Legal and ethical aspects of Platelet-Rich Plasma

Abstract

Platelet-Rich Plasma (PRP) is a widely used alternative option in the treatment of a variety of sports-related injuries in the hopes that the increased levels of autologous growth factors and secretory proteins provided by the concentrated platelets could enhance the biological processes associated with tissue repair and regeneration. There are a lot of good studies on the positive effects of PRP therapy on animals. Many commercial preparation systems are available, but the optimal preparation remains unknown. Increasing numbers of clinical studies evaluating PRP have been reported and have provided both positive and negative evidence for its effectiveness. Well-designed, controlled studies are still lacking, but PRP may have a benefit for patients with sport related injuries. Our question: is it safe to treat patients with PRP therapy if we can’t say to them if it is going to work? In other words, is PRP therapy ethical and legal in sports medicine? We developed an informed consent that explains what technology is, what the doctor is doing, and what the expectations are. Being very honest with the patient regardind the medical information suported by literature, we find this is both ethical and legal.

Full text

Rom J Leg Med [25] 405-408 [2017]
DOI: 10.4323/rjlm.2017.405
© 2017 Romanian Society of Legal Medicine
405
ETHICS, BIOETHICS AND SOCIAL SCIENCES
Legal and ethical aspects of Platelet-Rich Plasma
Ion-Bogdan Codorean1,*, Eduard Cernat, Dragos Popescu2, Ruxandra Diana Sinescu3, Paula Perlea4
_________________________________________________________________________________________
Abstract: Platelet-Rich Plasma (PRP) is a widely used alternative option in the treatment of a variety of sports-related
injuries in the hopes that the increased levels of autologous growth factors and secretory proteins provided by the concentrated
platelets could enhance the biological processes associated with tissue repair and regeneration. ere are a lot of good studies on
the positive eects of PRP therapy on animals. Many commercial preparation systems are available, but the optimal preparation
remains unknown. Increasing numbers of clinical studies evaluating PRP have been reported and have provided both positive
and negative evidence for its eectiveness. Well-designed, controlled studies are still lacking, but PRP may have a benet for
patients with sport related injuries. Our question: is it safe to treat patients with PRP therapy if we can’t say to them if it is going to
work? In other words, is PRP therapy ethical and legal in sports medicine? We developed an informed consent that explains what
technology is, what the doctor is doing, and what the expectations are. Being very honest with the patient regardind the medical
information suported by literature, we nd this is both ethical and legal.
Key Words: platelet-rich plasma, legal, informed consent.
1) “Carol Davila” University of Bucharest, Universitary Emergency Military Central Hospital, Bucharest, Romania
* Corresponding author: Tel: 40-722300313, E-mail: dr.codorean@traumatologie-sportiva.ro
2) University of Medicine and Pharmacy, Craiova, Romania
3) “Carol Davila” University of Bucharest, Emergency Teaching Hospital Elias, Bucharest, Romania
4) “Carol Davila” University of Bucharest, Faculty of Dental Medicine, Bucharest, Romania
The growing interest in the use of platelet-
rich plasma (PRP) to optimize the healing
response of tissues has sparked the development and
marketing of a plethora of commercial procedures that
are designed to concentrate platelets and suspend them
in plasma or a brin construct of varying densities [1].
Although these techniques and their resulting products
have been summarily grouped under the generic
term “platelet-rich plasma”, their precise makeup and,
therefore their potential ecacy, can vary widely. For
example, some PRP products include white blood cells,
whereas others do not. In some techniques, exogenous
thrombin or calcium chloride is added to activate platelets
or to initiate the clotting cascade. Finally, variations in
the initial volume of whole blood used as well as the
eciency of platelet recovery varies markedly among
PRP techniques and has resulted in a high variation (3- to
27-fold) of growth factor concentration and availability
[1]. erefore, because all PRP products are not the same,
the success or failure of a specic PRP or PRP-related
product for a specic pathologic indication cannot be
universally applied to all PRP products.
What is PRP?
PRP is obtained by centrifugation of autologous
blood of the patients. e result of this centrifugation
is a large concentration of platelets in a small volume
of plasma. ere are many methods for obtaining
PRP, each one with specic properties as to capacity
of concentration of the platelets and release process of
certain growth factors. In order for PRP to have greater
ecacy, the ideal concentration of platelets should be
roughly 1,000,000μL in a standard aliquot of 6mL [2].
In order to inform our patients we explain them
what PRP is and consent them for venous blood colection
(Fig. 1).

