The Clot Stopper
A brilliantly simple device saves thousands of lives a year using technology borrowed from the oil industry
One day in 1968 a young Oklahoma surgeon named Lazar Greenfield lost a patient. A motorcycle accident had left the 23-year-old man with broken legs and a broken pelvis, but the fractures weren’t what killed him. It was a pulmonary embolism, an accumulation of blood clots that had started in the man’s legs and then lodged in his lung, plugging up the body’s blood supply and threatening instant death. Greenfield had put the patient on a heart-lung machine, opened his chest, and scooped out the deadly clots, as was standard practice at the time. “I thought it was a triumph because we got all the clots out,” he recalls. But the lungs were too severely damaged by the procedure, and the patient bled to death.
Greenfield told himself, “There ought to be a better way.” And within two years he found the solution. A suggestion from an oil-industry engineer led the two men to create an implantable filter for trapping blood clots before they can reach the lungs. Since then more than half a million Greenfield filters have been placed in patients.
Pulmonary embolism is a major killer that barely registers in the public consciousness. Each year about 600,000 Americans experience a PE, roughly the same number that suffer strokes. At least 60,000 pulmonary-embolism deaths occur annually; no one is sure of the exact number, since many people die suddenly from heart failure and their clots go undetected. All kinds of people are at risk, but especially those getting kneeand hip-replacement surgery, cancer patients, and trauma victims, like the motorcycle rider.
In pulmonary embolism, clots form, usually in the leg, and then migrate through the circulatory system to the first structure that will stop them—the lung, with its network of tiny capillaries. When several clots accumulate, not only do they keep the lungs from oxygenating blood, they can back up the blood flow all the way to the heart. This back pressure keeps the heart’s right ventricle from pushing new blood to the lungs. Soon the entire circulatory system crashes to a halt, blood pressure plunges, and the oxygen-starved heart fails.
Before the Greenfield filter, doctors would try to prevent pulmonary embolism by surgically tying off the inferior vena cava (the thick collector vein that funnels blood from the lower body back to the heart), choking off all blood flow in it and forcing the blood to return to the heart through other veins. This usually led to massively swollen legs and other problems. In the late 1960s a colander-like filter was introduced, but it often filled up with accumulated clots and blocked the vein. This filter was eventually withdrawn from sale. Blood-thinning drugs have proved effective, but many people, especially trauma victims, can’t take them because of the risk of internal bleeding.
Greenfield took his dilemma to garman kimmell. Kimmell, a prolific inventor, ran a company that made valves and other machinery for oil and gas wells and pipes, but he also dabbled in medical devices. As Greenfield recalls, upon hearing about pulmonary embolism, Kimmell told him, “That sounds a lot like the problem we have in the oil field with sludge.”
In oil pipelines, sludge and debris are trapped by a cone-shaped filter. The geometry of the cone, Kimmell explained, allows oil to continue flowing around its edges while concentrating the sludge in the center, whereas a flat screen, with sludge spread across it, could completely clog the pipeline. Kimmell and Greenfield decided that the conical-filter idea was worth a try in blood vessels.
“Great invention is always metaphor,” says John Abele, a cofounder of Boston Scientific Corporation, which has manufactured the Greenfield filter since it acquired Kimmell’s medical-device company in 1980. “You look at the problem, and then you try to connect it to other areas which may have nothing to do with the problem you’re working on.”
The basic shape of the Greenfield filter is identical to that of the oil filter that inspired it, which in turn resembles a device patented in 1942 that was meant to protect a car’s gas tank from siphoning. It consists of six legs converging in the center. Greenfield added tiny hooks to secure it in place in the blood-vessel wall. He also incorporated corrugations into the legs to keep clots from slipping through. The filter’s streamlined taper allows uninterrupted blood flow even with a clot trapped in the tip.
