ORIGINAL ARTICLE
Platelet-rich plasma injections for the treatment of refractory Achilles
tendinopathy: results at 4 years
Giuseppe Filardo1, Elizaveta Kon2, Berardo Di Matteo1, Alessandro Di Martino1, Giulia Tesei1,
Patrizia Pelotti3, Annarita Cenacchi4, Maurilio Marcacci1
II Orthopaedic and Traumatology Clinic - Biomechanics and Technology Innovation Laboratory,
Nano-Biotechnology Laboratory, 3Radiology and Diagnostic Imaging Department, 4Immunohaematology andTransfusion Medicine Service, Rizzoli Orthopaedic Institute, Bologna, Italy

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Background. Chronic Achilles tendinopathy is responsible for a severe reduction in physicalperformance and persistent pain. There is currently a number of therapeutic options and the local
administration of growth factors is an emerging treatment strategy. In particular, platelet-rich plasma(PRP) is a widely used way to provide a local regenerative stimulus for tendon healing. The aim of thisstudy was to document the mid-term results obtained after treating recalcitrant Achilles tendinopathy
with injections of high concentrate, leucocyte-rich PRP.
Materials and methods. Twenty-seven patients (mean age: 44.6 years; 22 men and 5 women)
affected by chronic mid-portion Achilles tendinopathy (7 bilateral, for a total of 34 tendons),
refractory to previous treatments, were enrolled. Patients were treated with three ultrasound-guided
intra-tendinous injections of PRP at 2-week intervals. Patients were prospectively evaluated at baseline,
and then at 2, 6, and up to a mean of 54.1 months of follow-up (minimum 30 months), using thefollowing tools: Blanzina, VISA-A, EQ-VAS for general health, and Tegner scores.
Results. The VISA-A score showed a significant improvement: the baseline score of 49.9±18.1
increased to 62.9±19.8 at 2 months (p=0.002), with a further improvement at 6 months (84.3±17.1,
p<0.0005), and stable results at 4.5 years (90.0±13.9). The EQ-VAS score also showed a similar
positive trend. An evaluation of the activity level confirmed these findings, showing a significant
improvement in the Tegner score over time (p=0.017 for the final evaluation). The longer durationof symptoms before treatment was associated with a slower return to sport (p=0.041).
Discussion. PRP injections produced good overall results for the treatment of chronic recalcitrant
Achilles tendinopathy with a stable outcome up to a medium-term follow-up. Longer symptom
duration was related with a more difficult return to sporting activity.

Introduction©

Keywords: PRP, growth factors, Achilles tendinopathy, injections, long term.

Achilles tendinopathy, in particular pathology of the
mid-portion of the tendon, is one of the most common
findings in a sport-active population, especially among
long-distance runners, and is responsible for a severe
reduction in physical performance and persistent pain
over several years1,2. Despite being often considered a"sport-related injury", studies have revealed that thispathology may also affect an older population with lessinvolvement in sporting activities, thus explaining thesocial impact of Achilles tendinopathy3,4.
The treatment of this condition is a real challenge
for orthopaedic surgeons and sports medicine physicians
and it is not always possible to achieve a goodoutcome. A number of options5-7 are available, ranging
from rehabilitation protocols to injective treatment
and surgery. Among these, the local administrationof growth factors is an emerging treatment strategy
which aims at providing a regenerative stimulus ina tissue, the tendon, characterised by a poor healingability8. In particular, platelet-derived growth factors
are the most widely used way to provide a local
regenerative stimulus for tendon healing9,10. Platelet
granules are rich in important molecules involvedin the process of responding to damage and might
be beneficial in conditions characterised by chronic,
degenerative processes11-15. Platelet-rich plasma (PRP)
has been used to a variable degree in recent years in
the field of musculoskeletal pathologies16 and, in partas a consequence of the use of ultrasonography forselective intra-lesion administration, it has become
especially common in the management of tendinopathy.
Despite its widespread use for the treatment of Achilles
tendinopathy, only a few studies have described the

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Filardo G et al

PRP in tendinopathy. For this purpose it is essential toprovide data about different PRP formulations used totreat Achilles tendinopathy, especially in the case oflong-term studies, since such data might demonstrate
not only the safety and possible efficacy of PRP, butalso the stability of the clinical outcome.
The aim of this study was, therefore, to evaluate
the therapeutic effects of repeated injections oflaboratory-made, high-concentrate, leucocyte-rich
PRP, administered to promote the healing of chronic,
recalcitrant Achilles tendinopathy, documenting thequality and duration of clinical improvement in a large
cohort of patients up to a mid-term follow-up.

