Platelet-rich plasma (PRP) is a concentrate of platelet-rich plasma protein derived from whole blood, centrifuged to removed red blood cells. It has a greater concentration of growth factors than whole blood, and has been used to encourage a brisk healing response across several specialties, in particular dentistry, orthopedics and dermatology.
As a concentrated source of blood plasma and autologous conditioned plasma, PRP contains several different growth factors and other cytokines that can stimulate healing of soft tissue and joints. Main indication in sports medicine and orthopedics are acute muscle strains, tendinopathy and muscle-fascial injuries and osteoarthritis. Main indications in dermatology for PRP are androgenic alopecia, wound healing, and skin rejuvenation. For preparation of PRP, various protocols are used, with an underlying principle of concentrating platelets to 3-5 times physiological levels, then injecting this concentrate in the tissue where healing is desired.
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Medical use
In humans, PRP has been investigated and used as a clinical tool for several types of medical treatments, including chronic tendinitis, osteoarthritis, for bone repair and regeneration, in oral surgery, and in plastic surgery, for example using a platelet-rich fibrin matrix method.
Clinical validity
A 2015 meta-analysis reviewed 551 studies on PRP for osteoarthritic (OA) knee and found that only nine were worth considering and concluded that with respect to short term outcomes, PRP was not more efficacious than placebo in total WOMAC score but was more efficacious than hyaluronic acid (HA) on that measure; it was no different than placebo or HA with regard to adverse events.
As of 2016 results of basic science and preclinical trials have not yet been confirmed in large-scale randomized controlled trials. A 2009 systematic review of the scientific literature found there were few randomized controlled trials that adequately evaluated the safety and efficacy of PRP treatments and concluded that PRP was "a promising, but not proven, treatment option for joint, tendon, ligament, and muscle injuries".
In 2009 a pilot study investigating the effects of PRP on 20 male athletes with a mean injury history of 20.7 months of pain due to chronic patellar tendinosis, also known as jumpers knee, found statistically significant improvements in physical function and pain levels. 6 month follow up's after treatment showed participants returned to 90% of pre-injury sports activity levels, and 80% of participants were able to return to sports within 4 months of treatment.
A 2010 Cochrane analysis on PRP use in sinus lifts during dental implant placement found no evidence that PRP offered any benefit.
As of 2011, PRP use for nerve injury and sports medicine has produced "promising" but "inconsistent" results in early trials.
2011 study by Gosens et al. found PRP to be superior to cortisone for the treatment of lateral epicondylitis or tennis elbow at the 2 year mark.
Cerza 2012 Am Journal Sports Med, level 1, randomized control trial concluded that PRP was significantly better for OA knee than hyaluronic acid.
A 2013 review stated more evidence was needed to determine PRP's effectiveness for hair regrowth.
A 2014 Cochrane analysis for PRT use to treat musculoskeletal injuries found very weak (very low quality) evidence for a decrease in pain in the short term, up to three months and no difference in function in the short, medium or long term. There was weak evidence that suggested that harm occurred at comparable, low rates in treated and untreated people.
In 2014 the American Journal of Sports Medicine published a paper which concluded that "application of 3 consecutive PRP injections significantly improved symptoms and function in athletes with chronic patellar tendinopathy and allowed fast recovery and return to sport. There was return to normal architecture of the tendon as assessed by MRI.
A 2016 systematic review and meta-analysis of randomized controlled clinical trials for PRP use to augment bone graft found only one study reporting a significant difference in bone augmentation, while four studies found no significant difference.
An FDA sanctioned, randomized, double blind placebo controlled clinical trial published in the American Journal of Sports Medicine in 2016 concluded that PRP was safe and effective treatment for knee OA, with 78% improvement in WOMAC scores compared to 7% for placebo, after 1 year. Filardo et al. had concluded the same in 2011.
