Long-term beneficial effects of platelet-rich plasma for non-insertional Achilles tendinopathy

Abstract

The aim of this retrospective study is evaluating the long-term clinical outcome in patients affected by mid-portion Chronic Recalcitrant Achilles Tendinopathies (CRAT) treated with administration of single platelet-rich plasma (PRP).
A total of 83 tendons (73 patients, 59 males and 14 females; age 43±17.5 years) affected by non-insertional CRAT were treated with single PRP injection. These were evaluated with the Victorian Institute of Sport Assessment - Achilles (VISA-A) questionnaire, Blazina score and satisfaction index at baseline at intervals of 3 weeks, 3 months, 6 months. Final follow-up was carried out at a mean of 50.1 months (range, 24-96).
Baseline VISA-A was 45±15. Results relative to the final follow-up improved significantly to a mean of 88±8 (p<00.1). Blazina was used for patients practicing sports (54 tendons out of 46 different patients): 37 tendons were grade IIIa, 11 II, and 6 IIIbis. Final follow-up Blazina scores improved for 45 grade 0, 5 I, 4 II (p<00.5). Seventy-six tendons (91.6%) were rated as satisfactory and patients would repeat the treatment. Seven tendons (8.4%) were classified as unsatisfactory at the 6 months follow-up and underwent a second PRP injection. In addition to this, patients reported no Achilles tendon rupture.
The study shows beneficial effects and low complication rate following of single PRP injections on a large cohort of patients with mid-long-term follow-up. No cases reported Achilles tendon rupture, in contrast to literature, which described CRAT as one of the most common risk factors. The use of a single PRP injection can therefore be a safe and attractive alternative in the treatment of non-insertional CRATs.
Copyright © 2014 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

Full text

Long-term
beneficial
effects
of
platelet-rich
plasma
for
non-insertional
Achilles
tendinopathy
Matteo
Guelfi
a,
*,
Andrea
Pantalone
a
,
Daniele
Vanni
a
,
Michele
Abate
a
,
Marco
G.B.
Guelfi
b
,
Vincenzo
Salini
a
a
Orthopaedic
and
Traumatology
Division,
‘‘G.
d’Annunzio’’
University,
Via
dei
Vestini
35,
66013
Chieti,
Italy
b
Orthopaedic
Division,
Clinica
Montallegro,
Via
M.
Te
Zovetto
27,
16145
Genoa,
Italy
1.
Introduction
Non-insertional
Achilles
tendinopathies
are
typically
over-use
injuries
that
occur
2–6
cm
proximal
to
the
tendon
insertion,
region
with
a
lower
vascularization
[1–3].
The
pathogenesis
of
Achilles
tendinopathy
is
not
fully
understood
but
probably
related
to
poor
vascularization
and
high
blood
demand
during
activity.
This
is
a
painful
condition
affecting
mainly
active
middle-age
adults
and
it
is
responsible
of
a
severe
reduction
in
physical
performance
and
persistent
pain
[4,5].
Onset
of
symptoms
is
just
the
tip
of
the
iceberg
of
a
long
process
due
to
unknown
factors
such
as
injury,
overuse
and
metabolic
disorders.
It
is
in
practice
an
advanced
failure
of
a
chronic
healing
response
[6].
This
condition
has
always
been
difficult
to
treat
for
orthopedic
surgeons,
choices
are
multiple
from
conservative
to
surgery
without
unique
consensus.
As
the
pathogenesis
is
not
clear,
we
do
not
know
why
and
how
any
therapeutic
modality
work
[7–9].
Since
2006
with
Mishra
et
al.
[10]
and
Sanchez
et
al.
in
2007
[11]
local
administration
of
platelet-rich
plasma
(PRP)
has
become
a
hot-topic
in
treatment
in
tendinopathies
resistant
to
conservative
approach
[12,13].
Platelet-derived
growth
factors
provide
a
local
regenerative
stimulus
in
tendon
healing
[14].
To
date,
local
administration
of
growth
factors
contained
in
PRP
is
an
increasing
and
valuable
way
to
treat
tendinitis
and
in
particular
Achilles
tendinopathies.
There
are
many
PRP
formulations,
which
differ
in
terms
of
cell
type
content,
platelet
concentration,
storage
methods,
activation
methods
and
protocols
for
therapeutic
application
[15,16].
Foot
and
Ankle
Surgery
xxx
(2014)
xxx–xxx
A
R
T
I
C
L
E
I
N
F
O
Article
history:
Received
26
September
2014
Received
in
revised
form
3
November
2014
Accepted
13
November
2014
Keywords:
Achilles
tendinopathy
Non-insertional
Leukocyte-rich
Platelet-rich
plasma
L-PRP
PRP
Blazina
score
Long
term
Follow-up
Clinical
outcome
A
B
S
T
R
A
C
T
Background:
The
aim
of
this
retrospective
study
is
evaluating
the
long-term
clinical
outcome
in
patients
affected
by
mid-portion
Chronic
Recalcitrant
Achilles
Tendinopathies
(CRAT)
treated
with
administra-
tion
of
single
platelet-rich
plasma
(PRP).
Methods:
A
total
of
83
tendons
(73
patients,
59
males
and
14
females;
age
43