Materials and methods

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Patients
The clinical experimentation was approved by the
Hospital Ethics Committee and informed consent was
obtained from all patients. Twenty-seven patients (meanage: 44.6±10.6 years; mean body mass index: 25.6±4.0;
22 men, 5 women) affected by chronic mid-portion
Achilles tendinopathy were enrolled in this trial. Inclusion
criteria were: history (>3 months) of exercise-associatedpain, pain or tenderness on palpation and imaging findings(magnetic resonance imaging [MRI]or ultrasound [US]scans) of degenerative changes in the Achilles' tendon.
Seven of the patients enrolled had bilateral tendinopathy,
thus 34 tendons were treated in total. All tendons had
previously undergone unsuccessful conservative or
surgical management (Table I).

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clinical outcome after injection treatment with PRP,
and most of them were of poor methodological quality.
Up to now only one randomised controlled trial has
compared the effectiveness of a single PRP injection
against saline solution for the management of Achilles
tendinopathy in 54 patients17,18. The authors of this study
reported an improvement in both groups of patients,
without statistical difference in terms of clinical results
between patients treated with PRP or saline, both at 6 and12 months of follow-up. Although these findings might
discourage clinicians from using PRP to treat Achilles
tendinopathy, there are some important limitations in the
study design that need to be taken into account before
sentencing the ineffectiveness of PRP. First of all it
should be taken into consideration that, in the case of
saline injections, needling itself might be a treatment,
involving mechanical stimulation and bleeding of thedegenerated tendon tissue, and therefore the good results
reported after saline injections cannot be ascribed only
to a placebo effect. Furthermore, the mean age of thepatients in the study was notably higher than that of theusual sport-active population, which is normally treatedwith this regenerative approach; older subjects might beless responsive to the biological effects of PRP. Anotherpoint to consider is that a single injection of PRP was
administered, whereas other authors have preferred
to use repeated PRP injections to guarantee a betterand long-lasting action of the platelet-derived growth
factors. Another, potentially major, weakness of thestudy is that the PRP was not activated; the researchers
relied on in situ activation provided by the contact of
the PRP with autologous collagen. This choice might
be questioned because platelet gel formation is delayed
and tendon contraction might squeeze the liquid PRPaway from the injection site. Self-activation might,
therefore, be too slow or insufficient to guarantee thelocal release of adequate amounts of growth factors. Inview of these remarks, and also considering the positive
clinical results documented in other trials, this study
represents an important landmark in the field, but thequestion about the real role of PRP in the managementof Achilles tendinopathy still remains open and worthyof further investigation.
Another key aspect to consider is that there are several
different PRP formulations, which differ in terms of cell
type content, platelet concentration, storage modalities,
activation methods and protocols for therapeutic
application19. If a particular type of PRP has proven to
be less effective in treating Achilles tendinopathy, it does
not exclude other PRP formulations from being moresuitable and beneficial for this particular pathology. In
fact, the goal of current research is to establish whether
there are some particular characteristics of PRP andsome specific features of tendon lesions that might
represent clear indications for safe, effective use ofTechnique for preparing the platelet-rich plasma
A 150 mL venous blood sample was harvested foreach treatment cycle for each tendon. The sample wascentrifuged twice (the first time at 1,480 rpm for 6
minutes to separate erythrocytes, and the second time
at 3,400 rpm for 15 minutes to concentrate platelets) to
produce four small units of 5 mL of PRP each. One unit
was sent to the laboratory for quality control, one wasused immediately for the first treatment, and the other
Table I - Previous treatments of the patients included in the
study.
Type of treatment

Number of patients

Rehabilitation programme(minimum 12 weeks)

27 (7 bilateral)

Laser therapy

18 (4 bilateral)

