Platelet-rich plasma (PRP) is a concentrate of platelet-rich plasma protein derived from whole blood, centrifuged to remove 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.
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.
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[update] 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".
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.
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.
There are no studies to date that have reliably documented adverse effects associated with PRP treatment, possibly due to poor and inconsistent methodology.
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
As of 2009[update] 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.
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[where?] 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
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.
- Smith, Patrick A. (2016-04-01). "Intra-articular Autologous Conditioned Plasma Injections Provide Safe and Efficacious Treatment for Knee Osteoarthritis: An FDA-Sanctioned, Randomized, Double-blind, Placebo-controlled Clinical Trial". The American Journal of Sports Medicine. 44 (4): 884–891. doi:10.1177/0363546515624678. ISSN 1552-3365. PMID 26831629.
- "PRP Therapy | Hair Loss Treatment". OC Hair Restoration. Orange County, California. Retrieved 5 July 2016.
- Mishra A, Woodall J, Vieira A (2009). "Treatment of tendon and muscle using platelet-rich plasma". Clinics in Sports Medicine. 28 (1): 113–25. doi:10.1016/j.csm.2008.08.007. PMID 19064169.
- Andia I, Sanchez M, Maffulli N (2012). "joint pathology and platelet-rich plasma therapies". Expert Opinion in Biological Therapies. 12 (1): 7–22. doi:10.1517/14712598.2012.632765. PMID 22171664.
- Griffin XL, Smith CM, Costa ML (2009). "The clinical use of platelet-rich plasma in the promotion of bone healing: a systematic review". Injury. 40 (2): 158–62. doi:10.1016/j.injury.2008.06.025. PMID 19084836.
- Esposito M (Spring 2010). "Effectiveness of sinus lift procedures for dental implant rehabilitation: a Cochrane systematic review". Eur J Oral Implantol. 3 (1): 7–26. PMID 20467595.
- Por YC, Shi L, Samuel M, Song C, Yeow VK (2009). "Use of tissue sealants in face-lifts: a metaanalysis". Aesthetic Plastic Surgery. 33 (3): 336–9. doi:10.1007/s00266-008-9280-1. PMID 19089492.
- Kanchanatawan, W; Arirachakaran, A; Chaijenkij, K; Prasathaporn, N; Boonard, M; Piyapittayanun, P; Kongtharvonskul, J (May 2016). "Short-term outcomes of platelet-rich plasma injection for treatment of osteoarthritis of the knee". Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA. 24 (5): 1665–77. doi:10.1007/s00167-015-3784-4. PMID 26387122.
- Foster TE, Puskas BL, Mandelbaum BR, Gerhardt MB, Rodeo SA (2009). "Platelet-rich plasma: from basic science to clinical applications". Am J Sports Med. 37 (11): 2259–72. doi:10.1177/0363546509349921. PMID 19875361.
- American Journal of Sports Med 2012
- Valente Duarte de Sousa, Isabel Cristina; Tosti, Antonella (May 2013). "New investigational drugs for androgenetic alopecia". Expert Opinion on Investigational Drugs. 22 (5): 573–589. doi:10.1517/13543784.2013.784743. ISSN 1744-7658. PMID 23550739.
- Moraes VY (April 2014). "Platelet-rich therapies for musculoskeletal soft tissue injuries". Cochrane Database Syst Rev. 29 (4): CD010071. doi:10.1002/14651858.CD010071.pub3.
- Charousset, Christophe; Zaoui, Amine; Bellaiche, Laurence; Bouyer, Benjamin (2014-04-01). "Are Multiple Platelet-Rich Plasma Injections Useful for Treatment of Chronic Patellar Tendinopathy in Athletes?: A Prospective Study". The American Journal of Sports Medicine. 42 (4): 906–911. doi:10.1177/0363546513519964. ISSN 0363-5465.
- Pocaterra A, Caruso S, Bernardi S; et al. (2016). "Effectiveness of platelet-rich plasma as an adjunctive material to bone graft: a systematic review and meta-analysis of randomized controlled clinical trials". Int J Oral Maxillofac Surg. 45: 1027–1034. doi:10.1016/j.ijom.2016.02.012.
- Marx RE (2004). "Platelet-rich plasma: evidence to support its use" (PDF). Journal of Oral and Maxillofacial Surgery. 62 (4): 489–96. doi:10.1016/j.joms.2003.12.003. PMID 15085519.
- Yu W, Wang J, Yin J (2011). "Platelet-Rich Plasma: A Promising Product for Treatment of Peripheral Nerve Regeneration After Nerve Injury". Int J Neurosci. 121 (4): 176–180. doi:10.3109/00207454.2010.544432. PMID 21244302.
- Stefano Fiorentino, Luigi F. Rodella, Veronica Bonazza, Valerio Cervelli, Pietro Gentile (2014). Il tessuto adiposo. Monduzzi. ISBN 9788865210758.
- Pietro Gentile, Camilla Di Pasquali, Ilaria Bocchini, Micol Floris, Tati Eleonora, Valeria Fiaschetti, Roberto Floris, Valerio Cervelli (10 September 2012). "Breast Reconstruction With Autologous Fat Graft Mixed With Platelet-Rich Plasma" (PDF). Surgical Innovation - SAGE.