17.5
years)
affected
by
non-insertional
CRAT
were
treated
with
single
PRP
injection.
These
were
evaluated
with
the
Victorian
Institute
of
Sport
Assessment
–
Achilles
(VISA-A)
questionnaire,
Blazina
score
and
satisfaction
index
at
baseline
at
intervals
of
3
weeks,
3
months,
6
months.
Final
follow-up
was
carried
out
at
a
mean
of
50.1
months
(range,
24–96).
Results:
Baseline
VISA-A
was
45

15.
Results
relative
to
the
final
follow-up
improved
significantly
to
a
mean
of
88

8
(p
<
00.1).
Blazina
was
used
for
patients
practicing
sports
(54
tendons
out
of
46
different
patients):
37
tendons
were
grade
IIIa,
11
II,
and
6
IIIbis.
Final
follow-up
Blazina
scores
improved
for
45
grade
0,
5
I,
4
II
(p
<
00.5).
Seventy-six
tendons
(91.6%)
were
rated
as
satisfactory
and
patients
would
repeat
the
treatment.
Seven
tendons
(8.4%)
were
classified
as
unsatisfactory
at
the
6
months
follow-up
and
underwent
a
second
PRP
injection.
In
addition
to
this,
patients
reported
no
Achilles
tendon
rupture.
Conclusions:
The
study
shows
beneficial
effects
and
low
complication
rate
following
of
single
PRP
injections
on
a
large
cohort
of
patients
with
mid-long-term
follow-up.
No
cases
reported
Achilles
tendon
rupture,
in
contrast
to
literature,
which
described
CRAT
as
one
of
the
most
common
risk
factors.
The
use
of
a
single
PRP
injection
can
therefore
be
a
safe
and
attractive
alternative
in
the
treatment
of
non-
insertional
CRATs.
ß
2014
European
Foot
and
Ankle
Society.
Published
by
Elsevier
Ltd.
All
rights
reserved.
*Corresponding
author
at:
Via
Caprera
7/3,
16146
Genoa,
Italy.
Tel.:
+39
3483820425.
E-mail
address:
matteogue@hotmail.com
(M.
Guelfi).
G
Model
FAS-780;
No.
of
Pages
4
Please
cite
this
article
in
press
as:
Guelfi
M,
et
al.
Long-term
beneficial
effects
of
platelet-rich
plasma
for
non-insertional
Achilles
tendinopathy.
Foot
Ankle
Surg
(2014),
http://dx.doi.org/10.1016/j.fas.2014.11.005
Contents
lists
available
at
ScienceDirect
Foot
and
Ankle
Surgery
jou
r
nal
h
o
mep
age:
w
ww.els
evier
.co
m/lo
c
ate/fas
http://dx.doi.org/10.1016/j.fas.2014.11.005
1268-7731/ß
2014
European
Foot
and
Ankle
Society.
Published
by
Elsevier
Ltd.
All
rights
reserved.