External shock wave therapy

3

TENS therapy

8 (2 bilateral)

Ultrasound therapy

10 (3 bilateral)

Corticosteroids injections

10 (4 bilateral)

Surgical treatment

4 (1 bilateral): multiple longitudinaltenotomies and excision ofdegenerated areas

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PRP treatment for Achilles tendinopathy: long-term evaluation

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Treatment and evaluation protocol
The patient was placed prone with his or her ankle
in a neutral position. After sterile dressing and under US
control (Acuson Antares Ultrasound System, Premium
Edition; CH6-2 Convex Array Probe; Siemens AG,
Munich, Germany), a single skin injection with a 22 G
needle was performed and then the PRP was injected
directly into the lesion site with multiple penetrationsof the tendon.
After each injection the patient was sent home with
instructions on limiting the use of the leg for at least
24 hours and to use cold therapy/ice on the treated areafor pain. During this period the use of non-steroidal
anti-inflammatory drugs was forbidden. After thesecond injection the patients were instructed to start arehabilitation programme based on eccentric exercises tobe carried out for 12 weeks. A gradual return to sporting
activity was then promoted, by encouraging patients toperform stretching and eccentric exercises on a constantbasis as a part of their training to prevent relapse.
Patients were prospectively evaluated at baseline,
after 2 and 6 months, and then up to a mean of 54.1±19.7
months' follow-up (minimum evaluation at 30 months).
The following evaluation tools were used: Blanzina20,
VISA-A21, EQ-VAS for general health, and Tegner22scores. With regard to the scores used, the Blanzina
score give a clinical classification of the severity ofthe tendinopathy (ranging from grade I to grade IV,
which represents the worst clinical condition), VISA-A
provides a subjective functional evaluation of the
Achilles' tendon, and the Tegner score indicates thepatient's usual level of sporting activity.
The patients' overall satisfaction and time toreturn to sport were also reported. The treatment wasconsidered to have failed in patients who later underwent
injection or surgical treatment and the last scores before
the operation were reported for the analysis at thesubsequent follow-ups.

categorical variables are expressed as frequencies
and percentages. The Kolmogorov-Smirnov test was
performed to test the normality of continuous variables.
The repeated measures general linear model (GLM) with
post-hoc Sidak correction for multiple comparisons was
performed to compare normally distributed scores at thedifferent follow-up times. Friedman's test followed byWilcoxon's pairwise post-hoc test was used to compare
follow-up times of ordinal scores. The ANOVA test
was used to assess the between-group differences ofcontinuous, normally distributed and homoscedastic data,
the Mann-Whitney test was used otherwise. Spearman's
rank correlation was used to assess correlations between
scores and continuous data, whereas the Kendall-Tau
correlation was used to assess influence between ordinalvariables. Fisher's χ2 test was applied to investigate therelationships between dichotomous variables, whereas
Pearson's χ2 test evaluated by Monte Carlo methods
was performed to investigate the relationships between
grouping variables. Kaplan-Meier analysis was used toassess the return to sport. For all tests p values <0.05
were considered statistically significant.
All statistical analyses were performed using SPSS
v.19.0 (IBM Corp., Armonk, NY, USA).

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two units were stored at −30 °C. On average, the total
number of platelets per milliliter in the PRP was fivetimes greater than that in the whole blood. The plateletconcentrate also contained leucocytes, which had been
concentrated 1.2 times with respect to the normal bloodvalues. The treatment cycle consisted of three intratendinous injections of 5 mL PRP at 2-week intervals.
For the second and third treatments the samples were
thawed in a dry-thermostat at 37 °C for 30 minutes,
immediately prior to application. Before every injection,
10% of calcium chloride (Ca2+=0.22 mEq×dose) was
added to activate the PRP.

