Knee Surgery & Sports Medicine Unit

IRCCS Humanitas Clinical Institute, Milan

P. Volpi - M. Denti

C.Bait

M. Cervellin, E. Prospero

A. Quaglia

PRP in patellar tendinopathies

Corrado Bait, MD

LONDON, 18 Oct 2012

I have no financial relationships to disclose

Corrado Bait, MD

• Platelet Rich Plasma (PRP) is a therapy that utilizes a patient’s own blood to stimulate a healing response within a damaged tissue or joint

• PRP is made by taking a small sample of a patient’s own blood and spinning in a centrifuge for fifteen minutes

• This process concentrates platelets and white blood cells in what is called “buffy coat” that is extracted and delivered to the injuried area

• PRP is a sample of autologous blood with concentrations of platelets above baseline values • Growth factors in the platelets recruit and produce cells necessary for healing

WHAT IS PRP

Arnoczky et al 2011;19(3):142-148

Factor Principal Source Primary Activity Comments

PDGFplatelets, endothelial cells,

placenta

promotes proliferation of

connective tissue, glial and

smooth muscle cells

two different protein chains

form 3 distinct dimer forms;

AA, AB and BB

EGFsubmaxillary gland,

Brunners gland

promotes proliferation of

mesenchymal, glial and

epithelial cells

TGF-acommon in transformed

cells

may be important for

normal wound healingrelated to EGF

FGFwide range of cells; protein

is associated with the ECM

promotes proliferation of

many cells; inhibits some

stem cells; induces

mesoderm to form in early

embryos

at least 19 family members,

4 distinct receptors

NGFpromotes neurite outgrowth

and neural cell survival

several related proteins first

identified as proto-

oncogenes; trkA (trackA),

trkB, trkC

Erythropoietin kidneypromotes proliferation and

differentiation of

erythrocytes

TGF-b

activated TH1 cells (T-

helper) and natural killer

(NK) cells

anti-inflammatory

(suppresses cytokine

production and class II

MHC expression), promotes

wound healing, inhibits

macrophage and

lymphocyte proliferation

at least 100 different family

members, including BMPs

IGF-I primarily liverpromotes proliferation of

many cell types

related to IGF-II and

proinsulin, also called

Somatomedin C

IGF-II variety of cellspromotes proliferation of

many cell types primarily of

fetal origin

related to IGF-I and

proinsulin

Factor Principal Source Primary Activity Comments

PDGFplatelets, endothelial cells,

placenta

promotes proliferation of

connective tissue, glial and

smooth muscle cells

two different protein chains

form 3 distinct dimer forms;

AA, AB and BB

EGFsubmaxillary gland,

Brunners gland

promotes proliferation of

mesenchymal, glial and

epithelial cells

TGF-acommon in transformed

cells

may be important for

normal wound healingrelated to EGF

FGFwide range of cells; protein

is associated with the ECM

promotes proliferation of

many cells; inhibits some

stem cells; induces

mesoderm to form in early

embryos

at least 19 family members,

4 distinct receptors

NGFpromotes neurite outgrowth

and neural cell survival

several related proteins first

identified as proto-

oncogenes; trkA (trackA),

trkB, trkC

Erythropoietin kidneypromotes proliferation and

differentiation of

erythrocytes

TGF-b

activated TH1 cells (T-

helper) and natural killer

(NK) cells

anti-inflammatory

(suppresses cytokine

production and class II

MHC expression), promotes

wound healing, inhibits

macrophage and

lymphocyte proliferation

at least 100 different family

members, including BMPs

IGF-I primarily liverpromotes proliferation of

many cell types

related to IGF-II and

proinsulin, also called

Somatomedin C

IGF-II variety of cellspromotes proliferation of

many cell types primarily of

fetal origin

related to IGF-I and

proinsulin

GROWTH FACTORS

Kon E. et al. Platelet-rich plasma (PRP) to treat sports injuries: evidence to support its use. Knee Surg Sports Traumatol Arthrosc (2011) 19:516–527

P-PRP Pure-PRP

L-PRP Leukocyte rich

PRP

P-PRF Pure Platelet rich

Fibrin

Leukocyte and Platelet Rich Fibrin

• Autologous Conditioned

Plasma (ACPTM)-Arthrex 2.0 x

• Preparation Rich in Growth Factor (PRGF) -Biotechnology Institute

• GPS ® - Biomet

3.2 x

• Symphony TM II –DePuy 4.0 x

• Cascade ® - Muscoloskeletal transplantation foundation

1.6 x

• PRGF scaffold -

Biotechnology Institute

No specific sistem

Type of PRP

PRP PROCEDURE

Wide variations of Platelets numbers

Different preparation methods Intra-individual variability Inter-individual variability Age variability

PRP PROCEDURE

Platelet-rich plasma differs according to preparation method human variability.

Mazzocca A., et al - 2012

Are all PRP treatments the same ?

