Does Platelet-Rich Plasma Injection Work?

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. There’s a section summarizing all the major highlights from the literature further along here, but the bottom line is clear: if it works at all, it’s tricky and unreliable, probably heavily dependent on factors we don’t understand and cannot control.

Plus it can hurt a lot! One reader described it as “among the worst experiences of my life, definitely surpassing childbirth.”

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 with 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.

Why platelets?

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 …

Myotoxic? Myo-maybe!

Health Canada isn’t a fan, and notably they have safety concerns:6

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.

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.7 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.

The overly optimistic expert

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!8 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. It exists, and it’s technically positive, but it’s just not compelling.

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 mean much; indeed, most “positive” study results are actually just bogus.9

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 reported10 (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 significantly since. Highlights from the more recent literature:

• 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.11
• Moraes et al. found “insufficient evidence to support the use of PRT for treating musculoskeletal soft tissue injuries.”12
• Bell et al. concluded that PRP had “no additional benefit in the treatment of mid-portion Achilles tendinopathy.”13 And de Vos et al was super negative regarding tendinopathy:14

  “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.”

• One of the only really good trials done so far — just a straight up randomized controlled trial, adequately powered, published in the New England Journal of Medicine in 2014 — was just completely negative. PRP for muscle strains did not beat a placebo, period.15
• A 2018 review in Current Reviews In Musculoskeletal Medicine is both positive and negative, emphasizing how variable results are depending on the condition: some mildly encouraging results for some things (tennis elbow, patellar tendinopathy, plantar fasciitis), but definitely not others (Achilles tendinitis, muscle strain, fractures, and ACL tears).16

• In early 2018, the journal Sports Medicine piled on with a review of six (crappy) studies of PRP for muscle injury (“pulled” muscles, strains).17 Even the optimistic expert I mentioned above expressed her 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.”

• A 2018 meta-analysis of PRP for tendon and ligament healing18 was technically positive, but with small effect sizes and this weak-sauce conclusion: “may reduce the pain.” And the authors (predictably) emphasize the “significance” (statistical) of their results rather than the effect size.
• A 2019 meta-analysis of PRP for knee arthritis is underwhelming in exactly the same ways:19 technically positive, but not really trustworthy, and unimpressive in any case: PRP “might be more effective” than hyaluronic acid injections.20 Be still my beating heart.

Any good news? Any hope of any kind?

Most of the good news is coming from isolated or 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 are 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 strain, 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.21

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 as 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.22 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 for normal folks. 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”!

The equation is always different for elite athletes, of course: the slightest edge could be a big deal. But that sword cuts both ways! It might help just a little, and that might matter a lot… or it might hurt just a little, and that might matter a lot. Every athlete and coach is going to have a different opinion on whether that risk is worth it.

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About Paul Ingraham

I am a science writer in Vancouver, Canada. I was a Registered Massage Therapist for a decade and the assistant editor of ScienceBasedMedicine.org for several years. I’ve had many injuries as a runner and ultimate player, and I’ve been a chronic pain patient myself since 2015. Full bio. See you on Facebook or Twitter., or subscribe:

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Notes

1. “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.

2. 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.
3. ScienceBasedMedicine.org [Internet]. Jones V. A Case Study In Aggressive Quackery Marketing; 2009 Oct 22 [cited 12 Mar 9]. PainSci Bibliography 55587 ❐
4. 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 ❐
5. 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!
6. www.canada.ca [Internet]. Health Canada. Health Canada Policy Position Paper: Autologous Cell Therapy Products; 2019 May 15 [cited 19 May 31]. PainSci Bibliography 52439 ❐
7. Reurink G, Goudswaard GJ, Moen MH, et al. Platelet-rich plasma injections in acute muscle injury. N Engl J Med. 2014 Jun;370(26):2546–7. PubMed 24963588 ❐