Results

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No major complications related to the injections orsevere adverse events were observed during the treatment
and follow-up period, and an overall improvement in all
the scores was recorded over time.
The VISA-A score improved significantly (global
p<0.0005). In detail, the baseline score of 49.9±18.1
increased to 62.9±19.8 at 2 months (p=0.002), with afurther improvement at 6 months (84.3±17.1; p<0.0005),
and remained stable: 90.0±13.9 at 4.5 years (Figure 1).
The EQ-VAS score increased from 68.6±11.6 at baseline
to 78.7±13.3 at 2 months, 82.4±10.4 at 6 months, and
83.0±12.5 at 4.5 years, with a significant improvement
at 2 months (p=0.001) and then stable results overtime (Figure 2). Tendons were classified before theStatistical methods
All continuous data are expressed as a mean±standard
deviation or mean and 95% confidence intervals;

Figure 1 - VISA-A scores at baseline, 2 months, 6 months andat the mean final evaluation of 4.5 years' follow-up.

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treatment as Blanzina grade IIIa, IIIb, and II in 21, 6,
and 7 cases, respectively; at the 6 months' evaluation
14 grade 0, 12 grade I, 3 grade II, 1 grade IIIa, and 4
grade IIIb scores were recorded; finally, at the last 4.5
evaluation at 4.5 years there were 24 grade 0, 2 gradeI, 5 grade II, 0 grade IIIa, and 3 grade IIIb scores,
with a significant improvement at every assessment(p<0.0005 vs the baseline evaluation at both 6 months
and at the final evaluation, and with a tendency to further
improvement from 6 months to 4.5 years: p=0.06).
The evaluation of the activity level confirmed thesefindings, with the Tegner score showing a significant
improvement over time: 6.2±1.4 before the onset ofsymptoms, 3.7±1.7 before treatment, 4.0±1.4 at 2
months, 5.3±1.5 at 6 months, and 5.1±1.4 at 4.5 years'
follow-up (p=n.s. at 2 months, p=0.001 at 6 months, and
p=0.017 at 4.5 years with respect to the pre-treatment
level, but without achieving the level prior to the onsetof symptoms: p<0.0005; Figure 3). Moreover, 89% of
the patients returned to sport (Figure 4) and 93% of thepatients were satisfied and would repeat the treatment
if needed. Finally, the treatment failed in three patients(1 bilateral): one patient was treated with corticosteroid
injection before the 6 months' evaluation and the othertwo patients sought surgical intervention, in both cases
about 1 year after the PRP treatment.
Further analysis was undertaken to evaluate which
patients' characteristics might influence the treatment
outcome. Among these, age, sex, body mass index, unilateralor bilateral Achilles' tendon involvement, and previous
conservative or surgical treatment did not influence the resultsin this series. Longer duration of symptoms before treatment
was correlated with a slower return to sport (rho= 0.376,
p=0.041). Similarly, a poorer Blanzina score before treatment
was correlated with a lower VISA-A score at 2 months(tau= −0.464, p=0.001) and a tendency to return to sport later(tau= 0.282, p=0.071).

Figure 3 - Tegner score prior to the tendon injury, before
treatment, at 2 months, at 6 months and at the mean
final evaluation of 4.5 years' follow-up.

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Figure 4 - Time to return to sport and percentage of patients
returning to sport after PRP treatment.

Discussion
The main findings of the present study are thatpatients treated with repeated PRP injections for Achilles
tendinopathy obtained overall good results and that theclinical improvement was stable and maintained up
to a mid-term follow-up. Clinical improvement wassignificantly slower in patients with a higher pre-treatment
symptom level, and the return to sport was more difficultin patients with a longer history of symptoms.
Various mechanisms of action may have played arole in determining the good clinical outcome reported:(i) the dry needling stimulus responsible for internal
bleeding and consequently an inflammatory response
which might start a repair process in the degenerated
area of the lesion; (ii) the direct biological stimulus of
the platelet-derived growth factors stimulating gene
expression of matrix molecules, collagen production
and tendon cell proliferation; and (iii) the activation of
circulation-derived cells11, promoted by PRP releasate,
which play a crucial role in the tissue healing process12.
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PRP treatment for Achilles tendinopathy: long-term evaluation

