The debate over
plasma reaches far and wide, with clinical trials showing conflicting
results throughout Europe and the United States. Differing costs, regulations
and evidence bases have served to polarize physicians as they try to determine
exactly what, if any, uses the novel treatment has, and how they may be
clinically tested, according to physicians who spoke with Orthopaedics
Perhaps the most common sentiment regarding platelet-rich plasma (PRP),
however, is that it simply should not be marketed as a miracle drug.
“The way it is making news right now is as a cure-all for
everything, which is just not reasonable,” Freddie H. Fu, MD, DSc,
DPs(Hon), Orthopaedics Today Europe Editorial Board member, said.
Although other clinicians in his office use PRP to treat
and some muscle injuries, Fu said he does not use PRP in his sports medicine
Freddie H. Fu, MD, DSc, DPs(Hon), believes
there are still too many questions — including preparation, application
and proper indications — surrounding the use of PRP to consider it a
viable treatment option and would like to see strong, thorough clinical data in
support of its efficacy.
Image: Thomas M. Springer,
Orthopaedics Today Europe
“We are still trying to define the exact indications,” he
While Fu does not use PRP, there are other physicians who use it
regularly but still do not consider it the kind of treatment that can be
utilized across the board.
Omer Mei-Dan, MD, has worked with PRP for approximately 7 years,
publishing studies and using it to help professional athletes, recreational
athletes and regular patients get back to their normal activities. He noted
that currently, he sees PRP as most beneficial in boosting the healing process
initiated by the body.
“According to my clinical findings, even though PRP helps a lot
— and when I say it helps a lot I would back it up with scientific studies
I still feel it would be most beneficial in acute instances,” he said.
“I am not saying PRP helps for everything, but there are
definitely many indications if you know when to inject, how to inject, how much
to inject, the proper intervals, volume and technique,” he added.
“Many times you can get amazing results.”
Elizaveta Kon, MD, of the Biomechanics Laboratory at the Rizzoli
Orthopaedic Institute, has found PRP useful in certain circumstances but
stressed it should not be considered the “Holy Grail.”
“To be realistic, nothing works for everything,” she said.
“I use PRP a lot in my clinical practice, so I am convinced it works, but
I am not convinced it works for everybody or for every type of
study’s methodology examines the patient in the short time period just
after the treatment ... then you definitely see a major
— Omer Mei-Dan, MD
Before trying to properly determine the effectiveness of PRP, Fu said,
one has to determine the very definition of PRP. The future of the treatment is
unclear, he added, in part because of the inherent variables.
“Sometimes, people are not talking about the same product,” he
said. “There are different manufacturers, different preparations. It needs
to be better defined.”
According to Kon, the variability is a source of frustration for those
trying to prove PRP’s worth.
“We all say it is PRP, but in reality they are all different
compositions and everybody has different results,” she said.
Kon added, however, that clinically evaluating PRP’s usefulness
should not be considered an impossibility.
“For sure, if you are doing it in private practice, it is very
difficult to do serious randomized controlled studies. If you are with a
university or a big hospital, you can produce serious studies,” she said.
Mei-Dan referred to the variables inherent in PRP as “the main
downside” of studies and research in the field. He noted variables such as
proper timing, volume, concentration, location and number of PRP injections as
being major factors in every study that attempts to prove the treatment’s
“There are so many different variables that it is hard to take all
of those different studies and put them on one shelf,” he said.
Proper methods of delivery
Delivery of PRP is another major variable, Fu said.
“How should it get there?” he said. “Many times with the
liquid form, you do not know if it is really getting there. You shoot it in,
but it may leak right out. If you use a gel form you can sew it in. So how do
you look at that outcome?”
Fu uses a treatment similar to PRP that simplifies the issue of
“We remove 50 ccs of the patient’s own blood,” he said.
“Then, in a glass container, we stir the blood into a clotted form. The
clot will contain red cells and platelets and some of the growth factors and
the ingredients of PRP.”
This paste is then sewn into place, thereby ensuring that it cannot leak
or migrate to anywhere else in the area of the injury.
Fu noted he prefers the fibrin clot technique over PRP because the
latter adds unnecessary costs to surgery.
Difficult outcome measures
The nature of the potential benefits of PRP also provide a challenge to
physicians, as they have proven in some cases to be difficult to ascertain in
the rigid clinical parameters of a proper study environment.
“In many acute healing indications, we do not find a major
difference after 6 months or 1 or 2 years, but I think with acute indications
the place where PRP is most likely to help is shortening the return-to-play
time with professional and recreational athletes,” Mei-Dan said. “If
your study’s methodology examines the patient in the short time period
just after the treatment, say in the first 1 to 5 weeks, then you definitely
see a major improvement. If you go back and look after 6 months, it will even
up. Radiologically, however, we most likely will still find a better tendon or
muscle scar in the treated group.”