   No one knows for sure exactly how toxic, but permanent/serious harm is unlikely. Complete recovery should be possible in most cases. That was my reasoning before I did some reading, and then my reading confirmed it. Reurink et al.:

   Although the extent of muscular damage differs between specific agents and is dose dependent, the time course and the histological changes that are observed appear to be rather uniform. Within minutes after injection, hypercontraction of the fibres occurs, followed by degeneration of fibres, oedema and infiltration of inflammatory cells and necrosis over the following days. The pathogenesis of the myotoxicity is complex and not completely understood. The pathological mechanism is thought to be an interaction of local anaesthetics with the sarcoplasmic reticulum channels, initiating increased intracellular Ca2? levels and subsequent Ca2?-activated pathways of cell death. Initially, the histological damage appears severe, but the necrosis of fibres is reversible, and muscle regeneration usually occurs within 2–5 weeks.

   So it’s counterproductive for sure, but lasting damage would probably only occur in patients who got an unusually large dose and/or who had some special biological vulnerability.

8. 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.

9. Ingraham. Most Pain Treatments Damned With Faint Praise: Most controversial and alternative therapies are fighting over scraps of “positive” scientific evidence that damn them with the faint praise of small effect sizes that cannot impress. PainScience.com. 2796 words. Many seemingly evidence-based treatments for pain and injury are actually supported by evidence that damns with faint praise: results showing only a tiny benefit, which may not even be real. Frustratingly, unimpressive evidence like this is routinely integrated into scientific reviews and clinical guidelines, which carry more weight with the uninformed. This is all so common in alternative medicine, sports medicine, and physical therapy that it’s almost standard.
10. New York Times [Internet]. Kolata G. Popular Blood Therapy May Not Work; 2010 Jan 12 [cited 20 Jan 25]. PainSci Bibliography 55584 ❐
11. Sandrey MA. Autologous growth factor injections in chronic tendinopathy. J Athl Train. 2014 Jun;49(3):428–30. PubMed 24840581 ❐ PainSci Bibliography 53813 ❐
12. 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 ❐
13. 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 Bibliography 54578 ❐
14. 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 ❐
15. Reurink 2014, op. cit. In this randomized trial involving athletes with acute hamstring muscle injuries, injection of platelet-rich plasma did not result in shortening of the time until patients could resume their sports activity or in a reduction in reinjury rates, as compared with placebo.
16. Le ADK, Enweze L, DeBaun MR, Dragoo JL. Current Clinical Recommendations for Use of Platelet-Rich Plasma. Curr Rev Musculoskelet Med. 2018 Dec;11(4):624–634. PubMed 30353479 ❐ PainSci Bibliography 52517 ❐
17. 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 ❐
18. Chen X, Jones IA, Park C, Vangsness Jr. The Efficacy of Platelet-Rich Plasma on Tendon and Ligament Healing: A Systematic Review and Meta-analysis With Bias Assessment. Am J Sports Med. 2018 07;46(8):2020–2032. PubMed 29268037 ❐ PainSci Bibliography 52535 ❐
19. Han Y, Huang H, Pan J, et al. Meta-analysis Comparing Platelet-Rich Plasma vs Hyaluronic Acid Injection in Patients with Knee Osteoarthritis. Pain Med. 2019 07;20(7):1418–1429. PubMed 30849177 ❐ PainSci Bibliography 52532 ❐
20. “Lube” injections — a treatment which used to be associated with all the same hype and hope as PRP, but which is now widely regarded as ineffective (though it is still being sold to patients!), and therefore a decent sham to compare something else to. See Should You Get A Lube Job for Your Arthritic Knee? Reviewing the science of injecting artificial synovial fluid, especially for patellofemoral pain.
21. 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 ❐
22. 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 a little of what we think of as “the” placebo effect, which is actually a collection of diverse nonspecific effects and research artifacts For more information, see Placebo Power Hype: The placebo effect is fascinating, but its “power” isn’t all it’s cracked up to be.