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.(ABSTRACT TRUNCATED AT 250 WORDS)