The design showed promising results. After two years spent observing the device’s performance in dogs, Greenfield, with the permission of his employer, the Oklahoma City VA hospital, implanted his first filters in human patients. “The devices were, from current perspective, pretty primitive,” says Greenfield. “But the device worked well [and] the patients did well.” At the time, the Food and Drug Administration did not have to approve medical devices, so other surgeons soon began using the filter. Greenfield’s first major paper on the Kimray-Greenfield filter, as it was then called (Kimray was the name of Kimmell’s company), appeared in the journal Surgery in 1973.
The early years brought a number of technical challenges. The filter had to be robust enough to last a lifetime in the hostile environment of the human abdomen. It had to stand up to countless stresses and be mechanically safe, nontoxic, and biologically and chemically inert. An early problem arose when solder in the brazed tip of the filter, where the six legs came together, caused a physiological reaction in some patients that loosened the connection, leading one or more legs to detach. Patients weren’t immediately harmed when this happened, but the defect made the filter less effective at capturing clots. Kimmell’s machinist solved the design problem by using a machine that exerted high pressure on the cap, compressing the legs together tightly and eliminating the need for brazing.
The biggest problems, though, arose in the process of installing the device. Originally the filter was mounted at the tip of a catheter (a narrow tube). This was potentially hazardous because pulling back on the catheter could release the filter prematurely. So Greenfield and Kimmell designed a cylindrical carrier at the catheter tip to enclose the filter until deployment. Some filters, however, still deployed crookedly. That could lead to unequal pressure on the legs, and eventually the filter could penetrate the blood vessel’s walls. So Greenfield and Kimmell introduced a stiff guide wire that allowed the surgeon to orient the filter precisely, with the help of an X-ray monitor, before withdrawing the catheter and wire.
Viewed today, the Greenfield filter looks deceptively simple, like a metallic badminton shuttlecock or an open-ended wire whisk. Its six legs, when fully deployed, span roughly an inch across the vena cava. More than 10,000 Greenfield filters go into patients each year. Doctors have perfected a fast, safe, and nonsurgical way to insert the device, as Dr. Kyung Cho very kindly demonstrated for this article.
On a fall morning in Ann Arbor, Michigan, Cho has already started on his first case of the day. He leans over a patient, his gaze shifting back and forth to the X-ray monitor above. More than 250 people a year get filters installed here at the University of Michigan hospital. The middle-aged man on the table today was crushed in a construction-site accident. Damage to internal organs ruled out using blood-thinning drugs because they could cause bleeding and death.
With the procedure finished, the man is wheeled out and replaced by a young woman arriving from the intensive-care unit. She is recovering from a bad auto accident and lies face-up on the table, moving fitfully. Hemorrhage from her head injuries means that she can’t be given blood thinners. Cho and Todd Getzen, a radiology fellow, go to work. A drape covers the patient’s body except for a small patch at her groin, which Cho swabs with an antiseptic wash before injecting a local anesthetic. This badly injured woman is unconscious, but in most cases the procedure can be done with the patient fully awake.
Cho inserts a needle and finds the woman’s femoral vein. He withdraws the syringe, leaving the needle, and then passes a wire through the needle’s hollow core. The wire serves to guide a dilator into the vein, widening the opening for the eventual passage of the filter. A nick with a scalpel is all that’s needed to create an opening through which the dilator can get into the body. There’s only a tiny amount of bleeding. This “Seldinger technique,” named after its Swedish inventor, allows doctors to place catheters, stents, and filters in the circulatory system with just a local anesthetic and without the invasive surgery that was once mandatory.
Cho places a second, stiffer guide wire into the vein and, guided by the X-ray image onscreen, slides it all the way into the vena cava. Now the patient is ready for the filter. An injection of contrast dye lets Cho and Getzen see exactly where blood flow from the kidney joins the vena cava. This is the precise point where the filter’s tip needs to go. Cho carefully slides the sheathed filter along the guide wire and up the vein, stopping after about 10 seconds. As viewed on the screen, the filter, furled like an umbrella, emerges from the sheath. Cho operates a trigger device, and the filter instantly springs open, the tiny hooks securing it to the vessel walls. Then Cho pulls out the sheath and guide wire, Getzen places a bandage over the needle puncture, and they’re done. The whole procedure has taken less than 10 minutes. With the filter in place, the young woman’s odds of developing a pulmonary embolism are now smaller than 1 in 20.