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Codorean I.B. et al. Legal and ethical aspects of Platelet-Rich Plasma
e PRP terminology
PRP has been described in the literature under
dierent names and abbreviations. Some authors dene
PRP as only platelets, whereas others note that PRP
also contains increased concentrations of leukocytes,
brin, and some bioactive proteins. Based on these
descriptions, PRP was classied into pure plateletrich
plasma (P-PRP), leukocyte- and platelet-rich plasma
(L-PRP), and leukocyte- and platelet-rich brin (L-PRF)
[3, 4]. Still, some authors regard autology and growth
factors as unique advantages of PRP and prefer the terms
autologous platelet concentrate (APC), or plasma-rich
growth factors (PRGFs) [5]. Based on whether PRP is
activated to form gel or not, PRP was also divided into
platelet plasma (non-activated platelet) and platelet gel or
PRP clot (activated platelet) [6]. Various other terms are
also used in the literature, including autologous growth
factors (AGF) [7], platelet-leukocyte gel (PLG) [8],
autologous platelet gel (APG) [9], platelet-rich gel (PRG)
[10], and platelet-rich brin (PRF) [11]. In view of the
general confusion over PRP terminology, it should be
emphasized that dierent preparations of PRP may have
the same name despite having dierent properties, while
similar preparations of PRP might have dierent names
despite having the same properties.
We nd ethical to inform our patients about the
commercial name or the product, the biological type of
the product, and the content of the product [12]. We also
provide some disposable parts of the package in order to
give the patient the chance to read about it (Fig. 1).
Laboratory evidence
ere have been several animal studies evaluating
the use of PRP to augment tendon repair. Kajikawa
and associates injected PRP into a surgically created
patellar tendon injury in a rat model. ey evaluated the
tendons histologically and concluded that the number
of circulation-derived cells that inltrated the wounded
area was signicantly increased in the PRP group on day
3 and day 7. is, they argued, conrmed the value of PRP
as an activator of circulation-derived cells in the early
phases of tendon healing [13]. In a similar rat tendon
injury model, Lyras and coworkers compared application
of insulin like growth factor 1 (IGF-1) to a PRP gel. IGF-1
is a known stimulator of collagen production and a potent
stimulator of cell proliferation [14]. e PRP treated
group was found to have a denser appearance and fewer
elastic bers remaining with better tenocyte orientation
at 3 weeks [15]. e same investigators evaluated the
angiogenic eect of PRP in a rabbit patellar tendon
model. ey found an initial increase in the vascularity
in the PRP treated tendons followed by a decrease by
4 weeks. e PRP treated tendons also had improved
tenocyte orientation compared with the more immature
tissue seen in the control group [16].
ese are studies that are proving the ecacity
of the PRP in the animals. We inform our patients about
the laboratory evidence that supports the PRP, specially
when PRP is used to stimulate the tendons/so tissues
repair.
Clinical evidence
In a randomized, double-blind study by
Peerbooms and coworkers, 100 consecutive patients
were randomized to receive an injection of PRP (Recover,
Biomet, Warsaw, IN) or corticosteroid (triamcinolone 40
mg) for refractory lateral epicondylosis. All patients had
failed physical therapy and other non-operative measures
for a minimum of 6 months. At the 4 and 8 week follow-
up visits, the steroid group had a greater reduction in both
the VAS and Disability of the Arm, Shoulder, and Hand
(DASH) scores compared with the PRP group, though
these results were not statistically signicant. However,
at 6 months, 1 year, and 2 years the PRP group had a
signicantly greater reduction in both VAS and DASH
scores compared to the steroid group [17, 18]. is led
the investigators to conclude that PRP is a superior form
of treatment for refractory lateral epicondylosis. e
limitation of this study is the lack of true control group,
as the limited ecacy of steroid injections and possible
detrimental long-term eects have been previously
reported [19].
In a randomized, double-blind, placebo-
controlled trial, de Vos and colleagues evaluated the use
Figure 1. PRP Informed consent.

