PRP for tendinopathies and ostéoarthritis a technical analysis - 30-11-2019 - ECOSEP

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PRP for tendinopathies and ostéoarthritis:

a technical analysis

Physical Medicine, Rehabilitation and Sports Traumatology Department University and University Hospital of Liège, Belgium

Prof Jean-François KAUX

@SportS2_CHU @JFKaux

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• The treatment of tendinopathies can be difficult

• This is the reason why new treatments have been developed, among which platelet

rich plasma (PRP) injections

• Some clinical series have previously evaluated the effect of PRP in the treatment of

tendinopathies (Charousset et al 2014, Andia et al 2015, Kaux et al. 2015 & 2016)

• Recent systematic reviews concluded that PRP could be recommend (low evidence)

as a treatment in epicondylitis and patellar tendinopathies (Andia et al. 2014, Di Matteo et al. 2015, Filardo et al 2016, Fitzpatrick et al. 2017)

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• Knee osteoarthritis _(OA) = one of the major causes of pain and physical disability in

adults

• Symptomatic knee = in approximately 13% of people who are aged ≥ 60 years old (Cooper et al 2000 ; Felson et al. 2004)

• Treatments symptoms _{(Bruyère et al 2019 ; Mascarenhas et al. 2015 ; Carr et al. 2012 ; Hunter et} al. 2006):

• analgesics

• physical therapy

• exercise prescription

• intra-articular injections _{(corticosteroids and HA)} • joint replacements

• New therapeutic methods = platelet-rich plasma _{(PRP) (Mascarenhas et al. 2015)}

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• Removed from the doping list of the WADA • Controversies in literature

• No general agreement

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What’s PRP?

• Centrifugation of autologous blood

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45% cellular

elements

55% plasma

95% RC

4% platelets

1% WC

Blood

PRP

45% cellular

elements

55% plasma

> 95% plaquettes

< 4% RC

< 1% WC

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!8

•

PDGF

• stimulation production other GF

•

TGF-β

• cells proliferation and migration,

collagen synthesis

•

FGF

• angiogenesis, cells proliferation and

migration

•

VEGF

• angiogenesis

•

HGF

angiogenesis

•

IGF-1

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• Many papers were published on PRP for tendinopathies and osteoarthritis,

including RCT and systematic reviews

• Due to the mixed results from controlled studies, the clinical efficacy of PRP in

the treatment of tendinopathies is unclear with shortcomings in the current

literature

• Indeed, there are a lot of variations in the treatment approach including: • subject and outcome specific variables

• severity and localisation of tendinopathies

• PRP preparations techniques, platelet count, number of injections, interval/

frequency of administration, and a lack of volume standardization

• use of anticoagulants and activating agents ? • separation techniques ?

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• Many varied techniques ➙ different PRP

• variation of platelet concentration

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The objective of this study was to

evaluate the similarities and

differences between the variety of PRP formulations,

preparation, and uses of this techniques and to try to

determine characteristics of the PRP which tend to give the

best result to treat tendinopathies and osteoarthritis

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• A search for articles was conducted in the Pubmed and Pedro databases.

• The results were obtained by using the following key words and combinations of these

key words:

• PRP, platelet-rich plasma, injection, treatment, tennis elbow, greater trochanteric

pain syndrome, jumper’s knee, Achilles tendinopathy, plantar fasciitis,

anticoagulant, sodium chloride, local anesthetic, and centrifugation speed.

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• We listed the outcomes that were assessed and reported by each study

• Features included:

• anticoagulants used to preserve the best platelet function • speed of centrifugation used to extract the platelets

• platelet concentrations obtained

• impact of the concentration of red and while blood cells on PRP actions • platelet activators encouraging platelet degranulation and, hence, the

release of growth factors

• use or nonuse of local anesthetics when carrying out infiltration • use of ultrasound guidance during the injection with a view to

determining the influence they have on potential recovery.