- Valerio Cervelli, Ludovico Palla, Michele Pascali, Barbara De Angelis, Beniamino C. Curcio, Pietro Gentile (July 2009). "Autologous Platelet-Rich Plasma Mixed with Purified Fat Graft in Aesthetic Plastic Surgery" (PDF). Springer Science+Business Media, LLC and International Society of Aesthetic Plastic Surgery.
- Pietro Gentile, Barbara De Angelis, Methap Pasin, Giulio Cervelli, Cristiano B. Curcio, Micol Floris, Camilla Di Pasquali, Ilaria Bocchini, Alberto Balzani, Fabio Nicoli, Chiara Insalaco, Eleonora Tati, Lucilla Lucarini, Ludovico Palla, Michele Pascali, Pamela De Logu, Chiara Di Segni, Davide J. Bottini, Valerio Cervelli (2014). "Adipose-Derived Stromal Vascular Fraction Cells and Platelet-Rich Plasma: Basic and Clinical Evaluation for Cell-Based Therapies in Patients With Scars on the Face" (PDF). The Journal of Craniofacial Surgery. 25, n°1.
- V. Cervelli, S. Garcovich, A. Bielli, G. Cervelli, B. C. Curcio, M. G. Scioli, A. Orlandi, P. Gentile (2014). "The Effect of Autologous Activated Platelet Rich Plasma (AA-PRP) Injection on Pattern Hair Loss: Clinical and Histomorphometric Evaluation" (PDF). BioMed Research International.
- Pietro Gentile, Simone Garcovich, Alessandra Bielli, Maria Giovanna Scioli, Augusto Orlandi, Valerio Cervelli (2015). "The Effect of Platelet-Rich Plasma in Hair Regrowth: A Randomized Placebo-Controlled Trial" (PDF). STEM CELLS TRANSLATIONAL MEDICINE.
- Frautschi, RS; Hashem, AM; Halasa, B; Cakmakoglu, C; Zins, JE (1 March 2017). "Current Evidence for Clinical Efficacy of Platelet Rich Plasma in Aesthetic Surgery: A Systematic Review". Aesthetic surgery journal. 37 (3): 353–362. PMID 28207031.
- Pavlovic, V; Ciric, M; Jovanovic, V; Stojanovic, P (2016). "Platelet Rich Plasma: a short overview of certain bioactive components". Open medicine (Warsaw, Poland). 11 (1): 242–247. PMID 28352802.
- Bielecki, T; Dohan Ehrenfest, DM; Everts, PA; Wiczkowski, A (June 2012). "The role of leukocytes from L-PRP/L-PRF in wound healing and immune defense: new perspectives". Current pharmaceutical biotechnology. 13 (7): 1153–62. PMID 21740376.
- Borrione P, Gianfrancesco AD, Pereira MT, Pigozzi F (2010). "Platelet-rich plasma in muscle healing". Am J Phys Med Rehabil. 89 (10): 854–61. doi:10.1097/PHM.0b013e3181f1c1c7. PMID 20855985.
- Arora NS, Ramanayake T, Ren YF, Romanos GE (2009). "Platelet-rich plasma: a literature review". Implant Dent. 18 (4): 303–10. doi:10.1097/ID.0b013e31819e8ec6. PMID 19667818.
- Dohan Ehrenfest DM, Rasmusson L, Albrektsson T (2009). "Classification of platelet concentrates: from pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRF)". Trends in Biotechnology. 27 (3): 158–67. doi:10.1016/j.tibtech.2008.11.009. PMID 19187989.
- Gonshor A (2002). "Technique for producing platelet-rich plasma and platelet concentrate: background and process". The International Journal of Periodontics & Restorative Dentistry. 22 (6): 547–57. PMID 12516826.
- Weibrich G, Kleis WK, Hafner G, Hitzler WE, Wagner W (2003). "Comparison of platelet, leukocyte, and growth factor levels in point-of-care platelet-enriched plasma, prepared using a modified Curasan kit, with preparations received from a local blood bank". Clinical Oral Implants Research. 14 (3): 357–62. doi:10.1034/j.1600-0501.2003.00810.x. PMID 12755786.
- platelet-rich plasma evidence Results by year graph, PubMed.gov, National Center for Biotechnology Information, U.S. National Library of Medicine, retrieved 23 March 2016
- Gina Kolata (2010-01-12). "Popular Blood Therapy May Not Work". New York Times.
- Alan Schwarz (2009-02-16). "A Promising Treatment for Athletes, in Blood". New York Times. New York.
- Gretchen Reynolds (2011-01-26). "Phys Ed: Does Platelet-Rich Plasma Therapy Really Work?". New York Times.
- Carina Storrs (2009-12-18). "Is Platelet-Rich Plasma an Effective Healing Therapy?". Scientific American.
- "World Anti-Doping Agency announces changes to Prohibited List". Irish Medical Times. 2011-01-10.
- Dan Connolly Orioles first baseman Chris Davis receives two PRP injections Baltimore Sun, April 29, 2014