The blood Injections that might transform Orthopedics
THE BLOOD INJECTIONS THAT MIGHT TRANSFORM ORTHOPEDIC (The New Yorker)
Chris Waddell has been an élite athlete for more than two decades. He has won twelve medals in downhill skiing, including five golds, in four Paralympic Games events; he was a world-record-holding wheelchair track sprinter; and, in 2009, he became the first paraplegic to climb Mt. Kilimanjaro, using his arms to power a customized four-wheeled cycle. Even at forty-five, Waddell, who was paralyzed in a college skiing accident, has a muscular, sharply defined upper body, the product of thousands of hours of training.
But all this exercise has taken a toll. Several years ago, Waddell’s shoulders began to ache constantly. Last year, he tore a rotator cuff while weightlifting, and began having trouble lifting himself into and out of his wheelchair. “I had no control,” he said. “When I was getting off a couch, I had to marshal all of my strength.”
Waddell, who lives in Park City, Utah, went through a range of treatments. “I tried a lot of rehab, I did a lot of exercises, I had a cortisone injection,” he said. “I wasn’t making any progress.” Several orthopedists told him he would have to accept being in pain for the rest of his life.
Rotator-cuff surgery seemed like Waddell’s last option. It would mean losing the use of his arms, and his ability to move on his own, for several months. And he worried that, if surgery failed, he would have to give up any strenuous physical activity. “Being able to ask a lot of my body makes me feel good,” he said. “It’s a lot of who I am.”
As Waddell considered his options, a friend suggested looking into a treatment known as platelet-rich plasma, in which doctors inject a modified version of the patient’s own blood into injured tissue. Eager to avoid surgery, Waddell flew to Washington, D.C., to see Victor Ibrahim, a sports-medicine doctor who specializes in P.R.P. Ibrahim found that Waddell had a torn rotator cuff in one shoulder and a torn biceps tendon in the other. Using ultrasound to locate the precise locations of the injuries, Ibrahim injected the tendon and rotator cuff with P.R.P. Over the course of a month, he repeated the procedure twice more.
In the weeks afterward, Waddell saw his strength improve and his pain decrease; he says he is now “close to one hundred per cent,” and is no longer thinking about surgery. “I was shocked that I kept getting better,” he said. “It had been so bad for so long.”
The outcome didn’t surprise Ibrahim, who estimates that he has treated around five thousand people with P.R.P. over the past five years. He says that the treatment can repair tendons, ligaments, cartilage, and nerves, and can even regrow tissue that has been frayed or damaged. This, he suspects, is what happened with Waddell’s rotator cuff. “For a lot of conditions, it’s almost a wonder drug,” Ibrahim told me. “We’ve figured out a way to help the body regenerate itself.”
P.R.P. sounds implausible. But credible scientists and clinicians, many from major institutions, say that it can heal a range of orthopedic injuries, which are often difficult to treat. Dozens of studies, some in cells, some in animals, and some in humans, have found that the procedure can repair chronic tendon injuries, heal damaged muscles and ligaments, and reduce arthritis pain.
Interest in P.R.P. is growing in part because traditional treatments for joint problems, such as arthritis, torn ligaments, and damaged tendons, are only marginally effective. Surgery sometimes succeeds, but it often doesn’t help and can cause further damage; cortisone shots can temporarily reduce pain, but they don’t address the underlying problem; physical therapy can be effective, but it often doesn’t work. Many people are left to limp along with ice and ibuprofen.
“Patients have been dissatisfied with what we have to offer them,” said Allan Mishra, an orthopedic surgeon at Stanford University Medical Center, who has been researching the technique and has used it on his patients for more than a decade. He thinks it will revolutionize orthopedic treatment. “Fifty years ago, getting a new knee was unimaginable,” he said. “Now it’s commonplace. This will have the same trajectory.”
The process of making P.R.P. is relatively simple. A doctor draws between half an ounce and an ounce of the patient’s blood and spins it in a centrifuge to separate the platelets, the disc-shaped cells best known for their crucial role in clotting, from most of the red and white blood cells. The spinning concentrates the platelets in the plasma, the liquid part of blood. When the process is finished, the number of platelets in the plasma increases by a factor of between two and twenty, depending on the spinning method. The substance is then injected into the site of the injury, whether it’s a ligament, a tendon, or an arthritic joint.
The treatment was first used about thirty years ago by dental surgeons, to repair jaws and other facial bones that often don’t heal well. Researchers knew that these areas have fewer blood vessels than many other parts of the body, and wondered if the healing problem was related to a lack of blood. They found that P.R.P. could improve results in these situations, as well as for wounds that were slow to heal. The side effects were generally minimal—soreness, stiffness, and swelling from the injection—so doctors were willing to try it. In the mid-nineties, veterinarians began using it to treat tendon, ligament, and cartilage injuries in horses; like bone, these tissues tend to have a relatively limited blood supply. About a decade ago, P.R.P. moved back to human orthopedics and sports medicine. Practitioners estimate that P.R.P. is now used by a few hundred doctors around the country, mostly orthopedists and sports-medicine specialists. There are no statistics on how many people have been treated, but Ibrahim and others who use P.R.P. put the number in the tens of thousands, including hundreds of élite athletes like Waddell.
