Johannes Tol Sports medicine physician, Aspetar, Orthopaedic and Sports Medicine Hospital, Doha, Qatar. - PRP for acute hamstring injuries: a 3-arm RCT in Qatar (6th MuscleTech Network workshop) 14th October, Barcelona

2. Disclaimer
• No

3. Take
home
-­‐ The
magic
number
is
5
-­‐ In
professional
football:
“With
a
good
Rehab
program,
there
is
NO
need
for
PRP”

4. Catalan
Match
of
the
Magic
5
-­‐ Who?
1
*
5
years
for
FC
Barcelona
-­‐ When?
3
*
5
years
a7er
last
La
Liga
championship
-­‐ Why
important?
5
*
5
matches
without
loss
a7er
his
arrival
-­‐ Where?
100
*
5
km
South-­‐West
from
Barcelona
-­‐ Which
score?
*
5
*
5
*
5
*
5
*
5

5. Use
of
Complex
Growth
Factor
PreparaIons
in
the
Management
of
Muscle
Strain
Injury
ASPETAR
Consensus:
February
2009

6. Why
Platelet
Rich
Plasma?
• PRP
– 2-­‐8
Imes
increased
concentraIon
platelets
– Release
of
growth
factors
(GF)
– 2-­‐8
Imes
increased
GFs
– PDGF
(platelet
derived
GF)
– TGF-­‐beta
(transforming
GF)
– IGF-­‐I
(insuline-­‐like
GF)
– PDEGF
(platelet
derived
endothelial
GF)
– PDAF
(platelet
derived
angiogeneis
F)
– PF-­‐4
(platelet
factor)

7. PRP
in
muscle
injury
Animal
models:
• Growth
factors
released
by
platelets(1-­‐3)
– Myoblast
proliferaIon
↑
– Myofiber
regeneraIon
↑
– Force
↑
Menetrey
et
al.
2000,
Wright-­‐Carpenter
et
al.
2004,
Hammond
et
al.
2009

8. • Pilot
study
in
grade
2
muscle
injuries
• PRP:
N=18;
• RetrospecIve
controls
Actovegin/Traumeel:
N=11
• Non-­‐randomised,
Non-­‐blinded
• Average
5
injecIons
PRP!!
• Return
to
play
PRP:
17
days
-­‐
almost
normal
MRI
at
2
weeks!!!
(?)
Control:
22
days
-­‐
abnormal
MRI
5
days
earlier
RTP
Wright-­‐Carpenter
et
al.
IJSM
2004
Evidence
for
PRP
?

9. Evidence
for
PRP
?
• Conference
abstract
• 22
muscle
injuries
“Magic
Spanish
5”:
1. Full
funcIonal
recovery
2. 50%
earlier
than
EXPECTED
(?)
RTP
3. Sonography:
full
regenerated
muscle
Issue
4. No
fibrosis
5. No
re-­‐injuries
in
any
athlete,
Sanchez
et
al.
2005
2nd
InternaIonal
Conference
on
regeneraIve
medicine

10. Why
Platelet
Rich
Plasma?
Expected
increase
$45
million
(2009)
to
$126
million
in
2016

11. Two
recent
RCTs
Dutch
study:
• PRP
not
effecIve
in
acute
hamstring
injuries
LimitaIons:
1. Non-­‐professional
athletes
2. MulIcenter
Reurink
G,
Goudswaard
GJ,
Moen
MH,
Weir
A,
Verhaar
JA,
Bierma-­‐Zeinstra
SM,
Maas
M,
Tol
JL;
Dutch
Hamstring
Injec_on
Therapy
(HIT)
Study
Inves_gators.
Platelet-­‐rich
plasma
injec_ons
in
acute
muscle
injury.
N
Engl
J
Med.
2014
Jun
26;370(26):2546-­‐7.

12. Two
recent
RCTs
Malaysian
study:
• PRP
more
effecIve
than
physio
LimitaIon:
1. Non-­‐blinded
design
Hamid
MS,
Mohamed
Ali
MR,
Yusof
A,
George
J,
Lee
LP.
Am
J
Sports
Med.
2014
Jul
29.
46-­‐7.

