1/14/2010 Outline Platelet-rich Plasma: Current PlateletConcepts and Clinical Applications • • • • Richard J. Mason, MD PRP definition – what is it? Preparation of PRP Mechanism of action Nonsurgical and Surgical applications – Clinical Studies • Future Directions • Anti Anti--Doping regulations/conflicts • Summary PRP – What is it? Platelet Rich Plasma • A sample of autologous blood with • • • • Public Awareness concentrations of platelets above baseline values Pl l Platelets play l a key k role l in i healing h li response via secretion of growth factors and recruiting reparative cells Oral & plastic surgery use since early 90’s Recent use in treating Sports injuries • PRP Preparation Platelet Biology • Platelets are formed in bone marrow from • • precursor cells called megakaryocytes Platelets have no nucleus, cannot replicate, 5 to 9 day life span Platelets are activated when exposed to damaged blood vessels – They aggregate at the site and form a clot – At this time they release more than 30 bioactive proteins many of which have a fundamental role in hemostasis and/or tissue healing increased after use in Hines Ward and Troy Polamalu to treat MCL injuries prior to 2009 Superbowl NY Times article detailed its use and quicker healing/return to sports when injected after injury • Patients blood is taken • • • and centrifuged to separate red blood cells from white cells and platelets Different iff systems give i different platelet concentrations Ideal concentration yet to be defined Multiple companies have PRP preparation systems 1 1/14/2010 PRP - Preparation PRP - Preparation PRP - Preparation • Final PRP preparation yields 3 to 5 cc • Site can be pre • PRP – General Information • Since it is autologous, no rejection but • may have inflammatory reaction Contraindications: – Thrombocytopenia, anticoagulant rx, infection, cancer, pregnancy • Cost is $150 per syringe plus injection fee • Considered experimental and not currently i j t d with injected ith local l l anesthesia Use a multipass “peppering” technique to encourage healing PRP – General Information • Orthopedic uses of PRP fall into 4 categories – Chronic tendinopathies p – Acute ligamentous injuries – Muscle injuries – Intraoperative augmentation reimbursed by insurance 2 1/14/2010 PRP Mechanism of Action • PRP may accelerate initial inflammatory • phase of tendon repair making cells more receptive to earlier mechanical loading I skeletal In k l l muscle l PRP regulates l inflammatory phase and improves healing after injury – This increase healing is thought to be due to the direct effects of the growth factors in PRP on skeletal muscle (Table 1) PRP – Historical Studies • 1994 study in the maxillofacial surgical • literature showed earlier cancellous bone graft consolidation (4wks vs. 8wks) when platelet rich fibrin glue was added to bone graft This effect was thought to be secondary to enhanced osteoconduction stimulated by PDGF and TGF TGF--B PRP – Historical Studies • The Studies in the maxillofacial and plastic • surgery literature are largely case studies or case series The PRP concentration and method of delivery in these studies are case specific and cannot be expanded to other procedures without further study PRP – Non Surgical Applications • Used in epicondylitis, Patellar tendonitis, Plantar • • fasciitis, Muscle injuries, Acute ligamentous injuries and Osteoarthritis. The best studies have been done on lateral epicondylitis, but, no double blind, randomized studies to date Remainder of studies are retrospective – Show quicker recovery and good pain relief (Table 3) 3 1/14/2010 PRP – Acute Ligamentous Injuries PRP – Acute ligamentous injuries • Grade 2 MCL injuries in professional soccer players • Treatment group received PRP within 72 hours of injury • Control group treated with rest and rehab • Return to play time shortened by 27% compared to control group – Retrospective study, 22 participants, • Mandelbaum, Gerhardt unpublished data PRP – Acute Muscle Injuries • 8 pro soccer & 6 pro basketball players with • • direct muscle trauma/tears PRP injected with ultrasound guidance and aspiration of hematoma Greater than 50% reduction time in return to play noted when compared to standard treatment recovery times for similar injury patterns – Retrospective study, no control group • Sanchez,Cugat et al; ISOAKS, 2005 unpublished data Elbow Epicondylitis Study • 20 patients who had failed Physical • • therapy and conservative treatment and mean pain duration of 15 months All patients i were considering id i surgery 15 patients given PRP and 5 given bupivicaine injection (control group) Mishra et al. AM J SportsMed. 2006;34:17742006;34:1774-1778 PRP – Osteoarthritis Knee • 30 patients in each group matched for • • age, sex, BMI, radiographic severity OA 3 injection of PRP vs. 3 injections of HA over 3 week period PRP group significantly improved pain over HA group • Sanchez et al; Clin Exp Rheumatol. 2008;26(5):910--913 2008;26(5):910 Elbow Epicondylitis Study • At 8 wks post treatment 60% of prp and 16% control group improved • 3 of 5 control group withdrew from study at this point preventing further direct comparison • At 6 months 81% of prp group improved • At final follow up (mean 25 months) 93% of prp patients improved and did not need surgery Mishra et al. AM J SportsMed. 2006;34:17742006;34:1774-1778 4 1/14/2010 PRP – Surgical Applications • Has been used to augment and accelerate • healing in Achilles tendon and Rotator Cuff repairs Has also been used to accelerate ACL graft/tunnel incorporation with equivocal results PRP – Future Directions PRP – Future Directions • PRP represents a possible treatment • • option for stimulation and acceleration of soft--tissue healing and regeneration soft Cli i l trials Clinical i l are underway d to determine d i efficacy, standardized preparation and application techniques This will allow true comparison of results and outcomes PRP – Future Directions PRP – Future Directions • Reports of severe pain and acute • PRP may violate current AntiAnti-Doping • inflammatory response to PRP injections must be further investigated Post procedure rehab protocols must also be established to determine optimal muscle and tendon healing regulations • Concerns center around the IGFIGF-1 • component off PRP (IGF iis currently l prohibited) Concentrations of IGFIGF-1 in PRP are at a level subtherapeutic to produce systemic anabolic effects 5 1/14/2010 PRP – Future Directions PRP – Future Directions • United States AntiAnti-doping Agency issued • The World AntiAnti-Doping Agency in • an athletes advisory in April 2009 stating it considers PRP injection equivalent to an injection of growth factors and therefore is prohibited PRP can only be administered if the athlete has a Therapeutic Use Exemption determined by a “medical professional” Summary • • September 2009 prohibited PRP administration by an intramuscular route O h routes off PRP administration Other d i i i will ill be b required to meet international standards for Therapeutic Use Exemptions These rules will be enforced effective January 1, 2010 QUESTIONS? • PRP holds great promise in accelerating healing • • from injury and surgery involving ligaments as well as articular and meniscal cartilage. Due to its safety profile and ease of preparation the use of PRP in sports medicine will likely continue to grow Clinical use should proceed cautiously as there is little highhigh-level clinical evidence supporting its efficacy 6
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