THEMATIC ISSUE

Platelet-Rich Plasma Treatment for Ligament and

Tendon Injuries
Justin Paoloni, MBBS, PhD,* Robert J. De Vos, MD,† Bruce Hamilton, MBChB,*‡
George A. C. Murrell, MD, DPhil,§ and John Orchard, MBBS, MD¶

INTRODUCTION
Abstract: Platelet-rich plasma (PRP) is derived from centrifuging Platelet-rich plasma (PRP) is derived from centrifuging
whole blood, has a platelet concentration higher than that of the whole whole blood, has a platelet concentration higher than that
blood, is the cellular component of plasma that settles after centri-
of whole blood,1,2 and is the cellular component of plasma
fugation, and contains numerous growth factors. There is increasing
that settles after centrifugation. Platelet-rich plasma contains
interest in the sports medicine and athletic community about pro-
numerous growth factors, including transforming growth
viding endogenous growth factors directly to the injury site, using
factor-b1, insulin-like growth factors 1 and 2, vascular endo-
autologous blood products such as PRP, to potentially facilitate
thelial growth factor (VEGF), basic fibroblast growth factor,
healing and earlier return to sport after musculoskeletal injury. De-
and hepatocyte growth factor (HGF).3 There is increasing
spite this interest, and apparent widespread use, there is a lack of
interest in the sports medical and athletic community about
high-level evidence regarding randomized clinical trials assessing the
providing endogenous growth factors directly to the injury
efficacy of PRP in treating ligament and tendon injuries. Basic sci-
site, through the use of autologous blood products, such as
ence and animal studies and small case series reports on PRP in-
PRP, for facilitating early return to sport after musculoskeletal
jections for ligament or tendon injuries, but few randomized
injury.3 Despite this interest, and apparent widespread use,
controlled clinical trials have assessed the efficacy of PRP injections
there is a lack of high-level evidence regarding randomized
and none have demonstrated scientific evidence of efficacy. Scientific
clinical trials assessing the efficacy of PRP in treating ligament
studies should be performed to assess clinical indications, efficacy,
and tendon injuries.4–7
and safety of PRP, and this will require appropriately powered ran-
Ligament and tendon injuries can be either acute or
domized controlled trials with adequate and validated clinical and
chronic, and in clinical practice, any treatment should be
functional outcome measures and sound statistical analysis. Other
individualized to target specific pathology and diagnoses and
aspects of PRP use that need to be determined are (1) volume of
generally be combined with other treatment measures, such as
injection/application, (2) most effective preparation, (3) buffer-
ing/activation, (4) injection technique (1 depot vs multiple depots),
bracing or physiotherapy. Acute injuries involve tearing of
(5) timing of injection to injury, (6) single application versus series of collagen fibers, hematoma formation, and subsequent healing
injections, and (7) the most effective rehabilitation protocol to use through inflammation, cellular proliferation, regeneration and
after PRP injection. With all proposed treatments, the doctor and the repair, and remodeling processes.8 Chronic ligament and
patient should weigh up potential benefits of treatment, potential tendon injuries are common with increasing age and sports
risks, and costs. Based on the limited publications to date and the- participation, but there is still a lack of knowledge about the
oretical considerations, the potential risks involved with PRP are etiology and pathogenesis of these injuries.9 These chronic
fortunately very low. However, benefits remain unproven to date, injuries are associated with overuse and may involve degenera-
particularly when comparing PRP with other injections for ligament tive processes. The degenerative processes of chronic injuries
and tendon injuries. would include tendinopathy with collagen fiber disruption,
mucoid degeneration, neovascularization, and absence of
Key Words: platelet-rich plasma, PRP, ligament, tendon inflammation.10 Chronic ligament injuries generally represent
(Clin J Sport Med 2011;21:37–45) chronic instability from failure of acute ligament healing, often
involve fiber stretching or tearing and joint laxity, and may
have an inflammatory component.11,12 As with acute muscle
injury,13 for acute ligament and tendon injuries, there may be
an argument for the use of PRP to synergistically assist the
Submitted for publication February 14, 2010; accepted November 17, 2010. inflammatory cascade and regenerative processes in healing
From the *Sports Medicine, Aspetar, Doha, Qatar; †Department of Sports injured tissue. With chronic injuries, particularly tendon
Medicine, The Hague Medical Centre, the Netherlands; ‡Qatar
Orthopaedic and Sports Medicine Hospital, Doha, Qatar; §Orthopaedic injuries with no, or minimal, inflammatory component, the
Research Institute, St George Hospital, Sydney, New South Wales, rationale for use of autologous blood products, including PRP,
Australia; and {Sports Medicine, University of Sydney, Sydney, New is less clear. However, as is recognized in treating ligament and
South Wales, Australia. tendon injuries, the healing pathways are extremely complex
The authors report no conflicts of interest to disclose.
Corresponding Author: Justin Paoloni, MBBS, PhD, Sport Medicine, Aspetar,
and not fully understood with regard to stimulatory, inhibitory,
Doha, Qatar (e-mail: [email protected]). and regulatory influences on healing.14 In this setting, it is
Copyright Ó 2011 by Lippincott Williams & Wilkins difficult to conceptualize how delivering a bolus of growth

