Professor University of Leeds Leeds, England, United Kingdom
Background: The EkoSonic Endovascular System (EKOS) simultaneously delivers tPA and ultrasound (US) and is used for the treatment of venous thromboembolism (VTE). Despite studies supporting the use of EKOS to treat VTE, the mechanisms underlying acceleration of thrombolysis by EKOS are not fully understood.
Aims: Quantify the effects of EKOS on clot formation and structure, and tPA-mediated fibrinolysis.
Methods: For turbidity, plasma clots were formed in cuvettes containing EKOS catheters and optical density was measured at 340nm over 1hr. For scanning electron microscopy (SEM), clots were formed in open-ended tubes, with the EKOS catheter placed centrally. After US application, clots were immediately fixed and processed for SEM to analyse fibre thickness. For permeation experiments, clots were formed in cuvettes (with 4x1.5mm holes drilled at the bottom) containing EKOS catheters, and the volume of liquid flowing through the clot was measured at regular interval. For lysis, turbidity and permeation experiments were peformed in the presence of tPA. For all experiments, US were applied at 0, 8, 15, 30, or 47Watts, with coolant.
Results: Application of US at 0, 9 and 15W did not alter clot formation or lysis. Clot formation was unaffected by the application of US, but already formed clots exhibited a significant reduction in deltaOD during 30 and 47W US application, before returning to normal. SEM and permeation analysis indicated that the application of 47W US led to a 34% reduction in fibre thickness, and 26% increase in pore size, compared to no US. Internal lysis (turbidity) and external lysis (permeation) rates were significantly reduced at 30W (0.8-fold) and 47W (0.6-fold and 2.1-fold, respectively) US.
Conclusion(s): Our study indicates that EKOS promotes thrombolysis by thinning fibrin fibres and increasing clot permeability. These findings provide a structural underpinning for the mechanisms by which US accelerates fibrinolysis.
