  • Thrombophilia (drug therapy)
  • Thromboplastin (pharmacology)
  • Thrombosis (drug therapy, prevention & control)
  • Treatment Outcome

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