Augmentation of in-vitro clot dissolution by low frequency high-intensity ultrasound combined with antiplatelet and antithrombotic drugs

Background: Glycoprotein IIb/IIIa antagonists and heparin are increasingly used for treatment of acute coronary syndromes. There is no data on the effect of these drugs on clot dissolution when combined with low frequency high-intensity ultrasonic energy. We examined a possible additive effect of low frequency high-intensity ultrasound with an antithrombotic, an antiplatelet and a fibrinolytic agent alone or in combinations for in vitro blood clot dissolution. Methods: Human blood clots were incubated for 10', 15' and 30' in normal saline containing commonly used concentrations of heparin, tirofiban, t-PA and Optison (echocardiographic contrast agent) alone and in combinations. Clots were then randomly exposed to low frequency high-intensity ultrasound (27[emsp3 ]kHz) for 5 minutes. The percent difference in clot weight and the incremental effect of ultrasound energy were calculated. Results: The most significant additive effect of ultrasound energy was detected with the combination of tirofiban and heparin (39 +/-2% augmentation after 10' of incubation, p <0.0001). The greatest magnitude of percent clot weight reduction was observed with ultrasound energy combined with either t-PA alone (72 +/-1% after 30' incubation, p=0.0016) or with the combination of t-PA, tirofiban, heparin and Optison (68 +/-4% after 30' incubation, p=0.015). Conclusions: Application of low frequency high-intensity ultrasound has an additive effect to antiplatelet, antithrombotic and fibrinolytic drugs, specifically with the combination of tirofiban and heparin or with t-PA; this effect is observed after a short incubation period.