13. Aim
Establish
the
efficacy
of
PRP
injecIons
in
acute
hamstring
injuries

14. Methods
• Inclusion
criteria
ü Acute onset posterior thigh pain
ü MRI confirmed Hamstring Injury gr I And II
ü < 5 days from injury
ü Able to perform Physiotherapy at ASPETAR (5 / week)
ü Available for follow-up
ü Male
ü Age > 18 years
• 90
subjects
randomized
– PRP
group
(Biomet)
– PPP
group
– Physio
group
(Regular
care
/
no
injecIon)

15. Outcome
measures
• Time
to
return
to
play
(RTP)
StaIsIcal
analysis:
1. Cox
regression
(rate
to
RTP)
2. Generalized
linear
model
(average
RTP)
Adjusted
for
baseline
variables
that
influenced
the
primary
outcome
with
p
<
0.10
• Secondary
§ Re-­‐injury
rate
§ MRI
§ IsokineIc
strength

16. MRI
variables
• Size
of
edema
– length
(mm)
– width
(mm)
– depth
(mm)
– cross-­‐secIonal
area
(cm2)
– volume
(cm3)
• Extent
of
fibre
disrupIon
(mm)
• Grading
(0-­‐3)
Hamilton
B,
Whiteley
R,
Almusa
E,
et
al.
Excellent
reliability
for
MRI
grading
and
prognos@c
parameters
in
acute
hamstring
injuries.
Br
J
Sp
Med
2013
Nov
19.
doi:
10.1136/bjsports-­‐2013-­‐092450.
[Epub
ahead
of
print]

17. Study
interven_on
• InjecIon
procedure
– LocalizaIon
on
MRI
and
US
– One
procedure
3
injecIons
PPP
or
PRP
• <
5
days
a7er
injury

18. Standardized
rehabilita_on
program
• Protocol
created
by
Rehab
staff
(consensus)
• 3
experienced
physio’s
/
1
sports
rehabilitator
• Criteria-­‐based
6
stages,
including
field
tesIng1
• PT:
blinded
to
MRI
(grading)
and
therapy
• All
3
groups
standardized
Rehab
Tol
JL,
Hamilton
B,
Eirale
C,
Muxart
P,
Jacobsen
P,
Whiteley
R.
.
At
return
to
play
following
hamstring
injury
the
majority
of
professional
football
players
have
residual
isokine_c
deficits.
Br
J
Sports
Med.
2014
Feb
3

19. Downloaded from bjsm.bmj.com on May 16, 2014 - Published by group.bmj.com
Table 1 Criteria-based rehabilitation programme for hamstring injury
Stage Content Criteria to progress
Stage 1 All activity to be pain-free
2 leg squat, or if able, single leg squat
Maintain pelvis control, hip and knee alignment, squat to 45°, hold, return to start
Supine Bridge—2 leg
2 s up, 2 s down (4 s total per rep.) Begin at 45°. Must reach knee-hip-shoulder in alignment. 4×15
supine isometric heel digs
In supine, painlessly pull heel into bed through range. Can bias with tibial IR/ER when painless.
Exercise bike
Upright or recumbent, can substitute with elliptical trainer.
Isometric manual-resisted hamstring
Therapist applied resistance isometrically in varying angles in prone
Soft tissue massage
Proximal and distal to injury site, lymphatic drainage.
Active range of motion exercises
Supine active knee flexion and extension then Prone active flexion and extension
Criteria to progress to stage 2:
1. Painless single leg squat
2. Painless bike, 150W 5 min
3. Full knee extension supine
Stage 2 Any exercise from stage 1 permitted, additionally:
Supine bridge—1 leg
Same rate as for 2 legs, other knee in full extension, thighs parallel throughout exercise. 4×15
Walk-Jog
Walk 20 m corners, jog the 30 m straight, painless. Begin at 25% (self-rated) jog, progress to max
70%.
Triple extension walk
100 m laps, every third step triple extension—ie, alternating legs.
‘A’ drill
Walking late swing knee extension, painless. Alternating legs, 100 m lap.
Soft tissue massage
Can massage injured area. Maximum allowed pain VAS: 4/10. Therapist uses caution with any report
of discomfort, monitor symptoms, adjust accordingly
Stretching
Hamstring (supine, 90° hip flexion, knee extension);
SLR (supine to onset of discomfort add ankle DF)
Initially active, patient-controlled, progress to passive, end range. SLR mobilisation if indicated.
Resisted hamstring
Note tibial rotation as indicated. 4×15 repetitions, aiming for fatigue
Original article
Criteria to progress to stage 3:
1. Run !70% patient rated
2. ROM hamstrings !75% uninvolved side
3. ROM SLR !75% uninvolved side
Stage 3 Any exercises from stages 1 and 2, additionally:
Single leg bridge
1 s repetition, 2 s recovery. 4×8 repetitions.
Single leg bridge, foot on Swiss ball
2 s up, 2 s down. 4×8 repetitions.
Interval running
20 m jog 30 m run. Begin running at 70% (patient rated), progressing by 10% steps, painlessly. At
90%, progress by 5%. Monitor performance by hand timing.
Modified T-Drill
Direction changing running over T-Drill course. Begin at patient rated 70%, progress as able by 10%
until 90%, then by 5%. Monitor performance by hand timing.
Eccentric exercises
Nordic Hamstrings, manual-resisted eccentric, prone catches, Arabesque (single leg stance, trunk
flexion)
Criteria to progress to stage 4 (sport-specific rehab):
1. 100% running speed
2. Painless high-speed direction changes
Stage 4 Any exercises from stages 1–3, additionally on-field, football-specific drills:
Direction change drills
With and without the ball, 40 min
Jumping drills
10–15 min
Criteria to progress to stage 5 (sport-specific rehab):
1. Painless completion of stage 4
Stage 5 Passes and run
Long passes progression
Crosses (static)
Corner kicks
Crosses (dynamic)
Criteria to progress to stage 6 (sport-specific rehab):
1. Painless completion of stage 5
Stage 6 Passes and run
Shooting scenarios
Competitive 1 versus 1 drills
Shooting scenarios
Scoring scenarios
Criteria to progress to medical review for return to sport:
1. Painless completion of stage 6
DF, dorsiflexion; ER, external rotation; IR, internal rotation; Modified T-Drill, (always) forward running over the course of the Agility t test; ROM, range of motion; SLR, straight leg raise.