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clinical score and imaging appearance. Deans et al.32
published their results of treating 26 patients withrecalcitrant Achilles tendinopathy with one injection of
autologous-conditioned plasma combined with exercise
and therapeutic ultrasonography. At the short-term
evaluation at 6 weeks, the patients were found to have
had a significant clinical improvement. Subsequently,
Mautner et al.33 published a retrospective, multicentre,
cross-sectional study analysing clinical outcomes of
180 patients treated for different tendinopathies. The
Achilles' tendon was the third most common site treated(27 tendons) and the results were impressive, since 100%of the patients reported a "moderate improvement tocomplete resolution" on a Likert-scale: the group withAchilles tendinopathy responded best to PRP treatment.
Interestingly, this trial included patients treated in four
different medical centres, each employing its particular
PRP formulation and therapeutic protocol. In spite of
the study's limitations, the overall good clinical outcome
suggests that platelet-derived growth factors can beconsidered among the treatment options for Achilles
tendinopathy. Another trial by Ferrero et al.34 showed
good results at the 6-month evaluation in 24 patientstreated with a single injection of PRP. Besides thegood clinical outcome, follow-up US scans were also
performed and revealed a widespread improvementin the fibrillar echo texture of the tendon and reduced
hypervascularity as shown by power Doppler.
As far as concerns randomised controlled trials, theonly study available17,18 has already been discussed:
although the results of PRP were unfavourable incomparison with those for saline, some major limitationsof the study do not allow definitive conclusions to be
drawn about this biological approach, and actuallyprompt further studies targeted at finding the bestformulations, the optimum methods of applicationand the most precise indications. In fact, besides
considerations regarding the level of evidence of theaforementioned studies, the most controversial aspectremains the marked inter-product variability and thedifferent application strategies. PRP is an off-the-shelfproduct whose characteristics can vary greatly dependingon the different production techniques adopted. The
different types of cells and the variable concentrations
provided by the different procedures and applied to thesite of the lesion are fundamental aspects16 since growth
factors are potent molecules, and small variations intheir concentrations can produce very different effects35,
some of which may even be detrimental in relation to
the particular tissue in question36. Timing and numberof injections are also important details that should befurther investigated since they might have an influenceon clinical outcome37. Other seminal aspects regard
cellularity, since not only platelets but also leucocytes,
monocytes, macrophages, and mast cells might be

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Regardless of the real contribution of each of thesemechanisms of action, in animal studies the overall effects ofapplying PRP were improvement in tendon callus strengthand stiffness 13,14 and a better histological pattern23-26.
With regards to the use of PRP for the treatmentof tendinopathy in humans, the currently available
clinical evidence is drawn mainly from low-quality
trials reporting overall good clinical outcomes, inthe short-term, after PRP injections (Table II). The
first study was a case report about the managementof a partial Achilles' tendon rupture in a 34-year oldbasketball player treated with three intra-tendinous
injections of 5 mL PRP at 1 week intervals27. The
athlete was able to return to sporting activities 64 days
after the original trauma, and by 75 days was playing
a full game. MRI and ultrasonography performed
before and after the treatment showed a marked
improvement in tendon signal and tissue structure.
Gaweda et al.28 injected PRP in 14 patients (15 tendons
in total) with non-insertional Achilles tendinopathy.
A marked and significant improvement was recorded,
and ultrasonography revealed normalisation of theperitendineum, a reduction in tendon thickness, and areduction in hypoechoic lesions. Power-Doppler studies
showed an initial increase in tendon vascularity up to
3 months and then a reduction at the final follow-up.
Finoff et al.29 treated chronic tendinopathy with USguided needle tenotomy and PRP injections. The study
focused on tendinopathy in numerous sites, in both theupper and lower extremities: 14 Achilles' tendons weretreated and the follow-up evaluation was carried out atmean of 14 months. The investigators found a significant
decrease in pain and concomitant functional recovery.
No correlation was found between clinical outcome
and parameters such as age, body mass index, smoking
status, site of tendinopathy, duration of symptoms or PRP
platelet concentration. Owens et al.30 retrospectively
reviewed a small cohort of ten patients all treated withintra-tendinous PRP injections: an improvement was
found in each clinical score used but MRI evaluation did
not reveal a better appearance in most tendons treated,which remained similar to the state prior to treatment. A
study by Monto et al.31 confirmed the positive clinicaloutcome in the aforementioned studies in a larger
series of patients: they treated 30 patients affected bychronic tendinopathy refractory to at least 6 months of
traditional non-operative management. Each patient
received a single US-guided injection of autologous
PRP. The clinical results were positive, with a significant
improvement with respect to the first evaluation, andthis improvement was confirmed up to the final followup at 24 months. In this series, even MRI/US control
scans revealed signs of tendon healing in 27 out of
29 patients. The rate of return to full occupational
activity and sport confirmed the trend revealed by the
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Achillestendinopathy

Achillestendinopathy(plus othersites
tendinopathies)

Case series

Retrospective
study

Deans et al.
J Foot Ankle
Surgery2012

Mautner et al.
PM R
2013

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N.A.

