Dr. John Klimkiewicz, Washington Orthopaedics and Sports Medicine

1. PRP Update
From basic science to clinical
application
John J. Klimkiewicz, MD
Washington Orthopedics and Sports Medicine
Head Team Physician
Washington Capitals Hockey Club & Georgetown University Hoyas

2. PRP: Platelet Rich Plasma
• Definition: sample of blood
platelet concentration above
baseline produced by centrifugal
separation of whole blood
• Provides increased
concentration of autologous
growth factors and secretory
proteins that may enhance the
healing process on a cellular
level

3. PRP History
• Utilized and studied since 1970’s
• Over 86,000 injections performed in
orthopedics in 2013
• Market PRP : $45 million in 2009, expected to
be $125 million in 2016
• Clinical applications:
• Oral surgery
• Plastic surgery
• Vascular Surgery
• Hair transplantation
• Orthopedic Applications
• Muscle/Tendon injury
• Acute vs chronic
• Ligamentous injury
• Cartilage injury
• Osteoarthritis

4. Composition of PRP
• PRP obtained by commercially
available systems that separate
blood components by
centrifugation
• Plasma-fluid portion of blood
containing clotting factor, proteins,
ions
• Platelet: Normal concentration in
blood 150,000/ul – 300,000 /ul
• PRP: platelet concentration of at
least 1,000,000 ul
• Leukocytes : WBC’s
• Erythrocytes: RBC’s

5. Regulation
• World Anti-doping agency
temporarily banned PRP injections in
2009-2011.
• Currently not a banned substance,
individual growth factors however still
banned
• No Regulation by NCAA, NHL,
NBA,NFL
• FDA approved for use with Bone graft
substitutes, office use is “off label”
• Currently not covered under
insurance for orthopedic application

6. Platelets importance: Multiple Applications
• a – granules in platelets contain
various growth factors and
cytokines with concentrations
equal to platelets
• Increase anabolic cytokine activity
• Transforming growth factor: TGF-B
• Platelet Derived Growth factor: PDGF
• Insulin like growth factor : IGF-1, IGFII
• Fibroblast growth factor: FGF
• Vascular epithelial growth factor:
VEGF
• Endothelial growth factor

7. Leukocytes
• Different preparations have different
concentrations of Leukocytes that
dictate function
• Defined as either Leukocyte rich or
Leukocyte poor as compared to whole
blood
• Increased concentration of leukocytes
correlates with platelet concentration
• Leukocyte rich preparations have
increased amounts of IL-1 and TNF –a
(inflammatory cytokines-catabolic)
• Have increased amounts of VEGF
(anabolic)

8. Multiple system preparations
• Multiple commercial systems
available. Over 80 on market.
• Each system differs in time
centrifuged as well as number of
cycles
• Differ in platelet, wbc , and growth
factor concentration
• Oh , AJSM, 2013
• Be careful in comparing studies
• All PRP not similar
• Different preps may be better for
different conditions

9. Optimal PRP performance
• Platelet number: “more not
necessarily better”
• 1.5 million/ul may be optimal
• Above this may have catabolic
effect
• Timing: During or after
inflammatory phase of healing
may be optimal

10. PRP Effects on Tendon Tissue
• Increase in PDGF an TGF –B to
area essential to healing
• Increase in VEGF: increases
vascularity at injured site
• Both act to enhance tenocyte
proliferation at injured site
• Results in Vitro:
• Earlier healing
• Superior quality to healed tendon
• Better organization of fibroblasts
and collagen

11. PRP Effects on Muscle
• IGF-1 and FGF -2 have should
beneficial effects in muscle healing
• In murine model IGF-1 ,b FGF
cytokines improved healing and
significant fast twitch and tetanus
strength
• TGF-B can cause detrimental
increase in fibrosis and lead to
recurrent injury
• Anecdotal reports report decrease
in time to return to play

12. PRP Effects on cartilage
• Increases synthetic capacity of
chondrocytes
• Increases gene expression
through upregulation
• Increases proteoglycan
production
• Increases deposition of type II
collagen
• Inhibits catabolic effect of IL-B,
TNF-a on chondrocytes

