There is Synergism Between High-Intensity, Low-Frequency Ultrasound and Streptokinase but not with Eptifibatide, Heparin, and Aspirin: Differential Effects on Fresh and Aged Blood Clots. An In Vitro Study

Objective: Ultrasound is emerging as a promising modality for recanalization of acutely thrombosed blood vessels, especially when associated with fibrinolytics. We assessed the efficacy of ultrasound combined with saline, heparin, eptifibatide, aspirin, and streptokinase in disruption of fresh as well as aged human blood clots, using an in vitro model. Methods: Blood clots from five donors, 2–4 or 48 hours old, were cut into 250–400 mg slices and immersed for 1, 15, or 30 min in 10 ml saline containing either heparin, eptifibatide, aspirin, streptokinase, or saline alone. Clots were then randomized to 10 s of 20 kHz ultrasound or immersion alone. After treatment, the percentage difference in weight was calculated. Results: Immersion of fresh clots without ultrasound in eptifibatide and heparin resulted in significantly more clot lysis than immersion in saline, aspirin, and streptokinase. Immersion of aged thrombi without ultrasound in heparin, eptifibatide, and aspirin had no additive effect over immersion in saline. Ultrasound enhanced clot disruption in all five solutions, in each immersion time and both in fresh and aged clots. Heparin and aspirin had no additive effect, compared with saline, on ultrasound disruption of both fresh and aged clots, whereas eptifibatide was less effective than saline. In contrast, streptokinase greatly enhanced disruption of both fresh ( P=.004) and aged ( P