The effects of streptokinase and hydroxyethyl starch on in vitro clot disruption by ultrasound

Background: In vitro studies showed that low-frequency ultrasound (US) causes blood clot dissolution. This effect is augmented with thrombolytics, microbubbles and microparticles. However, in animal models of transcutaneous delivery, US alone is not effective, probably due to attenuation of US energy by overlying skin. When combined with thrombolytics or microbubbles, transcutaneous US is highly effective. Purpose: To assess the synergistic effect of low-intensity low-frequency US and saline, hydroxyethyl starch (HAES) (a non-gas filled microparticle containing solution), streptokinase (STK), and their combination on blood clot disruption. Methods: Human blood clots from 4 healthy donors, 2-4 hours old, were immersed for 0, 15, or 30 min in 37°C in 10 ml of the above-mentioned solutions, and then were randomized to 10 sec of 20 kHz US or no US. The % difference in weight was calculated. Results: Immersion for 30 min without US resulted in 13.8±1.2% clot lysis in saline, and 22.0±1.3%, 21.7±2.1%, and 23.2±1.9% in STK, HAES, and STK+HAES, respectively (p=0.002). US augmented clot lysis in all groups and at all time points. With lowintensity US, HAES was not better than saline. However, the combination of HAES+STK with US resulted in larger clot disruption at 15 sec incubation time (46.7±3.2%) than with saline (29.6±2.1%), HAES (29.6±2.5%), and STK (32.8±3.6%) (p>0.001). Conclusion: Low-frequency, low-intensity US combined with HAES and STK resulted in greater clot disruption at short incubation times. This combination may assist in achieving faster reperfusion in in vivo models.