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In recent years, platelet rich plasma (PRP) has been receiving increasing attention for the treatment of soft tissue injuries. These numerous applications have raised a great deal of questions and debate about the effectiveness of this method. This study aimed to determine the efficacy of PRP in improving sports injuries and subsequently throw some light on these controversies.
A systematic review of the literature and meta-analysis of results were undertaken. All related databases, such as PubMed, Cochrane Database of Systematic Reviews, DARE, and EMBASE, were searched on the use of PRP on athletes and in sports medicine. The search was conducted from June 2013 to February 2014.
Our search retrieved 905 studies, of which 13 randomized control trials (RCT) met our inclusion criteria for systematic review and meta-analysis. All articles were appraised by Critical Appraisal Skills Program (CASP) checklist for RCT studies. The analysis of the results of pain scores and physical activity/functions did not show any superiority for PRP as opposed to the other options.
The meta-analysis showed no more effectiveness for PRP application in sports-related injuries in terms of physical function improvement and pain relief. Therefore, the extensive use of PRP for such injuries should be limited. Well-designed RCTs are needed to support the findings.
Platelets are discoid structures blood cells that have no nuclei and are involved in a variety of critical functions in the body. The main function of platelets is hemostasis (coagulation), as well as inflammation, antimicrobial host defense, angiogenesis, and wound healing (1). In healthy individuals normal platelet counts can range from approximately 150,000 to 350,000/μL, whereas platelet rich plasma (PRP) is often defined as at least 1,000,000 platelets/μL suspended in plasma (2). The logical thought behind PRP is that platelets are the first materials to arrive at the site of injured tissues and thus have the potential to release growth factors that have a critical role in the healing process (3). Sports-related injuries are the main cause of time lost in athletes and teams, and they have a significant effect on society in terms of health care resources, personal disability, and restricted activity. In 2002, an estimated $15.8 billion in total health care expenditures were used in the medical management of these injuries (4). Tendinopathy and muscle strain injuries are common sporting injuries for which there are limited treatment options. Until recently, rest, eccentric exercises, biophysical procedures, drugs, such as corticosteroids, and operative treatment have been the mainstays of therapy (5). Despite the lack of authentic evidence through randomized clinical trials (RCT), the use of PRP in people has increased significantly. In recent years, the use of PRP has increased extensively in various fields, including mandibular bone grafts, sinus lifts, cosmetic surgeries, bone regeneration, and wound healing. However, rigorous evidence is lacking on the effectiveness of this method. Accordingly, the aim of this systematic review was to evaluate the efficacy and safety of the use of PRP to treat sports-related injuries.
A systematic review of English-language articles was performed by searching randomized control trials in a wide range of electronic databases, including PubMed/Medline, EMBASE Wiley Online Library, Elsevier, Cochrane Database of Systematic Reviews, HTA Databases (TRIP, INAHTA), Database of Abstracts of Reviews of Effects (DARE), and NHS Economic Evaluation Database (NHS EED). For a comprehensive search, reference mining and contact with authors also were considered to cover ongoing or missed studies. The search was conducted between June 2013 and February 2014 utilizing the search terms and strategy provided below:
(((((((((((((((sport[tiab] OR (sport[tiab] AND medicine[tiab])) OR (sport[tiab] AND injury[tiab])) OR (sport[tiab] AND injuries[tiab])) OR (Sport[tiab] AND medecine[tiab])) OR Athlete[tiab]) OR Athletic[tiab]) OR tendon[tiab] OR tendinopathy[tiab]) OR (rotator[tiab] AND cuff[tiab])) OR (tennis[tiab] AND elbow[tiab])) OR achilles[tiab]) OR tendinitis[tiab]) OR Knee[tiab]) OR sholder[tiab]) OR shoulder[tiab]) OR ligament[tiab]) AND ((PRP [tiab] OR (platelet[tiab] AND rich[tiab])) OR (platelet[tiab] AND rich[tiab] AND plasma[tiab])).
In this study, articles with evidence levels of I and II were included (Randomized Controlled Trials and well-designed experimental trials).
Because professional athletes are older than 18, we included patients of both genders who were older than 18 and had been treated with PRP for sports-related injuries or orthopedic problems.
Every form of Platelet rich Plasma component (e.g., injection and gel) was included, and there was not any limitation in preparing the process of PRP.
Because of the lack of relevant, matching studies, there was no limitation in comparators.
The main outcomes were as follows: 1) Primary outcomes: Pain, activity of daily life, functions, and returning to the sports activity, 2) Secondary outcomes: Satisfaction and Quality of life: because most studies reported mean and SD of each group (cases/controls), quantitative analyses were done on pooling and calculating total mean differences of each group.
