Give your blood … to yourself!
Blood therapy, anyone? Platelet-rich plasma (PRP) injections bathe troubled cells in a concentrated mixture made from your own blood. Hopefully this stimulates healing where it is otherwise failing — especially stubborn, slow-motion injuries like tendinitis1 — but no one really knows for sure yet.
Despite all the not-knowing, it’s easy to pay someone to do this for you these days: extract some of your blood, spin it in a centrifuge to get the platelets, and then pump them back into you. It’s not cheap, but PRP injections have become super popular, particularly with elite athletes (ever the guinea pigs for unproven, expensive new treatments for musculoskeletal injuries). It sounds perfect for injuries like patellofemoral pain, an extremely common pseudo-arthritis of the knee in runners,2 or IT band syndrome, another kind of common runner’s knee — a huge potential market, in other words. In the fall of 2009, ScienceBasedMedicine.org scathingly criticized the marketing of PRP:3
Without any clear evidence of benefit beyond placebo, 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. … a nation-wide marketing initiative has begun, using sports celebrities as guinea pigs.
~ A Case Study In Aggressive Quackery Marketing, Jones (ScienceBasedMedicine.org)
At that time, the problem was that the marketing was irresponsible in light of the lack of evidence. It was a short wait for more. Today, the marketing is irresponsible in light of the evidence we now have …
Cynics can stop reading here. You know this doesn’t end well.
Relationship to stem cell therapy
Stem cells are generic cells that do not yet have a job. In theory, they can become what we need them to be, which is a potentially powerful tool in medicine. Stem cell therapy is a broad concept in regenerative medicine, and it is a hot hot hot topic right now.
Stem cell therapy is identical in spirit to the other two main regenerative therapies in musculoskeletal and pain medicine: platelet-rich plasma and autologous chondrocyte implantation. But neither PRP or ACI is technically a stem cell therapy — they use mature, specialized cells, so they are just cell therapies.
But regeneration is the goal of all of these methods, and the topic of stem cell therapy overlaps so much with PRP and ACI that they are practically the same thing regards to safety, efficacy, and the concerns of skeptical consumers and regulators. They are biologically intriguing treatments that might amount to something someday — after all, we know regeneration is possible, thanks to salamanders! — but it’s a depressing mess so far, instead of being inspiring and promising. These treatments are all being rushed to market in the same way, all sold as high-tech medicine to desperate consumers long before the science is done.
Meet the Clotters! Platelets are the major clotting tool in your blood, and they are curious critters, neither cells nor molecules, but a strange hybrid often called “cell fragments”: platelets are to blood cells what wood chips are to a log … if the chips were extremely clever. Platelets have a bunch of interesting biological features, but they are best known for their work in clotting — and that’s mainly what gives them that healing mystique.
There are countless biochemical factors that regulate healing — it’s complex, to say the least. Platelets are part of that equation, playing “a critical role in tissue repair and regeneration”; specifically they “regulate fundamental mechanisms involved in the healing process including cellular migration, proliferation, and angiogenesis.”4 Since they are involved in healing, more of them must be good, right?
That is the basic rationale for PRP.
The ruffled white one in the middle is a platelet — an “activated” platelet, specifically. When calm, they are smaller & smoother.
In fact, PRP is often called “regenerative medicine,” because the idea of genuinely accelerated healing is so tantalizing, happy science fiction. But it’s more marketing than biology, surprise surprise.5 You could probably talk people into drinking a platelet smoothie if you told them it would “regenerate” them.
But it is not safe to assume a soup of platelets is regenerative. In fact, it’s not even safe to assume it’s safe …
Injecting medications into muscles might not be harmless. (No one’s surprised by that, right? Good!) Anaesthetics and NSAIDs probably are a little myotoxic — poisonous to muscles — and there’s “conflicting evidence” about PRP. It might be fine, but it’s important to bear in mind that faddish new injection treatments are never risk free.
Like a salad spinner
To make PRP, blood is spun in a centrifuge. Different blood components separate into layers.
