Clot-Busters, the Sequel

If you have a clogged drain in your sink, you have two choices: Pour in some chemical and wait a while for it to clear, or use a rooter of some sort and clear the clog instantly.

But if you have a clog in a blood vessel in your brain, you now have only one of those options: Add a clot-busting enzyme to your blood and wait a couple of hours for it to dissolve the clot. An estimated 260,000 Americans were treated with the enzymes last year.

While you are waiting for the clot to break up, however, brain cells deprived of oxygen and nourishment are dying. After a stroke, “time is brain,” says Dr. Thomas Tomsick of the University of Cincinnati, meaning that the more time elapses, the more cells are damaged.

But physicians in stroke centers may soon have a second option. Researchers are developing tiny catheters that can be threaded through the tangled blood vessels of the brain and vaporize the clot with a laser, pulverize it with ultrasonic energy or suck it out with a vacuum line.

Such mechanical intervention has not been possible in the past because the devices were too large and too stiff to pass through the twists and turns of the tiny vessels of the brain. But new, smaller and more flexible catheters are allowing surgeons to explore once-forbidden passageways of the mind.

A Chance to Widen the ‘Golden Window’

Direct intervention could widen the “golden window” for treating stroke victims beyond the three hours now available, perhaps doubling or even tripling it. It could also reduce the risk of excessive bleeding associated with enzyme treatment. And it could increase the success rate in treating stroke victims. Currently, clot-busters are successful in only about 30% of patients.

“One of these [vaporizing, pulverizing or vacuuming techniques] is going to be the treatment of the future,” said Dr. Wayne Clark of the Oregon Stroke Center. “Which one, I don’t know yet.”

Although all the techniques have been tested in animals, only a handful of people have been treated with them so far. One was Louise Quashnick, a 78-year-old Oregon woman who suffered a severe stroke last summer that left her unable to talk and paralyzed on her left side.

Because of the size of the clot and delay in getting her to the stroke center, Clark was not able to treat her with a clot-buster. Instead, Quashnick volunteered to be a subject in a test of an experimental laser developed by LaTis Inc. of Coon Rapids, Minn.

Guided by an angiogram view of her vessels, Clark and his colleagues carefully threaded a small catheter containing the laser through Quashnick’s brain so the tip ended up within half an inch of the clot.

When the laser is activated, its colored light energy is absorbed only by the red clot, not by the white walls of the blood vessel surrounding the clot.

“The light only [releases] energy when it hits something red,” Clark said. “The laser will hit the clot and vaporize it.”

Within three months, Quashnick was living independently and taking care of herself, Clark told a recent meeting of the American Stroke Assn.

Clark said he has used the technique on five stroke patients. The first two times, the team could not reach the clot because the catheter was too stiff. After it was redesigned, they used it on three more patients, including Quashnick.

One patient had indeterminate results and one died from bleeding in the brain, although it is not clear whether the bleeding was a result of the massive stroke or of the procedure, Clark said. He has permission from the Food and Drug Administration to perform the procedure in seven more cases.

Another company, EndoSonix Inc. of Belmont, Calif., is manufacturing a similar laser developed at the Lawrence Livermore National Laboratory. The device is now being tested in people, according to Stephen Johnson, chief financial officer of EndoSonix, but the company will not report any results until the end of the year.

A much different approach has been initiated by EKOS Corp. of Bothell, Wash. That company has developed an ultrasonic probe that is used in conjunction with clot-busting drugs. The ultrasonic energy, for reasons that are not yet clear, accelerates the action of the enzyme, causing the clot to be destroyed more quickly.

Several researchers have been testing the device in clots in the leg. Dr. Keith Sterling of Georgetown University recently reported results from the first 10 patients. He found that the device gave a 50% improvement in speed and reduced the amount of drug used by half.

The company has a small trial in progress in Vancouver, Canada, on stroke patients and is seeking approval to study the technique in the United States, according to Douglas Hansmann, vice president for research and development.

A more unusual approach has been developed by Possis Medical Inc. of Minneapolis. The firm’s device uses a water jet to create suction at the end of the catheter. Between the jet and the suction, a clot is broken up and sucked out of the blood vessel.

Possis has a similar device for clearing coronary arteries that has already been approved by the Food and Drug Administration and is in use at 394 medical centers around the country. The company has now developed a smaller version that would be suitable for use in the brain, according to Eapen Chacko, vice president of investor relations.

Possis has received FDA approval to test the device in 30 stroke patients at six hospitals, and the trials began last month, he said.

Conceptually, the Possis device is the most attractive, if it works, said Tomsick. “If the clot can be sucked out, there would be no pieces left around, and nothing flowing downstream” to possibly cause another blockage, he said. With the laser device, the possibility of fragmenting causes “some concern.”

Experts caution that intervening in the brain is a delicate and risky procedure. If any of the devices should puncture a blood vessel, for example, they could cause debilitating or fatal hemorrhaging. And dislodging a clot could lead to another stroke.

But whichever approach proves to be best, “This is where stroke treatment will be five years from now,” Clark said.

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New Techniques

Researchers are attempting to use physical techniques to remove blood clots in the brain, rather than waiting two to three hours for enzymes to treat a stroke by destroying clots.

In all the approaches, a thin, flexible catheter such as that in the photograph below is threaded through the tiny blood vessels of the brain to the clot.

At the clot, several techniques are being used:

Sources: Possis Medical Inc., LaTis Inc., EKOS Corp.