It’s been about a decade since newspapers started reporting on the first elite athletes undergoing injections of their own blood to heal their injuries.
Golf giant Tiger Woods received shots of his own blood platelets after knee surgery, before he went on to play in four professional majors in 2009. Two Pittsburgh Steelers got shots of their blood plasma before winning the Super Bowl. A major league pitcher received an injection of his blood platelets into his elbow. A dozen or so professional soccer players were getting plasma injections, as was Olympic sprinter Donovan Bailey.
Fast-forward 10 years, and platelet-rich plasma injection – or PRP therapy – is no longer the exclusive medicine of super-athletes. It’s almost mainstream, with more than 500 clinics in the United States alone offering the therapy.
Almost mainstream, but not mainstream – yet – because most insurance companies, including public health agencies, refuse to cover the procedure, claiming evidence for PRP’s effectiveness is inconclusive. What does the science say? Does it work?
If you search for “platelet-rich plasma” on the US National Library of Medicine website (pubmed.gov), roughly 10,000 references pop up. Just in 2019 alone, studies have reported its use experimentally to treat gunshot wounds,1 diabetic ulcers,2 Bell’s palsy,3 male pattern hair loss,4 infertility5 and even in dentistry.6
Most of the studies, however, provide evidence for the therapy’s usefulness in accelerating healing after orthopedic surgery and treating soft tissue injuries: tears of ligaments, tendons and meniscus (a strip of fibrocartilage on the knee), tendinitis, rotator cuff injuries, tennis elbow, frozen shoulder and arthritis – especially knee arthritis.
“There’s actually a lot of scientific evidence to support PRP now,” says University of Lincoln professor Paul Lee, an orthopedic surgeon who specializes in sports medicine. “In a way, there’s too much information, it’s hard to keep up with such a huge amount of data.”
PRP is certainly transforming orthopedics, but there is so much research “noise” on it, Lee adds, that it is easy to cherry-pick data to support or refute its usefulness. “But if you have the correct diagnosis for specific conditions, it’s a very powerful tool.”
The field of platelet research is exploding and still in its infancy, says Lee. “The properties of platelets drawn a day after exercise or a day after fasting differ from each other,” he says, and new studies on what makes them differ and how platelet ingredients modify the healing process are appearing daily.
Simple procedure
As a procedure, PRP injection is relatively simple and usually all done in under half an hour. The patient has a few ounces of blood drawn, which is then spun at high speeds in a centrifuge.
There are many variations to the next part of the process, but in most cases, in less than 10 minutes, a platelet-rich layer (containing two to five times the normal concentration of platelets as regular blood) is extracted and then injected back into the patient’s site of injury, where the platelets are believed to release their storehouses of activating proteins.
Joints and their tissues, which have less blood flow normally, are thought to particularly benefit from the infusion of healing agents.
Some people describe the shots as pain-free and others as toe-curling. “It’s no different from any other injection,” says surgeon Lee, who offers the procedure at MSK Doctors in Lincoln and Nottingham, England.
It may be less painful than a standard corticosteroid injection, which is quite acidic, he says. Because it contains your own blood, it will be less reactive, but “anytime you stick a needle into an inflamed, tender area, you might have pain.”
Patients are told not to take nonsteroidal anti-inflammatory painkillers (NSAIDs), because they could inhibit the platelet-induced inflammatory reaction that triggers the healing cascade, but they can take other painkillers like acetaminophen (paracetamol), and they may be told to ice their injection site and not to push the joint in exercise for a week or so.
Although PRP is often promoted as “regenerative medicine” and people sometimes confuse it with stem cell therapy, “there are actually no cells in PRP,” says surgeon Lee. Because PRP is “autologous” – made from your own blood – it’s considered safe, and there is nothing for government watchdogs like the US Food and Drug Administration (FDA) to approve. The centrifuge machines are already licensed.
“It’s basically glorified bruising,” says Lee. Not that bruising should be underestimated. The ingredients in your own platelets are potent, but they can’t be bottled by a drug company.
In the past decade, the research on PRP has grown exponentially, and its use in arthritis has been particularly promising. Osteoarthritis, the most common form of arthritis, affects 30 million American adults and 8.75 million Britons, most often hitting them in the knees.
Arthritis is a leading cause of pain and disability, and it costs the US hospital system $16.5 billion a year trying to alleviate. The story is the same in the UK and other Western countries, where the frontline treatment is drug therapy, mostly limited to pain control with NSAIDs and corticosteroid injections.
