November 28, 2020

The Niche

Knoepfler lab stem cell blog

Patient Q&A #3: what is PRP & is it worth trying?

PRP injection into a hand
PRP (Platelet Rich Plasma) being injected into a hand. Creative Commons open source image credited to Alice Pien, MD.

I’m continuing my patient Q&A series of posts and today is questions & answers post #3, which is on platelet-rich plasma, also known as PRP.

You can read Q&A #1 on the potential for stem cell clinics to put patients at risk of graft-vs-host disease, and Q&A #2 on whether stem cell transplant recipients and autoimmune patients may be at higher risk of COVID-19.

At left you can see an image of a PRP injection. In this case PRP is being injected into a patient’s hand.

It is often also injected for orthopedic applications such as into joints.

Data for many applications like these are not clear as to benefit. You can find papers pointing to possible small benefit if you want or you an find papers indicating no benefit.

I’ve made a table of contents for this post so that if you want you can jump to the sections you find most interesting.

You may also find my new infographic with the key facts about platelet rich plasma to be useful below.

My Q&A posts overall are based on questions I get from patients and sometimes from other colleagues.

platelet-rich plasma or PRP listings on Clinicaltrials.gov
Map of platelet-rich plasma or PRP listings on Clinicaltrials.gov.

An increasing number of clinics are selling PRP to patients and some university medical centers are getting in the act too of trying it, with the latter mainly for orthopedic conditions.

Sometimes PRP is offered as a stand-alone therapy, while in other cases it is combined with various kinds of stem cells for injection.

While it is most often used within the orthopedics world, you can also find it marketed for almost any ailment. It’s getting more popular to see it marketed for hair loss treatment, for instance. See some of my past posts on regenerative therapies (mostly stem cells) for baldness here.

There are now almost 1,000 listings on Clinicaltrials.gov for a search for platelet-rich plasma as of May 2020. The listings are a mix of a range of real clinical trial studies and also for-profit clinic listings. Some of the listings are much less rigorous studies, sometimes having no controls and lacking a good experimental design. You can see a map of the listings further below. The geographic spread is more all over the globe than for many other biologics listings.

PRP infographic
The Niche PRP infographic by Paul Knoepfler.

Many questions about platelet-rich plasma boil down to: is it worth it?

Patients regularly reach out to me about PRP with questions, which sparked this post.

What is PRP?

Does it work? If so, for what conditions?

Is it worth the cost?

Is it safe?

How long does it last?

In today’s post, which is in a sense a review of platelet rich plasma as a possible treatment option, I try to answer some of these and other PRP-related questions from patients.

Some of the questions were my own too that I read up on to try to address. If you have more questions go ahead and ask them via the comments.

What exactly is PRP?

PRP is an autologous (your own) blood product that can come in various forms depending on how it is made.

It is in essence functionally a concentrated soup of your own growth factors and other molecules mainly from platelets, which are enriched above the typical concentration found in blood. This growth factor “stew” is hoped to have some therapeutic or even regenerative benefits. Again, you might value the infographic above.

By the way I found a YouTube video below from Drew Lansdown, MD of UCSF to be very useful as a source of information. Also see my interview from last week with him where he answered some key questions about this biologic.

You make it by spinning a small amount of blood in a centrifuge, with some protocols involving different steps for further concentration such as additional centrifugation. Three products result from the prep:

  • platelet-rich plasma
  • platelet-poor plasma
  • red blood cells

Every given batch of the kind of platelet-rich portion is likely to vary depending on the protocol for making it and the particular patient it’s made from because of differences in health, age, and perhaps genetic factors.

Some clinic firms claim their protocol produces a more concentrated (and hence better) preparation.

Lack of standardization; some regulatory perspectives

Unfortunately, with a few exceptions, there is little standardization in this area, and many practitioners literally have no quantitative idea what’s in the syringe that they are injecting into patients. That’s got to change.

While the FDA hasn’t fully clarified whether such platelet plasma derivatives can be a drug at times, most often it appears from various agency statements and actions (or lack of action) that when it is used in a standard, stand-alone kind of way for orthopedic conditions it is probably not a drug. In this context, many uses are likely FDA-compliant, but not always. It is also possible the FDA will define specific forms of the product as a drug, but especially with its hands full with COVID-19, that’s probably not happening any time soon.

While the FDA has also approved some devices for use in preparing platelet-rich plasma, the product itself is not “FDA approved”.

There’s a big difference between compliant and approved.

Again the basic idea here with this product is that it is a liquid of your own concentrated growth factors coming from your body that when injected can potentially tell cells and tissues to do specific helpful (or unhelpful) things.

These kinds of instructions may be complicated because there are so many factors in the mix, but the net result might be pushing cells not die, tissues to have less inflammation, etc.

There’s no particular reason PRP “knows” to only do helpful things though so it’s not risk-free. Still, risk seems low for orthopedic uses in particular. So far. When it doubt, talk to your doctor. I’m not a physician.

How much does PRP cost and how long does it last?

The price varies dramatically, but I’d put the average cost that I’ve seen recently at around $1,000-$1,200 per injection. In his video, Dr. Landsdown said $500-$1,500 per injection (but remember patients often get many injections) with average per-patient total cost (maybe the most important figure) of $1,755. You can see my ongoing polling on cost here and for stem cell injections. If you’ve had some kind of therapy in this area please take the polls. The results so far as also interesting so check it out.