20. Sports
specific
func_onal
field
tes_ng
Staged
progression
of
volume
and
intensity
of
:
•
direcIon
changes
•
sprints
•
jumps
•
(cross-­‐)
passes
•
shooIng
•
interval
running
•
one
-­‐
on
-­‐
one
aracking
•
defence
drills
mimicking
muscle
faIgue
and
compeIIveness
during
football
training
and
game
situaIons

21. Return
to
sport
decision
• Blinded
sports
medicine
physician
• Clinical-­‐based
decision
• Successful
and
asymptomaIc
compleIon
of
the
progressive
criteria-­‐based
rehabilitaIon
programme,
including
the
sports
specific
funcIonal
field
tesIng
• ReflecIon
of
daily
pracIce

22. Results
• Age
25.8,
SD
5.7
• 90%
professional
athletes
/
83%
Football/Futsal
• PRP
increase
of
platelets:
factor
3.2
• Baseline
variables
associated
with
RTP
were
(P<0.10):
– Pain
score
at
injury
(0-­‐10)
– Volume
of
edema
on
MRI
(cm3)

23. Results
PRP:
22.0
(Unadjusted
95%CI:
17.8-­‐24.1)
PPP:
27.7
(Unadjusted
95%CI:
20.6-­‐33.5)
Physio:
24.9
(Unadjusted
95%CI:
21.5-­‐28.5)
PRP
PPP
Physio

24. Adjusted
Hazard
Ra_o
Adj
HR:
PRP
vs.
PPP
=
2.29
(95%
CI
1.30
to
4.04)
P=0.004
Adj
HR:
Physio
vs.
PRP
=
0
.67
(95%
CI
0.39
to
-­‐1.16)
P=0.15
Adj
HR:
Physio
vs
PPP
=
1.57
(95%
CI
0.88
to
-­‐
2.80)
P=0.13
-­‐
Weeks

25. Adjusted
results
• Time
to
RTP:
– PRP
vs
PPP:
mean
difference
5
days
(adj
95%CI
-­‐10.1
to
-­‐
1.4)
P=0.01
– No
difference
between:
–
PRP
vs
Physio
–
Physio
vs
PPP
PRP
PPP
PHYS

26. UEFA
study
16%
(2
months)
Re-­‐injury
rate
7%
7%
7%
8%
11%
11%
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
PRP
PPP
Physio
Re-­‐injury-­‐
≤2m
Re-­‐injury-­‐
<6m

27. Decrease
of
edema
on
MRI
(3
planes)

28. Decrease
of
edema
on
MRI
(volume)

29. Isokine_c
strength
at
RTP
Compared
to
contralateral
leg

30. Conclusion
• No
benefit
of
PRP
compared
to
Physio
• Benefit
of
PRP
compared
to
PPP
ExplanaIon?
Relevance?
• No
difference
re-­‐injuries,
MRI,
strength

31. Discussion
• Strength:
– Professional
athletes
– Single
center
criteria-­‐based
Rehab
program
– Placebo
controlled
double
blind
design
(PRP,PPP)
• LimitaIons
– Third
arm
(physio
group)
not
blinded
(bias?)
– Specific
elite
athlete
seung
(generalizability?)
– GF
content
PRP
and
PPP
(pending)

32. Take
home
-­‐ The
magic
number
is
5
-­‐ In
professional
football:
“With
a
good
Rehab
program,
there
is
NO
need
for
PRP”

