Aurintricarboxylic Acid Prevents Acute Rethrombosis in a Canine Model of Arterial Thrombosis

Abstract

Abstract 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 platelet 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 current and partial arterial constriction. Blood flow was monitored with an electromagnetic flow probe, and primary thrombosis was considered to have occurred when blood flow was reduced to and remained at zero. Reperfusion was induced by intravenous streptokinase 30 minutes after thrombosis. Streptokinase reduced plasma fibrinogen levels from an average of 144 mg/dL to <5 mg/dL resulting in inhibition of ADP- and epinephrine-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 platelets and erythrocytes with no detectable fibrin. In the two other study groups, ATA was infused in conjunction with thrombolytic therapy (10 arteries) or at near completion of acute rethrombosis following fibrinolytic activator treatment (6 arteries). In each case ATA prevented rethrombosis. However, concomitant administration of ATA and thrombolytic therapy delayed restoration of blood flow. ATA had no direct effect on hemodynamics, thrombin time, platelet count, or platelet aggregation response to ADP, epinephrine, or collagen. These data indicate that inhibition 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 antithrombotics.