13. Systemic Effects of PRP
• Serum IGF, VEGF, an BFGF levels
are significantly elevated after
PRP injection
• Activates biologic pathways that
increase growth factor levels
• VEGF levels are elevated up to 4
days after injection and can
serve as a testing marker
• Wasteriain et al. AJSM,
2013

14. PRP and Lateral Epicondylitis
Study # Participants Control Effectiveness Follow-up
Krogh
AJSM-2013
JBJS 2014
60 Control, GLU EQUAL 3 months
Mishra
AJSM-2014
230 control 3 months equal
PRP-R superior
at 6 months
3 and 6 months 84% vs 63% for
control
Gosens
AJSM-2011
100 GLU PRP: Better
DASH and VAS
scores
2 year
Joost
AJMS
100 GLU PRP: Better DAS
scores
1 year

15. PRP and Lateral epicondylitis: Meta-Analysis
Krogh , AJSM, 2013
• 17 trials, 1381 participants
• 8 different treatments: PRP, GLU,
Bo Tox, autologous blood, HA,
prolotherapy, GAG
• 3/17 trails unbiased
• Conclusion: Paucity of evidence
from unbiased trials to support
treatment recommendation
• Trend towards PRP being effective,
not statistically signif., not cost
effective

16. PRP and Rotator cuff repair
study Number
participants
Control Follow up Results
Flury
AJSM 2016
120 Prp vs ropivicaine 24 months Equal
Malavolta
AJSM 2014
54 control 24 months Equal
Weber
AJSM 2013
60 control 12 months Equal
Wang
AJSM2015
60 control 4 months No difference in
function or MRI

17. PRP and Patellar tendonitis
Study Number of
participants
control Follow up Results
Dragoo
AJSM 2014
23 Dry needling
Vs PRP-leuko rich
12 and 26 weeks VISAS: better at 12
weeks, equal at 26
weeks
Charousset
AJSM 2012
28 None—3 injections
one week apart
3 months 3 months: 21/28
back to sport
Almeida
AJSM
27 Placebo: at harvest
site after acl
6 month Improved post-op
pain and better
healing mri at 6
months

18. MRI: Patella Tendonitis and PRP
Pre-PRP injection 6 months s/p PRP injection

19. PRP and Muscular Injuries: Clinical Trial
• 28 pts with acute hamstring
injuries
• Randomized into PRP + rehab, vs
rehab alone
• Lower pain level in PRP group
• Hamid et al, AJSM, 2014
0
5
10
15
20
25
30
35
40
45
PRP + rehab Rehab
DAYStoreturn
Treatment

20. PRP and Achilles Tendonitis
study Number
participants
control Follow up Result
Krogh
AJSM 2016
24 Prp vs saline 3 months No change in sx
Positive in tendon
thickness
DeJonge
AJSM 2011
70 PRP vs saline and
exercises
1 year EQUAL
DeVOS
JAMA, 2010
24 PRP vs saline 1 year EQUAL

21. PRP and arthritis
• Effects seem to increase
endogenous HA production, and
decrease cartilage catabolism
• IL-1 B and MMP activity
decreased with PRP
• Leukocyte poor PRP more
effective than Leukocyte rich
preparations

22. Treatment using PRP: Consensus Agreement
• No anti-inflammatories 1-2
weeks before and after injection,
“Washout period”
• No local anesthetic to injection
site—Alters pH which may alter
function
• Ultrasound use preferred for
tendons and Muscular injections

23. PRP Treatment : Requires more study
• Optimal conditions
• Optimal concentration of Platelets
and fractionated WBC’s
• Number and sequence of injections
• Post injection rehab routines
• Evidence still lacking to prove
definite benefit
• Appears safe when used judiciously
• Cost –Benefit analysis lacking

24. Efficacy of autologous Platelet Rich Plasma use for
Orthopaedic Indications: A Meta-analysis
• 33 studies that were randomized
controlled or prospective cohort
studies that compared prp with
control for orthopaedic injury
• Conclusion: The current literature
is complicated by a lack of
standardization of study protocols,
platelet separation techniques, and
outcome measures. As a result,
there is an uncertainty to support
the increasing use of prp as a
treatment modality for orthopedic
injuries Sheth et al., 2012

25. THANK YOU!!