Since 2004, proponents of PRP therapy have argued that negative clinical results are associated with poor-quality PRP produced by inadequate single spin devices. The fact that most gathering devices capture a percentage of a given thrombocyte count could bias results, because of inter-individual variability in the platelet concentration of human plasma and more would not necessarily be better. The variability in platelet concentrating techniques may alter platelet degranulation characteristics that could affect clinical outcomes.
In the field of aesthetics and plastic surgery, the clinical application is particularly wide and is under the name of Regenerative Plastic Surgery. PRP associated with adipose tissue, is given for breast reconstruction, facial soft tissues defects, lower extremity ulcers and scars. Promising results were obtained in the treatment of androgenetic alopecia, as emerged from scientific studies published since 2013. Among these, the most significant by impact factor is the randomized scientific-clinical study of the clinical-instrumental evaluation of the effect of PRP in androgenetic alopecia published in 2015 by Pietro Gentile et al and a multidisciplinary team at the University of Rome Tor Vergata The Effect of Platelet Rich Plasma in Hair Regrowth: A Randomized Placebo-Controlled Trial.
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Adverse effects
There are no studies to date that have reliably documented adverse effects associated with PRP treatment, possibly due to poor and inconsistent methodology.
Composition
There are four general categories of preparation of PRP based on its leukocyte and fibrin content: leukocyte-rich PRP (L-PRP), leukocyte reduced PRP (P-PRP; leukocyte reduced or pure PRP), leukocyte platelet-rich fibrin and pure platelet-rich fibrin.
The efficacy of certain growth factors in healing various injuries and the concentrations of these growth factors found within PRP are the theoretical basis for the use of PRP in tissue repair. The platelets collected in PRP are activated by the addition of thrombin and calcium chloride, which induces the release of the mentioned factors from alpha granules. The growth factors and other cytokines present in PRP include:
- platelet-derived growth factor
- transforming growth factor beta
- fibroblast growth factor
- insulin-like growth factor 1
- insulin-like growth factor 2
- vascular endothelial growth factor
- epidermal growth factor
- Interleukin 8
- keratinocyte growth factor
- connective tissue growth factor
Manufacturing
As of 2009 there have been two PRP preparation methods approved by the U.S. Food and Drug Administration. Both processes involve the collection of the patient's whole blood (that is anticoagulated with citrate dextrose) before undergoing two stages of centrifugation (TruPRP) (Harvest) (Pure PRP) designed to separate the PRP aliquot from platelet-poor plasma and red blood cells. In humans, the typical baseline blood platelet count is approximately 200,000 per µL; therapeutic PRP concentrates the platelets by roughly five-fold. There is broad variability in the production of PRP by various concentrating equipment and techniques.
History
PRP was first developed in the 1970s and first used in Italy in 1987 in an open heart surgery procedure. PRP therapy began gaining popularity in the mid 1990s. It has since been applied to many different medical fields such as cosmetic surgery, dentistry, sports medicine and pain management.
The number of peer reviewed publications studying the PRP's efficacy has increased dramatically since 2007.
Society and culture
The cost of a PRP treatment in the U.S. has been quoted as $1000 out-of-pocket expenses, as it is usually not covered by health insurance.
PRP has received attention in the popular media as a result of its use in treating sports injuries in professional athletes.
Risk of use in doping
Some concern exists as to whether PRP treatments violate anti-doping rules. As of 2010 it was not clear if local injections of PRP could have a systemic impact on circulating cytokine levels, affecting doping tests and whether PRP treatments have systemic anabolic effects or affect performance. In January 2011, the World Anti-Doping Agency removed intramuscular injections of PRP from its prohibitions after determining that there is a "lack of any current evidence concerning the use of these methods for purposes of performance enhancement".
According to the Baltimore Sun, Zach Britton had PRP injections in his left shoulder in March 2012, Orioles first baseman Chris Davis underwent two PRP injections to speed the healing and recovery of an oblique injury in April 2014, and Dylan Bundy had the procedure in April before undergoing Tommy John surgery in June 2014.
Veterinary use
Platelet-rich plasma is used in horses for treatment of equine lameness due to tendon and ligament injury, wounds, fractures, bone cysts, and osteoarthritis.
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