Lucas J. Bader M.D.Orthopaedic Surgeon

Fellowship Trained Foot & Ankle Surgeon

DisclosureNone

GoalsDefinition of PRPReview Basic ScienceCurrent Clinical ApplicationsReview of the LiteratureFuture

IntroductionEmerging field of

BiologicsPRP utilized and

studied since the 1970’s

Origins in fields of maxillofacial and general surgery

Definition Platelet Rich PlasmaNonnucleated

bodies in peripheral blood

Autoglous blood with a concentration of platelets above a baseline value

Fluid portion of blood

Bioactive FactorsPotentially enhance healing by delivery of

various growth factors and cytokines α granulesDense granules

α-GranulesCell proliferationChemotaxisCell differentiationAngiogenesisConductive Scaffold

Platelet Derived Growth FactorCell replicationAngiogenesisMitogen for

fibroblasts

Vascular Endothelial Growth FactorAngiogenesis

Transforming Growth Factor-β1Regulator in balance

between fibrosis and myocyte regeneration

Fibroblast Growth FactorProliferation of

myoblasts, Angiogenesis

Epidermal Growth FactorProliferation of

mesenchymal and epithelial cells

Hepatocyte Growth FactorAngiogenesis,Mitogen for

endothelial cellsAntifibrotic

Insulin-like growth factor-1Stimulates

myoblasts/fibroblastsMediates

growth/repair skeletal muscle

Adhesive ProteinsFibrinogenFibronectinVitronectin“scaffold”

Dense GranulesNon-Growth Bioactive MoleculesFundamental effect on the biologic aspects of

inflammationCell migrationConductive Matrix

Serotonin & HistamineIncrease capillary

permeabilityInflammatory cell

accessMacrophage

Activation

Adenosine Receptor ActivationModulates

inflammation

AdvantageNormal biologic ratios vs Exogenous Factors

Formulation of PRPCan only be made from anticoagulated bloodCannot be made form clotted whole bloodCannot be made from serum

Preparation 30-60 cc DrawnAdd citrate to bind

ionized calcium and prohibit clotting cascade

CentrifugationStep 1

Red blood cellsLeukocytes Platelets

Step 2Platelet-Poor

PortionPlatelet-Rich

Portion

Activating AgentsCalcium Chloride

and/or Thrombin (OR)

Collagen (Office)Initiates

Platelet activationClot formationGrowth Factor

Release

Growth Factor Release70 % within 10 minutesNearly 100% within 1 hr

PRP Preparations SystemsSeveral AvailableQualitative and Quantitative Variability

Volume of autologous bloodCentrifuge rate/timeDelivery MethodActivating AgentLeukocyte concentration (?)Final PRP volumeFinal Platelet and Growth Factor

Concentration

Safety ConcernsAutologous BloodAseptic techniqueRelative Contraindications

Hx of thrombocytopeniaAnticoagulant therapyActive infectionTumorMetastatic Disease

Cost$150-$180 small kits$200 large KitsCentrifuge $1800PRP is currently

considered experimental and is not reimbursed by most third party payers

Effects of PRP on Soft Tissues& Bone- Basic Science3 phases of healing

InflammationProliferationRemodeling

Basic Metabolic ProcessesProliferationChemotaxisAngiogenesisDifferentiationEC Matrix Production

Effects PRP on TendonCollagen gene expressionVascular endothelial growth factorHepatocyte growth factorMatrix MetalloproteinaseTendon strength and callus formationCell formation and angiogenesis

Effects PRP on MuscleIGF-1 & basic FGF improve healing and

increase fast twitch and tetanus strengthAccelerated satellite cell activationIncreased diameter of regenerating

myofibrils

Effects PRP on BoneStimulate OsteoblastsStmulate FibroblastsUp regulate OsteoclacinEncourage differentiation of MSC into bone

forming cells

Further StudyAcute injuryChronic injuryTiming of injectionEffect of serial

injections

Orthopaedic Applications for PRPChronic

TendinopathiesBone healingAcute Ligamentous

InjuriesMuscle injuriesIntraoperative

Augmentation

Chronic TendinopathyLateral/medial

EpicondylitisAchilles

TendinopathyPatellar

TendinopathyPosterior Tibial

TendinopathyPlantar Fasciitis

Bone HealingFracture HealingDistraction

OsteogenesisOsteoarthritis

Acute Ligamentous InjuryKnee medial

collateral ligamentAnkle syndesmosisAnkle lateral

ligament complex

Intraoperative UseTotal Knee

arthroplastyACL reconstructionAchilles Tendon

RepairRotator Cuff RepairAcute Articular

Cartilage Repair

Review of the literatureNumerous basic science, animal studies, and

small case reportsFew controlled clinical studiesMajority of studies are small, anecdotal, and

underpoweredNon-standardized techniques

Ongoing Positive Effect of Platelet-Rich Plasma Versus Corticosteroid Injection in Lateral Epicondylitis: A Double-Blind Randomized Controlled Trial With 2-Year Follow-Up.Gosens T, Peerbooms JC, van Laar W, den Oudsten BL.

Randomized controlled trial; Level 1 of evidence

PRP group (n = 51) or the corticosteroid group (n = 49)

PRP group was more often successfully treated than the corticosteroid group (P < .0001). Success was defined as a reduction of 25% on VAS or DASH scores without a re-intervention after 2 years.

Platelet-Rich Plasma Injection for Chronic Achilles Tendinopathy A Randomized Controlled TrialRobert J. de Vos, MD; Adam Weir, MBBS; Hans T. M. van Schie, DVM, PhD; Sita M. A. Bierma-Zeinstra, PhD; Jan A. N.

Verhaar, MD, PhD; Harrie Weinans, PhD; Johannes L. Tol, MD, PhD

Eccentric exercises (usual care) with either a PRP injection (PRP group) or saline injection (placebo group)

PRP group (n = 27) or placebo group (n = 27)

The mean VISA-A score improved significantly after 24 weeks in the PRP group and in the placebo group, but the increase was not significantly different between both groups

Platelet-rich Fibrin Matrix in Arthroscopic Rotator Cuff Repair: A Prospective, Randomized StudyStephen C Weber, MD Sacramento CA Jeffrey I Kauffman, MD Sacramento CA

Sample size of 30 patients in each groupSerial VAS scores were obtained, as well as

SST scores at each interval. Final scores for each group included UCLA and ASES scores.

Early follow-up does not show significant improvement in perioperative pain or clinical outcome.

Platelet Rich Plasma (PRP) Effectively Treats Chronic Achilles TendonosisRaymond R Monto, MD

Prospective study of thirty patientsNo controlsAOFAS scores improved to 92 at 6 months.

Resolution of Achilles abnormalities were seen in post treatment MRI/ultrasound studies and 28/30 were clinically satisfied with their clinical results.

Literature SummaryGreatest support in treating tendinopathy

Lateral EpicondylitisPatellar TendinopathyAchilles TendinopathyPlantar Fasciitis

Caution with Acute InjuriesRisk of FibrosisReturn to activity too early

FuturePRP promising, but not provenAppropriately powered studiesSophisticated models of healingMore precise formulations of PRP Narrower indications, but more definitive

My ProtocolTreatment of last resort prior to surgeryIndicated for chronic tendinopathiesPerformed under ultrasound guidanceNSAIDS discontinuation 1 week prior and 2

weeks post procedureActivity modification for 7 days