• We contacted all of the authors by e-mail because of insufficient data in the

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• We selected the studies included in the systematic review of meta-analyses of

Campbell et al. published in 2015, evaluating platelet-rich plasma injection in the

treatment of knee OA

• One RCT was excluded because it was written in Chinese _{(Li et al. 2011)}

• Two other RCTs were added, after an updated literature search _{(Acosta-Olivo et al.} 2014; filardo et al. 2015)

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• We listed the outcomes that were assessed and reported by each study, including: • Visual Analog Scale _(VAS)

• Western Ontario and McMaster Universities Osteoarthritis Index _(WOMAC) • International Knee Documentation Committee _(IKDC)

• Knee Injury and Osteoarthritis Outcome Score _(KOOS)

• The minimal clinically important improvement _(MCII) was defined to help

determining whether an observed difference is clinically important

• Tubach et al. ₍₂₀₁₂₎ determined the value of 15 of 100 for absolute improvement

or 20% for relative improvement as the value of MCII in knee OA

• Classification of the different studies in 2 groups depending on the outcomes: • bad responders group ₍_{BRG < MCII)}

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• To classify the PRP of the different studies, we used the PAW and Mishra

classifications (Delong et al. 2012 ; Mishra et al. 2012) • To easily know:

• level of platelets concentration

• activation before injection or not • presence or absence of WBC

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• A total of 58 articles were selected • 14 - epicondylitis • 14 - patellar tendinopathies • 17 - calcaneal tendinopathies • 13 - plantar fasciitis

Tendinopathies

• A total of 19 articles were selected • 5 authors _{(Acosta-Olivo, Jang, Patel, Say, and}

Vaquerizo) out of 19 (26.3%) gave us more

information about the quality of the PRP they used in their study

• The separation between BRG _{(𝑁 = 4 )} and

VGRG (𝑁 = 7 ) was made from these values

(8 studies were not included in any group)

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• Anticoagulant generally used: citrate,

ACD-A

• Numerous protocols describing the optimal

conditions for centrifugation but single

spinning centrifugation seems to be better

• 1 to 3 injections

• Infiltration under ultrasound

guidance, even if PRP diffusion is observed

after injection

Tendinopathies

Osteoarthritis

• Anticoagulation = citrate

• Single spinning technique was used

the most (6/11) and this technique

appears to give better results than double spinning technique

• In 4 out 7 studies of the VGRG, 1 or 2

injections were given, against 3 in all

the studies of the BRG

• Time between injections tends to be

more important in the VGRG (2 to 3 weeks in contrast to 1 in BRG)

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• Time after blood puncture before injections was less than 2 hours • Best to use an aphaeresis machine _{(reproducibility)}

• Use of a local anesthetic is not recommended as it may compromise the

therapeutic potential of PRP —> reduce local pH —> inhibition, reduction, or absence of platelet degranulation

• Freezing technique was used to conserve the PRP units when other injections were

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• It is interesting to note that almost all best results were obtained Mishra 4B and

PAWP2B𝛽

• This corresponds to:

• activated

• leukocyte-poor PRP

• platelet concentration of less than 5x baseline _{(Mishra classification)} or more

precisely between baseline and 750000 platelets/𝜇 L (PAW classification)

• The use of leukocyte poor PRP is recommended to avoid any local

inflammatory reaction which can be painful for the patient and reduce the proliferative phase of the healing process

• However, results can also be good with the use of L-PRP to treat tendinopathies • The exact count of RBC and the use of NaHCO₃ were never available

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• There is a lack of standardization in PRP preparation technique

• Our study helped identify features of PRP recommended for tendinopathies and knee

OA treatment, such as:

• the use of a single spinning technique

• a platelet concentration lower than 5 times the baseline _{(from3 to 4)} • avoiding RBC and WBC _{(Leukocyte-rich PRP is only used in the BRG !!)}

• the use of CaCl₂ and citrate is frequent • volume of PRP is inconstant

• So, a general agreement on the preparation and the type of the PRP to use in

orthopedics is still need

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TITRE

SOUSTITRE

orbi.uliege.be

Thank you

for your attention !

@SportS2_CHU @JFKaux