Several
clinical
trials
are
available
about
the
use
of
PRP
in
Achilles
tendinopathies
but
literature
data
is
controversial
and
there
are
only
a
few
studies
with
mid–long-term
follow-up
demonstrating
the
stability
of
clinical
outcome.
Our
retrospective
study
aims
at
filling
this
gap
via
evaluating
the
long-term
clinical
outcome
in
a
large
sample
of
patients
treated
with
single
leukocyte-rich
PRP
(L-PRP)
for
healing
of
mid-portion
chronic
recalcitrant
Achilles
tendinopathies
(CRAT).
2.
Materials
and
methods
From
2006
to
mid-2012
PRP
injections
were
performed
in
98
Achilles
tendons
of
85
different
patients
(13
bilaterally).
All
patients
were
affected
by
mid-portion
chronic
recalcitrant
Achilles
tendinopathies
(CRAT)
with
a
history
of
more
than
4
months
of
Achilles
pain
and
not
responding
to
conservative
treatment
as
NSAIDs,
physiotherapy,
TENS
or
laser
therapy.
MRI
or
ultrasound
(US)
was
also
performed
as
confirmation
(Fig.
1).
2.1.
Technique
for
preparing
and
administering
leukocyte
and
platelet-rich
plasma
L-PRP
preparations
occur
from
a
venous
blood
sample
and
citrate
anticoagulant
in
10:1
proportion,
for
a
final
volume
of
60
ml
then
processed
by
the
GPS
TM
II
Platelet
Concentration
System
(Biomet
Biologics
1
,
Warsaw,
IN).
This
system
is
designed
to
produce
a
consistent
8x
baseline
count
while
capturing
over
80%
of
the
available
platelets
within
the
sample
[17].
The
sample
is
centrifuged
for
15
min
at
3200
rpm.
After
withdrawing
platelet-
poor
plasma
(PPP),
the
buffy
coat
containing
the
majority
of
the
platelets
was
shaken
for
30
s.
Six
cc
of
PRP
was
then
suctioned.
We
performed
just
one
L-PRP
administration
both
in
the
lesion
location,
intratendon
and
in
the
peritendon
area,
always
in
local
or
locoregional
anesthesia,
with
patient
prone
and
under
US
control.
2.2.
Aftercare
and
evaluation
After
the
injection
patients
stayed
3
h
supine
then
were
discharged.
They
were
asked
to
rest,
no
weightbearing
and
to
use
ice
for
the
first
24
h,
then
ambulated
for
7
days
with
crutches
and
partial
weightbearing.
After
3
weeks
they
started
a
rehabilita-
tion
program
based
on
eccentric
exercises.
Progressive
return
to
sport
and
daily
activity
was
allowed
after
3
months,
in
according
to
their
clinical
status.
Criterions
investigated
were
age,
sex,
contralateral
side
state
and
treatment
received
prior
to
PRP.
We
evaluated
our
patients
with
the
Victorian
Institute
of
Sport
Assessment
–
Achilles
(VISA-A)
[18]
questionnaire
and
the
Blazina
score
[19]
(Table
1)
before
they
underwent
PRP
(baseline)
and
at
3
weeks,
3
and
6
months
intervals.
Final
follow-up
was
at
a
mean
of
50.1
months
(range,
24–96),
where
patients
were
evaluated
with
VISA-A,
Blazina
functional
score
and
satisfaction
index
(Fig.
2).
Blazina
score
is
a
score
limited
to
assessing
the
clinical
index
of
the
severity
of
tendinopathies.
This
ranges
from
grade
I,
when
tendinopathy
does
not
affect
activity,
to
IV
grade
where
there
is
a
major
functional
damage
and
activity
is
not
possible.
VISA-A
questionnaire
is
the
most
used
and
easy
index
of
the
severity
of
Achilles
tendinopathies.
The
Satisfaction
index
was
divided
in
three
scores:
satisfied,
satisfied
with
reservation
and
dissatisfied.
Kaplan–Meier
analysis
was
also
used,
all
tests
with
p
<
0.05
were
considered
statistically
significant.
3.
Results
Seventy-three
patients
(59
males
and
14
females;
age
43

17.5
years;
3
type
2
diabetics)
of
85
treated
were
assessed
in
the
study
for
a
total
of
83
tendons
(10
treated
bilaterally).
Others
were
not
included
because
they
were
not
available
for
the
final
follow-up.
The
final
follow-up
took
place
on
average
after
50.1
months
(range,
24–96).
At
baseline,
VISA-A
score
was
45

15.
At
the
final
follow-up,
this
improved
significantly
to
a
mean
of
88

8,
with
a
mean
delta
of
43
points
(p
<
00.1).
In
particular,
patients
at
the
6
months
follow-up
reported
a
VISA-A
of
84

15
(Fig.
3).
Forty-six
of
these
patients
practiced
sports
recreationally
or
at
agonistic
level,
1
professionally
(21
runners,
10
football,
8
tennis,
1
basketballs,
6
others
sports
players).
54
tendons
of
these
patients
(8
bilaterally)
were
classified
with
a
Blazina
score:
37
tendons
were
grade
IIIa,
11
II
and
6
IIIbis.
At
final
follow-up
Blazina
score
improved
in
45
grade
0,
5
I,
4
II
(p
<
00.5)
(Fig.
4).
Seventy
(84.4%)
tendons
were
rated
by
patients
as
satisfactory,
6
(7.2%)
were
rated
as
satisfactory
with
reservations:
a
total
of
91.6%
(76
tendons)
of
satisfied
patients
expressed
positive
view
that
going
back
they
would
have
chosen
again
to
opt
for
this
treatment.
Seven
patients
(8.4%,
no
bilaterally),
5
not
practicing
sports,
were
classified
as
unsatisfactory
and
did
not
reach
acceptable
healing
(VISA-A
54

