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PRP Update: From basic science to clinical application
This document discusses platelet rich plasma (PRP), its history and uses, mechanisms of action, and clinical evidence. Some key points: - PRP is concentrated platelets derived from centrifuging blood that delivers increased growth factors to enhance healing. - It has been used since the 1970s and over 86,000 injections in 2013, though regulation and insurance coverage varies. - Clinical applications include orthopedic injuries like tendinopathy and arthritis, as well as plastic surgery and hair restoration. - Platelets contain growth factors that increase tissue healing through proliferation and vascularization. Composition and leukocyte concentration impact effects. - Evidence for PRP in lateral epicondylitis and patellar tendin
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PRP Update: From basic science to clinical application
- 1. PRP Update From basicscience to clinical application John J. Klimkiewicz, MD Washington Orthopedics and Sports Medicine Head Team Physician Washington Capitals Hockey Club & Georgetown University Hoyas
- 2. PRP: Platelet RichPlasma • Definition: sample of blood platelet concentration above baseline produced by centrifugal separation of whole blood • Provides increased concentration of autologous growth factors and secretory proteins that may enhance the healing process on a cellular level
- 3. PRP History • Utilizedand studied since 1970’s • Over 86,000 injections performed in orthopedics in 2013 • Market PRP : $45 million in 2009, expected to be $125 million in 2016 • Clinical applications: • Oral surgery • Plastic surgery • Vascular Surgery • Hair transplantation • Orthopedic Applications • Muscle/Tendon injury • Acute vs chronic • Ligamentous injury • Cartilage injury • Osteoarthritis
- 4. Composition of PRP •PRP obtained by commercially available systems that separate blood components by centrifugation • Plasma-fluid portion of blood containing clotting factor, proteins, ions • Platelet: Normal concentration in blood 150,000/ul – 300,000 /ul • PRP: platelet concentration of at least 1,000,000 ul • Leukocytes : WBC’s • Erythrocytes: RBC’s
- 5. Regulation • World Anti-dopingagency temporarily banned PRP injections in 2009-2011. • Currently not a banned substance, individual growth factors however still banned • No Regulation by NCAA, NHL, NBA,NFL • FDA approved for use with Bone graft substitutes, office use is “off label” • Currently not covered under insurance for orthopedic application
- 6. Platelets importance: MultipleApplications • a – granules in platelets contain various growth factors and cytokines with concentrations equal to platelets • Increase anabolic cytokine activity • Transforming growth factor: TGF-B • Platelet Derived Growth factor: PDGF • Insulin like growth factor : IGF-1, IGFII • Fibroblast growth factor: FGF • Vascular epithelial growth factor: VEGF • Endothelial growth factor
- 7. Leukocytes • Different preparationshave different concentrations of Leukocytes that dictate function • Defined as either Leukocyte rich or Leukocyte poor as compared to whole blood • Increased concentration of leukocytes correlates with platelet concentration • Leukocyte rich preparations have increased amounts of IL-1 and TNF –a (inflammatory cytokines-catabolic) • Have increased amounts of VEGF (anabolic)
- 8. Multiple system preparations •Multiple commercial systems available. Over 80 on market. • Each system differs in time centrifuged as well as number of cycles • Differ in platelet, wbc , and growth factor concentration • Oh , AJSM, 2013 • Be careful in comparing studies • All PRP not similar • Different preps may be better for different conditions
- 9. Optimal PRP performance •Platelet number: “more not necessarily better” • 1.5 million/ul may be optimal • Above this may have catabolic effect • Timing: During or after inflammatory phase of healing may be optimal
- 10. PRP Effects onTendon Tissue • Increase in PDGF an TGF –B to area essential to healing • Increase in VEGF: increases vascularity at injured site • Both act to enhance tenocyte proliferation at injured site • Results in Vitro: • Earlier healing • Superior quality to healed tendon • Better organization of fibroblasts and collagen