Who says more platelets stimulates healing? Is that in the Platelet User Guide? “For extra healing, generously apply platelets to wound.” Dosage is critical with many medicines. More is not only not always better, it’s usually worse. Do other cells like being bathed in ten times the normal number of platelets? Or is it a suffocating mess that throws everything off kilter?
Or is it just kind of ho hum?
In PRP marketing and hype, it’s common to see claims that it’s a “natural” treatment — because it’s your own blood being returned to you, see? — and what could be safer and healthier than you-stuff? But this is bio-illogical: there’s lots of stuff inside of me that I do not want to be extracted, concentrated, and returned! Pick any hormone, for instance: many of those are just as involved in healing as platelets, but too much of most of them is just a disaster.
For instance, there is a disease of excessive iron, hemochromatosis — a major component of red blood cells, essential to life, something you could easily think you want a lot of for vitality and healing. And indeed you do, if you’re anemic. But chronically absorb too much, and it’s a serious disease.
What you want in biology is just-right amounts of everything, rarely lots of extra anything. It’s really quite odd to assume that a platelet-rich sauce o’ blood is natural and safe and helpful just because the stuff came from you. Which is why this treatment needs to be tested, not assumed — like every treatment.
Science says “probably not”
PRP fans and purveyors will tell you there is good evidence that PRP works, but they are cherry picking from a few studies that worked out in their favour one way or another. A few positive studies never not mean much; indeed, most “positive” study results are actually just bogus.6
Taken as a whole, the evidence is somewhere between inconclusive and discouraging. Although more research is needed (of course!) enough decent studies have now been done that the evidence reviews have started to come out. They all warn that most of the evidence is poor quality, and they are all basing their conclusions on just barely enough good data. They all emphasize that PRP methods are not standardized — there are many versions of PRP, all based on speculation, not data.
The bad news got rolling in 2010. The New York Times reported7 (very) bad science news:
Now, though, the first rigorous study asking whether the platelet injections actually work finds they are no more effective than saltwater.
Nothing has improved since. Three noteworthy reviews were published in 2014:
- Sandrey found “strong evidence” that PRP does not improve plantar fasciitis when combined with several other therapies, and limited evidence that it might be beneficial on its own.8
- Moraes et al found “insufficient evidence to support the use of PRT for treating musculoskeletal soft tissue injuries.”9
- Bell et al concluded that PRP had “no additional benefit in the treatment of mid-portion Achilles tendinopathy.”10 And de Vos et al was super negative regarding tendinopathy:11
Three high-quality studies (75%) and two low-quality studies showed no significant benefit at the final follow-up measurement or predefined primary outcome score when compared with a control group. One high-quality study (25%) showed a beneficial effect of a PRP injection when compared with a corticosteroid injection (corticosteroid injections are harmful in tendinopathy). Based on the best evidence synthesis, there is strong evidence that PRP injections are not efficacious in chronic lateral epicondylar tendinopathy.
In a 2018 podcast, I listened to a really credible expert guest boldly state that “there’s very strong evidence for platelet-rich plasma in osteoarthritis.” Thinking I must have missed something, I checked the primary reference in the show notes, which is also still the most recent review of PRP for osteoarthritis. Did it back up the expert? Not even close!12 As far as I can tell, there is just zero justification for what she said: it’s not “very strong,” it’s actually very weak.
In early 2018, the journal Sports Medicine piled on with a review of six (crappy) studies of PRP for muscle injury (“pulled” muscles, strains).13 Even the optimistic expert I mentioned above expressed doubts about PRP for muscle injury!
The promising biological rationale, the positive preclinical findings, and the successful early clinical experience of PRP injections are not confirmed by the recent high-level RCTs.
And one last slam: Health Canada isn’t a fan, and they have safety concerns:14
Many emerging autologous cell therapy products may eventually prove to be safe and effective. However, most of these products are currently at the investigational stage of development with an on-going need to gather supporting scientific evidence.
Any good news?
The only good news seems to be coming from isolated or fatally flawed studies. Isolated positive evidence about over-hyped treatments is a huge red flag, which usually means “researchers made errors in their favour.” It’s the pattern of evidence that counts, and so far the pattern is distinctly bad.