Extra cost isn’t the only concern Fu has regarding the use of PRP:
He noted that the difficulty of pinning down reliable outcome measures is a
significant factor in his reluctance to use the treatment.
“Right now it is very hard to prove,” he said. “Looking
just at functional return is hard. It is hard to know if being able to play
tennis again is an end result of PRP. The outcome measurement is probably not
good. You cannot just look at PRP; you have to look at a number of things.
“We need MRI, we need functional evaluation, we need all of those
things together to see how it works,” he added. “Not just being
selective and saying, ‘well, they came back to play.’ Placebo does
the same thing.”
According to Mei-Dan, though studies have been and are being conducted,
physicians may have to become comfortable with the notion that PRP is something
that is simply difficult to truly measure and gather evidence for certain
indications. Physicians should therefore concentrate on those indications which
have validated outcome measures in order to observe the precise differences.
“Many times, if you try to take a control group with an acute
muscle tear, it is hard to find and control the exact same muscle tear when it
comes to size, location, type of athlete or sport … so it is something
that is very hard to control,” he said.
“In these cases, we must use objective measures in a timely
controlled fashion, like ultrasound follow-ups, when we want to shorten
return-to-play for a professional athlete after injection.”
Fu said the benefit of PRP may be more psychological, comparing it to
the oxygen tanks football teams would keep on the sidelines for players to use
— a practice which has no clinical effect.
“I mean, PRP almost certainly does not cause any harm, but I think
if the patient has a false sense of security with healing and pain control they
may go back to playing and hurt themselves,” Fu said.
PRP in Europe
One of the factors blocking PRP’s growing success across Europe is
the variation in regulations across different countries. Legislation has, in
some cases, been slow to catch up.
“[PRP] was essentially born in Spain, and there it is widely used
and there are no limitations,” Kon said. “In Italy, the PRP has to be
prepared inside — or with the approval of — the hematology bank and
transfusion unit. A hematologist has to come and authorize me to do it, or he
has to do it himself.”
Kon added that in Italy, PRP is considered a blood product. This means
it is subject to some of the same regulations as transfusions, meaning it
cannot be done in just any office. This restricts the use of PRP to major
Still, she noted, Italy has developed a
“fascination” with PRP.
“It is simple, it is new,” she said. “Patients like the
concept. It has become more and more widespread.”
Comparing the use of PRP in Europe and the United States comes down to a
few factors, Fu noted, one of which is certainly cost.
“There is a cost factor, I think,” he said. “In Europe,
the price may be a bit more reasonable. In America, the price is higher: up to
$2,000. In Europe it can be as low as $50 to $100. Some of it depends on the
marketing, too. I know in some countries I have visited, they do not really use
it all that much because there is little incentive.”
Proving PRP works
Though proving empirically that PRP is useful has been difficult for
several of its applications, the amount of anecdotal evidence has certainly
“There is a small amount of really serious clinical studies for
PRP,” Kon said. “It is all anecdotal experience. There are a couple
of randomized controlled studies published, some say it works and some say it
does not. There is a lot of advertising, a lot of noise, a lot of
Still, Kon added she sees some potential for clinical evidence not too
far down the line.
“There are a lot of serious clinical studies running,” she
said. “I think in the next 2 years we will see some serious randomized
controlled studies coming out.”
For Fu, PRP becoming more widely used and proven — or just the
opposite — is only a matter of time.
“A treatment like this will likely not go away very quickly because
it is hard to prove it is bad,” he said. “Especially since it will
not harm people.”
“I go to meetings and people tell me it takes 15 to 20 years for a
good product to come out on the market,” he added. “But also, we know
it takes probably another 15 to 20 years for a bad product to come off the
market. It will be a long time before we really find out if PRP is good or bad.
I do not know where it is in that spectrum, and I hope in some way it can be
Mei-Dan believes PRP will eventually prove itself as a viable treatment,
but also believes that it will take time.
“Right now we are in the peak of the hype,” he said. “But
I think there are good studies coming … and finally, when you have enough
studies — when you find the right methodology and outcome measures —
we will have enough to support the indications.”
The need for studies across multiple applications is critical to
figuring out those methodologies, Kon said.
“We need randomized controlled studies for every type of
application,” she said. “If we prove that it is good for tendons,
that does not mean it is good for cartilage. It does not mean it is good for
Ultimately, Fu said, the most important aspect of performing trials for
PRP viability comes down to a matter of making sure physicians and companies
are not wasting time or money in the chase of something that may not have the
impact for which they are hoping.