- 11. PRP Effects onMuscle • IGF-1 and FGF -2 have should beneficial effects in muscle healing • In murine model IGF-1 ,b FGF cytokines improved healing and significant fast twitch and tetanus strength • TGF-B can cause detrimental increase in fibrosis and lead to recurrent injury • Anecdotal reports report decrease in time to return to play
- 12. PRP Effects oncartilage • Increases synthetic capacity of chondrocytes • Increases gene expression through upregulation • Increases proteoglycan production • Increases deposition of type II collagen • Inhibits catabolic effect of IL-B, TNF-a on chondrocytes
- 13. Systemic Effects ofPRP • Serum IGF, VEGF, an BFGF levels are significantly elevated after PRP injection • Activates biologic pathways that increase growth factor levels • VEGF levels are elevated up to 4 days after injection and can serve as a testing marker • Wasteriain et al. AJSM, 2013
- 14. PRP and LateralEpicondylitis Study # Participants Control Effectiveness Follow-up Krogh AJSM-2013 JBJS 2014 60 Control, GLU EQUAL 3 months Mishra AJSM-2014 230 control 3 months equal PRP-R superior at 6 months 3 and 6 months 84% vs 63% for control Gosens AJSM-2011 100 GLU PRP: Better DASH and VAS scores 2 year Joost AJMS 100 GLU PRP: Better DAS scores 1 year
- 15. PRP and Lateralepicondylitis: Meta-Analysis Krogh , AJSM, 2013 • 17 trials, 1381 participants • 8 different treatments: PRP, GLU, Bo Tox, autologous blood, HA, prolotherapy, GAG • 3/17 trails unbiased • Conclusion: Paucity of evidence from unbiased trials to support treatment recommendation • Trend towards PRP being effective, not statistically signif., not cost effective
- 16. PRP and Rotatorcuff repair study Number participants Control Follow up Results Flury AJSM 2016 120 Prp vs ropivicaine 24 months Equal Malavolta AJSM 2014 54 control 24 months Equal Weber AJSM 2013 60 control 12 months Equal Wang AJSM2015 60 control 4 months No difference in function or MRI
- 17. PRP and Patellartendonitis Study Number of participants control Follow up Results Dragoo AJSM 2014 23 Dry needling Vs PRP-leuko rich 12 and 26 weeks VISAS: better at 12 weeks, equal at 26 weeks Charousset AJSM 2012 28 None—3 injections one week apart 3 months 3 months: 21/28 back to sport Almeida AJSM 27 Placebo: at harvest site after acl 6 month Improved post-op pain and better healing mri at 6 months
- 18. MRI: Patella Tendonitisand PRP Pre-PRP injection 6 months s/p PRP injection
- 19. PRP and MuscularInjuries: Clinical Trial • 28 pts with acute hamstring injuries • Randomized into PRP + rehab, vs rehab alone • Lower pain level in PRP group • Hamid et al, AJSM, 2014 0 5 10 15 20 25 30 35 40 45 PRP + rehab Rehab DAYStoreturn Treatment
- 20. PRP and AchillesTendonitis study Number participants control Follow up Result Krogh AJSM 2016 24 Prp vs saline 3 months No change in sx Positive in tendon thickness DeJonge AJSM 2011 70 PRP vs saline and exercises 1 year EQUAL DeVOS JAMA, 2010 24 PRP vs saline 1 year EQUAL
- 21. PRP and arthritis •Effects seem to increase endogenous HA production, and decrease cartilage catabolism • IL-1 B and MMP activity decreased with PRP • Leukocyte poor PRP more effective than Leukocyte rich preparations
- 22. Treatment using PRP:Consensus Agreement • No anti-inflammatories 1-2 weeks before and after injection, “Washout period” • No local anesthetic to injection site—Alters pH which may alter function • Ultrasound use preferred for tendons and Muscular injections
- 23. PRP Treatment :Requires more study • Optimal conditions • Optimal concentration of Platelets and fractionated WBC’s • Number and sequence of injections • Post injection rehab routines • Evidence still lacking to prove definite benefit • Appears safe when used judiciously • Cost –Benefit analysis lacking
- 24. Efficacy of autologousPlatelet Rich Plasma use for Orthopaedic Indications: A Meta-analysis • 33 studies that were randomized controlled or prospective cohort studies that compared prp with control for orthopaedic injury • Conclusion: The current literature is complicated by a lack of standardization of study protocols, platelet separation techniques, and outcome measures. As a result, there is an uncertainty to support the increasing use of prp as a treatment modality for orthopedic injuries Sheth et al., 2012
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