Pulmonary embolism is a fact of life for trauma surgeons and intensive-care-unit doctors because an immobile patient will almost always develop some kind of clot. The nineteenth-century German pathologist Rudolf Virchow was the first to figure out why: Damage to the blood-vessel wall results in a state of hypercoagulability, or elevated tendency to clot. Then the lack of movement adds to the risk of clots and venous thrombosis—clotting in the veins, usually in the legs. Clots that sit in the vein can break loose and head downstream. The result: pulmonary embolisms that are fatal 30 percent of the time if left untreated.
Just sitting still for a few hours can cause clots. Cho recalls the case of a woman who flew from the Philippines to Canada, collapsed in the airplane before arrival, and was rushed to the hospital. “She had massive PE and was dying on the table,” says Cho. “She needed resuscitation twice.” Doctors broke up the clot in her lungs with drugs and dislodged it with a catheter, and Cho placed a filter. The woman survived—barely.
Besides its suddenness, what makes pulmonary embolism so dangerous is that it has few symptoms, and those are ambiguous. Shortness of breath and mild chest pain signal pulmonary embolism, but they could just as easily mean pneumonia.
Mark Cipolle, a trauma surgeon in Allentown, Pennsylvania, has seen hundreds of pulmonary embolisms, but his own PE caught him completely by surprise. A few years ago he was in a rollover auto accident and fractured a vertebra in his neck. Lucky to escape without paralysis, he was sent home in a neck collar and mostly sat around for three days. Then he developed a clot. “I almost died,” he recalls. “I got delirious from lack of oxygen to my brain.”
A friend rushed him to the hospital. Because he had bleeding in an eye from the rollover accident, he couldn’t receive a blood thinner. So Mark Cipolle, who had collaborated with Lazar Greenfield on several filter-research projects, got his own Greenfield filter. That prevented more clots from piling onto the original clot in the lung and may have saved his life.
Once the Greenfield filter is in, it stays in for life (though other filters designed to do the same job are removable). The vast majority of patients never have to think about it again. Over time the inner vessel wall spreads over the filter’s hooks, making the filter almost part of the body. Clots collecting in the filter’s conical nose almost always dissolve amid the continuous flow of blood, which has natural clot-dissolving properties.
“We don’t limit the activities of any patient who’s had a filter,” says Greenfield. “We have patients with the device who’ve gone back to very active lifestyles. They’ve gone back to playing football, we’ve had fighter pilots taking huge G stresses… . We’ve even said a boxer could go back to boxing, but the boxing commission didn’t think too highly of that.”
The filter is remarkably durable and stable, with only a few cases of broken filters reported. Yet it’s flexible enough to fold tightly into its narrow sheath for easy delivery. In conceiving and perfecting it, the skills and personalities of its two inventors, Greenfield and Kimmell, meshed well. They had worked together on two devices prior to the filter, one of them a suction cup mounted on the end of a catheter that’s still occasionally used to clear clots in the lung during life-threatening emergencies.
Garman Kimmell’s contributions to the filter went far beyond that first conceptual leap. “Renaissance man” is how Greenfield describes his former partner. In the 1940s Kimmell invented a pressure regulator for natural-gas wells that is still the industry standard. Kimmell’s medical-device company occupied a single room in his oil and gas business, but out of it came a blood pump for open-heart surgery and an early blood oxygenation machine for the Mayo Clinic, in addition to the Greenfield inventions and many others.
Greenfield was an ideal partner. Until his recent retirement he was among the “top 5 or 10” vascular surgeons in the country, according to Cipolle. Greenfield grew up in Houston with his grandfather, who raised chickens and pigeons. At age six, after watching his grandfather sew up the neck of an injured squab, which then recovered fully, Greenfield decided that he wanted to be a doctor. His career trajectory was phenomenal. At age 32 he was assistant professor of surgery at the University of Oklahoma and chief of surgical services at the VA hospital in Oklahoma City; before turning 40 he was named chairman of surgery at the Medical College of Virginia; and in 1987, at age 52, he moved to the University of Michigan as surgery chair, later serving as interim CEO of the university’s vast medical campus.