Any hope? Maybe a little. There are different ways of doing PRP, and there different conditions in different stages may respond better or worse. It’s biologically plausible that PRP could fail with chronic tendinitis but still succeed with an acute muscle strains, for instance, or even fail with one kind of muscle strain and succeed with another. Hammond et al, an experiment on rats — rats were harmed and treated for our edification — reported a difference between two kinds of muscle strain. It worked better on a more serious injury, where regeneration of muscle tissue was part of the healing process. PRP might assist with that regenerative process, but have no effect on a less serious strain where no regeneration is occurring.15
But these are faint hopes. In general, one would hope that the methods and conditions tested so far are at least in shouting distance of being the right formula — close enough to be at least a little more encouraging.
Initially promising in principle, I predict that PRP will now be mired in trumped-up controversy for years. It will die a slow death, only beaten into submission over many years by a growing pile of underwhelming evidence, while its proponents continue to overconfidently sell the service and defend it from detractors, mainly by betting — with dwindling odds — that just the right formula can still be proven effective for just the right kind of patient. If so, great: I will be pleased to admit that my prediction was wrong! But I’m betting against them for now.
After the centrifuge treatment, platelets are separated from the other components of blood.
Platelets give good placebo
My final word on this topic has to be “placebo” — PRP is a perfect storm for it. It’s got everything! Bearing in mind that it’s been thoroughly demonstrated that people get stronger placebo effects from treatment features trivial as a more potent pill colour …
- People expect injected medicines to be more powerful.
- People are also strongly influenced by what elite athletes are doing.
- And of course it’s both high-tech and “natural” — a rare combination. Usually these qualities are contradictory, but PRP is blessed by both.
I can hardly imagine a better formula for a powerful expectation effect or “relief from belief.” Unfortunately, despite placebo’s weirdly good reputation, its powers are quite limited.16 The next time you hear a positive anecdote about PRP, remember: it’s probably the placebo talking.
Is it worth a try anyway?
The bar for “worth a try” is fairly high. No invasive treatment can qualify for it without being proven at least safe. And you really need clear, consistent evidence of non-trivial benefit across several good trials before anything injected is “worth a try.” Before that it’s more like “hey, it’s your knee, don’t stab it”!
About Paul Ingraham
I am a science writer, former massage therapist, and I was the assistant editor at ScienceBasedMedicine.org for several years. I have had my share of injuries and pain challenges as a runner and ultimate player. My wife and I live in downtown Vancouver, Canada. See my full bio and qualifications, or my blog, Writerly. You might run into me on Facebook or Twitter.
What’s new in this article?
July — General editing and minor updates. Spelled out the relationship to other cell and stem cell therapies much more clearly than before.
2018 — Cited Mascarenhas et al on PRP for osteoarthritis (and it’s the usual story: garbage in, garbage out, no conclusion, no compelling evidence).
2018 — Science update, added new meta-analysis of PRP for muscle strain, Grassi et al.
2014 — Publication.
“Tendinitis” versus “tendonitis”: Both spellings are acceptable these days, but the first is the more legitimate, while the second is just an old misspelling that has become acceptable only through popular use, which is a thing that happens in English. The word is based on the Latin “tendo” which has a genitive singular form of tendinis, and a combining form that is therefore tendin. (Source: Stedmans Electronic Medical Dictionary.)
