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Precision-Targeted Low-Dose Treatment for Large Clots in the Lungs

Date: 05/27/2015

Precision-Targeted Low-Dose Treatment for Large Clots in the Lungs

Anobel Tamrazi, left, and Clifford Weiss are collecting data on outcomes in a quest to perfect existing approaches and inform new ones.

The patient, a woman in her 50s, had a history of deep vein thrombosis in the legs, so when she developed fatigue and shortness of breath in the fall of 2013, she prudently went to the local emergency room. Her physical exam was unremarkable and her blood work came back normal, so the patient was discharged with instructions to rest.

But a few months later, the episode repeated itself — this time rather more dramatically. The woman could barely climb a flight of stairs; the short walk from her office to the car left her gasping for breath. An ECG performed in her primary physician’s office showed nonspecific changes, made more ominous in the context of another finding — oxygen saturation in the mid-80s. An echocardiogram showed an enlarged and dysfunctional right ventricle and elevated pulmonary artery pressures.

The patient was transferred to Johns Hopkins, where a CT scan revealed two large emboli lodged in the left and right pulmonary arteries. Cardiologist Steven Schulman, knowing time was of the essence, conferred with interventional radiologist Clifford Weiss, who had recently started using a new transcatheter treatment for patients with large emboli: ultrasound-enhanced lysis that drives thrombolytic agents directly into the clot. Because the system’s cardinal feature is precision-targeted lysis, it is best suited for patients with massive clots, particularly those already exhibiting signs of right ventricular strain or those in full-blown respiratory or cardiac failure. The approach is rapidly emerging as a more efficient and safer alternative to traditional catheter-based treatment or high-dose intravenous clot-busting therapy for massive emboli and may have similar promise for large yet submassive clots. High-dose intravenous tPA — used for massive clots — can cause brain bleeds in 3 to 5 percent of patients, but the use of ultrasound-enhanced lysis can cut the total tPA dose from 100 milligrams to 12 to 24 milligrams, Weiss explains.

“We’re plumbers. We like treating the problem directly and locally,” adds Weiss’s colleague, interventional radiologist Anobel Tamrazi. “It’s precision-targeting at its best, and the response we see is rather remarkable.”

After the treatment, the patient’s pulmonary artery pressure dropped from 82/37 to 42/12 mm Hg in a matter of hours and continued to decrease slowly over the next day.

“We restored the pulmonary vasculature, allowing the body to take care of the rest,” Weiss says. “In less than 12 hours, we took this patient from critically ill to stable and, most importantly, we gave her rapidly decompensating heart a new life.”

Weiss and Tamrazi have used the treatment in about 20 people thus far — all of them with excellent results.

Now, says Tamrazi, “we’re gathering biomarker information that reveals the tipping point at which critically ill patients become stable following treatment. Knowing the trajectory of recovery can help us optimize dose titration and tweak treatment in real time.”

“We like treating the problem directly and locally."

- Anobel Tamrazi