9;
Blazina
IIIa)
at
the
6
months
follow-up.
For
these
patients
with
minimal
or
no
improvement
Fig.
1.
A
clinical
and
MRI
case
of
CRAT.
Table
1
Blazina
score
system.
Blazina
score
Grade
I
Pain
after
excercising
does
not
affect
athletic
activity
Grade
II
Pain
at
the
beginning
of
physical
activity
that
disappears
after
warming
up
and
comes
back
after
exercising
Grade
III
Pain
during
and
after
exercise,
which
progressively
affects
athletic
performance
Grade
III
bis
All
athletic
activities
are
stopped
because
of
pain
Grade
IV
Major
functional
damage
M.
Guelfi
et
al.
/
Foot
and
Ankle
Surgery
xxx
(2014)
xxx–xxx
2
G
Model
FAS-780;
No.
of
Pages
4
Please
cite
this
article
in
press
as:
Guelfi
M,
et
al.
Long-term
beneficial
effects
of
platelet-rich
plasma
for
non-insertional
Achilles
tendinopathy.
Foot
Ankle
Surg
(2014),
http://dx.doi.org/10.1016/j.fas.2014.11.005

(5
males
and
2
females,
age
55

5.5
years,
2
type
2
diabetics)
we
performed
a
second
L-PRP
injection
which
took
place
after
a
mean
of
12