Romanian Journal of Legal Medicine Vol. XXV, No 4(2017)
407
of PRP injection in conjunction with eccentric exercises
for the treatment of Achilles tendinopathy. ey were
unable to nd a signicant dierence in the change in
neovascularization score from baseline to 6 or 24 weeks
in either group. Given these results, the investigators
argue against the use of PRP injections for the treatment
of Achilles tendinopathy [20].
Gaweda and colleagues published encouraging
results from a prospective cohort of 15 subjects treated
with PRP injection aer failure of other non-operative
measures [21]. Patients experienced a signicant
improvement in both American Orthopaedic Foot and
Ankle Society (AOFAS) and VISA-A scores beginning
at 6 weeks and at all-time points until conclusion of the
study at 18 months. Aer only 3 months, they also found
decreased tendon thickening on ultrasound evaluation in
11 out of 15 patients.
Patellar tendinopathy can be a particularly
vexing condition with an average duration of symptoms
of 3 years with 53% of patients reporting that they quit
their sporting career due to the condition at 15 year
follow-up [22, 23]. Kon and coworkers evaluated the use
of PRP in 20 consecutive patients with “jumper’s knee”
of at least 3 months duration with persistent patellar
tendinopathy and magenetic resonance imaging (MRI) or
ultrasound ndings consistent with degenerative changes
in the tendon [24]. Patients received three injections
every 15 days with an average 600% increase in platelet
concentration compared with normal serum levels. At 6
months follow-up, they found a signicant improvement
in VAS, Short Form -36 (SF-36) and Tegner scores with
80% of patients satised with their treatment. Given
this improvement, the investigators supported PRP use
in refractory cases of patellar tendinopathy. A study
from the same institution compared 15 patients with a
similar PRP treatment and rehab protocol to a matched
historical cohort who received a standardized physical
therapy program alone. Both groups improved in VAS
and Tegner scores at 6 months with 86.7% satisfaction
in the PRP group compared to 68.8% in the control.
However, no statistical dierences were found between
groups.
Ethical and legal concerns
We tried to outline the major concerns regarding
the PRP and to put it in the informed consent that needs
to be read and signed by the patient.
e procedure – needs to be explained in detail;
many patients get scared about the amount of blood that
needs to be prelevated (20-60 cc); there’s a waiting time
that depends on the product; there’s pain and bruising
associated with the injection – the Achilles tendon
injection is more painful.
e product – we state the name of the product
and the type: P-PRP, L-PRP, L-PRF
e pathology – regarding the pathology that is
intended to be treated, we present clinical evidence that
supports the use of PRP.
Doctors opinion – it is important to state that
overall, the doctor feels that using PRP is giving a better
chance to the patient to heal; if the patient is asking for
PRP it is important to state if the doctor feels that PRP is
not the best solution.
Risks - Pain or itching at the injection site;
Bleeding, bruising or swelling; Short lasting pinkness/
redness of the skin
Contraindications – the patient is interrogated
and asked to declare that he’s compliant regarding the
contraindications
Costs – the PRP cost is industry driven and is not
covered by the insurance, so the patient should be aware
of the price of the therapy
We split the consent form in two part – one to be
lled by the patient, one to be lled by the doctor. Each
part of the consent needs to marked by the patient and by
the doctor in order to be sure the all the information is
read by the patient and provided by the doctor.
CONCLUSION
It is important to realize that patient’s expectations
are dierent - as their level of activity, the PRP product, the
pathology and the metabolic conditions. Well-designed
studies will be vital in determining what conditions PRP
is best suited to treat, and what type of product is best
suited for each condition. Until then, being honest with
the patient regarding the medical information and the
expectations is a condition in order to be ethical and to
respect the patient’s rights.
Our informed consent was developed taking
into consideration all the aspects of the PRP therapy, for
giving to the patient a clear view. We hope this will meet
the patient’s expectation and will improve the feedback.
Conict of interest. e authors declare that
there is no conict of interest.
Contribution Note. All authors contributed
equally to the manuscript.
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