prp update from basic science to clinical application basic science to clinical application john j....
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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
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