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Conflicts of Interest
I have no conflicts of interest regarding this presentation
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PLATELET RICH PLASMA: AN UPDATE WHERE ARE WE NOW?
Ramon Ylanan MD CAQSM
Team Physician University of Arkansas
Advanced Orthopeadic Specialists
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Goals
BackgroundHealing Response
The Basic Science Uses Evidence Based Summary
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Goals
BackgroundHealing Response
The Basic Science Uses Evidence Based Summary
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Background
What is PRP (Platelet Rich Plasma)?Biologic, “regenerative biomedicine”Concentrated platelets
○ Ideally 3-8XProcessed from autologous, whole bloodProvides “Supra-physiologic” concentrations
of growth factors No universal definition of what constitutes
PRP vs PPP Ideal concentration is opinion based
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Background
How is it made?Centrifuged whole bloodCoagulation inhibitors may be used
○ Previous issues with bovine inhibitorsPlatelet activators may be usedVolume produced depends on which system
usedApplied in either
○ Injectable form○ Solid, matrix form
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BackgroundSystem Platelet Conc. Activator Centrifuge time Leukocytes Blood Volume
needed(ml)
PRP volume
Arthrex ACP 2-3X No(use within 30
minutes)
1, 5 min step No 9 3
Biomet GPS III 3-8x Autologous thrombin and
calcium chloride
1, 15 minute step Yes 27-110 3-12
Cascade 1-1.5x Calcium chloride 1, 6 minute for PRP2, 15 minute for fibrin
matrix
No 9-18 4-9
SmartPReP2 4-6x Bovine thrombin or calcium
2, 14 minute step Yes 20-120 3-20
PRGF 2-3x Calcium chloride 1, 8 minute step No 9-72 4-32
Magellan 3-7x Calcium chloride 2, 4-6 minute steps Yes 30-60 6
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Goals
BackgroundHealing Response
The Basic Science Uses Evidence Based Summary
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Background: The Healing Response Inflammatory phase
First week after injury○ Hemostasis recruitment of macrophages
and fibroblasts
Proliferative phaseWithin first 2 days to 2 weeks
○ Formation of extra-cellular scaffold
Maturation/remodeling phaseUp to first year
○ Type 1 collagen replacing scaffold
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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,
angiogenesisPDGF facilitates proliferation of other
growth factors○ Attracts stem cells and contributes to
remodeling
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Background: The Healing Response Growth factors
VEGF peaks after inflammatory phase○ Promotes angiogenesis and neo-
vascularizationb-FGF angiogenesis, cell migration,
creates collagenase, production of granulation tissue
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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
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Background: The Healing Response Alpha granules
Theory that activators will increase de-granulation○ Reason why some systems include external
activatorsSome studies show injured collagen fibers
will stimulate de-granulation as well
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Goals
BackgroundHealing Response
The Basic Science Uses
Limit to Muscle, Tendon, Ligament Evidence Based Summary
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The Basic Science
Horse tendons Schnabel et al.Culture in PRP vs other blood productsHigher anabolic gene expression in PRP
Human tenocytes de Mos et al.PRP vs. PPP
○ PRP increase in matrix degrading enzymes (faster recovery)
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The Basic Science
Rabbit skeletal muscle stem cellsGates et al.Increased expression of myogenic activity
Mesenchymal stem cells Mishra et al.Buffered in PRP, increased proliferation
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Goals
BackgroundHealing Response
The Basic Science Uses
Limit to Muscle, Tendon, Ligament Evidence Based Summary
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Uses: Muscle
Hammond et al (2009)Animal study (rats)Tibialis anterior strain
○ large strain vs small strainPRP shortened healing by 14-21 days in
small strain groupLittle change in large strain group
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Uses: Tendon
Lots of studiesLateral epicondylitisPatellar tendinopathyAchilles tendinopathyRotator Cuff tendinopathy
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Uses: Lateral Epicondylitis
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Uses: Lateral Epicondylitis
Mishra and Pavelko (2006)One of the most cited articlesChronic, refractory lateral epicondylitis15 patients, failed conservative measuresSingle PRP injection
○ control was bupivicaine
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Uses: Lateral Epicondylitis
Mishra and Pavelko (2006)Measures VAS and Mayo elbow scores at 2,
6 and 25 monthsOutcomes
○ 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
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Uses: Lateral Epicondylitis
Peerbooms et al (2010)RCT, Level 1 data
○ Only true RCT to date100 patients (51 PRP:49 CSI)1 yr f/u
○ 73% success in PRP group○ 49% in CSI group
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Uses: Patellar Tendinopathy
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Uses: Patellar Tendinopathy Human Data is limited Filardo et al (2010)
Non-RCT, N=31Serial PRP + PT (15) vs. PT alone (16)3 PRP, 2 weeks apart with eccentric
strengtheningPRP group
○ Improved in all measures○ Continued to improve at 6 months○ Higher improvement in sports activity
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Uses: Patellar Tendinopathy Kon et al (2009)
Prospective, pilot study (no control)3 PRP injections, 15 days apart6 month f/u
○ 70% stated complete or significant improvement
○ 80% satisfied with results
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Uses: Achilles Tendinopathy
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Uses: Achilles Tendinopathy
de Vos et al (2010)Double blinded, placebo control, RCTN=54, chronic Achilles tendinopathy
2 months of symptomsExcluded if had previous eccentric strengthening
program27 PRP, 27 isotonic saline, US guidance used
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Uses: Achilles Tendinopathy
de Vos et al (2010)Double blinded, placebo control, RCTN=54, chronic Achilles tendinopathy
Both did 12 week supervised eccentric programf/u at 6, 12, 24 weeks
- Both groups improved, No difference found- Used bupivicaine for anesthetic
- ? Inhibit effectiveness
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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 controlRepair with PRP vs repair without PRP
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Uses: MCL
No human studies Letson and Dahners (1994)
Rat MCL injury○ Injected with PDGF
73% (+/- 55%) stronger than contralateral controls
Human results anecdotal2-3 weeks earlier than anticipated
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Goals
BackgroundHealing Response
The Basic Science Uses
Limit to Muscle, Tendon, Ligament Evidence Based Summary
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What does the evidence say?
Increasing number of basic science and animal studies
Paucity of human trialsNo standardization of treatmentAnecdotally improves recovery by 2 weeks
1 vs. multiple injections1 seems to be effective, fenestration may helpThe multiple injection “protocol” is without
consistency
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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?
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What does the evidence say?
ExerciseEarly ROM can be helpfulEarly light aerobic activity can be helpfulI begin eccentric strengthening program as
early as toleratedGoal is RTP by 3 weeks
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What does the evidence say?
NSAIDsMost hold for minimum of 10 days priorNot proven to inhibit, but possible
○ Don’t withhold ASA if cardio-protective
Ideal platelet concentration600K-1mil per ml (no evidence for that)
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What does the evidence say?
WBC in preparationInhibit or help?
○ Help anti-infective property○ Inhibit inhibitory effects on inflammatory
mediators
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What does the evidence say?
Local anesthetics and corticosteroidsCarofino et al (2012)
○ Co-administration decreased PRP effectiveness
External platelet activatorsNo consensus on if or when
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What does the evidence say?
MSK US guidance improves results0232T tracking CPT code
○ Includes imaging assisted guidance○ I use it with every PRP
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Where are we with PRP?
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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
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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.
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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