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?
So when did all this
information about
platelets get
discovered?
Is this Twitter
Worthy News????
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. 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
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•
•
•
•
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?
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
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•
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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
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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
Early but good for Office Injection
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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 !