Like many people who are physically active, I have had my share of sports injuries, which seem to occur more frequently and last longer as I get older. Trying to fight against the inevitability of ageing is hard work, and no matter the activity, minor injuries seem to follow. Achilles injuries plagued my running. An intercostal strain from barbell training disrupted my sleep for weeks. And those newly aching elbows? Apparently I’m now getting some sort of tendinopathy. More trips to the physiotherapist. Sports medicine is quite possibly the worst area of medicine for pseudoscience, and it is difficult, if not impossible, to find a clinic that is pseudoscience-free. One service that is commonly offered and is seemingly very popular are injections of “platelet-rich plasma” or PRP. PRP is touted as an effective treatment for musculoskeletal injuries, where vials of your own blood are centrifuged and the platelets are injected back into you. PRP may be expensive, but does it work?
What is PRP?
Platelets are small cells in the blood that promote blood clotting. When you cut yourself and it clots, that’s your platelets working. Without platelets you would bleed to death. When platelets reach the site of a tissue injury they release chemical signals and growth factors to promote cell healing and recovery. Platelet-rich plasma is plasma (the liquid component of blood) with a concentrated amount of platelets. When vials of blood are spun rapidly in a centrifuge, the red blood cells, being more dense, separate. There are different methods to extract and separate out the platelets, but the final product will contain several times the normal concentration of platelets. This is then injected back into the injured area. PRP is a general term and there is no standardized product or manufacturing process that is used consistently by clinics that offer PRP. Moreover, as the evidence shows, there is no one method that has been clearly shown to be more effective than other forms. The variety of manufacturing processes complicates the evaluation of clinical trials. Like clinical trials of herbal remedies, the lack of standardization and consistency means that clinical trials may be complicated by slightly different “versions” of PRP.
What does the evidence tell us?
Surprisingly, no one has blogged about PRP at this blog since way back in 2009. (Isn’t it remarkable that SBM is still going strong 10 years later?). Val Jones noted at the time:
Without any clear evidence of benefit beyond placebo, platelet-rich plasma (PRP) is now being marketed aggressively as a cure-all for sports injuries. And at about $300 per injection (the NYT reports $2000/treatment), there’s plenty of money to be made.
She reviewed the literature and found it lacking, noting almost no published research on tendon injuries, and small trials in other conditions which were unconvincing. So what’s happened in ten years? In order to keep this blog post at a reasonable length, I’ll cite the evidence from the most comprehensive and current reviews that I could find.
The Alberta College of Family Physicians has an excellent Tools for Practice publication which answer clinical questions comprehensively. They recently published a summary of the evidence of PRP for Achilles tendinopathy, lateral epicondylitis (tennis elbow), and rotator cuff tendinopathy (the most common cause of shoulder pain). They restricted their search to randomized, placebo-controlled trials with patient-relevant outcomes measured. They noted:
Chronic Achilles Tendinopathy: Three RCTs comparing PRP to saline injections found no significant differences in pain, function, return to sport or patient satisfaction after 6, 12, and 24 weeks. They cite a meta-analysis which noted:
PRP injection with eccentric training did not improve VISA-A scores, reduce tendon thickness, or reduce color Doppler activity in patients with chronic Achilles tendinopathy compared with saline injection. Larger randomized trials are needed to confirm these results, but until or unless a clear benefit has been demonstrated in favor of the new treatment, we cannot recommend it for general use.
Chronic Lateral Epicondylitis: Two RCTs of PRP vs. saline found no difference at 12 or 24 weeks.
Rotator Cuff Tendinopathy: Two RCTs compared PRP to plasma or dry needling, finding no difference in pain or disability scores.
The review concludes:
The best quality evidence shows no difference in pain, function or return to sport between platelet-rich plasma, dry needling, or saline for patients with Achilles tendinopathy, lateral epicondylitis, or rotator cuff tendinopathy.
When it comes to summaries of the literature it is worth seeking out multiple reviews, to further minimize the risk of bias. Fortunately there is a 2014 Cochrane summary of PRP (called PRT, or platelet-rich therapy) for musculoskeletal injuries included a literature search up to 2013. It notes the following:
The quality of the evidence is very low, partly because most trials used flawed methods that mean their results may not be reliable. The trials also used different ways of preparing and applying the platelet-rich plasma. We were only able to pool data for our primary outcomes (function, pain, adverse events) for a maximum of 11 studies and 45% of participants.
When we pooled the limited data that was available for all these conditions, we found very weak (very low quality) evidence for a slight benefit of PRT in pain in the short term (up to three months). However, pooled data do not show that PRT makes a difference in function in the short, medium or long term. There was weak evidence that suggested that adverse events (harms) occurred at comparable, low rates in people treated with PRT and people not treated with PRT.
And they concluded:
Overall, and for the individual clinical conditions, there is currently insufficient evidence to support the use of PRT for treating musculoskeletal soft tissue injuries. Researchers contemplating RCTs should consider the coverage of currently ongoing trials when assessing the need for future RCTs on specific conditions. There is need for standardisation of PRP preparation methods.
Is PRP safe?
There is the widespread belief that because PRP are your own cellular materials, injected back, that there are no risks to the treatment. Setting aside any sterility risks and the risks of infection that accompany any injection, PRP side effects tend to be minor and include pain, bleeding, bruising, and swelling. However, earlier this year Health Canada published a policy position paper, noting the following risks with autologous cell therapies (which include treatments like PRP injections):
With the exception of donor-derived infections and anti-donor immune responses, autologous cell therapy products present the same risks to patients as their allogeneic counterparts, including:
- the potential introduction of bacteria or viruses;
- between-patient cross contamination, for example if equipment is not properly sterilized;
- risks resulting from processing activities and exposure to processing reagents; and
- the stimulation of unwanted immune reactions, ectopic tissue and/or tumour formation.
From a clinical perspective, cell therapy products have unique absorption, distribution, metabolism, and elimination characteristics compared to other drugs, and have the potential to persist in recipients for a prolonged period of time. This prolonged exposure, relative to the duration of exposure to most drugs, carries the potential for both long-term benefits and long-term risks. Indeed, a number of serious adverse events have been associated with use of autologous cell therapies and strategies to mitigate these risks are needed.
But I’m injured! Is there anything to PRP worth pursuing?
Despite the enthusiasm and aggressive marketing, there are few well-controlled and rigorous clinical trials of platelet-rich plasma. These highest quality trials are consistently negative. It could be that the variety of manufacturing practices and administration techniques are confounding clinical trials, and that there is something actually worth still pursuing. No research has yet shown that to be the case. But it’s far more likely that what we see with PRP are simply placebo effects – the non-specific positive expectations initiated by health practitioners who are charging you a large sum of money for an injection (of cells!), backed by their personal assurances, patient testimonials, and glossy advertising. Until there is convincing evidence to demonstrate otherwise, there is little reason to accept the risk of PRP, regardless of your injury.