One investigator (MGH) screened the titles and abstracts of the identified articles. Those that partly met the inclusion criteria were retrieved and assessed for relevance by other members of the research team (EJ and HR). Disagreements were resolved through discussion. The CASP Checklist for RCTs was used to extract the data and to assess the quality of the studies. Each article had a quality appraisal that was performed by two reviewers (MG and EJ). All discrepancies in the quality assessment were resolved through consensus.
Data from eligible studies were pooled and analyzed using a fixed-effects model. Meta-analysis was conducted on the studies with the following criteria for outcomes: 1) Used same scales for same outcomes, 2) Outcomes with same follow-up times, and 3) Studies that reported mean and SD scores before and after intervention in both groups. STATA 11 software was used to conduct the statistical analysis of the data.
Publication bias was examined by the Begg Test and Egger regression. There was no considerable publication bias (Figure 2).
There were many outcomes and scales for assessment of orthopedic issues. Our main outcomes were:
Quality of life: This was assessed in three studies (9, 13, 23), and the results indicated that PRP was not superior to the other comparators. To assess the patients’ satisfaction, the researchers various tools, such as SF-12 and EQ-5D. Satisfaction: There was no consistency in the assessment methods of satisfaction, and there was no significant difference in this secondary outcome measure (8, 19).
PRP was used in many tendons, such as Achilles, knee, elbow, patellar, and talus, but there was no similarity in the clinical improvements. In three RCTs, within which PRP was used on the Achilles tendon (18, 19, 23), the overall result was unsatisfactory. Filardo et al. (20), Valentí Nin et al. (22), and Aggarwal (10) evaluated the effect of PRP on the knee. However, the results were just in favor of PRP in Aggarwal et al.’s study. From five studies of the elbow (6, 7, 12, 16, 17), only two studies (Gosens and Thanasas et al.) confirmed PRP. Moreover, five studies of the Patellar Tendon and Talus (8, 12, 13, 21, 24) showed some benefit for PRP, with the exception of Omar et al. (12). Castricini et al. (15), Randelli et al. (11), and Kesikburun et al. (14) studied the effects of PRP on Rotator Cuff with Randelli’s study in favor of PRP.
Our systematic review and meta-analysis results showed inconclusive evidence concerning the clinical benefit of using PRP for orthopedics and sports-related injuries. Of 18 RCTs, 11 did not show any clinical benefit for PRP, and the rest was not strong enough in terms of population and effect size to support the efficacy of PRP in pain reduction (p=0.663) or function improvement (p=0.820). Although this systematic review and meta-analysis showed that PRP was as effective as other comparators in pain reduction, its results were inconsistent with Malavolta et al. (25) and Hamid et al. (26), but, still, there are studies that have shown more benefit in pain relief, such as Gosens et al. (6) and de Almeida et al. (21). Despite these well designed RCT’s, a large number of the studies that claimed more benefits on pain reduction of PRP generally were not RCT (27, 28). In some studies, PRP was used along with an orthopedic operation, within them anatomical improvements were also expected besides other outcomes (e.g., pain relief). For example, Castricini et al. (15) and Valentí Nin et al. (22) reported no effect from PRP on Arthroscopic Rotator Cuff Repair and Anterior Cruciate Ligament Allograft Healing. Nonetheless, de Almeida et al. (21), Aggarwal et al. (10) and Randelli et al. (11), who used PRP during surgery, reported some benefits, such as repair, less pain, and less bleeding after surgery. As mentioned earlier, PRP had no effect on the time to return to sports. The main problem in assessment of this outcome was finding similar and measurable scales to compare the studies. Overall, the results on PRP effectiveness in muscle and skeleton problems were largely inconsistent. Improvement or otherwise by PRP can be discussed from various perspectives:
Regarding the study limitations, there were different protocols to prepare and use the PRP (single or double-spinning approach); various forms of PRP (gel, injection or scaffold), final volume of PRP (2–8 ml), kits used, time and number of centrifuge, PRP with/without coagulant and activators, Platelet count, PRP multiple application (2–4). Some studies did not have any description about PRP preparation system. According to these limitations, judgment on the effectiveness of PRP across the published studies might be made prudently.
Although this study could not argue in favor of PRP application for physical activity improvement and pain reduction, there are some studies that showed some sort of benefits for PRP. These results show that, until strong evidence can be produced, there should be some limitations on the current applications of PRP. Further well-designed RCTs are needed with large populations to investigate the real effects of PRP on sports-related injuries. It is necessary to define a standard protocol for PRP preparation and application.
This study was extracted from the first author’s postgraduate thesis, and it was funded by the National Institute of Health Research (No. 241/91372).
iThenticate screening: January 30, 2016, English editing: April 16, 2016, Quality control: May 05, 2016
Conflict of Interest: There is no conflict of interest to be declared.
Authors’ contributions: All authors contributed to this project and article equally. All authors read and approved the final manuscript.