“Melting” Clot with Ultrasound-Accelerated Thrombolysis

What is ultrasound-accelerated thrombolysis? Ultrasound-accelerated thrombolysis involves the breaking down or “melting” of blood clots that can form in the leg arteries or veins. The standard or older method has been to simply give blood thinners, either intravenously or by mouth, and then over two to four months, those blood clots can get resolved. This methodology uses ultrasound energy along with thrombolytics to help accelerate the process of thrombolysis. tPA (tissue plasminogen activator) is the typical thrombolytic utilized to dissolve clot rapidly, within hours or overnight. Although that’s very nice for veins, it’s even more important for arteries. How does the ultrasound affect the clot? Clot is made up of different elements, such as fibrin, that weave themselves together like a net. Acoustic energy creates a pressure wave that helps disrupt the cross-linking of the fibrin. The ultrasound energy also helps create a way for the thrombolytic to get into the clot by loosening up the fibrin cross-links. The ultrasound energy doesn’t really break up the clot, it just alters the shape of the fibrin network. Now the clot is more porous, meaning the drug can get inside the clot and have greater effect, instead of just being dripped in around it, which is how the old catheter systems work. We’ve had catheters that deliver the drug for many years, but they just delivered it. They weren’t adding anything other than just getting the drug to the leg. Ultrasound-accelerated thrombolysis helps the drug get into the clot directly. What about mechanical thrombectomy catheters? There’s no problem with mechanical thrombectomy; this system just offers a different way of handling the clot. In general, we can divide how to deal with blood clots into two categories. Like with an ice cube, you can either break it with a hard force (mechanical thrombectomy) or you can melt it. Ultrasound with tPA is more like melting the ice cube. Mechanical thrombectomy works by generating super high pressure that breaks up the clot. It may have some theoretical disadvantages in its potential damage to the vein, the vein wall or the valves, because it’s shooting out the saline at super-high pressure. But I’d say that right now this is potential or theoretical damage. Those devices work well. But imagine just dripping in a drug and accessing the clot with an ultrasound wave. We believe it’s the most gentle way of breaking down the clot, thereby, hopefully, preserving the valve function and not injuring the vein wall, which is very, very sensitive. As far as which one works better, we can’t say that one is better at getting rid of the clot versus the other. There are some differences depending on the age of the clot. The mechanical thrombectomy devices may not be as good for some older clot, because those fibrin cross-links are a little bit stronger. In theory, the ultrasound energy with tPA might be better, because it might break things up chemically that can’t be broken up mechanically. For super-soft clot, mechanical devices are fine. Soft clot is like jelly; pretty much anything will work. There are some issues with the mechanical devices as far as what they do to the blood. Mechanical thrombectomy literally breaks up not only the blood clot but the blood itself. When you break down the blood itself, there are elements in the blood which are potentially dangerous and can cause a change in heart rate. If you break down too much blood, there can be some kidney damage from hemolysis. How does ultrasound-accelerated thrombolysis compare in duration to blood thinners and mechanical thrombectomy? The Ekos ultrasound-accelerated thrombolysis system works to resolve clots immediately, within hours to a day. Mechanical thrombectomy can resolve clots very quickly as well, within hours. With mechanical thrombectomy, you put the device in, turn on the jet and it gets rid of the clot right in front of your eyes. It may not get rid of everything, but it gets rid of a fair amount. The remaining clot may have to be dealt with using long-term blood thinners. With ultrasound energy, within a day, you hope to dissolve all the clot. So both mechanical thrombectomy and ultrasound-driven technology work quickly. In reality, mechanical thrombectomy might work the quickest, but perhaps using more forceful energy. Ultrasound-driven may take from a few hours to a day, but more gently. Whereas blood thinners may take weeks or months. So you’re treating these clots much more quickly than in the past? Let’s say someone comes in with a deep vein thrombosis. A patient can get heparin followed by warfarin, which they would stay on for three months. Technically, you are starting treatment on day one, the same day that ultrasound-accelerated thrombolysis can be done, or mechanical thrombectomy. The more quickly you resolve the clot, however, the greater the likelihood of preserving the valve function. If the clot takes two or three months to resolve, then the irritating or inflammatory effect of that clot on the veins and the valves will result in post-thrombotic syndrome. If we can get rid of that clot quickly, within hours or a day, we can potentially reduce the damage to the valves and the veins, reduce the chance of patients developing venous stasis ulcers, and, hopefully, reduce their chance of getting clots again in the future. The main issue here is to reduce the chance of a patient developing chronic venous stasis disease and the significant disability associated with the formation of ulcers. These ulcers are exquisitely painful and result in a major impact on the cost of health care and industry, as time lost from work in order to render treatment is substantial. What is post-thrombotic syndrome? Normally, the valves in the veins keep blood from moving back down towards the ankle or the knee. Post-thrombotic syndrome occurs after the development of blood clots that have been allowed to linger. The valves have been affected by the clot to the point that they can no longer keep the blood in check. Without the valves working, the blood just pools in the leg, causing changes to the actual structures of the leg. All this static pressure of blood leads to what we call post-thrombotic syndrome: tissue swelling in the leg and discoloration of the skin from hemosiderin deposit (a breakdown product of red blood cells). It is a very difficult problem. Along with swelling of the limb, ulcerations can develop, which are literally the irritating effect of the broken red blood cells and the high pressure, resulting in a true breakdown of the skin. There is a wound, usually on the inside of the ankle. Not only is it unsightly, it itches and it’s exquisitely painful. This wound is part of a syndrome called chronic venous stasis ulcer disease. Many times it’s related to a post-thrombotic syndrome. Chronic venous stasis ulcer disease is treatable with a lot of wound care and with compression stockings. Some types of chronic venous stasis disease are reversible with the more superficial veins, like the saphenous vein. If you get rid of the saphenous vein, or the bridging veins, called perforating veins, that lead to the skin area, you can decrease the pressure to the local area and those wounds can heal. So although the syndrome may not be reversible, you can treat and heal the wounds. But of course it’s much better that patients never get to this stage. How does ultrasound-accelerated thrombolysis fit into last year’s release of the American Chest Physician guidelines? The American College of Chest Physicians (ACCP) guidelines (published in July 2008) include sections containing suggestions and recommendations for antithrombotic/ thrombolytic therapy for peripheral artery occlusive disease, chronic limb ischemia, and intermittent claudication that align closely with the benefits of ultrasound-accelerated thrombolysis. Have you found any other advantages to ultrasound use? By resolving the clot more quickly, we can use less thrombolytics. All thrombolytics have their risks, so by using ultrasound energy, we might be able to reduce the potential side effects of the drug, such as excessive bleeding. Unlike mechanical thrombectomy, where there are a number of different devices out on the market (some vacuum, some rinse, some generate pressure, some whip the clot around), as far as I know, this current technology is the only one proven to break up clot using the combination of ultrasound with lytics. It’s a novel technology and usage as opposed to mechanical forms, which have been around for years. In the old days, we used to do a cut down on the groin, put in a thrombectomy balloon and pull the clot out. Then we would use a s-mark, which is like a tight rubber band, wrap the leg up and squeeze the clot up and out. Although tPA, streptokinase, and urokinase have been around for many years for thrombolysis, this is the first time that ultrasound has been added. In our patient population, we are seeing some nice results early on, in the 24-48 hour period. No longer do we say to patients, “Let’s see how you are in 3 months.” Dr. Simonian can be contacted at gsimonian@aol.com

NULL