Some places will also offer a discounted series of injections from one prep from a single patient at a lower price per injection, such as $800 each for two for a total of $1,600. As another example, from one person’s individual prep they may get 4 injections in different body locations for $2,500 total. My polling (admittedly limited responses for platelet rich plasma so far) suggest some folks are paying far more than around a thousand dollars.

My impression is that for cosmetic uses like hair loss the price is far more expensive than for orthopedic uses. For hair loss, I’ve seen that there are a larger series of injections so the price adds up usually much higher into the thousands.

As a take-home on cost, Dr. Lansdown doesn’t think that most patients are getting their money’s worth for PRP:

“I think that many patients are not having a cost-effective experience with PRP. Since these injections are rarely covered by health insurance and are paid for directly by the patients, there is no real standardization for the amount charged for the injections as there is for other medications/treatments. That was part of the motivation for this study, to try and provide some relative cost based on other treatments that are commonly used for knee osteoarthritis.”

As to the question of “how long does PRP last?”, there isn’t a whole lot of data out there. Benefits mostly seem transient though as in months, although longer-term studies are needed to be sure. When I asked Lansdown about how long it lasts, he said, “It seems from the studies that we have that results may last for about 1 year. This expected duration of benefit though does need to be clarified.” If you need a new injection for $1,000 or so every six months or a year that’s going to add up.

What are objective views on clinical use of PRP?

It’s easy to find a lot of enthusiasm and skepticism out there on this product including from physicians.

Here are some parts of a mostly cautionary piece from the American Academy of Orthopedic Surgeons:

“At this time, the results of these studies are inconclusive because the effectiveness of PRP therapy can vary…Treatment with PRP could hold promise, however, current research studies to back up the claims in the media are lacking. Although PRP does appear to be effective in the treatment of chronic tendon injuries about the elbow, the medical community needs more scientific evidence before it can determine whether PRP therapy is truly effective in other conditions.”

Importantly, they note minimal risks as well. This fits my general sense from following this product for many years in that there haven’t been many mentions of safety issues in the media or published papers. That doesn’t mean it’s by definition safe, but I’d say it’s most often going to be safer than a living cell biologic.

Also, I found 2 in-depth review pieces from Cochrane Review, but they are somewhat outdated:

The first, Autologous platelet-rich plasma (PRP) for chronic wounds, concludes, “The results were non-conclusive as to whether autologous PRP improves the healing of chronic wounds generally compared with standard treatment.” That’s not exactly a ringing endorsement.

Then this second one, Platelet-rich therapies for musculoskeletal soft tissue injuries, is more relevant to the stem cell clinic sphere. It analyzed a set of studies finding overall:

“The quality of the evidence is very low, partly because most trials used flawed methods that mean their results may not be reliable” and concluding, “In conclusion, the available evidence is insufficient to support the use of PRT for treating musculoskeletal soft tissue injuries or show whether the effects of PRT vary according to the type of injury. Any future research in this area should bear in mind the several studies currently going on and should consider the need for standardisation of the PRP preparation”.

Again, not exactly much enthusiasm is evident there.

Admittedly these reviews are a few years old so hopefully Cochrane will do a newer analysis soon. Cochrane does have a relevant 2019 piece, but it’s a protocol and not a review.

Note that Cochrane is a charitable organization focused on providing unbiased information about medical intervention guided by evidence.

Published literature

My own scanning of the literature on platelet-rich plasma finds papers with conclusions that are all over the place. The sheer number of publications here is striking and hard to digest.

The papers range from reports of no effect to some usually relatively moderate apparent benefit in certain cases such as in this meta-analysis. In contrast, a 2020 published meta-analysis for knee arthritis found no benefit of PRP over HA or steroid injection.

You can find a surprisingly large number of meta-analyses in this area, sometimes asking almost the same questions, but finding different conclusions. A meta-analysis is a “high level” study of other studies from a big picture standpoint to see if there are consistent trends from other people’s work. Think of it kind of like a scientist comparing and combining findings from 10 other published studies into one new paper trying to draw the overall gist of the papers.

Digging into a few individual research papers myself, I found that some report usually small  to moderate benefit of PRP over HA or steroids, but others including some strong studies like these two don’t:

“Statistical differences between groups were not found for the majority of the outcome variables, although the magnitude of improvements tended to be greater in the PRP group.”

“We found no difference between HA and PRP at any time point in the primary outcome measure”

So overall is PRP worth it?

It’s a tough call and depends on many things.

My overall “meta” sense at this time is that PRP might have some moderate benefit in specific cases, but that will depend on how it’s prepared, how it is injected, who is making and injecting it as well as their training, and for what conditions as well as in which patients.

Yes, there are lots of variables here, which makes things noisy data-wise and so difficult in terms of predicting outcomes.

Again, part of the problem is that due to lack of standardization this product is actually in reality probably dozens of different kinds of related products under one umbrella term, which throws things into further confusion.

Dr. Lansdown suggests that some very specific orthopedic conditions probably benefit from PRP so again you might check out my interview with him, but my sense from him is that more data is needed to move some specific applications to be the “standard of care.”

Since there are few other helpful non-surgical alternatives for some conditions where PRP is being deployed like osteoarthritis of certain joints, and PRP so far does not seem to pose major risks in some orthopedic contexts, some patients may feel it’s worth the cost and risk.

Patients need to do their homework, talk to their doctor (in my view preferably at least one physician not trying to sell them on PRP), and try to get into the scientific literature if they can too. That last task is a tough one though in this particular area.

Note that you should discuss the potential use of PRP or other biologics like stem cells with your physician before making any decision and this post is not meant as medical advice. I’m a PhD and a stem cell and cancer researcher, not a physician.

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