Aurin tricarboxylic acid inhibits experimental venous thrombosis.
In vitro, aurin tricarboxylic acid (ATA) inhibited ristocetin-induced human platelet agglutination in a dose-dependent manner. The IC50 value (dose which inhibits 50% of platelet agglutination) was 60 +/- 8.7 micrograms/ml. In vivo, the i.v. administration of ATA to rats reduced the thrombus formation in an arteriovenous shunt with an ED50 value of 9.0 +/- 1.6 mg/kg. In a venous thrombosis model, using a combination of a thrombogenic challenge and stasis, ATA displayed a significant, dose-dependent antithrombotic effect, the ED50 value being of 18.3 +/- 2.0 mg/kg. In an experimental model of disseminated intravascular coagulation, ATA protected mice from the lethal effect of thromboplastin-induced thromboembolism with a ED50 value of 1.1 +/- 0.15 mg/kg, being in that respect 12 times less potent than standard heparin (ED50 = 90 +/- 15 micrograms/kg). These observations therefore show that ATA is active in both arterial- or venous-type thrombosis models and suggest that von Willebrand Factor might be important not only in arterial but also in venous thrombosis.
Bernat
A
A
Sanofi Recherche, Toulouse, France.
Lale
A
A
Herbert
J M
JM
D000371:Agglutination; D000818:Animals; D001166:Arteriovenous Shunt, Surgical; D001312:Aurintricarboxylic Acid / Q000627:therapeutic use*; D001760:Bleeding Time; D001792:Blood Platelets / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006487:Hemostasis; D006801:Humans; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D012310:Ristocetin / Q000037:antagonists & inhibitors; D013924:Thrombophlebitis / Q000139:chemically induced / Q000517:prevention & control*
D012310:Ristocetin; D001312:Aurintricarboxylic Acid