6
months.
At
the
final
follow-up
(41

20
months),
after
the
second
injection,
VISA-A
in
these
patients
has
been
77

5
and
all
patients
ranked
grade
I
for
Blazina.
All
athletes
returned
to
sports
within
6
months,
2
without
reaching
the
same
sport
fitness
level.
Complications
due
to
the
treatment
such
as
infections,
inflammations,
edema
or
vasculo-nervous
complication
were
not
observed.
In
addition
to
this,
patients
reported
no
Achilles
tendon
ruptures.
4.
Discussion
Our
study
shows
a
good
clinical
outcome
within
single
L-PRP
injections
on
a
large
cohort
of
patients
with
mid–long-term
follow-
up.
Injection
of
PRP
to
Achilles
tendon
has
proved
safe
as
no
complications
have
occurred.
No
patient
reported
Achilles
tendon
rupture,
in
contrast
with
existing
literature
data
which
identifies
CRAT
as
one
of
the
risk
factors
[20,21].
We
hypothesize
therefore
that
L-PRP
could
have
a
beneficial
and
protective
role
in
Achilles
tendon
ruptures.
Further
studies
are
required
to
deepen
analysis
and
detail
and
to
further
strengthen
our
findings.
PRP
is
an
autologous
preparation
of
concentrated
platelets
in
a
small
volume
of
plasma,
is
safe,
free
of
transmissible
diseases
and
well
accepted
by
patients
and
surgeons
[22].
Recent
clinical
studies
reporting
a
higher
level
of
evidence
fail
to
show
consistent
positive
results
for
the
use
of
various
PRP
[23]
and
to
date
no
EBM
support
for
the
use
of
PRP.
This
could
be
due
to
a
failure
in
standardization
of
procedures.
A
variety
of
different
production
methods
for
PRP
have
been
published
in
literature
or
presented
by
medical
companies
[24].
This
results
in
numerous
PRP
treatments
being
available,
which
differ
in
terms
of
number
of
platelets,
white
blood
cell
content,
fibrin
concentration
and
method
of
platelet
activation
[25].
Some
authors
define
PRP
as
only
platelets,
whereas
others
note
that
PRP
also
contains
increased
concentrations
of
leukocytes,
fibrin
and
some
bioactive
proteins
[26].
For
this
reason,
PRP
was
classified
into
pure
platelet-rich
plasma
(P-PRP),
leukocyte
and
platelet-rich
plasma
(L-PRP)
and
leukocyte
and
platelet-rich
fibrin
(L-PRF)
[6].
Still,
some
authors
prefer
the
term
platelet-rich
growth
factors
(PRGF)
as
they
believe
unique
advantages
of
PRP
are
richness
in
growth
factors
[27].
Another
crucial
point
in
PRP
standardization
is
its
autologous
origin:
naturally,
blood
from
one
patient
may
have
a
very
different
composition
from
another,
although
blood
from
an
individual
can
also
vary
greatly
between
each
draw.
Therefore,
the
final
PRP
is
ultimately
determined
by
the
nature
and
characteristics
of
the
patient’s
blood
at
the
time
of
the
draw
[28].
Notwithstanding
the
above,
the
use
of
PRP
in
treatment
of
musculoskeletal
injuries
is
backed
mainly
by
good
clinical
outcomes,
validated
by
numerous
low-quality
short-term
fol-
low-up
trials
[29].
The
rationale
of
the
treatment
is
to
carry
many
growth
factors
and
cytokines
contained
in
platelet
granules
that
are
known
to
play
a
key
role
in
hard
and
soft
tissue
repair
[30–34].
PRP
contains
high
concentrations
of
growth
factors
including
transforming
growth
factor
beta
(TGF-B),
vascular
endothelial
growth
factor
(VEGF),
platelet-derived
growth
factor
(PDGF),
epithelial
growth
factor
(EGF),
hepatocyte
growth
factor
(EGF)
and
insuline-like
growth
factor
(IGF-I).
These
modulate
the
healing
of
bone,
muscle
and
tendon
through
interactions
with
specific
cells
[35].
The
first
study
focusing
on
the
value
of
PRP
in
CRAT
was
Gaweda
et
al.
[36]
in
2010.
He
treated
15
tendons
with
significant
improvement
and
functional
recovery
at
14
months
of
follow-up.
Since
Gaweda’s
assessment,
numerous
studies
have
taken
place
although
almost
all
of
them
with
short-term
follow-ups.
Non-insertional
Achilles
tendinopathies
are
one
of
the
most
common
tendinitis
affecting
both
athletes
and
common
people.
NSAIDs,
physiotherapy
and
Hyaluronic
acid
injections
do
not
seem
to
have
demonstrated
any
long-term
efficacy.
Eccentric
exercise
of
the
gastrosoleus
complex
was
considered
the
only
helpful
treatment
prior
to
surgery
but
it
shows
good
results
only
in
around
50%
[22,37]
of
the
cases.
Operative
treatments
for
patients
where
conservative
management
has
proved
ineffective
for
at
least
six
months
has
been
debated
and
not
validated.
In
any
case,
operative
treatment
should
be
considered
as
last
option
only
if
other
options
have
proven
not
effective.
5.
Conclusion
In
light
of
the
above
results,
we
can
confirm
that
one
injection
of
autologous
leukocyte-rich
PRP
safely
provides
mid–long-term
clinical
benefits
within
treatment
of
CRAT.
The
symptoms
showing
Fig.
2.
MRI
of
a
CRAT
case
successfully
treated
with
leukocyte-rich
PRP.
(A)
MRI
at
baseline;
(B)
MRI
at
55
months
of
follow-up.
Fig.
3.
VISA-A
scores
at
baseline,
6
months
and
final
follow-up.
Fig.
4.
Blazina
ranked
at
baseline
and
at
final
follow-up.
M.
Guelfi
et
al.
/
Foot
and
Ankle
Surgery
xxx
(2014)
xxx–xxx
3
G
Model
FAS-780;
No.
of
Pages
4
Please
cite
this
article
in
press
as:
Guelfi
M,
et
al.
Long-term
beneficial
effects
of
platelet-rich
plasma
for
non-insertional
Achilles
tendinopathy.
Foot
Ankle
Surg
(2014),
http://dx.doi.org/10.1016/j.fas.2014.11.005

improvement
and
functional
recovery
are
experienced
over
time
in
mid–long-term
follow-up.
In
conclusion,
our
study,
notwithstanding
many
limitations
as
the
lack
of
a
control
group
and
final
imaging
evaluation,
is
one
of
the
firsts
studies
evaluating
mid–long-term
results
in
treating
non-
insertional
Achilles
tendinopathies
with
one
single
L-PRP
injection.
Conflict
of
interest
The
author(s)
declared
no
potential
conflicts
of
interest
with
respect
to
the
research,
authorship,
and/or
publication
of
this
article.
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M.
Guelfi
et
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/
Foot
and
Ankle
Surgery
xxx
(2014)
xxx–xxx
4
G
Model
FAS-780;
No.
of
Pages
4
Please
cite
this
article
in
press
as:
Guelfi
M,
et
al.
Long-term
beneficial
effects
of
platelet-rich
plasma
for
non-insertional
Achilles
tendinopathy.
Foot
Ankle
Surg
(2014),
http://dx.doi.org/10.1016/j.fas.2014.11.005