AURINTRICARBOXYLIC ACID PREVENTS ACUTE RETHROMBOSIS IN A CANINE MODELOF ARTERIAL THROMBOSIS

Acute rethrombosis following thrombolytic therapy occurs in 5% to 25% of patients. We evaluated the effect of aurintricarboxylic acid (ATA), a triphenyl dye that blocks von Willebrand factor (VWF) binding to pl atelet glycoprotein Ib, on arterial reperfusion and acute rethrombosis following fibrinolytic therapy. Primary thrombosis was induced in the femoral arteries of anesthetized dogs by application of anodal curren t and partial arterial constriction. Blood flow was monitored with an electromagnetic flow probe, and primary thrombosis was considered to h ave occurred when blood flow was reduced to and remained at zero. Repe rfusion was induced by intravenous streptokinase 30 minutes after thro mbosis. Streptokinase reduced plasma fibrinogen levels from an average of 144 mg/dL to <5 mg/dL resulting in inhibition of ADP- and epinephr ine-induced platelet aggregation ex vivo. Acute rethrombosis following reperfusion occurred within 37+/-18 (mean+/-SD) minutes in 89% (16/18 ) of animals receiving thrombolytic activator treatment. Histological examination of reoccluding thrombi revealed densely aggregated platele ts and erythrocytes with no detectable fibrin. In the two other study groups, ATA was infused in conjunction with thrombolytic therapy (10 a rteries) or at near completion of acute rethrombosis following fibrino lytic activator treatment (6 arteries). In each case ATA prevented ret hrombosis. However, concomitant administration of ATA and thrombolytic therapy delayed restoration of blood flow. ATA had no direct effect o n hemodynamics, thrombin time, platelet count, or platelet aggregation response to ADP, epinephrine, or collagen. These data indicate that i nhibition of vWF-platelet glycoprotein Ib interaction is effective in preventing acute rethrombosis following thrombolytic therapy. However, the complex paradoxical effects of ATA on platelet activity should be considered when it, or agents of its class, are used as antithromboti cs.