“We should not pursue PRP for our ego, but for patient-care
effectiveness,” he said. – by Robert Press
- Freddie H. Fu, MD, DSc(Hon), DPs(Hon), can be reached at the
University of Pittsburgh, Department of Orthopedic Surgery, 3471 Fifth Ave.,
Suite 1011, Pittsburgh, PA 15213 USA; +1-412-687-3900; e-mail:
- Elizaveta Kon, MD, can be reached at the Biomechanics Laboratory
– III Clinic, Rizzoli Orthopaedic Institute, Via Di Barbiano 1/10 –
40136 Bologna, Italy; +39-051-6366567; e-mail:
- Omer Mei-Dan, MD, can be reached at Meir University Hospital,
Department of Orthopaedic Surgery and the Sports Injury Unit, Kfar Saba,
Israel; e-mail: email@example.com.
- Disclosures: Fu, Kon and Mei-Dan have no relevant financial
What are your indications for using PRP and why?
Indicated when healing is compromised
We have good results with PRP in the treatment of tendinopathies in any
anatomical location. Indeed PRP is indicated when healing is compromised due to
an inadequate biologic environment. In these conditions, PRP is effective
because it modifies the biological milieu and triggers regenerative mechanisms
and may stop the progress of disease.
Treatment of muscle injuries is a good indication but efficacy is higher
in acute conditions when applied within 24 to 48 hours post-injury. Here, the
foundation for the use of PRP involves replacing the blood clot with PRP, thus
minimizing the presence of red blood cells (about 95% in volume) while
increasing platelet concentration at the injury site and supraphysiological
concentrations of healing factors.
We also use PRP routinely with arthroscopy and open surgery —
mainly because it helps in healing both target and adjacent tissues that were
damaged when accessing the surgical site. Patients have reported less pain and
have less inflammation.
When discussing PRP therapies, differences should be established between
preparations and re-administration procedures. Generally speaking we use the
term PRP therapies to include all PRP formulations and re-administration
procedures to patients. But some formulations are not comparable to each other
in terms of leukocyte content, platelet count and plasma volume.
We need a comprehensive description of the relation between PRP
components, healing mechanisms and functional outcome. The effectors of the
beneficial function of PRPs have not been identified; platelets contain more
than 300 proteins, thus the primacy of growth factors may be undermined by
unveiling new classes of molecules; so it is difficult to optimize the
formulations. Moreover it may involve different formulations for different
tissues or at different stages of healing or for patients with different
histopathological or clinical features. So PRP therapies are much more complex
than previously believed.
We should also differentiate between liquid or clotted PRP (fibrin) and
the frequency of application. A distinction should be made between chronic and
acute pathologies and between surgical and nonsurgical conditions.
Mikel Sánchez, MD, is from USP
Hospitales, Unidad de Cirugia Arthroscopica, Clinica USP-La Esperanza,
Disclosure: He has no relevant financial
Lacks scientific evidence
Platelet-rich plasma therapies aim to improve the process of tissue
repair through local delivery of autologous bioactive agents to influence
critical mechanisms such as inflammation, angiogenesis or extracellular matrix
synthesis. Platelet-rich plasma has been used for just about any and all
conditions in orthopaedic sports medicine, and some practitioners swear by it.
I am more cautious: I am fascinated by this new technology, and by the
opportunity that PRP may afford to get my athletes back to health and fit to
fight faster. However, I am aware of the fact that there is still relatively
little level 1 evidence in favor of PRP. Indeed, the well-performed level 1
studies seem to paint a different view from what is outlined in the press. The
early studies were impressive, and PRP seems to be effective in the management
of tennis elbow. However, subsequent well-performed randomized controlled
trials in Achilles tendinopathy from Holland and our own in rotator cuff tears
do not show any advantage. Another randomized controlled trial using PRP in
open repair of Achilles tendon ruptures from Sweden shows that it is at best of
no use, and possibly harmful. I am aware of another trial in rotator cuff
repair which shows early advantages, and of another that shows no advantages.
We performed systematic reviews with the Dutch group and with the group
who introduced the concept of PRP in the management of musculoskeletal
injuries, led by Drs. Anitua, Sánchez and Andia, in Spain, and found
that the scientific evidence is just not there. The same applies to muscle
injuries. Therefore, at present, I am happy to perform studies on PRP (and we
are doing so), but I do not use it in clinical practice, at least not yet!
Nicola Maffulli, MD, MS, PhD,
FRCS(Orth) is the centre lead and professor of sports and exercise medicine,
consultant trauma and orthopaedic surgeon, Queen Mary University of London
Barts and London School of Medicine and Dentistry, William Harvey Research
Institute Centre for Sports and Exercise Medicine, Mile End Hospital, London.
Disclosure: He is the owner of SportsMed(UK) Ltd.