Rom J Leg Med 25 405-408 2017 [613846]

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 SCIENCESLegal 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. 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. 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.ro2) University of Medicine and Pharmacy, Craiova, Romania3) “Carol Davila” University of Bucharest, Emergency Teaching Hospital Elias, Bucharest, Romania4) “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 fibrin 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 efficacy, 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
efficiency 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]. Therefore, because all PRP products are not the same, the success or failure of a specific PRP or PRP-related product for a specific pathologic indication cannot be
universally applied to all PRP products.
What is PRP?
PRP is obtained by centrifugation of autologous
blood of the patients. The result of this centrifugation
is a large concentration of platelets in a small volume
of plasma. There are many methods for obtaining
PRP , each one with specific properties as to capacity of concentration of the platelets and release process of certain growth factors. In order for PRP to have greater efficacy, 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).

406
Codorean I.B. et al. Legal and ethical aspects of Platelet-Rich Plasma The PRP terminology
PRP has been described in the literature under
different names and abbreviations. Some authors define
PRP as only platelets, whereas others note that PRP
also contains increased concentrations of leukocytes, fibrin, and some bioactive proteins. Based on these descriptions, PRP was classified into pure plateletrich plasma (P-PRP), leukocyte- and platelet-rich plasma (L-PRP), and leukocyte- and platelet-rich fibrin (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 fibrin (PRF) [11]. In view of the
general confusion over PRP terminology, it should be
emphasized that different preparations of PRP may have the same name despite having different properties, while similar preparations of PRP might have different names despite having the same properties.
We find 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
There 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. They evaluated the tendons histologically and concluded that the number
of circulation-derived cells that infiltrated the wounded
area was significantly increased in the PRP group on day 3 and day 7. This, they argued, confirmed 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]. The PRP treated group was found to have a denser appearance and fewer elastic fibers remaining with better tenocyte orientation
at 3 weeks [15]. The same investigators evaluated the
angiogenic effect of PRP in a rabbit patellar tendon model. They found an initial increase in the vascularity in the PRP treated tendons followed by a decrease by 4 weeks. The PRP treated tendons also had improved
tenocyte orientation compared with the more immature
tissue seen in the control group [16]. These are studies that are proving the efficacity
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/soft 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 V AS and Disability of the Arm, Shoulder, and Hand
(DASH) scores compared with the PRP group, though these results were not statistically significant. However, at 6 months, 1 year, and 2 years the PRP group had a significantly greater reduction in both V AS and DASH
scores compared to the steroid group [17, 18]. This led
the investigators to conclude that PRP is a superior form of treatment for refractory lateral epicondylosis. The limitation of this study is the lack of true control group, as the limited efficacy of steroid injections and possible detrimental long-term effects 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)407of PRP injection in conjunction with eccentric exercises
for the treatment of Achilles tendinopathy. They were unable to find a significant difference 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 after failure of other non-operative
measures [21]. Patients experienced a significant 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. After 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 findings 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 significant improvement in V AS, Short Form -36 (SF-36) and Tegner scores with
80% of patients satisfied 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 V AS and Tegner scores at 6 months with 86.7% satisfaction in the PRP group compared to 68.8% in the control. However, no statistical differences 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.
The 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.
The product – we state the name of the product
and the type: P-PRP , L-PRP , L-PRF The 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
filled by the patient, one to be filled 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 different – 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.
Conflict of interest. The authors declare that
there is no conflict of interest.
Contribution Note. All authors contributed
equally to the manuscript.
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