Greenfield’s strengths as an inventor were twofold. First, says Abele, “he was great at asking the right question.” Few thought pulmonary embolism could safely be prevented with a filter, but Greenfield wanted to give it a try. His other strength was persistence. “He was very, very tenacious at improving the device,” says James Stanley, a vascular surgeon at the University of Michigan. Even after the filter was a success and was selling well, “he didn’t just give up and say, ‘Let it be’; he was continually working at it.”
In 1973, at a meeting of the American Heart Association, Greenfield gave a talk about his lung-clot suction cup, with a side presentation on the filter. In the audience was Abele, who was scouting for products for his new medical-device company. Abele introduced himself to Greenfield after the talk, launching a 30-year collaboration. First Abele took on the manufacture of the suction cup, and then, in 1980, when he bought Kimmell’s medical-device company, the Kimray-Greenfield filter became part of Boston Scientific’s catalogue. Abele renamed it the Greenfield filter. The filter helped Abele’s company to grow from two million dollars in sales to six billion today, and Boston Scientific is now the largest life-sciences company in Massachusetts.
Greenfield never earned a dime in royalties from his filter. His Oklahoma superiors told him that a patent was impossible because he worked for a public university and because, as a doctor treating patients with the device, having a patent would be a conflict of interest. So Kimmell patented the device by himself. “I was young and naive, never talked to the lawyer or anyone else,” Greenfield recalls. One positive outcome, though, was a certain independence when it came to his relationship with Boston Scientific. “I never hesitated to criticize and essentially force them to maintain the highest quality standards for production, and for the changes that I thought were needed,” Greenfield says. In return for his input, Boston Scientific supported his filter research over the years. “They’ve been very good to work with,” he says, “because it’s been very profitable for the company.”
The filter has gone through two major design changes. In the late 1980s the company switched from stainless steel to titanium to allow compression of the filter into a sheath for delivery through a catheter. Then, in the mid-1990s, at Greenfield’s insistence, the company switched back to stainless steel to make the filter compatible with a guide wire, since some of the titanium filters weren’t going in straight. Each change involved years of design work and animal trials.
The basic patent expired long ago, and other filters, most of them inspired by the original, now compete with the Greenfield. The FDA has approved eight designs, including the Greenfield, some with multiple versions. One of them, a removable filter called the Gunther Tulip, was the filter Cho placed in the young woman at Michigan. While such filters have their roles, says Cho, “the Greenfield filter is the best. It’s proven over 30 years.” Cipolle agrees: “How are you going to improve on a complication rate of 2, 3, 4 percent?” The filter’s clean lines and minimalist design are the keys to its success. “If you have additional levels of metal, or too much complexity of the device, you set up turbulence and stagnant areas that are actually clot-promoting,” Greenfield says.
The risks of having a Greenfield filter inserted are small but real. In a tiny fraction of patients, insertion of the filter itself causes clots. And, very rarely, a doctor positions the filter improperly, and it later moves, which means it must then be captured and repositioned. Finally, the filter doesn’t always work perfectly. Occasionally a big enough clot gets through it to cause a pulmonary embolism. But studies show that it is more than 95 percent safe and effective—the best long-term record of any filter on the market.
During the filter’s long history, occasional controversies have erupted over its use. For example, in the 1990s many doctors placed filters not only in patients with existing blood clots in their legs but also in those who were merely at risk for such clots, including cancer patients. After some surgeons questioned such prophylactic use, it began to decline. That’s fine with Greenfield. “I never supported that concept, because the filter only addresses pulmonary embolism,” he says.
No one questions the Greenfield filter’s effectiveness. “Everybody acknowledges this has saved many lives,” says Stanley. Greenfield, characteristically, underplays its impact on modern medicine: “It’s just plumbing.”