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Conflicts of Interest

Conflicts of Interest. I have no conflicts of interest regarding this presentation. Ramon Ylanan MD CAQSM Team Physician University of Arkansas Advanced Orthopeadic Specialists. Platelet rich plasma: an update where are we now?. Goals. Background Healing Response The Basic Science Uses

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Conflicts of Interest

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  1. Conflicts of Interest • I have no conflicts of interest regarding this presentation

  2. Ramon Ylanan MD CAQSM Team Physician University of Arkansas Advanced Orthopeadic Specialists Platelet rich plasma: an update where are we now?

  3. Goals • Background • Healing Response • The Basic Science • Uses • Evidence Based • Summary

  4. Goals • Background • Healing Response • The Basic Science • Uses • Evidence Based • Summary

  5. Background • What is PRP (Platelet Rich Plasma)? • Biologic, “regenerative biomedicine” • Concentrated platelets • Ideally 3-8X • Processed from autologous, whole blood • Provides “Supra-physiologic” concentrations of growth factors • No universal definition of what constitutes PRP vs PPP • Ideal concentration is opinion based

  6. Background • How is it made? • Centrifuged whole blood • Coagulation inhibitors may be used • Previous issues with bovine inhibitors • Platelet activators may be used • Volume produced depends on which system used • Applied in either • Injectable form • Solid, matrix form

  7. Background

  8. Goals • Background • Healing Response • The Basic Science • Uses • Evidence Based • Summary

  9. Background: The Healing Response • Inflammatory phase • First week after injury • Hemostasis  recruitment of macrophages and fibroblasts • Proliferative phase • Within first 2 days to 2 weeks • Formation of extra-cellular scaffold • Maturation/remodeling phase • Up to first year • Type 1 collagen replacing scaffold

  10. Background: The Healing Response • Growth factors • IGF-1  early inflammatory phase • Enhances collagen and matrix synthesis • TGF-B  pro-inflammatory • Enhances matrix and collagen synthesis, angiogenesis • PDGF  facilitates proliferation of other growth factors • Attracts stem cells and contributes to remodeling

  11. Background: The Healing Response • Growth factors • VEGF  peaks after inflammatory phase • Promotes angiogenesis and neo-vascularization • b-FGF  angiogenesis, cell migration, creates collagenase, production of granulation tissue

  12. Background: The Healing Response • What does PRP bring to the healing table? • Alpha granules • The storage packets of growth factors • Each platelet contains 50-80 granules • The de-granulation releases the growth factors needed to augment healing

  13. Background: The Healing Response • Alpha granules • Theory that activators will increase de-granulation • Reason why some systems include external activators • Some studies show injured collagen fibers will stimulate de-granulation as well

  14. Goals • Background • Healing Response • The Basic Science • Uses • Limit to Muscle, Tendon, Ligament • Evidence Based • Summary

  15. The Basic Science • Horse tendons • Schnabel et al. • Culture in PRP vs other blood products • Higher anabolic gene expression in PRP • Human tenocytes • de Mos et al. • PRP vs. PPP • PRP increase in matrix degrading enzymes (faster recovery)

  16. The Basic Science • Rabbit skeletal muscle stem cells • Gates et al. • Increased expression of myogenic activity • Mesenchymal stem cells • Mishra et al. • Buffered in PRP, increased proliferation

  17. Goals • Background • Healing Response • The Basic Science • Uses • Limit to Muscle, Tendon, Ligament • Evidence Based • Summary

  18. Uses: Muscle • Hammond et al (2009) • Animal study (rats) • Tibialis anterior strain • large strain vs small strain • PRP shortened healing by 14-21 days in small strain group • Little change in large strain group

  19. Uses: Tendon • Lots of studies • Lateral epicondylitis • Patellar tendinopathy • Achilles tendinopathy • Rotator Cuff tendinopathy

  20. Uses: Lateral Epicondylitis

  21. Uses: Lateral Epicondylitis • Mishra and Pavelko (2006) • One of the most cited articles • Chronic, refractory lateral epicondylitis • 15 patients, failed conservative measures • Single PRP injection • control was bupivicaine

  22. Uses: Lateral Epicondylitis • Mishra and Pavelko (2006) • Measures VAS and Mayo elbow scores at 2, 6 and 25 months • Outcomes • 2 months  60% vs 16% improvement (P=.001) • Final f/u 93% reduction in pain, no complications • 60% of control group withdrew for other treatment

  23. Uses: Lateral Epicondylitis • Peerbooms et al (2010) • RCT, Level 1 data • Only true RCT to date • 100 patients (51 PRP:49 CSI) • 1 yr f/u • 73% success in PRP group • 49% in CSI group

  24. Uses: Patellar Tendinopathy

  25. Uses: Patellar Tendinopathy • Human Data is limited • Filardo et al (2010) • Non-RCT, N=31 • Serial PRP + PT (15) vs. PT alone (16) • 3 PRP, 2 weeks apart with eccentric strengthening • PRP group • Improved in all measures • Continued to improve at 6 months • Higher improvement in sports activity

  26. Uses: Patellar Tendinopathy • Kon et al (2009) • Prospective, pilot study (no control) • 3 PRP injections, 15 days apart • 6 month f/u • 70% stated complete or significant improvement • 80% satisfied with results

  27. Uses: Achilles Tendinopathy

  28. Uses: Achilles Tendinopathy • de Vos et al (2010) • Double blinded, placebo control, RCT • N=54, chronic Achilles tendinopathy • 2 months of symptoms • Excluded if had previous eccentric strengthening program • 27 PRP, 27 isotonic saline, US guidance used

