PRP Update From basic science to clinical

application JohnJ.Klimkiewicz,MD

WashingtonOrthopedicsandSportsMedicineHeadTeamPhysician

WashingtonCapitalsHockeyClub&GeorgetownUniversityHoyas

PRP: Plasma Rich Platelets

• DefiniIon:sampleofbloodplateletconcentraIonabovebaselineproducedbycentrifugalseparaIonofwholeblood

• ProvidesincreasedconcentraIonofautologousgrowthfactorsandsecretoryproteinsthatmayenhancethehealingprocessonacellularlevel

PRP History •  UIlizedandstudiedsince1970’s•  Over86,000injecIonsperformedinorthopedicsin2013

•  MarketPRP:$45millionin2009,expectedtobe$125millionin2016

•  ClinicalapplicaIons:•  Oralsurgery•  PlasIcsurgery•  VascularSurgery•  HairtransplantaIon

•  OrthopedicApplicaIons•  Muscle/Tendoninjury

•  Acutevschronic•  Ligamentousinjury•  CarIlageinjury•  OsteoarthriIs

Composition of PRP •  PRPobtainedbycommerciallyavailablesystemsthatseparatebloodcomponentsbycentrifugaIon

•  Plasma-fluidporIonofbloodcontainingcloangfactor,proteins,ions

•  Platelet:NormalconcentraIoninblood150,000/ul–300,000/ul

•  PRP:plateletconcentraIonofatleast1,000,000ul

•  Leukocytes:WBC’s•  Erthrocytes:RBC’s

Regulation • WorldAnI-dopingagencytemporarilybannedPRPinjecIonsin2009-2011.

•  Currentlynotabannedsubstance,individualgrowthfactorshoweversIllbanned

•  NoRegulaIonbyNCAA,NHL,NBA,NFL

•  FDAapprovedforusewithBonegragsubsItutes,officeuseis“offlabel”

•  CurrentlynotcoveredunderinsurancefororthopedicapplicaIon

Platelets importance: Multiple Applications •  α –granulesinplateletscontainvariousgrowthfactorsandcytokineswithconcentraIonsequaltoplatelets

•  IncreaseanaboliccytokineacIvity•  Transforminggrowthfactor:TGF-Β•  PlateletDerivedGrowthfactor:PDGF•  Insulinlikegrowthfactor:IGF-1,IGFII•  Fibroblastgrowthfactor:FGF•  Vascularepithelialgrowthfactor:VEGF

•  Endothelialgrowthfactor

Leukocytes •  DifferentpreparaIonshavedifferentconcentraIonsofLeukocytesthatdictatefuncIon

•  DefinedaseitherLeukocyterichorLeukocytepoorascomparedtowholeblood

•  IncreasedconcentraIonofleukocytescorrelateswithplateletconcentraIon

•  LeukocyterichpreparaIonshaveincreasedamountsofIL-1andTNF–α (inflammatorycytokines-catabolic)

•  HaveincreasedamountsofVEGF(anabolic)

Multiple system preparations • MulIplecommercialsystemsavailable.Over80onmarket.

•  EachsystemdiffersinImecentrifugedaswellasnumberofcycles

•  Differinplatelet,wbc,andgrowthfactorconcentraIon

•  Oh,AJSM,2013

•  Becarefulincomparingstudies•  AllPRPnotsimilar•  DifferentprepsmaybebeperfordifferentcondiIons

Optimal PRP performance

• Plateletnumber:“morenotnecessarilybeper”

•  1.5million/ulmaybeopImal•  Abovethismayhavecataboliceffect

•  Timing:DuringoragerinflammatoryphaseofhealingmaybeopImal

PRP Effects on Tendon Tissue

•  IncreaseinPDGFanTGF–Β toareaessenIaltohealing

•  IncreaseinVEGF:increasesvascularityatinjuredsite

• BothacttoenhancetenocyteproliferaIonatinjuredsite

• ResultsinVitro:•  Earlierhealing•  Superiorqualitytohealedtendon•  BeperorganizaIonoffibrobastsandcollagen

PRP Effects on Muscle •  IGF-1andFGF-2haveshouldbeneficialeffectsinmusclehealing

•  InmurinemodelIGF-1,β FGFcytokinesimprovedhealingandsignificantfasttwitchandtetanusstrength