NSAID dangers
NSAIDs do alleviate arthritis pain in the short-term, although they do nothing to address the underlying damage. But the FDA warns that NSAIDs are linked to an increased risk of heart attack and stroke even within the first week of use, and this risk increases the longer and more frequently they’re used.
These go-to painkillers for arthritis have also been associated with a host of other severe side-effects including gastric bleeding, ulcers and kidney damage.
What’s more, a recent study suggests that taking a painkiller like an NSAID can actually worsen arthritis in the long run. Researchers at Johns Hopkins University compared people taking painkillers (two-thirds were taking an NSAID) for knee arthritis with others who weren’t taking any drugs, and followed them all for three years, taking x-rays of their knees at regular intervals.
Those taking the painkillers were more likely to have knee arthritis that was visibly worse on x-rays, and were also more likely to undergo knee replacement surgery compared with people not taking the drugs.7
Non-pharmaceutical interventions include encouraging weight loss, exercise, physiotherapy and the use of supplements including omega-3 fish oils and glucosamine. Patients who don’t respond to any of these interventions are lined up for surgery – often costly, whole-joint replacement which can take up to a year to recover from but can cause persist pain and loss of function afterward.8
PRP vs. hyaluronic acid
Injection with hyaluronic acid (HA) is another very common osteoarthritis treatment. HA is a component of the lubricating synovial fluid between joints, which is reduced in arthritic disease, and it plays an important role in cartilage repair by protecting and healing the joints.9
HA concentrations are lower in the knee joint cavity of patients with osteoarthritis, which may contribute to reducing the knee’s ability to resist mechanical stress and damage.
HA injections have been established to help alleviate pain and improve function in knee osteoarthritis by many clinical studies,10 and HA is frequently used as the ‘standard of care’ that PRP is compared against. But unlike PRP, HA is not “autologous” – medical injections of HA are synthetically manufactured and not drawn from the patient’s blood.
The difference in their o
rigin may explain why most studies comparing PRP to HA injections have found PRP to be more effective at alleviating pain and restoring function.11
A 2019 review of 15 randomized controlled trials comparing PRP to HA concluded that both groups experienced significant benefit within one to three months, but long-term pain relief and functional improvement between six and 12 months post-injection in the PRP group were superior to those of the HA group.12
A 2014 review paper found that patients who received PRP injections experienced greater, longer-lasting improvements than those receiving HA treatment, but that it was most effective for early or mild to moderate forms of knee osteoarthritis. Its effects were limited in advanced arthritis.13
‘Pleasantly surprised’
Robert Lean, 59, had wrecked his knees in his youth playing contact sports – a hockey injury on the left knee and a football injury on the right one a few years later. He’d torn the ACL on both of them and had surgeries to repair the damage. Then he developed severe arthritic symptoms – swelling, a grating feeling when the knees moved, and throbbing, ever-present pain that frequently woke him at night.
“I was told long ago that replacement was really the only option left, but I didn’t want to do that,” Lean says. “I hadn’t heard a lot of good results about replacement surgery.”
He had heard about people having good results from PRP injections, however, and about a year ago he decided to look into it. For about $450 each, he thought it was worth a try even though the surgeon who did the procedure, Toronto orthopedist Robert Gordon, told him it probably wouldn’t work – not at all for the very bad left knee and perhaps a 50/50 chance for his bad, but not as bad, right knee.
“I was really pleasantly surprised,” Lean says. “Immediately, I felt some relief. Especially for the right knee.” Even though no anesthetic was used, the procedure was over in under an hour and “quite benign,” he recalls. He had no swelling or bruising.
By the evening of the same day, he was more active. There seemed to be “less grating – it was a lot smoother,” and he slept through the night without pain. Because there was less pain, he was able to walk further and enjoy his golf game more.
The effects lasted for three to four months in his right knee, but only one to two months in his left knee. “Still,” he says. “It was relief. I’m thinking about doing it again for the right knee. If I was in early-stage arthritis, I’d definitely do it. I know it has some effect.”
“PRP works very, very well for Grade 1 or 2 early arthritis,” says Dr Gordon, who adds that 80 percent of patients who have PRP are better off for a year. In advanced stages of the disease – Grade 3 or 4 – like Lean’s case, “it helps sometimes.”
Julio Prudant, a 54-year old Toronto science and former phys-ed teacher, also developed arthritis – although his doctors thought it was related to his immune system and his psoriatic skin condition.