  29. Uses: Achilles Tendinopathy • de Vos et al (2010) • Double blinded, placebo control, RCT • N=54, chronic Achilles tendinopathy • Both did 12 week supervised eccentric program • f/u at 6, 12, 24 weeks • Both groups improved, No difference found • Used bupivicaine for anesthetic • ? Inhibit effectiveness

  30. Uses: Rotator Cuff • Mostly as surgical repair adjuncts • Studies have been +/- • Only one major prospective, Level 1 randomized research • Weber et al (2010) • No major difference in structural integrity compared with control • Repair with PRP vs repair without PRP

  31. Uses: MCL • No human studies • Letson and Dahners (1994) • Rat MCL injury • Injected with PDGF  • 73% (+/- 55%) stronger than contralateral controls • Human results anecdotal • 2-3 weeks earlier than anticipated

  32. Goals • Background • Healing Response • The Basic Science • Uses • Limit to Muscle, Tendon, Ligament • Evidence Based • Summary

  33. What does the evidence say? • Increasing number of basic science and animal studies • Paucity of human trials • No standardization of treatment • Anecdotally improves recovery by 2 weeks • 1 vs. multiple injections • 1 seems to be effective, fenestration may help • The multiple injection “protocol” is without consistency

  34. What does the evidence say? • When is best time to administer in acute setting? • Chan et al  • Better results at day 7 than day 3 • At elite level, who waits 7 days?

  35. What does the evidence say? • Exercise • Early ROM can be helpful • Early light aerobic activity can be helpful • I begin eccentric strengthening program as early as tolerated • Goal is RTP by 3 weeks

  36. What does the evidence say? • NSAIDs • Most hold for minimum of 10 days prior • Not proven to inhibit, but possible • Don’t withhold ASA if cardio-protective • Ideal platelet concentration • 600K-1mil per ml (no evidence for that)

  37. What does the evidence say? • WBC in preparation • Inhibit or help? • Help  anti-infective property • Inhibit  inhibitory effects on inflammatory mediators

  38. What does the evidence say? • Local anesthetics and corticosteroids • Carofino et al (2012) • Co-administration decreased PRP effectiveness • External platelet activators • No consensus on if or when

  39. What does the evidence say? • MSK US guidance improves results • 0232T tracking CPT code • Includes imaging assisted guidance • I use it with every PRP

  40. Where are we with PRP?

  41. Summary • Limited human research • Tendon>Muscle>Ligament for now • Limit NSAID use around the injection • Don’t add local anesthetic • Still more to learn • Medicare tracking code now • IOC had banned it in 2010, removed in 2011

  42. References • Nguyen RT, Borg-Stein J, McInnis, K. Applications of Platelet-Rish Plasma in Musculoskeletal and Sports Medicine: An Evidence-Based Approach. PM R 2011;3:226-250 • Schnabel LV, Mohammed HO, Miller BJ, et al. Platelet rich plasma (PRP) enhances anabolic gene expression patterns in flexor digitorum superficialis tendons. J Orthop Res 2007;25:230-240. • de Mos M, van der Windt AE, Jahr H, et al. Can platelet-rich plasma enhance tendon repair? A cell culture study. Am J Sports Med 2008; 36:1171-1178. • Mishra A, Tummala P, King A, et al. Buffered platelet-rich plasma enhances mesenchymal stem cell proliferation and chondrogenic differentiation. Tissue Eng Part C Methods 2009;15:431-435. • Gates CB, Karthikeyan T, Fu F, Huard J. Regenerative medicine for the musculoskeletal system based on muscle-derived stem cells. J Am Acad Orthop Surg 2008;16:68-76. • Hammon JW, Hinton RY, et al. Use of autologous platelet-rich plasma to treat muscle strain injuries. Am J Sports Med 2009;37:1135-1142 • Mishra A, Pavelko T. Treatment of chronic elbow tendinosis with buffered platelet-rich plasma. Am J Sports Med 2006;34:1774-1778. • Peerbooms JC, Sluimer J, Bruijn DJ, Gosens T. Positive effect of an autologous platelet concentrate in lateral epicondylitis in a double- blind randomized controlled trial: Platelet-rich plasma versus cortico- steroid injection with a 1-year follow-up. Am J Sports Med 2010;38: 255-262. • Filardo G, Kon E, Della Villa S, Vincentelli F, Fornasari PM, Marcacci M. Use of platelet-rich plasma for the treatment of refractory jumper’s knee. Int Orthop 2010;34:909-915. • Kon E, Filardo G et al. Platelet-rich plasma: New clinical application: A Pilot study for treatment of jumper’s knee. Injury 2009;40:598-603 • de Vos RJ, Weir A, van Schie HT, et al. Platelet-rich plasma injection for chronic Achilles tendinopathy: A randomized controlled trial. JAMA 2010;303:144-149. • WeberSC,PariseC,KatzSD,WeberSJ.Platelet-richfibrin-membrane in arthroscopic rotator cuff repair: A prospective, randomized study. Proc Am Acad Orthop Surg 2010;11:345. • Weber SC, Katz SD, Parise C, Weber SJ. Platelet-rich fibrin matrix in the management of arthroscopic repair of the rotator cuff: A prospec- tive, randomized study (SS-07). Arthroscopy 2010;26:e4. • Carofino B, Chowaniec Dm, et al. Corticosteroids and local anesthetics decrease positive effects of platelet-rich plasma: an in vitro study on human tendon cells. Arthroscopy. 2012 May;28(5):711-9 • Engebreatsen L, Steffen K et al. IOC consensus paper on the use of platelet-rich plasma in sports medicine. BJSM 2010;44:1072-81

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