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Paoloni et al Clin J Sport Med  Volume 21, Number 1, January 2011

factors into an injured area could enhance healing when, Despite basic science evidence of enhanced early
presumably, these growth factors are, or will have been, acting healing of acute ligament injuries with PRP application,
on this injured region at some stage. In general, despite many human randomized controlled trials (RCTs) have failed to
basic science and animal studies and some small case reports show an effect, and thus, PRP single-application treatment
on PRP injections for ligament or tendon injuries, there are few cannot be recommended in combination with ACL reconstruc-
randomized controlled clinical trials assessing the efficacy of tion. There is a need for good quality RCTs to assess the
PRP injections, and the level of scientific evidence of efficacy efficacy of PRP injections in the treatment of acute extra-
is lacking.7 articular ligament injury, such as MCL injury or ankle
To better understand how PRP may assist in healing, we ligament injuries (deltoid or lateral ligament complex).
analyzed the existing evidence regarding PRP treatment for
specific ligament and tendon injuries.
ACUTE TENDON INJURY
In acute tendon injury models in animals, there is evi-
dence that circulation-derived cells, such as macrophages and
ACUTE LIGAMENT INJURY fibroblasts, are present in the early stages of tendon healing and
There is basic science evidence that specific growth decrease with time.24 Healthy tendon or ligament tissue explants
factors (in this case, platelet-derived growth factor) improve cultured in PRP showed increased COL1A1:COL3A1 ratios
healing and mechanical strength in the early stages of animal and decreased matrix metalloprotease 13 expression.17 Platelet-
acute medial collateral ligament (MCL) injury.15,16 The rich plasma enhanced the number of fibroblasts in tendon, and
greatest effect was seen with early PRP administration, within the amount of collagen synthesis, in the initial stage after
24 hours, and there seemed to be a plateau in the dose– injury,14 and in the longer term (24 weeks), equine studies show
response effect.16 Tendon or ligament cultured in PRP shows that there are increases in collagen, glycosaminoglycans, and
increased COL1A1:COL3A1 ratio and decreased matrix DNA content; collagen organization; metabolic activity;
metalloprotease 13 expression, suggesting an enhanced tendon improved load to failure; and elastic modulus.25 Platelet-rich
collagen type I production and decreased degradation. plasma has been demonstrated to increase the synthesis of
Furthermore, expression and growth factor concentration VEGF and HGF within cultured human tendon cells and as such
correlate with platelet concentration in PRP.17 It has been noted may provide both an angiogenic response and a cellular
that extra-articular ligaments, such as the MCL, have greater proliferative response.26,27 Platelet-derived growth factor con-
physiological wound site filling and increased presence of tributes to cell proliferation, whereas transforming growth
fibrinogen and growth factors when healing as compared with factor-b1 increases collagen synthesis but inhibits cellular
intra-articular ligaments, such as the anterior cruciate ligament proliferation possibly through the increase in VEGF and
(ACL), although the application of PRP to injured ACL can reciprocal decrease in HGF in cultured human tendon cells.26
ameliorate these differences.18 There is early improvement in There is evidence that single PRP injection significantly
load to failure, maximum load, and stiffness of porcine ACL increased tendon force to failure, stiffness, and ultimate stress
suture repairs with the application of PRP8 but no in the early stages of tendon healing in rats; however, this effect
improvement in laxity, maximum tensile load, or linear seems to abate with time in both patellar tendon28 and Achilles
stiffness with longer follow-up.19 tendon29 injury models. Achilles tendon repair in a sheep model
A level 120 (Table 1) double-blind randomized clinical showed that surgical repair using a scaffold (in this case, a cross-
trial evaluated PRP application to the central aspect and the linked acellular porcine dermal patch) was effective and that the
tunnels of bone-patellar tendon-bone allograft and found no addition of PRP fibrin matrix to the scaffold did not alter the
statistically significant differences in inflammatory parame- repair process.30
ters, appearance of the graft in magnetic resonance imaging In a case-controlled study of the surgical repair of
(MRI), or clinical evaluation using validated scores.21 Another Achilles tendon rupture, Sanchez et al31 showed a significant
prospective clinical study showed that 3 months after ACL improvement in the PRP adjunctive group for earlier ankle
reconstruction using hamstring allograft, there was no range of motion, early return to gentle running and to sports
difference in graft fixation, as measured by MRI Sharpey training, and decreased tendon cross-sectional area. This study
fiber integration in the fibrous interzone, with PRP delivered used a fibrin scaffold in addition to PRP, but had small patient
into the graft tunnels or combined treatment of PRP into the group numbers (N = 6), and suggests that randomized
graft tunnels and PRP intra-articular injections at subsequent controlled clinical trials with large patient cohorts are required
intervals of 2 and 4 weeks after surgery.22 Single application of to assess the efficacy of this treatment. Very recently, a
PRP into the femoral and tibial tunnels during ACL randomized clinical trial was performed on 30 patients with
reconstruction using hamstring allograft did not affect clinical ruptured Achilles tendons. Before final skin suture, random-
or functional outcome measures.23 There was a significant ization was performed and 16 patients were injected with
difference in ACL graft density on computed tomographic 10 mL of PRP, whereas 14 were not. The Achilles tendon Total
scan in the PRP group compared with that in the control group, Rupture Score, a validated patient-reported instrument for
with the ACL density approximating that of the posterior measuring outcome after treatment in patients with a total
cruciate ligament. One complication/side effect in the PRP Achilles tendon rupture, was used as an outcome measure.
group was a noted synovitic reaction with ACL hypertrophy At 1-year follow-up, there was no significant difference in
and surrounding soft tissue reaction. heel raise index between groups, but the Achilles tendon Total

