Platelet Rich Plasma: Emerging Role in Orthopaedic Surgery Lucas J. Bader M.D. Orthopaedic Surgeon Fellowship Trained Foot & Ankle Surgeon

Disclosure None

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

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

Definition Platelet Rich Plasma Nonnucleated bodies in peripheral blood Autoglous blood with a concentration of platelets above a baseline value Fluid portion of blood

Bioactive Factors Potentially enhance healing by delivery of various growth factors and cytokines α granules Dense granules

α-Granules Cell proliferation Chemotaxis Cell differentiation Angiogenesis Conductive Scaffold

Platelet Derived Growth Factor Cell replication Angiogenesis Mitogen for fibroblasts

Vascular Endothelial Growth Factor Angiogenesis

Transforming Growth Factor-β1 Regulator in balance between fibrosis and myocyte regeneration

Fibroblast Growth Factor Proliferation of myoblasts, Angiogenesis

Epidermal Growth Factor Proliferation of mesenchymal and epithelial cells

Hepatocyte Growth Factor Angiogenesis, Mitogen for endothelial cells Antifibrotic

Insulin-like growth factor-1 Stimulates myoblasts/fibroblasts Mediates growth/repair skeletal muscle

Adhesive Proteins Fibrinogen Fibronectin Vitronectin “scaffold”

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

Serotonin & Histamine Increase capillary permeability Inflammatory cell access Macrophage Activation

Adenosine Receptor Activation Modulates inflammation

Advantage Normal biologic ratios vs Exogenous Factors

Formulation of PRP Can only be made from anticoagulated blood Cannot be made form clotted whole blood Cannot be made from serum

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

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

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

Growth Factor Release 70 % within 10 minutes Nearly 100% within 1 hr

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

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

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

Effects of PRP on Soft Tissues & Bone- Basic Science 3 phases of healing Inflammation Proliferation Remodeling Basic Metabolic Processes Chemotaxis Angiogenesis Differentiation EC Matrix Production

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

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

Effects PRP on Bone Stimulate Osteoblasts Stmulate Fibroblasts Up regulate Osteoclacin Encourage differentiation of MSC into bone forming cells

Further Study Acute injury Chronic injury Timing of injection Effect of serial injections

Orthopaedic Applications for PRP Chronic Tendinopathies Bone healing Acute Ligamentous Injuries Muscle injuries Intraoperative Augmentation

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

Bone Healing Fracture Healing Distraction Osteogenesis Osteoarthritis

Acute Ligamentous Injury Knee medial collateral ligament Ankle syndesmosis Ankle lateral ligament complex

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

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

Randomized controlled trial; Level 1 of evidence 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.

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

Sample size of 30 patients in each group Platelet-rich Fibrin Matrix in Arthroscopic Rotator Cuff Repair: A Prospective, Randomized Study Stephen 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.

Prospective study of thirty patients No controls Platelet Rich Plasma (PRP) Effectively Treats Chronic Achilles Tendonosis Raymond 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.

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

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

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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