VEITHSymposium: Ultrasound-Enhanced Thrombolysis for Deep Venous Thrombosis

At the VEITHSymposium, you presented data regarding your experience with the EkoSonic ultrasound-accelerated thrombolysis system. 

Our experience is good. Ninety percent (90%) of patients treated so far have had successful thrombolysis of their obstructed deep iliac veins; the majority in < 24 hrs. We use the EkoSonic system for patients with fresh thrombus, but also the so-called “organized,” thrombus; patients with a deep venous thrombosis of more than 1 to 2 weeks and up to 10 to 12 weeks. The Ekosonic system is capable of dissolution of older thrombus and older clots, and of course, the freshly occluded deep venous system. The added value is that even if the thrombus is organized, it can be dissolved with the EkoSonic system. 

When you say “organized”, what does that mean?

There is a difference between clots of 1 or 2 days, and older clots. As clots become older, the amount of fibrin inside the clot increases, and that is what is called “organized.” Some people say it is a chronic thrombus when it is older than 1-2 weeks. It can be very hard to dissolve organized thrombus with the conventional therapy, standard catheter-directed thrombolysis. The EkoSonic system helps to allow the penetration of the thrombolytics into the fibrin fibers of the organized clot.

Which thrombolytic are you using with the system?

In Europe, and especially in The Netherlands, it is mainly urokinase. The primary use of urokinase in The Netherlands is for peripheral arterial disease, peripheral thrombotic disease in the veins, and especially, for pulmonary emboli. 

Are there particular considerations to be aware of when using the Ekos system?

It is key to involve the entire thrombus, so the tip of the Ekosonic system should be in a non-thrombosed segment distally of the thrombus to ensure some flow. You should choose an EkoSonic system length that matches the length of the thrombus. Advance it into the thrombus and through the entire clot, and then start the therapy. It is not labor-intensive, because the EkoSonic system will work in the ward [rather than requiring the patient to remain in the cath lab]. It is not like pharmaco-mechanical therapy, where you have to try to dissolve the clots in the angio suite. With the EkoSonic system, it is not necessary to be with your patient during the entire treatment.

The system is put in place, but the physician does not need to remain present for the entire treatment?

Correct. When the clinical symptoms improve, you can shoot the next venography to see if the clot has dissolved. On the arterial side, it is easier, because if the ankle-brachial index improves or there is really good pulsatile flow at the foot or ankle, then we can shoot the next angio. For a venous thrombosis, per protocol, we perform a venography every six hours to see if there is remaining clot. In venous thrombosis patients, when there is good flow, but perhaps still some remaining clot, it is acceptable to stop the thrombolysis at that point. This is because in the majority of patients, the deep venous thrombosis is the result of an underlying cause, like May-Turner syndrome or some kind of obstruction. In the majority of the patients, we must perform additional percutaneous transluminal angioplasty and stenting. So, first the thrombus has to be cleared, or 90-95% cleared, and then a final venography is done to diagnose the reason for the deep venous thrombosis. Any underlying cause of deep venous thrombosis must be directly treated, because otherwise, the risk of re-thrombosis is substantial.

What about the risk of pulmonary embolism for deep venous thrombosis patients?

It is our standard practice to have a computed tomography scan to check for pulmonary emboli, because more than 50% of patients with deep venous thrombosis do have some kind of pulmonary embolism. It is also the main cause of mortality for patients with deep venous thrombosis. If the pulmonary embolism is not severe, it does not need active treatment, so the patient will go on warfarin. If the pulmonary embolism is severe, the EkoSonic system can also be used to treat it, with good results. 

How long have you been using ultrasound-accelerated thrombolysis with the EkoSonic system?

We began at least five years ago, and first began use with peripheral arterial thrombosis as part of the DUET trial.¹ DUET compared use of the EkoSonic system to standard catheter-directed thrombolysis for the treatment of acute peripheral arterial thrombotic occlusions. In that trial, ultrasound-accelerated thrombolysis significantly reduced treatment time by an average of 12 hours, with no increase of (serious) adverse events. Plans for DUET II, a non-randomized trial evaluating a lower hourly drug dose with the EkoSonic system, are underway.

What about safety?

While results regarding the dissolution of clot with ultrasound-accelerated thrombolysis are excellent, and better than compared to the standard therapy, it is important to note that the risk of major bleeding is also low. Hemorrhage and other bleeding complications are one of the major complications of thrombolysis, so if their occurrence can be minimized, it is also part of the advantage of the EkoSonic system. 

The reduction in bleeding complications is because of the total dose of drug administered, which is lower than with the standard therapy.

Yes, and the shorter the amount of time you have to treat your patients with thrombolysis, the less bleeding complications there will be. 

Disclosure: Dr. de Vries reports no conflicts of interest regarding the content herein.

Dr. Jean-Paul de Vries can be contacted at j.vries@antoniusziekenhuis.nl.

References and suggested reading

1. DUET: randomized, controlled, multi-center trial demonstrates reduced treatment time and drug dose with EKOS vs. catheter-directed thrombolysis in peripheral arterial occlusions. Press release: Ekos Corporation. April 15, 2013. Available online at https://www.cathlabdigest.com/DUET-Randomized-Controlled-Multi-Center-Trial-Demonstrates-Reduced-Treatment-Time-Drug-Dose-EKOS-vs. Accessed December 11, 2013.
2. Schrijver AM, Reijnen MM, van Oostayen JA, Hoksbergen AW, Lely RJ, van Leersum M, de Vries JP. Initial results of catheter-directed ultrasound-accelerated thrombolysis for thromboembolic obstructions of the aortofemoral arteries: a feasibility study. Cardiovasc Intervent Radiol. 2012 Apr;35(2):279-85. doi: 10.1007/s00270-011-0164-4.