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Clin J Sport Med  Volume 21, Number 1, January 2011 PRP Treatment for Ligament and Tendon Injuries

TABLE 1. Levels of Evidence from the Oxford Centre for Evidence Based Medicine, March 2009, Last Edited January 2010
Differential
Therapy/Prevention, Diagnosis/Symptom Economic and
Level Aetiology/Harm Prognosis Diagnosis Prevalence Study Decision Analyses
1a SR (with homogeneity*) SR (with homogeneity*) SR (with homogeneity*) SR (with homogeneity*) SR (with homogeneity*)
of RCTs of inception cohort of Level 1 diagnostic of prospective cohort of Level 1 economic
studies; CDR" validated studies; CDR" with studies studies
in different populations 1b studies from
different clinical
centres
1b Individual RCT Individual inception cohort Validating** cohort Prospective cohort Analysis based on clinically
(with narrow Confidence study with .80% study with study with good sensible costs or
Interval"¡) follow-up; CDR" good‘‘ ’’ ‘‘ reference follow-up**** alternatives; systematic
validated in a single standards; or CDR’’ review(s) of the evidence;
population tested within one and including multi-way
clinical centre sensitivity analyses
1c All or none§ All or none case-series Absolute SpPins and All or none Absolute better-value
SnNouts‘‘ ’’ case-series or worse-value
analyses ‘‘ ’’ ‘‘ ’’
2a SR (with homogeneity*) SR (with homogeneity*) SR (with homogeneity*) SR (with SR (with homogeneity*)
of cohort studies of either retrospective of Level .2 diagnostic homogeneity*) of Level .2 economic
cohort studies or studies of 2b and better studies
untreated control studies
groups in RCTs
2b Individual cohort study Retrospective cohort Exploratory** cohort study Retrospective Analysis based on clinically
(including low quality RCT; study or follow-up with good‘‘ ’’‘‘reference cohort sensible costs or
eg, ,80% follow-up) of untreated control standards; CDR’’ after study, or poor alternatives; limited
patients in an RCT; derivation, or validated follow-up review(s) of the evidence,
Derivation of CDR" only on split-sample§§§ or single studies; and
or validated on or databases including multi-way
split-sample§§§ sensitivity analyses
only
2c ‘‘Outcomes’’ Research; ‘‘Outcomes’’ Research Ecological studies Audit or outcomes research
Ecological studies
3a SR (with homogeneity*) SR (with homogeneity*) SR (with SR (with homogeneity*)
of case-control studies of 3b and better studies homogeneity*) of 3b and better studies
of 3b and better
studies
3b Individual Case-Control Non-consecutive study; Non-consecutive Analysis based on limited
Study or without consistently cohort study, alternatives or costs,
applied reference or very limited poor quality estimates
standards population of data, but including
sensitivity analyses
incorporating clinically
sensible variations
4 Case-series (and poor Case-series (and poor Case-control study, poor Case-series or Analysis with no
quality cohort and quality prognostic or non-independent superseded sensitivity analysis
case-control studies§§) cohort studies***) reference standard reference
standards
5 Expert opinion without Expert opinion without Expert opinion without Expert opinion Expert opinion without
explicit critical appraisal, explicit critical explicit critical without explicit explicit critical
or based on physiology, appraisal, or based appraisal, or based critical appraisal, appraisal, or based on
bench research or on physiology, on physiology, or based on economic theory or
‘‘first principles’’ bench research or bench research or physiology, ‘‘first principles’’
‘‘first principles’’ ‘‘first principles’’ bench research or
‘‘first principles’’

