901-110 Three-Dimensional Ultrasound Can Accurately Reconstruct Intravascular Thrombi: In Vitro Validation

High-frequency ultrasound can potentially display gross morphologic changes during thrombus formation and lysis. Current intravascular ultrasound (IVUS) devices, however, provide only 2-dimensional cross-sectional images with limited overall appreciation of thrombus size and 3-dimensional (3D) configuration. The purpose of this study was to explore the ability of 3D reconstruction of serial ultrasound images to provide a quantitative assessment of intravascular thrombi. We therefore imaged 11 arterial thrombi of varying shape and volume (10 to 116mm3). To avoid thrombus disruption, we used an epivascular approach (also suitable for transvenous imaging) with a 20MHz IVUS catheter withdrawn at 1mm/sec. A 3D voxel image intensity data set was reconstructed, and thrombus volume was semiautomatically extracted based on its intensity. Calculated volume was compared with directly measured values by volume displacement in a miniature cylinder.Results3D reconstruction provided previously unobtainable longitudinal and 3D views that improved spatial appreciation of thrombus size, shape and channel formation. Calculated thrombus volumes agreed well with actual volumes: y=0.92x+2.4, r=0.98, SEE=5mm3, mean error = 1±5mm3(ns vs 0).Conclusion3D reconstruction can improve spatial appreciation of the shape of thrombi and accurately measure their volumes. This approach, suitable for epivascular or transvenous imaging, could potentially be used to study thrombus formation and lysis in research and clinical studies

Bleeding time prolongation and bleeding during infusion of recombinant tissue-type plasminogen activator in dogs: Potentiation by aspirin and reversal with aprotinin

AbstractThrombolytic therapy is associated with a bleeding tendency that may be exacerbated by adjunctive antiplatelet agents. The effect of recombinant tissue-type plasminogen activator (rt-PA) alone or in combination with aspirin on serial measurements of template bleeding time, ex vivo platelet aggregation and coagulation factors and the frequency of bleeding was studied in dogs. During infusion of rt-PA (15, 30 or 60 μg/kg per min for 90 min), a dose-related increase in bleeding tine was observed.In a randomized blinded study of 25 dogs, the baseline bleeding time (mean ± SD) was 3.5 ± 1 min in control animals and 4 ± 2 min after oral aspirin (15 mg/kg body weight). Infusion of rt-PA (15 μg/kg per min for 90 min) prolonged the bleeding time to a maximum of 15 ± 12 min. In contrast, combined aspirin and rt-PA therapy produced an increase to >30 min during infusion, reverting to 13 ± 10 min within 2 h after cessation of infusion. Recurrent continuous bleeding from incision sites occurred in one of six dogs given aspirin alone, two of seven given rt-PA alone and all six dogs given both aspirin and rt-PA (p = 0.02). Bleeding time >9 min correlated significantly with bleeding frequency (p < 0.0001), with a sensitivity of 100% and a specificity of 87%.Intravenous bolus injection of aprotinin (29,000 kallikrein inhibitor units/kg body weight) in six dogs given both rt-PA and aspirin produced a decrease in bleeding time from >30 min to 9.5 ± 9 min and resulted in cessation of bleeding. Thus, bleeding and bleeding time prolongation te this canine model are potentiated by a marked interactive effect of rt-PA and aspirin that is rapidly reversible. Template bleeding times may provide a useful quantitative index for monitoring the bleeding tendency associated with thrombolytic therapy