“Tendinitis” vs “tendinopathy”: Both are acceptable labels for ticked off tendons. Tendinopathy (and tendinosis) are often used to avoid the implication of inflammation that is baked into the term tendinitis, because the condition involves no signs of gross, acute inflammation. However, recent research has shown that inflammation is actually there, it’s just not obvious. So tendinitis remains a fair label, and much more familiar to patients to boot.BACK TO TEXT
- It’s not really an arthritis at all, but it is often perceived that way because of the way it feels — a nagging ache — and a loose correlation with a slight degeneration of the kneecap cartilage (chondromalacia patellae). But, because it is perceived as being arthritis-y, it is a popular target for PRP. BACK TO TEXT
- ScienceBasedMedicine.org [Internet]. Jones V. A Case Study In Aggressive Quackery Marketing; 2009 Oct 22 [cited 12 Mar 9]. BACK TO TEXT
- Gawaz M, Vogel S. Platelets in tissue repair: control of apoptosis and interactions with regenerative cells. Blood. 2013 Oct;122(15):2550–4. PubMed #23963043. ❐ BACK TO TEXT
- Gawaz et al writes (emphasis mine): “Control of apoptosis/cell survival and interaction with progenitor cells, which are clinically relevant but poorly understood aspects of platelets in tissue repair, will be highlighted in this review. Gaining deeper insight into the less well-characterized molecular mechanisms is necessary to develop new therapeutic platelet-based options.” Deeper insight is necessary? An understatement! BACK TO TEXT
- PS Ingraham. The “Impress Me” Test: Most controversial therapies are fighting over scraps of “positive” evidence that damn them with faint praise. ❐ PainScience.com. 2535 words. BACK TO TEXT
- New York Times [Internet]. Kolata G. Popular Blood Therapy May Not Work; 2010 Jan 12 [cited 12 Mar 9]. BACK TO TEXT
- Sandrey MA. Autologous growth factor injections in chronic tendinopathy. J Athl Train. 2014 Jun;49(3):428–30. PubMed #24840581. ❐ PainSci #53813. ❐ BACK TO TEXT
- Moraes VY, Lenza M, Tamaoki MJ, Faloppa F, Belloti JC. Platelet-rich therapies for musculoskeletal soft tissue injuries. Cochrane Database Syst Rev. 2014;4:CD010071. PubMed #24782334. ❐ BACK TO TEXT
- Bell KJ, Fulcher ML, Rowlands DS, Kerse N. Impact of autologous blood injections in treatment of mid-portion Achilles tendinopathy: double blind randomised controlled trial. BMJ. 2013;346:f2310. PubMed #23599320. ❐ PainSci #54578. ❐ BACK TO TEXT
- de Vos RJ, Windt J, Weir A. Strong evidence against platelet-rich plasma injections for chronic lateral epicondylar tendinopathy: a systematic review. Br J Sports Med. 2014 Jun;48(12):952–6. PubMed #24563387. ❐ BACK TO TEXT
- Mascarenhas R, Saltzman BM, Fortier LA, Cole BJ. Role of platelet-rich plasma in articular cartilage injury and disease. J Knee Surg. 2015 Feb;28(1):3–10. PubMed #25068847. ❐
The full text of this paper concludes:
Recent systematic reviews on the topic conclude that there is still a paucity of high-quality data providing sufficient evidence to support or disprove the clinical utility of PRP in symptomatic osteoarthritis of the knee. There is even less clinical evidence supporting its use in other joints or in the treatment of focal osteochondral defects despite the basic science evidence in favor of its use. In addition, not all basic science and clinical studies on PRP have concluded it has positive effects.
So garbage in, garbage out, no real conclusions possible: not enough good data even for the knee, even less for other joints. And there’s contradictory evidence.BACK TO TEXT
- Grassi A, Napoli F, Romandini I, et al. Is Platelet-Rich Plasma (PRP) Effective in the Treatment of Acute Muscle Injuries? A Systematic Review and Meta-Analysis. Sports Med. 2018 Jan. PubMed #29363053. ❐ BACK TO TEXT
- www.canada.ca [Internet]. Health Canada. Health Canada Policy Position Paper: Autologous Cell Therapy Products; 2019 May 15 [cited 19 May 31]. BACK TO TEXT
- Hammond JW, Hinton RY, Curl LA, Muriel JM, Lovering RM. Use of autologous platelet-rich plasma to treat muscle strain injuries. Am J Sports Med. 2009 Jun;37(6):1135–42. PubMed #19282509. ❐ BACK TO TEXT
- Placebo is fascinating, but its “power” isn’t all it’s cracked up to be: the power of belief is strictly limited and accounts for only some of what we think of as “the” placebo effect. There are no mentally-mediated healing miracles. But there is an awful lot of ideologically motivated hype about placebo! For more information, see Placebo Power Hype: The placebo effect is fascinating, but its “power” isn’t all it’s cracked up to be. BACK TO TEXT