Produced by Bob Phillips, Chris Ball, Dave Sackett, Doug Badenoch, Sharon Straus, Brian Haynes, Martin Dawes since November 1998.
Updated by Jeremy Howick, March 2009.
Notes
Users can add a minus-sign ‘‘-’’ to denote the level that fails to provide a conclusive answer because of
EITHER a single result with a wide Confidence Interval
OR a Systematic Review with troublesome heterogeneity.
Such evidence is inconclusive, and therefore can only generate Grade D recommendations.

(continued on next page)

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Paoloni et al Clin J Sport Med  Volume 21, Number 1, January 2011

TABLE 1. (continued ) Levels of Evidence from the Oxford Centre for Evidence Based Medicine, March 2009, Last Edited
January 2010
* By homogeneity we mean a systematic review that is free of worrisome variations (heterogeneity) in the directions and degrees of results between
individual studies. Not all systematic reviews with statistically significant heterogeneity need be worrisome, and not all worrisome heterogeneity
need be statistically significant. As noted above, studies displaying worrisome heterogeneity should be tagged with a ‘‘-’’ at the end of their
designated level.
‘‘ Clinical Decision Rule. (These are algorithms or scoring systems that lead to a prognostic estimation or a diagnostic category.)
‘‘¡ See note above for advice on how to understand, rate, and use trials or other studies with wide confidence intervals.
§ Met when all patients died before the Rx became available, but some now survive on it; or when some patients died before the Rx became
available, but none now die on it.
§§ By poor quality cohort study we mean one that failed to clearly define comparison groups and/or failed to measure exposures and outcomes in the
same (preferably blinded), objective way in both exposed and non-exposed individuals and/or failed to identify or appropriately control known
confounders and/or failed to carry out a sufficiently long and complete follow-up of patients. By poor quality case-control study we mean one
that failed to clearly define comparison groups and/or failed to measure exposures and outcomes in the same (preferably blinded), objective way
in both cases and controls and/or failed to identify or appropriately control known confounders.
§§§ Split-sample validation is achieved by collecting all the information in a single tranche, then artificially dividing this into ‘‘derivation’’ and
‘‘validation’’ samples.
‘‘ ’’ An ‘‘Absolute SpPin’’ is a diagnostic finding whose Specificity is so high that a Positive result rules-in the diagnosis. An ‘‘Absolute SnNout’’ is a
diagnostic finding whose Sensitivity is so high that a Negative result rules-out the diagnosis.
‘‘¡’’¡ Good, better, bad, and worse refer to the comparisons between treatments in terms of their clinical risks and benefits.
‘‘ ’’ " Good reference standards are independent of the test, and applied blindly or objectively to all patients. Poor reference standards are
haphazardly applied, but still independent of the test. Use of a non-independent reference standard (where the ÔtestÕ is included in the ÔreferenceÕ,
or where the ÔtestingÕ affects the ÔreferenceÕ) implies a Level 4 study.
‘‘ ’’ ‘‘ ’’ Better-value treatments are clearly as good but cheaper, or better at the same or reduced cost. Worse-value treatments are as good and more
expensive, or worse and equally or more expensive.
** Validating studies test the quality of a specific diagnostic test, based on prior evidence. An exploratory study collects information and trawls
the data (eg, using a regression analysis) to find which factors are ÔsignificantÕ.
*** By poor quality prognostic cohort study we mean one in which sampling was biased in favour of patients who already had the target outcome,
or the measurement of outcomes was accomplished in ,80% of study patients, or outcomes were determined in an unblinded, nonobjective way,
or there was no correction for confounding factors.
**** Good follow-up in a differential diagnosis study is .80%, with adequate time for alternative diagnoses to emerge (for example 1-6 months
acute, 1-5 years chronic)

