Platelet Rich Plasma: Emerging Role in Orthopaedic Surgery

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Platelet Rich PlasmaEmerging Role in
Orthopaedic Surgery

• Lucas J. Bader M.D.
• Orthopaedic Surgeon
• Fellowship Trained Foot Ankle Surgeon

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Disclosure

• None

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Goals

• Definition of PRP
• Review Basic Science
• Current Clinical Applications
• Review of the Literature
• Future

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Introduction

• Emerging field of Biologics
• PRP utilized and studied since the 1970s
• Origins in fields of maxillofacial and general
  surgery

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Definition Platelet Rich Plasma

• Nonnucleated bodies in peripheral blood
• Autoglous blood with a concentration of platelets
  above a baseline value
• Fluid portion of blood

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Bioactive Factors

• Potentially enhance healing by delivery of
  various growth factors and cytokines
• a granules
• Dense granules

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a-Granules

• Cell proliferation
• Chemotaxis
• Cell differentiation
• Angiogenesis
• Conductive Scaffold

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Platelet Derived Growth Factor

• Cell replication
• Angiogenesis
• Mitogen for fibroblasts

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Vascular Endothelial Growth Factor

• Angiogenesis

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Transforming Growth Factor-ß1

• Regulator in balance between fibrosis and myocyte
  regeneration

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Fibroblast Growth Factor

• Proliferation of myoblasts,
• Angiogenesis

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Epidermal Growth Factor

• Proliferation of mesenchymal and epithelial cells

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Hepatocyte Growth Factor

• Angiogenesis,
• Mitogen for endothelial cells
• Antifibrotic

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Insulin-like growth factor-1

• Stimulates myoblasts/fibroblasts
• Mediates growth/repair skeletal muscle

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Adhesive Proteins

• Fibrinogen
• Fibronectin
• Vitronectin
• scaffold

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Dense Granules

• Non-Growth Bioactive Molecules
• Fundamental effect on the biologic aspects of
  inflammation
• Cell migration
• Conductive Matrix

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Serotonin Histamine

• Increase capillary permeability
• Inflammatory cell access
• Macrophage Activation

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Adenosine Receptor Activation

• Modulates inflammation

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Advantage

• Normal biologic ratios vs Exogenous Factors

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Formulation of PRP

• Can only be made from anticoagulated blood
• Cannot be made form clotted whole blood
• Cannot be made from serum

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Preparation

• 30-60 cc Drawn
• Add citrate to bind ionized calcium and prohibit
  clotting cascade

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Centrifugation

• Step 1
• Red blood cells
• Leukocytes
• Platelets
• Step 2
• Platelet-Poor Portion
• Platelet-Rich Portion

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Activating Agents

• Calcium Chloride and/or Thrombin (OR)
• Collagen (Office)
• Initiates
• Platelet activation
• Clot formation
• Growth Factor Release

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Growth Factor Release

• 70 within 10 minutes
• Nearly 100 within 1 hr

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PRP Preparations Systems

• Several Available
• Qualitative and Quantitative Variability
• Volume of autologous blood
• Centrifuge rate/time
• Delivery Method
• Activating Agent
• Leukocyte concentration (?)
• Final PRP volume
• Final Platelet and Growth Factor Concentration

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Safety Concerns

• Autologous Blood
• Aseptic technique
• Relative Contraindications
• Hx of thrombocytopenia
• Anticoagulant therapy
• Active infection
• Tumor
• Metastatic Disease

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Cost

• 150-180 small kits
• 200 large Kits
• Centrifuge 1800
• PRP is currently considered experimental and is
  not reimbursed by most third party payers

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Effects of PRP on Soft Tissues Bone- Basic
Science

• 3 phases of healing
• Inflammation
• Proliferation
• Remodeling
• Basic Metabolic Processes
• Proliferation
• Chemotaxis
• Angiogenesis
• Differentiation
• EC Matrix Production

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Effects PRP on Tendon

• ?Collagen gene expression
• ?Vascular endothelial growth factor
• ?Hepatocyte growth factor
• ?Matrix Metalloproteinase
• ?Tendon strength and callus formation
• ?Cell formation and angiogenesis

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Effects PRP on Muscle

• IGF-1 basic FGF improve healing and increase
  fast twitch and tetanus strength
• Accelerated satellite cell activation
• Increased diameter of regenerating myofibrils

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Effects PRP on Bone

• Stimulate Osteoblasts
• Stmulate Fibroblasts
• Up regulate Osteoclacin
• Encourage differentiation of MSC into bone
  forming cells

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Further Study

• Acute injury
• Chronic injury
• Timing of injection
• Effect of serial injections

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Orthopaedic Applications for PRP

• Chronic Tendinopathies
• Bone healing
• Acute Ligamentous Injuries
• Muscle injuries
• Intraoperative Augmentation

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Chronic Tendinopathy

• Lateral/medial Epicondylitis
• Achilles Tendinopathy
• Patellar Tendinopathy
• Posterior Tibial Tendinopathy
• Plantar Fasciitis

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Bone Healing

• Fracture Healing
• Distraction Osteogenesis
• Osteoarthritis

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Acute Ligamentous Injury

• Knee medial collateral ligament
• Ankle syndesmosis
• Ankle lateral ligament complex

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Intraoperative Use

• Total Knee arthroplasty
• ACL reconstruction
• Achilles Tendon Repair
• Rotator Cuff Repair
• Acute Articular Cartilage Repair

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Review of the literature

• Numerous basic science, animal studies, and small
  case reports
• Few controlled clinical studies
• Majority of studies are small, anecdotal, and
  underpowered
• Non-standardized techniques

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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 lt .0001).
  Success was defined as a reduction of 25 on VAS
  or DASH scores without a re-intervention after 2
  years.

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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

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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 group
• Serial 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.

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

• Prospective study of thirty patients
• No controls
• AOFAS 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.

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Literature Summary

• Greatest support in treating tendinopathy
• Lateral Epicondylitis
• Patellar Tendinopathy
• Achilles Tendinopathy
• Plantar Fasciitis
• Caution with Acute Injuries
• Risk of Fibrosis
• Return to activity too early

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Future

• PRP promising, but not proven
• Appropriately powered studies
• Sophisticated models of healing
• More precise formulations of PRP
• Narrower indications, but more definitive

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My Protocol

• Treatment of last resort prior to surgery
• Indicated for chronic tendinopathies
• Performed under ultrasound guidance
• NSAIDS discontinuation 1 week prior and 2 weeks
  post procedure
• Activity modification for 7 days

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Thanks!