NO !!! Because one treatment is not the same as another treatment for

different reasons: • Platelets level base it’s different in every patient • There are different type and use of PRP (liquid or gel forms) • Some treatments contain red or white blood cells, thrombin or calcium chloride • The right indications for use are important to understand and for talking about the outcomes of PRP treatments…..we need to make sure we are talking about similar comparisons

Vol. 28, N 7, 2012 :pag 998 - 1009

“PAW classification system offers a simple, effective method for quickly documenting the cellular components and activation method used. The

acronym PAW is for Platelets, Activation, and White cells, and the subcategories are thoughtfully organized to enhance recall”

All blood manipulation must be done under Hospital Hematologic Service Control

(DL 19-08-2005 N° 191)

ITALIAN RULE

•Effective concentration it’s about 1 milion/µL, 3 to 5X platelet level baseline • Fibroblasts are better stimulated with concentration around 2,5X Platelet baseline • Expression of Growth Factors receptors decrease with age

Weibrich g et al, Bone 34:665-671, 2004

De Mos et al. Am J sports Med 36:1171-1178, 2008

Vavaken P. et al. Age dependence of expression of growth factor receptors in porcine ACL fibroblasts 2010, J Orthop Res 28:1107-1112.

PRP CONCENTRATION

• Injection therapy: biological & mechanical action

• Improve surgical procedure

PRP in Patellar Tendinopathies

Multiple PRP injections in patellar tendon

with good results

Clinical applications

Better clinical results Physiotherapy & multiple PRP injection (3 injection)

Vs only Physioth • 31 patients

• 6 months of follow up

Clinical applications

NO significant difference in painless or functional recovery in PRP Vs placebo study

54 patients (27 each group) • 24 months of follow up

• Level 1 of evidence

JAMA 2010;13(303):144–149

PRP PROCEDURE

Clinical applications

FINDING NO DIFFERENCE DOES NOT

MEAN THERE IS NO DIFFERENCE

PRP PROCEDURE

MATERIAL & METHODS

Blood sample of 30 ml

Our experience

PRP PROCEDURE

Spinning

GPS® - Biomet 3,2 X

Extraction of Platelet Poor Plasma (PPP)‏

Extraction of Platelet Rich Plasma (PRP)‏

Added to the PRP of sodium bicarbonate (8.4%) to neutralize the PH

PRP PROCEDURE

US guide multiple injection of L-PRP

Our experience in patellar tendinopathies

PRP PROCEDURE

• after 7 days for 3 weeks • swim • ROM recovery • stretching

• after 5 weeks • excentric & concentric exercise

• after 7 weeks • running

• after 9 weeks • sport-specific training

• after 12 weeks return to sport

Post Injection

PRP PROCEDURE

Statistically significant painless reduction at 90 days of follow up

after L-PRP treatment

Volpi P et Al. Med Sports 2007;60: 595-603

PRP PROCEDURE

Volpi P et Al J Sports Med Phys Fitness 2010; 50: 494-500

Same better results in other

site at 24 months of follow up

Our experience

PRP PROCEDURE

post 120 gg

75,00

controllo a 24

mesi

70,29

Pre

39,25

10

20

30

40

50

60

70

80V

isa

Sc

ore

PRE POST

•Randomized control trial

•2008-2009 :40 patients:

20 control group (A)

20 PRP group (B)

•F.U. :12 mths (VAS, VISA, RM)

VAS VISA

Pre Post Pre Post

CTRL

Group 3.8±2.1 1±1.4 59.8±23.2 84.5±

11.8*

PRP

Group 1.2±2.2 0.6±0.

9 64.4±18.2

97.8±

2.5*§

PRP PROCEDURE

Our experience

PRP PROCEDURE

GOLD MEDAL 1500 MT WOMAN

Multiple scar & L-PRP

PRP PROCEDURE

WADA (The World Anti-Doping Agency)

World Anti-doping Code The prohibited list 2011 – Summary of modifications

S2. Peptide Hormones, Growth factors and related substances Intramuscle injection of PRP

was removed of WADA prohibited list

World Anti-doping Code The prohibited list 2010 S2. Peptide Hormones, Growth factors

and related substances Platelet-derived preparations (e.g. Platelet

Rich Plasma, “blood spinning”) administredred by intramuscolar route.

Other routes of administration will require a declaration of use in compliance with the

international Standard for Therapeutic Use Exemptions.

Take Home Message

• More talk than outcomes. Fashion topic

• Larger preclinical and clinical studies (RCT) are still needed to define the real

benefits and indications of its use

• Different procedure and type of PRP, extreme variability of GF.

• No standardized indications

• Rules & Costs

The current evidence shows that stem cells can have a positive effect on tendon healing. This is most likely because stem cells have regeneration potential, producing tissue that is similar to the preinjury state but the results can be variable

“The use of adjuncts such as molecular signaling, mechanical stimulation, and augmentation devices can potentially

enhance stem cell therapy”

Ahmad Z et al; Arthroscopy, Vol 28, No 7 (July), 2012: pp 1018-1029

GOOD MEDICAL PRACTICE

CORRECT INDICATION

& THERAPY

BIOTECHNOLOGY

INNOVATIONS

HIGH LEVEL RESEARCH

CONCLUSION

PRP in patellar tendinopathies

Corrado Bait, MD

LONDON, 18 Oct 2012