At the same time, P.R.P. remains controversial. One of the leading skeptics is Stephen Weber, an orthopedic surgeon in Sacramento. Six years ago, he became interested in P.R.P. and set up a study to see if it could help patients recover from shoulder surgery more quickly. He operated on the rotator cuffs of sixty people, half of whom received a P.R.P. injection afterward. His study, which was published last year, found that P.R.P. made no difference in patients’ recovery speeds. “We need to be very cautious,” he said. “Just because a Los Angeles Laker gets it doesn’t mean that it works.”
Even some pro-P.R.P. doctors worry that marketing and hype have overtaken science. Vijay Vad, a sports-medicine specialist at the Hospital for Special Surgery, in Manhattan, uses P.R.P. in his practice and says the treatment can work especially well for tendon injuries. But he thinks some doctors are using it indiscriminately. “It has merit,” he said. “But people have gone way overboard. Some of it is a moneymaking gimmick. Medicine needs to be careful.”
As sometimes happens in medicine, doctors are offering a treatment before science has figured out how best to administer it. “We did it backwards,” said Lisa Fortier, a veterinary surgeon at Cornell and a leading researcher. “We got to clinical practice before we figured out the best methods.”
How P.R.P. works remains an open question. “To be honest, we barely understand the biology of this,” Mishra said. Platelets contain more than a thousand different proteins and hormones that stimulate cell growth and repair, such as vascular endothelial growth factor and the insulin-like growth factor-1. On their own, many of these chemicals are known for their ability to heal injury and relieve pain. Together, they may have a synergistic effect, which could explain the treatment’s power.
Given this uncertainty, it’s not surprising that there is a good deal of controversy over the best way to make P.R.P. About twenty companies make the centrifuges, and each brand produces a different blend. “P.R.P. is not P.R.P. is not P.R.P.,” said Martha Murray, an assistant professor of orthopedic surgery at Harvard Medical School who has been studying the how the treatment works in ligament injuries. Probably the most heated debate is over white blood cells. Depending on how it is processed, P.R.P. can contain hundreds of white cells or almost none. These cells are part of the immune system; to discourage infection and remove damaged tissue, they cause inflammation at the site of an injury.
Some doctors and researchers, including Fortier and Ibrahim, argue that P.R.P. should contain few white cells, because the inflammation impedes healing. But another faction argues that white cells are crucial for repair. Some doctors even tell their patients to stop taking anti-inflammatory medicines, such as aspirin or ibuprofen, a few days before treatment, to ensure that nothing inhibits the post-injection tenderness and swelling.
Both sides may be right, according to Mishra and other researchers. For chronic tendon injuries, which involve scarring and degeneration but no inflamed tissue, a mixture that triggers inflammation may spark healing; for arthritis, in which damaged cartilage is already inflamed, a version with few white cells could be more effective. “We’re still trying to figure out what the best recipe is for each condition,” said Fortier.
Fortier is a P.R.P. pioneer: in the mid-nineties, she was among the first vets to try the procedure for joint problems. Most of the animals she treats are top-level equine athletes—racing horses, jumping horses, and roping horses—that often have impatient owners who are willing to experiment. “In veterinary medicine, you try new things faster,” she says. “There’s less regulation, and there’s so much pressure on our athletes to get back to performance.”
For the past five years, she has collaborated on research with several prominent human orthopedists, including Brian Cole, an orthopedic surgeon at Rush University Medical Center, in Chicago, and a team doctor for the Chicago Bulls and the Chicago White Sox. Together they are examining several issues, including whether P.R.P. can do more if it stays in contact with the injury for longer. To increase its stickiness, they and other research groups are experimenting with fat, collagen, and fibrin, a protein that helps clot blood.
In part because of the many uncertainties surrounding P.R.P., insurance companies rarely cover the treatment, which can be expensive; a single injection costs between five hundred and two thousand dollars, depending on the doctor and the amount of blood needed. Most patients get two or three injections. The University of Pittsburgh orthopedic surgeon James Bradley, who does research on P.R.P. and uses it in his practice, understands insurers’ hesitation. “They’re not going to pay for it until we have really concrete evidence,” he said.
That evidence may not arrive soon. Many positive P.R.P. studies have been published in recent years, but none were large human trials with thousands of subjects—the sort of research that typically persuades insurance companies to change reimbursement policies—because studies such as these can cost millions of dollars, and are almost always paid for by a major drug company that wants F.D.A. approval of a patented drug. P.R.P. is not patented, and is already on the market—the F.D.A. allows the procedure, and approves the centrifuges based on whether they modify blood safely and in accordance with manufacturers’ claims. As a result, the makers of P.R.P. machines have little incentive to conduct large trials.
Despite these issues, P.R.P. continues to spread. “We do not have a perfect grasp of how to use this yet,” Mishra said. “We have a lot of work to do. But it’s beyond the promising stage. We know there is tremendous value in this.” The bottom line, he says, is that even as doctors and scientists refine it, P.R.P. is helping a lot of people.
Last month, Waddell completed a month-long, fifteen-hundred-mile cycling trip from Seattle to San Diego, raising awareness about his educational foundation along the way. Using his arms to power a custom-fitted three-wheeled bike, he rode about sixty miles a day. He says he couldn’t have done it without P.R.P. “For me, it’s been a total godsend,” he said. “I didn’t want to sit on the couch for the rest of my life.”
David Kohn writes about medicine and science. He lives in Baltimore.
Photograph: Science Picture/Getty