Clot Chronicles: Busting Out Pulmonary Embolism

Dr. Samuel Goldhaber discusses the latest developments in tPA.

Hello, This is Dr. Sam Goldhaber. I am president of NATF, and today on the Clot Chronicles I’m going to talk to you about a new way to do clot busting of potentially fatal pulmonary embolism. There is a clot buster called tPA, tissue plasminogen activator, which we’ve been using in studies since the 1980s for dissolution of pulmonary embolism blood clots. The FDA approved a high dose of tPA in 1990, 100 mg infused over two hours through an intravenous line, and this works very well to dissolve  some of the clot of a pulmonary embolism. However, with that dose of 100 mg, there is a risk of about two percent of this catastrophic bleeding into the brain problem.

So, the idea is to come up with a lower dose of tPA because the lower the dose, the less chance there is of major bleeding complications. At first, a dose of 50 mg, half dose of tPA, was popularized in one small study and is still used often around the country, even though that dose does not have formal FDA approval. But, more recently and something that has really caught on across the United States and in other countries, is using catheter directed therapy with tPA in doses as low as 24 mg. That is one quarter of the standard 100 mg dose of tPA.

Now these are not just ordinary catheters that are placed into the pulmonary artery clot. The catheters that are used most frequently have little ultrasound probes that are emitting a low power of energy and this is called ultrasound-facilitated, catheter-directed thrombolysis. With the ultrasound buzzing the clot, the blood clot itself spreads out and the tPA can sneak into the interstices of the clot. So, much lower than standard doses are required. In addition, the ultra sound causes what we call acoustic streaming. This is little wavelets forming of blood, and then the tPA sneaks in and rides the waves into the middle of the blood clot to work in small doses to dissolve some of the clot.

With lower dose tPA, we believe that the rate of major bleeding complications will decrease quite a bit. About four years ago, the FDA approved a lower dose of tPA, 24 mg, to be used in conjunction with ultrasound-facilitation catheters. Now what we’re doing, what we’ve just published in one of the cardiology journals, is a new study where we’re trying to see how low can you go. We have found in our most recent studies that doses of tPA as low as 8 mg, infused in as little time as two hours, seem to have an equally beneficial effect in restoring the contour of the heart to normal and probably to dissolving a blood clot as effectively.

These low doses of tPA, down to 8 mg over two hours, have not yet been FDA approved but they open up a very promising avenue for future clinical management of patients with a seriously large or seriously impactful pulmonary embolism.

So, we’re quite pleased with the way we’ve been able to refine the treatment of PE with tPA over the past couple of decades, going from 100 mg over two hours through a peripheral vein, to 50 mg over two hours through a peripheral vein, down to 24 mg over 12 hours through ultrasound-facilitated, catheter-directed thrombolysis, and, in our most recent studies that are hot off the press, doses of tPA as low as 8 mg infused through these special catheters over two hours.

This is Dr. Sam Goldhaber, signing off.