33. Thanks
Key
people
• Dr
Hakim
Chalabi
• Dr
Mohammed
Ghanem
• Dr
Khalifa
Alkuwari
Aspetar
Consensus
mee_ng:
• Dr
JusIn
Grantham
• Patrick
Schamasch
IOC
• Alain
Garnier
WADA
• Bengt
SalIn
• Xavier
Bigard
• Burhan
Gharaibeh
• Antonio
Gigante
• Ramon
Cugat
• Donald
Kuah
• Franco
Benazzo
• Francois
Kelberine
• Brent
Kirkbride
• Tarek
El
Nidani
• Riadh
Miladi
Aspetar
• Peter
Fowler
Aspetar
• Dean
Kenneally
Aspetar
SMP:
• Dr
JusIn
Paoloni
• Dr
Bruce
Hamilton
• Dr
Claude
Tremblay
• Dr
Massimiliano
Sala
• Dr
Eduardo
Mauri
• Dr
Celeste
Geertsema
• Dr
Robbart
van
Linschoten
• Dr
Johannes
Tol
• Dr
Aston
Ngai
• Dr
Andrew
Miller
• Dr
Stephen
Targer
• Dr
Adam
Weir
• Dr
Frank
van
Hellmondt
• Dr
Liesel
Geertsema
• Dr
Massimo
Manara
• Dr
Paul
DIJKSTRA
Fellows:
• Dr
Bhavesh
Kumar
• Dr
Mar
Robinson
• Dr
Floor
Groot
• Dr
Robert
Johannes
de
Vos
• Dr
Elke
van
den
Steen
Research
Nurse:
• Sirine
Boukarroum
Physiotherapist:
• Rod
Whiteley
• Philipp
Jacobsen
• Patrice
Muxart
• Roald
Oren
• Mohsen
Abassi
Research
assistance/
Researcher:
• Faten
Smiley
• Arnlaug
Wangensteen
• Andreas
Serner
• Dr
Vidya
Mohammad
Ali
• Wade
Knez
• Rima
Tabanji
Other
nurses
:
• Pascale
Tahtouh
• Nelly
Khalil
Orthopaedic
surgeons:
• Dr
Phillipe
Landreau
• Dr
Nebojsa
Popovic
• Dr
Mareo
Regusci
• Dr
Pieter
D’Hooghe

34. Thanks
Radiologist:
• Dr
Nabil
Jomaah
Lab
technicians
&
Phlebotomists:
• BharaI
Shery
• Sorainie
Nunez
• Maria
Galabo
• Khalidah
Mansour
• Maya
Kemaldean
Gharziddine
• Dr
Emad
Almusa
• Dr
Bernard
Roger
Radiographers
:
• Andrew
Roshan
• Brendan
Mundey
• Donna
Smith
• Eihab
AbouHashem
• LaIfa
Saifeldin
• Mohamed
Nawas
• Mahmooda
Banu
• Toni
Evans
• Tessa
Smith
Other
Radiology
Staff:
• Salwa
Allenjawi
• Natalia
Hatamova
• Rachid
Aiaou
Clubs
and
Federa_ons:
• Al
Ahli
Sports
Club
• Al
Arabi
Sports
club
• Al
Gharafa
Sports
Club
• Al
jaish
team
• Al
khariIyath
Sports
Club
• Al
Khor
Sports
Club
• Al
Markhiya
Sports
Club
• Al
Rayyan
Sports
Club
• Al
Sadd
Sports
Club
• Al
Sailiya
Sports
Club
• Al
Shahaniya
Sports
Club
• Al
Shamal
Sports
Club
• Al
Wakrah
Sports
Club
• Mesaimeer
Sports
Club
• Military
Sports
AssociaIon
• Moaither
Sports
Club
• Olympic
commiree
• InternaIonal
Athlete
• Lakhwaya
Sports
Club
• QATAR
HOCKEY
FederaIon
• Qatar
Sports
Club
• Qatar
Armed
Forces
• Qatar
Basketball
FederaIon
• Qatar
Football
AssociaIon
• Qatar
Taekwondo
&
Karate
FederaIon
• Qatar
Weightli7ing
&
body
building
FederaIon
• Qatar
NaIonal
team
• Um
Salal
Sports
Club

35. Take
home
-­‐ The
magic
number
is
5
-­‐ In
professional
football:
“With
a
good
Rehab
program,
there
is
NO
need
for
PRP”

36. Catalan
Match
of
the
Magic
5
-­‐ Who?
1
*
5
years
for
FC
Barcelona
-­‐ When?
3
*
5
years
a7er
last
La
Liga
championship
-­‐ Why
important?
5
*
5
matches
without
loss
a7er
his
arrival
-­‐ Where?
100
*
5
km
South-­‐West
from
Barcelona
-­‐ Which
score?
*
5
*
5
*
5
*
5
*
5

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