Effect of ultrasound on fibrin clot structure

Abstract

A commercially available catheter (EKOS EkoSonic catheter) has been used in the clinic with lytic drugs to clear blood clots associated with pulmonary embolism, deep vein thrombosis and peripheral arterial occlusion. Operating at 2.3 MHz, transducers within the catheter deliver short, variable amplitude pulses at intensities between 3.4 and 11.5 W/cm2. Lysis enhancement in the presence of ultrasound is non-thermal and generally attributed to increased transport and, therefore, increased efficiency of the lytic. The enhanced lytic effect may also be associated with increased availability of lytic binding sites associated with changes in the clot’s fibrin structure. To better understand the specific effects of ultrasound on fibrin networks within blood clots, we utilized scanning electron microscopy (SEM) and clot turbidity measurements to observe and quantify changes in fibrin mesh. SEM images of Factor XIII-depleted fibrinogen clots show a significant decrease (p < 0.05) in fibrin fiber diameter in the presence of ultrasound (33.8 ± 17.2 nm) compared to control (63.4 ± 24.0 nm). Clot turbidity is reduced following treatment with ultrasound, which correlates with decreased fiber diameter. These results indicate that ultrasound alters fibrin structure, which may contribute to enhanced binding of lytic drug and clot lysis.