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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