Conflicts of Interest

Conflicts of Interest

I have no conflicts of interest regarding this presentation

PLATELET RICH PLASMA: AN UPDATE WHERE ARE WE NOW?

Ramon Ylanan MD CAQSM

Team Physician University of Arkansas

Advanced Orthopeadic Specialists

Goals

BackgroundHealing Response

The Basic Science Uses Evidence Based Summary

Goals



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

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

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

Goals



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

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

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

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

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

Goals


The Basic Science Uses

Limit to Muscle, Tendon, Ligament Evidence Based Summary

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)

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

Goals




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

Uses: Tendon

Lots of studiesLateral epicondylitisPatellar tendinopathyAchilles tendinopathyRotator Cuff tendinopathy

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


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


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

Uses: Patellar Tendinopathy

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

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

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


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

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

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

Goals




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


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?


ExerciseEarly ROM can be helpfulEarly light aerobic activity can be helpfulI begin eccentric strengthening program as

early as toleratedGoal is RTP by 3 weeks


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)


WBC in preparationInhibit or help?

○ Help anti-infective property○ Inhibit inhibitory effects on inflammatory

mediators


Local anesthetics and corticosteroidsCarofino et al (2012)

○ Co-administration decreased PRP effectiveness

External platelet activatorsNo consensus on if or when


MSK US guidance improves results0232T tracking CPT code

○ Includes imaging assisted guidance○ I use it with every PRP

Where are we with PRP?

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

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 prospective, 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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