PRP UpdateFrom basic science to

clinical applicationJohn J. Klimkiewicz, MD

Washington Orthopedics and Sports MedicineHead Team Physician

Washington Capitals Hockey Club & Georgetown University Hoyas

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

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

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

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

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

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)

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

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

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

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

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

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

PRP and Lateral EpicondylitisStudy # Participants Control Effectiveness Follow-up

Krogh AJSM-2013JBJS 2014

60 Control, GLU EQUAL 3 months

MishraAJSM-2014

230 control 3 months equalPRP-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

JoostAJMS

100 GLU PRP: Better DAS scores

1 year

PRP and Lateral epicondylitis: Meta-AnalysisKrogh , 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

PRP and Rotator cuff repairstudy Number

participantsControl Follow up Results

FluryAJSM 2016

120 Prp vs ropivicaine 24 months Equal

MalavoltaAJSM 2014

54 control 24 months Equal

Weber AJSM 2013

60 control 12 months Equal

WangAJSM2015

60 control 4 months No difference in function or MRI

PRP and Patellar tendonitis

Study Number of participants

control Follow up Results

DragooAJSM 2014

23 Dry needlingVs PRP-leuko rich

12 and 26 weeks VISAS: better at 12 weeks, equal at 26 weeks

CharoussetAJSM 2012

28 None—3 injections one week apart

3 months 3 months: 21/28 back to sport

AlmeidaAJSM

27 Placebo: at harvest site after acl

6 month Improved post-op pain and better healing mri at 6 months

MRI: Patella Tendonitis and PRP

Pre-PRP injection 6 months s/p PRP injection

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

PRP + rehab Rehab0

5

10

15

20

25

30

35

40

45

Treatment

DAYS

to re

turn

PRP and Achilles Tendonitisstudy Number

participantscontrol Follow up Result

KroghAJSM 2016

24 Prp vs saline 3 months No change in sxPositive in tendon thickness

DeJongeAJSM 2011

70 PRP vs saline and exercises

1 year EQUAL

DeVOSJAMA, 2010

24 PRP vs saline 1 year EQUAL

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

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

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

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

THANK YOU!!