PRP Update From basic science to clinical application basic science to clinical application John J....
Transcript of PRP Update From basic science to clinical application basic science to clinical application John J....
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
PRP and Muscular Injuries: Clinical Trial
• 28ptswithacutehamstringinjuries
• RandomizedintoPRP+rehab,vsrehabalone
• LowerpainlevelinPRPgroup
• Hamidetal,AJSM,2014
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DAYSto
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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