A year ago, both his knees were swollen and angry, and he thinks hobbling around on them contributed to low back pain as well. He was taking the opioid painkiller Percocet for the pain. Then he had PRP injected into his “good” knee and says that the procedure was painful to do but gave him relief.
A few months later, he worked up the courage to do the second “more troublesome” right knee. Now that one is even better off than the first, and he is thinking about having the first knee re-injected. “I would say you have to do it once a year,” says Prudant, who is back to cycling 37 miles (60 km) three times a week. “It definitely helped. It definitely took away the pain.”
Testimonials on YouTube from patients post-PRP injection tell similar stories. Arbida Khurshid demonstrates how arthritis used to make climbing the stairs an ordeal, and while walking, she would shuffle and drag her right leg after the left. “I used to cry a lot,” she says. After PRP injections, she enthusiastically demonstrates walking forward and backward, bending her knee and squatting. “I’m very happy,” she gushes.
A 59-year-old forklift driver describes being 90 to 95 percent better. “I really don’t have to think about it much. It’s really quite amazing.”
A physically active 64-year-old woman says, “Every year after I get my PRP injection, it seems that my knee gets a little stronger and a little more stable.” She shows a picture of herself water skiing, holding the ski rope on her leg that has had a PRP injection.
“Instead of snow skiing one day and then the next day, icing and elevating, I can snow ski two or three days in a row. Instead of hiking for an hour or two, I can hike a serious mountain for 10 hours.”
She climbed Kilimanjaro and to Everest base camp after PRP injection therapy. “I’m certain I would not have been able to do that with my old knee.”
Hip and ankle?
Aside from studies including patients with knee arthritis, a growing number of randomized clinical trials have investigated the use of PRP and HA for treating arthritis of the hip and ankle – a speciality of some practitioners.
Orthopedic surgeon Robert Gordon, who specializes in knees, advises seeking out experts experienced in doing joint injections, rather than a practitioner who does them occasionally.
“You need accuracy,” he says. Ankles and hips are “more difficult,” he thinks, and would require using a radiologist for ultrasound guidance to perform the procedure.
A meta-analysis of studies of PRP in the hip reported that the technique could reduce pain scores at two months of follow-up, but not much longer.14 Several studies have also looked at the use of PRP in patients with ankle arthritis, which comprises about 13 percent of arthritis cases. Again, the results so far indicate that PRP can significantly reduce pain in this patient population.15
Dangers?
Numerous studies remark on the minimal side-effects for both HA and PRP injections. The chief concern is an infection stemming from the injection, but the most common reported side-effect is pain at the injection site.
This magazine could only find two case reports of serious PRP adverse events. One describes a 14-year-old boy’s allergic reaction following PRP injection into a bone cyst. He developed an itchy skin rash, sore throat and swollen eyelids and was found to have had an allergic reaction not to his own blood contents but to the calcium chloride that was used in preparing the PRP solution – something not done frequently.16
Some practices add an anticoagulant or other contents to blood platelets, and avoiding this kind of processing would eliminate the allergic potential.
The second adverse event report describes a 40-year-old soccer player whose patellar (knee) tendon ruptured several months after he had received a series of four ultrasound-guided PRP injections.17 It’s difficult to know if this was actually from PRP or was just a sports injury.
Pushback
“I firmly believe biologic injection treatment for knee osteoarthritis is both safe and efficacious,” says orthopedic surgeon Patrick Smith of the Department of Orthopaedic Surgery at the University of Missouri in a recent clinical update paper on PRP therapy.18
“The major challenge going forward is obtaining approval for this important treatment for our patients from major insurance companies and the government,” says Smith. “It bothers me that the lack of regulation has led to many providers charging high fees to patients for biologic injections, which is all out-of-pocket.”
Prices for the therapy range from
$300 to $1,700 per shot – the latter a figure way out of proportion to the cost of providing the therapy.
Dr Corey Cook from the Columbia Orthopaedic Group, who coauthored the paper, thinks having a consensus about the best PRP practices – centrifugation processes and the number of injections in a treatment, for example – will help overcome the “pushback” to PRP injection therapy that he believes may stem from the pharmaceutical industry, which manufactures the standard-of-care injection products like steroids and stands to lose when the innovation takes hold.
“Arthritis is a kind of ongoing war, a constant state of change and degradation in the bone, and the challenge is to do anything to stop it,” says Cook. “We definitely know, symptomatically, patients show a lot of improvement after PRP, especially in early arthritis.
“I would say that all of our patients definitely notice a difference.”
If that is the case, PRP is looking like it will soon be a first line of defense in the battle.