N.A.

N.A.

N.A.

N.A.

N.A.

N.A.

Single centrifugation(ACP double syringe system,
Arthrex Inc, Naples, USA)

Single centrifugation(Laboratory-made)Single centrifugation(Accelerate platelet concentration
system - Exactech Inc,
Gainesville, USA)

Single centrifugation(Symphony System- DePuy
Orthopaedics Inc., Warsaw, USA)

Single centrifugation(Magellan Autologous Platelet
Separator System - Arteriocyte
Medical System Inc, Cleveland,
USA - or GPS III Platelet
Separation System - Biomet Inc)

N.A.

No

N.A.

No

No

1 injectionof 2.5-3.5 mL
PRP

1 injectionof 4 mL PRP

1 injectionof 3 mL PRP

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1 PRP injection
if 80% global
improvement;a second or evenmore injections
performed in caseof poorer results

1 injectionof PRP;
2 patients received
a second injection
after 6 weeks

2 injectionsof 6 mL of PRP ata mean interval of
3 weeks

1 injectionof 4 mL PRP

1 injectionof 6 mL PRP

Local anaesthesia
Needling

I n j e c t i o nadministered in OR

Local anaesthesia
US-guided needling

Local anaesthesia
Needling

Needling

Needling

Combinedtreatments (orother notes)

27

26

No US-guidance
No local anaesthesia

N.A.

24

30

10

14

54
(27 PRPvs 27
saline)14

1Patients

Local anaesthesia
Needling

Srl

3 weekly injectionsof 5 mL PRP

Protocol

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No

N.A.

No

N.A.

Cachloride

Activation
methodN.A.

Leucocyterich PRP

Leucocytes

M

Single centrifugation(Platelet Separation System Biomet Inc, Warsaw, USA)

Single centrifugation(PRP Kit - Curasan AG,
Kleinostheim, Germany)

Double centrifugation(laboratory-made)PRP preparation method

N.A.: not assessed, meaning that the study does not provide specific information on the particular aspect considered in the table.

Achillestendinopathy

Achillestendinopathy

Case series

Owens et al.
Foot Ankle Int
2011

Case series

Achillestendinopthay(plus other sites
tendinopathies)

Case series

Finoff et al.
PM R
2011

Ferrero et al.
J Ultrasound2012

Achillestendinopathy

Randomised
trial

De Vos et al.
JAMA2010 +De Jonge et al.
Am J Sports
Med 2011

Achillestendinopathy

Achillestendinopathy

Case series

Gaweda et al.
Int J Sports Med
2010

Case series

Achilles partial
ruptureCase report

Filardo et al.
Orthopedics
2010

Monto et al.
Foot Ankle Int
2012

DiseaseLevel ofevidence

Authors,journal andyear

Table II - Synopsis of the trials dealing with PRP treatment for Achilles tendinopathy.

6months6weeks

6months24months24months14months12months18
months18
monthsFollowup

100% of Achilles' tendon
patients reported "moderate
to complete resolution ofsymptoms".

80% of patients reported
improved symptoms whereas
20% had slightly worse
symptoms.

Significant clinicalimprovement and also better
appearance in tendon fibrillar
structure, associated with
reduced hypervascularity at
power Doppler.

28 patients reported asatisfactory outcome up to
the final evaluation

Modest clinical improvement
but not MRI changes over time

Positive clinical results but noevidence of better tissue repair
at US evaluation

PRP treatment was notsuperior to saline injection.
Similar findings at US
evaluation at each follow-up

Significant reduction in pain
and recovery of function

Return to full sport practicein 75 days

Results

Filardo G et al

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Figure 5 - Comparison of US scans at the baseline evaluation(A) and after PRP treatment (B).