•  TGF-Βcancausedetrimentalincreaseinfibrosisandleadtorecurrentinjury

•  AnecdotalreportsreportdecreaseinImetoreturntoplay

PRP Effects on cartilage

•  IncreasessyntheIccapacityofchondrocytes

•  IncreasesgeneexpressionthroughupregulaIon

•  IncreasesproteoglycanproducIon

•  IncreasesdeposiIonoftypeIIcollagen

•  InhibitscataboliceffectofIL-Β, TNF-α onchondrocytes

Systemic Effects of PRP

•  SerumIGF,VEGF,anBFGFlevelsaresignificantlyelevatedagerPRPinjecIon

• AcIvatesbiologicpathwaysthatincreasegrowthfactorlevels

• VEGFlevelsareelevatedupto4daysagerinjecIonandcanserveasatesIngmarker

•  Wasteriainetal.AJSM,2013

PRP and Lateral Epicondylitis Study #Par+cipants Control Effec+veness Follow-up

KroghAJSM-2013JBJS2014

60 Control,GLU EQUAL 3months

MishraAJSM-2014

230 control 3monthsequalPRP-Rsuperiorat6months

3and6months 84%vs63%forcontrol

GosensAJSM-2011

100 GLU PRP:BeperDASHandVASscores

2year

JoostAJMS

100 GLU PRP:BeperDASscores

1year

PRP and Lateral epicondylitis: Meta-Analysis

Krogh , AJSM, 2013 •  17trials,1381parIcipants•  8differenttreatments:PRP,GLU,BoTox,autologousblood,HA,prolotherpy,GAG

•  3/17trailsunbiased•  Conclusion:PaucityofevidencefromunbiasedtrialstosupporttreatmentrecommendaIon

•  TrendtowardsPRPbeingeffecIve,notstaIsIcallysignif.,notcosteffecIve

PRP and Rotator cuff repair

study Numberpar+cipants

Control Followup Results

FluryAJSM2016

120 Prpvsropivicaine 24months Equal

MalavoltaAJSM2014

54 control 24months Equal

WeberAJSM2013

60 control 12months Equal

WangAJSM2015

60 control 4months NodifferenceinfuncIonorMRI

PRP and Patellar tendonitis

Study Numberofpar+cipants

control Followup Results

DragooAJSM2014

23 DryneedlingVsPRP-leukorich

12and26weeks VISAS:beperat12weeks,equalat26weeks

CharoussetAJSM2012

28 None—3injecIonsoneweekapart

3months 3months:21/28backtosport

AlmeidaAJSM

27 Placebo:atharvestsiteageracl

6month Improvedpost-oppainandbeperhealingmriat6months

MRI: Patella Tendonitis and PRP

Pre-PRPinjec+on 6monthss/pPRPinjec+on

PRP and Muscular Injuries: Clinical Trial

•  28ptswithacutehamstringinjuries

• RandomizedintoPRP+rehab,vsrehabalone

•  LowerpainlevelinPRPgroup

•  Hamidetal,AJSM,2014

0

5

10

15

20

25

30

35

40

45

PRP+rehab Rehab

DAYSto

return

Treatment

PRP and Achilles Tendonitis study Number

par+cipantscontrol Followup Result

KroghAJSM2016

24 Prpvssaline 3months NochangeinsxPosiIveintendonthickness

DeJongeAJSM2011

70 PRPvssalineandexercises

1year EQUAL

DeVOSJAMA,2010

24 PRPvssaline 1year EQUAL

PRP and arthritis •  EffectsseemtoincreaseendogenousHAproducIon,anddecreasecarIlagecatabolism

•  IL-1BandMMPacIvitydecreasedwithPRP

•  LeukocytepoorPRPmoreeffecIvethanLeukocyterichpreparaIons

Treatment using PRP: Consensus Agreement • NoanI-inflammatories1-2weeksbeforeandagerinjecIon,“Washoutperiod”

• NolocalanestheIctoinjecIonsite—AlterspHwhichmayalterfuncIon

• UltrasoundusepreferredfortendonsandMuscularinjecIons

PRP Treatment : Requires more study

•  OpImalcondiIons•  OpImalconcentraIonofPlateletsandfracIonatedWBC’s

•  NumberandsequenceofinjecIons•  PostinjecIonrehabrouInes•  EvidencesIlllackingtoprovedefinitebenefit

•  Appearssafewhenusedjudiciously•  Cost–Benefitanalysislacking

Efficacy of autologous Platelet Rich Plasma use for Orthopaedic Indications: A Meta-analysis

•  33studiesthatwererandomizedcontrolledorprospecIvecohortstudiesthatcomparedprpwithcontrolfororthopaedicinjury

•  Conclusion:ThecurrentliteratureiscomplicatedbyalackofstandardizaIonofstudyprotocols,plateletseparaIontechniques,andoutcomemeasures.Asaresult,thereisanuncertaintytosupporttheincreasinguseofprpasatreatmentmodalityfororthopedicinjuries Shethetal.,2012

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