The power of platelets
Platelets are small, circulating cell fragments in the blood that originate in the bone marrow. They don’t have a nucleus like normal cells, but, like cells, they do have membranes and come packed with proteins and mitochondria – the energy packs of every living cell.
Doctors have known for decades that they are an important driver in the healing process – injure your body, and platelets rush to the scene and trigger cascades of clotting, swelling and bruising that initiate repair.
Platelets contain more than 800 proteins and other molecules needed for tissue regeneration, including growth factors and immune signaling proteins that regulate inflammation by acting like magnets to draw in stem cells and promote the regeneration of cartilage and other tissues.
It’s these properties that have led to the development of PRP injections to repair the damaged cartilage of a joint while reducing the pain and inflammatory response associated with arthritis and joint injury.
Short-term help, long-term harm
Corticosteroid injections have been associated with post-injection flare-ups in up to a quarter of recipients, and side-effects limit their repeated use to a few injections. While some studies have found they help pain in the short term, a recent study found they may worsen joint degradation over time.
A double-blind study of 140 men and women who suffered from painful knee arthritis and were randomly assigned to receive injections of either a corticosteroid or a saline placebo every three months for two years found no measurable difference between the two groups in terms of joint pain, stiffness and ability to stand from a seated position at the end of the study. However, there was “significantly greater cartilage volume loss” visible on MRI scans in the steroid group.1
Better than placebo
The usual claim against studies of injection therapies is that a portion of people will experience a powerful placebo effect – no matter what is injected, their brain tells them they are getting better and their body responds in kind.
Critics of PRP have claimed that it is merely a placebo, but when injection therapies are compared, as in a review of six studies including a total of 577 patients, with 264 patients (45.8 percent) given PRP and 313 patients (54.2 percent) receiving hyaluronic acid (HA) or normal saline solution, those receiving PRP experienced significantly greater improvements.1
“This is clearly not just a placebo effect,” says Toronto orthopedic surgeon Robert Gordon of the PRP Arthritis Clinic in Toronto, Canada.
In another FDA-approved, double-blind randomized clinical trial, PRP provided “significant benefits for pain relief and functional improvement compared to saline that lasted up to 12 months.”2
A double whammy
Preliminary lab evidence suggests that the most powerful treatment of all for regenerating cartilage could be PRP and HA combined. Researchers from Taipei Medical University harvested the articular cells (the cartilage cells that cover bone) from five people with osteoarthritis, and examined the effect of PRP and HA together in a 3D model. The researchers showed that the combo could “efficiently suppress” certain inflammatory elements in the body related to osteoarthritis and halt cartilage breakdown. Although the study was small and didn’t examine the final effect in anyone’s body, the study authors were optimistic, concluding: “The combination of HA+PRP can synergistically promote cartilage regeneration and inhibit OA inflammation.” 1
RESOURCES
Professor Paul Lee: www.professorlee.uk
Dr Robert Gordon: www.topsmedical.ca
References
1 J Wound Ostomy Continence Nurs, 2018; 45: 359-63
2 Wound Repair Regen, 2019; 27: 170-82
3 Plast Reconstr Surg Glob Open, 2017; 5: e1376
4 Clin Drug Investig. 2019 Jun 21
5 Gynecol Endocrinol, 2019 Apr 10: 1-4
6 Laser Ther, 2017; 26: 223-7
7 Osteoarthritis Cartilage, 2016; 24: 597-604
8 Clin Orthop Relat Res, 2010; 468: 57-63
9 Gerontology, 2013; 59: 71-6
10 Arthritis Rheum, 2007; 56: 3610-9
11 Curr Rev Musculoskelet Med, 2018; 11: 583-92
12 Pain Med, 2019; 20: 1418-29
13 Arch Phys Med Rehabil, 2014; 95: 562-75
14 Int J Surg. 2018; 53: 279-87
15 Foot Ankle Int, 2017; 38: 596-604; Foot Ankle Int, 2018; 39: 1141-50
16 Medicine (Baltimore), 2019; 98: e14702
17 Clin J Sport Med, 2018 Dec 3
18 Curr Rev Musculoskelet Med, 2018; 11: 583-92
Double whammy
References
1 Biomaterials, 2014; 35: 9599-607
Better than placebo
References
1 Arthroscopy, 2013; 29: 2037-48
2 Curr Rev Musculoskeletal Med, 2018; 11: 583-92
Short-term help, long-term harm
References
1 JAMA, 2017; 317: 1967-75