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It can be seen that there is a reduction Achilles' tendon
thickness and an overall improvement of tendon echostructure. The patient's clinical scores were also satisfactory.

a cycle of injections with a laboratory-made, highconcentrate, leucocyte-rich PRP. Even though these datacannot demonstrate the real potential of this particular
PRP formulation, which would require level I studies,
they show that the good short-term results observed inother studies on the Achilles' tendon are confirmed in the
mid-term follow-up, and that even patients affected byrecalcitrant tendinopathy can benefit from this treatment
approach with stable results over time.

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contained in platelet concentrates and play a role in theeffects obtained in the injected tissue11-13. Furthermore,
the storage procedure, if used, is thought to affectthe amount and pattern of growth factors released:in particular freeze-thawing is considered by someauthors to affect the performance of PRP negatively,
although no clinical study up to now has revealed poorer
clinical outcomes in case of freeze-thawing PRP38.
The activation method may also influence the results,
because activation may regulate the amount and speedof growth factor release and also the molecules used
may themselves exert their own effect on the physiologyof tissue healing and remodelling39, without forgettingthat the time of gel formation might also determine theamount of releasate actually being delivered into thetreated area, as previously discussed.
In the light of these remarks, it appears clearthat different types of PRP have different biologicalproperties and whereas some might offer good results
others might be ineffective or even detrimental36 for the
specific pathology. Unfortunately, the large number offactors involved makes comparisons of studies very
difficult. There is a need to investigate specific PRP
formulations, specific therapeutic protocols and specificphases of tendon disease and patients' characteristics
to determine whether they might be related to a better
clinical outcome. Randomised controlled trials are
required to shed light on what, based on the current
evidence, is still a debated and controversial topic. Lastly,
we must bear in mind that all trials concerning the useof PRP include a rehabilitation protocol after the cycleof injections, which might itself provide a contribution
to symptom relief and functional improvement. Thisis also an important aspect to consider because anappropriate biomechanical stimulus after a biologicaltreatment might increase the regenerative potential of
PRP and enhance tendon tissue maturation synergically,
as suggested by both preclinical and clinical studies13,40.
This study shows that the treatment of a high numberof tendons with repeated PRP injections produced stable
results over time, with a good outcome maintained up
to 4.5 years' follow-up (Figure 5). Another finding of
this study was poorer results in patients with a longer
history of symptoms and limited function.
With respect to other applications of PRP in
tendinopathy, such as patellar tendinopathy, the returnto sport was slower41, but this might be related to thedifferent biomechanical properties between the patellar
and the Achilles' tendon (which might also imply
different aetiopathological pathways) or even the older
age of the patients treated in this study.
The present study has some major limitations, suchas the lack of a randomised control group and imaging
evaluation. However, to the authors' knowledge, thisis the first study to report the mid-term outcome after

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PRP treatment for Achilles tendinopathy: long-term evaluation

Conclusions
Repeated intra-tendinous injections of autologous
PRP produced good results in the treatment of chronic
recalcitrant Achilles tendinopathy, with a stable clinicalimprovement maintained up to a mid-term follow-up.
Longer duration of symptoms and lower pre-treatment
functional level were responsible for a more difficult
return to sporting activities.

Acknowledgements
We thank Pier Maria Fornasari and Milena Vaccari
from the Immunohaematology and Transfusion Medicine
Service, Rizzoli Orthopedic Institute, Bologna, Italy andElettra Pignotti and Keith Smith, Task Force, Rizzoli
Orthopedic Institute, Bologna, Italy.
The Authors declare no conflicts of interest.

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Arrived: 26 October 2013 - Revision accepted: 11 February 2014
Correspondence: Berardo Di Matteo
II Orthopaedic and Traumatology Clinic
Biomechanics and Technology Innovation Laboratory
Rizzoli Orthopaedic Institute
Via Di Barbiano 1/10
40136 Bologna, Italye-mail: berardo.dimatteo@gmail.com

Blood Transfus 2014; 12: 533-40 DOI 10.2450/2014.0289-13
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All rights reserved - For personal use only
No other uses without permission