Grades of Recommendation
A: consistent Level 1 studies
B: consistent Level 2 or 3 studies or extrapolations from Level 1 studies
C: Level 4 studies or extrapolations from Level 2 or 3 studies
D: Level 5 evidence or troublingly inconsistent or inconclusive studies of any level

‘‘Extrapolations’’ are where data is used in a situation that has potentially clinically important differences than the original
study situation.
Page last edited: January 3, 2010

Rupture Score was significantly lower in the PRP group, factors on collagen synthesis differ in intrasynovial and
suggesting that PRP may have a detrimental effect.32 extrasynovial tendons.35
Overall, there is conflicting evidence of efficacy20 in In one RCT assessing PRP injection in chronic
surgically repaired acute Achilles tendon ruptures. Further- tendinopathy, de Vos et al36 used 4 mL of PRP injected in
more, there is no evidence of PRP enhancement of fibroblast small depots in the degenerated area of the Achilles tendon
numbers occurring in acute tendon injury in humans. under Doppler ultrasound guidance. This study showed no
difference in outcome measures when compared with the
placebo saline injection, although both groups improved
CHRONIC TENDON INJURY approximately 21 points on the Victorian Institute of Sports
Chronic tendon injury, such as tendinopathy, frequently Assessment-Achilles score (21.7 vs 20.5 for the PRP and
has histopathological features of collagen fiber disruption, saline groups, respectively, at the 6-month stage, n = 27 each
mucoid degeneration, neovascularization, and absence of group) and both groups had similar return-to-sport rates (57%
inflammation.10 There is an absence of basic science studies on for both groups at 12 weeks and 67% to 78% at 24 weeks with
growth factors and PRP in chronic tendon injury models, but it a slight but nonsignificant increased rate in the PRP group). In
is suggested that growth factors may be useful in treating this study, patients were selected before they had started
tendinopathy due to effects on angiogenesis and collagen eccentric exercise therapy. One might speculate that PRP
synthesis.3,33,34 There is evidence that the effects of growth treatment is better indicated as an alternative for resistant

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Clin J Sport Med  Volume 21, Number 1, January 2011 PRP Treatment for Ligament and Tendon Injuries

