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.
Pottier
P
P
Service de Médecine Interne A, Service d'Hématologie Biologique and Service d'Orthopédie, Hôtel Dieu, C.H.U. Nantes, France. pierre.pottier@sante.univ-nantes.fr
Planchon
B
B
Truchaud
F
F
Leftheriotis
G
G
Herbert
J M
JM
Bressollette
L
L
Passuti
N
N
D000818:Animals; D000990:Antithrombin III / Q000032:analysis; D001794:Blood Pressure; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000077425:Fondaparinux; D006487:Hemostasis; D008297:Male; D010447:Peptide Hydrolases / Q000032:analysis; D011134:Polysaccharides / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D019851:Thrombophilia / Q000188:drug therapy; D013925:Thromboplastin / Q000494:pharmacology; D013927:Thrombosis / Q000188:drug therapy / Q000517:prevention & control*; D016896:Treatment Outcome
D011134:Polysaccharides; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D013925:Thromboplastin; D010447:Peptide Hydrolases; D000077425:Fondaparinux