Inhibition by aurintricarboxylic acid of von Willebrand factor binding to platelet GPIb, platelet retention, and thrombus formation in vivo

Abstract

Abstract Commercial aurintricarboxylic acid (ATA) was separated into molecular‐weight (MW) fractions of <210 to >25,000, using gel permeation chromatography. Fractions with MW >1,300 effectively inhibited both botrocetin‐induced vWF and bovine vWF binding to fixed human platelets. These activities decreased with a MW >17,000. Platelet retention for a human in vitro was reduced by ATA at 150 μ, as was that for rats ex vivo at 3 mg/kg. ATA prolonged tail transection bleeding time in rats but had only a weak effect on buccal mucosal bleeding time in dogs. ATA had no effect on platelet count but markedly prolonged PTT. ATA at 10 mg/kg exhibited antithrombotic activity and caused a marked improvement in patency status following successful thrombolysis by t‐PA in electrically and copper coil‐induced thrombosis models. These results suggest that specific inhibitors of the vWF‐GPIb interaction such as ATA may prove useful as antithrombotic agents. © 1994 Wiley‐Liss, Inc.