PRP Update By Kenneth A. Jurist, M.D.

What is PRP? PRP is simply whole blood that is centrifuged to create an increased concentration of platelets with or without WBC’s

What’s so special about Platelets? Platelets contain granules that store large numbers of “growth factors” Alpha granules released (activated) when platelets aggregate and adhere to a site of injury or inflammation Listing of other growth factors: interleukin-1, tumor necrosis factor, transforming growth factor, insulin growth factor and more It is the activation of platelets and release of the various growth factors that makes them special and is the key to enhancing tissue repair and healing!

Platelet Rich Plasma Biology What do these Growth Factors Do?? Chemotaxis Directional movement in response to a chemical stimulus Stems cells are attracted to the growth factors and migrate into the area Cell proliferation Significant increase in cellular reproduction activity Possibly even a systemc effect Performance enhancing?

The Primary Growth Factors Role in Soft Tissue Healing and Repair PDGF 2 polypeptide chains AB, BB and AA types (AB in human platelets) Stored in alpha granules in platelets Receptors are found in tendon, cartilage, synovium and elsewhere TGF beta Also polypeptide, multiple chains, TGF beta-1 most studied form Found in platelets and bone, cartilage Also found in macrophages Receptors are universal in cells throughout the body

Effect of PDGF on Tissues Immediate (within 5 minutes) Second messenger stimulation Inflammatory response Early (30min to 4 hours) M-RNA stimulation, protein synthesis Chemotaxis (draws cells to the area) Late (4-24 hours) Fibroblast mitosis

Effect of TGF-Beta on Tissues Actually inhibits cell growth More of a modulator of cell growth, differentiation Very important in wound repair

Summary of Effect of Platelet Growth Factors on Tissues It appears that through a complex series of biochemical and cellular events, these growth factors cause a rapid and sustained increase in the number of fibroblasts in an area and then through a poorly understood interaction among factors modulates cellular activity to cause stem cell maturation.

Breaking News? Is this Twitter Worthy News???? So when did all this information about platelets get discovered? Is this Twitter Worthy News????

AOSSM sponsored Sports Induced Inflammation Workshop AOSSM sponsored Sports Induced Inflammation Workshop. Bethesda, Maryland. May 1989. “Although the cellular events involved in the healing and repair of musculoskeletal connective tissue injuries are reasonably well described, the molecular mechanisms regulating these responses are incompletely understood. New information, particularly on the roles of various cytokines and growth factors in inflammation and wound healing, however, is continually being published. This information may ultimately have far reaching therapeutic implications.”

Round Table Discussion on Clinical uses of PRP Dr Round Table Discussion on Clinical uses of PRP Dr. Steven Arnoczky - moderator. Orthopedics Today March 2009 “Platelet rich plasma (PRP) is generically defined as an increase (above baseline) in the concentration of platelets and their associated growth factors. While the clinical benefits of PRP in enhancing the healing of musculoskeletal tissues are only beginning to be explored, the substantial amount of basic science data supporting the role of growth factors in enhancing cell migration, proliferation and matrix synthesis has provided a compelling rationale for use of PRP in the treatment and repair of various connective tissue structures.”

PRP IS NOT! Stem cells MSC’s Lipocytes Bone Marrow

Current Clinical Uses of PRP Everything and anything! Internet marketing for host of ailments Snake oil of today “Cures rheumatism, grows hair, gets rid of wrinkles, etc., etc.”

Current Clinical Uses of PRP Compelling Rationale! Meniscus repair Tendonitis (office based injection) Arthritis? Ligament surgery? Tendon repairs? Acute injury?

Past Clinical Use in Improving Healing of Meniscus Repairs Using - Fibrin Clot Dr. Warren and Dr. Arnoczky at HSS Whole blood, clotted and injected Difficult to handle, difficult to inject No commercial backing Fell out of favor

Why the interest in PRP? Historically there has been interest for a long time at the research level. Clinical interest started with an hypothesis by Mishra et al. Could the treatment of a common clinical disorder - lateral epicondylitis be improved by injecting PRP into the tendon?

(aka lateral epicondylitis/tennis elbow) Clinical Model Lateral Tendinosis (aka lateral epicondylitis/tennis elbow) Common Disorder 5 per 1000 pts per year seen in general practice Natural history— Highly variable - lack of uniform response to treatment Typically seen over age 35 Repetitive activities Most common cause May occur from injury (acutely)

Tendinopathy or Tendinosis Definitions - Histologically Speaking Loss of longitudinal alignment of collagen fibers Hypercellularity with neovascularization -No acute inflammatory cells Angiofibroblastic Hyperplasia (Nirschl) Grossly--no longer white but rather gray

Disappointing Effects of Current Clinical Rx of Inflammation Oral NSAID’S or Corticosteroid injection interrupts the inflammatory cycle GI intolerance of many oral meds decreases proteoglycan synthesis weakens tendon tissue atrophy of subQ fat skin discoloration

Clinical Application for Use of PRP In the Treatment of Tendinopathy - Mishra Current clinical investigations being performed in the treatment of lateral epicondylitis Difficult patient mix with some having failed surgery or multiple cortisone injections Part of approval process for FDA certification for this use First step towards insurance co recognition of this as treatment modality worthy of reimbursement

Office Injection of PRP - The Protocol PRP Application Technique Withdraw 30 cc of peripheral blood Place blood in GPS canister Centrifuge for 15 minutes at 3200 RPMs

Office Injection of PRP - The Protocol PRP Application Technique Remove PPP Shake vigorously for 30 seconds Platelet Poor Plasma (PPP) Platelet Rich Plasma (PRP) Packed Red Blood Cells

Office Injection of PRP - The Protocol PRP Application Technique Inject 2-3 cc of PRP into the ECRB--Peppering technique Average Dose 3.3 million platelets per patient

Post injection Management Rest (sling/crutches) for a few days to a week NO NSAID’S PT (HEP or Rx) Slow stretching program Low weight/hi rep pain free isotonic PRE’s No high loading activities until criteria met No rest pain Minimal tenderness Full motion Normal strength

Platelet Rich Plasma Conclusions Platelet Rich Plasma has emerged as a valuable biologic treatment for chronic tendonitis of the elbow Level I support for use only in the Elbow Since giving in office injections I have Only rarely needed to do surgery. A recent study found that office injection For tennis elbow was more cost effective And just as successful as an outpatient surgery.!

PRP use in RCR Despite a Compelling Rationale There have been a handful of good Level I studies that have shown no benefit in terms of clinical scores or healing rate when PRP is used to augment the surgical repair of a rotator cuff tear.

Future of PRP Expanding role in the treatment of many conditions and an adjunct to healing in the care of connective and musculoskeletal tissues. We have only scratched the surface. Future use will likely involve staged biochemical manipulation of the healing and inflammatory process. The future is bright but uncertain until more clinical series are completed.

Limitations in the use of PRP Efficacy Lack of clinical data Number of studies being done Indications are being developed Uniformity of prep PRP classification Insurance recognition CMS tracking code $$$$$$$ - Evidence based? Shady clinics

My Experience with PRP Also used in OR for tendon repair Augment Early but good for Office Injection Achilles tendonitis Lateral/Medial epicondylitis Patella tendonitis Chronic Hamstring Labral tear shoulder Rotator Cuff Tendonitis Knee/Shoulder Arthritis Also used in OR for tendon repair Augment

Thank you !