tendinopathy, which fails to respond to eccentric loading. measured by DASH (Disabilities of the Arm, Shoulder, and
Whether this specific patient group may benefit from PRP Hand) outcome measure score of 70, and at 12 months, the
treatment needs further investigation. Another criticism of the PRP group showed average pain decrease on VAS of 45 and
above study is that the eccentric exercises may have improvement in DASH function of 105. The main outcome
overshadowed the possible beneficial effect of PRP.37 From measure in this study was a 25% reduction in VAS score or
this study, one can conclude that the additive value of PRP DASH outcome measure; statistical analysis used a ‘‘pre-
injection to these exercises is limited. established analysis plan’’ and did not seem to perform
In one of the few other human studies on tendinopathy, a between-group comparison of means. This is an unusual
albeit uncontrolled, Kon et al38 used three 5-mL PRP injections statistical analysis and makes the results difficult to interpret.
separated by 15 days each to treat patellar tendinopathy In this study, the investigators also performed further
and showed a significant improvement in pain and physical interventions at periods between 2 and 6 months in 18
function using health quality of life scales (SF-36 and patients throughout the study follow-up period (in the PRP
EQ-VAS; N = 20). The scale of these improvements from group, 3 patients had surgery and 2 patients had corticosteroid
baseline for pain and physical function was approximately injections; in the corticosteroid injection group, 6 patients had
25 to 28 by the end of the 3-injection treatment series and 30 to surgery, 6 patients had PRP injections, and 1 patient had
36 at the 6-month follow-up. This same research group39 a second corticosteroid injection). The reasons for these
conducted a comparative study in 31 patients with chronic interventions are not stated, there is no description of planned
patellar tendinopathy. One group received 3 PRP injections crossover in the methods section, and the data seem to have
with a rehabilitation protocol starting after the second and third been analyzed on an intention-to-treat basis, with these
injections, and the other group received only the stretching and patients’ treatment being classified as ‘‘unsuccessful’’;
strengthening exercises prescribed. The PRP was obtained however, the between-group means of pain VAS and DASH
using a double-spin centrifugation process. Patients were not scores were not statistically analyzed. Furthermore, the
randomized at baseline. In both groups, the VAS score (PRP negative effects of corticosteroid injections and the markedly
group 26 points on a 0-100 scale) and the functional Tegner fair natural healing response on the longer term in wrist
score (PRP group 2.9 points on a 0-10 scale) improved extensor tendinopathy have been described previously, making
significantly after the 6-month follow-up. The authors reported the between-group differences even harder to interpret.42
no between-group difference in VAS score, but the improve- Randelli et al43 reported a case series (N = 14) pilot
ment in Tegner score was higher in the PRP group. However, study of PRP application in arthroscopic rotator cuff repair and
the statistical baseline difference in Tegner score between these showed decreased VAS of 18 at 4 weeks and 51 at 6 months
groups was not reported. Another possible explanation for this and improved functional scores of 16 and 31 at 2-year follow-
difference might be that the response is amplified when up (UCLA and Constant scores, respectively).
a treatment is invasive and raises high expectations. Gaweda et al44 performed a case series in 14 patients
In the cohort study by Mishra and Pavelko,40 a single (15 tendons) with chronic midportion Achilles tendinopathy.
(2-3 mL) injection of PRP was delivered in 5 small depots into They injected 3 mL of PRP under ultrasound guidance into the
the tender symptomatic area of either the medial epicondylar hypoechoic area of the tendon. The patients had to use elbow
region or lateral epicondylar region (N = 15) to treat wrist crutches for 6 weeks, and in 6 cases, the injection and
flexor tendinopathy or wrist extensor tendinopathy, respec- rehabilitation protocol was repeated. Normal activities of
tively. An unblinded cohort control group (N = 5, of which daily living were resumed between week 6 and week 12, and
3 patients dropped out of the study by 8 weeks to seek sports activities were discouraged. The Victorian Institute of
alternative treatment) had 2 to 3 mL of bupivacaine injected in Sports Assessment-Achilles score improved from 24 to 96 at
a similar manner. The PRP group showed significant 18 months follow-up (P , 0.00005), and the American
improvements in visual analog pain scores at all follow-ups Orthopaedic Foot and Ankle Society (AOFAS) scale (0-100)
and significant improvements in Mayo elbow scores at 8 weeks improved from 55 to 96 at 18 months follow-up. The authors
and at greater than 12 months (mean, 25.6 months; range, 12- also reported an improvement in qualitative gray-scale
38 months) relative to the small control group. The scale of ultrasound characteristics. Fusiform thickening, peritendi-
these improvements from baseline for pain and physical neum thickening, hypoechoic foci, and intrasubstance tears
function was an average improvement of 48 by visual analog decreased in almost all cases at follow-up. There was a
scale (VAS) and 26 on the Mayo elbow scale at 8 weeks and 65 temporary increase in neovascularization until 3 months, and
by VAS and 36 on the Mayo elbow scale at the 6-month after that, the vascularity diminished in most patients. How-
follow-up. Interestingly, 1 of the 2 control cohort patients ever, currently, we lack the knowledge of the natural progress
tested at 6 months was completely asymptomatic, with no pain of tendon structure disorganization and vascularity after a
and full function on Mayo elbow scale. Peerbooms et al41 rehabilitation program.
conducted an RCT comparing a single 1-mL PRP injection (n It is difficult to compare these various studies due to
= 51) in multiple small depots in wrist extensor tendinopathy marked methodological differences and particularly with
with a ‘‘gold standard’’ corticosteroid injection (n = 49) and regard to different tendinopathy sites and outcome measures
showed significant decreases in pain and improvement in used. It is impossible to compare tendon-specific scales with
function at 6 months and 12 months in the PRP group. At 6 general health quality of life scales, but the magnitude of the
months with PRP injection, there was an average decrease in response to any injection used in these studies is similar,
pain by VAS of 27 and an improvement in function as whether single PRP or series of PRP injections. We may expect

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Paoloni et al Clin J Sport Med  Volume 21, Number 1, January 2011

TABLE 2. Human Clinical Trials on PRP in Ligament and Tendon Injuries, Description of the Type of Study, Level of Evidence,
Results, and Relevant Comments
Level of
Authors Diagnosis Design Results Comments Evidence
Nin et al21 Ligament injury: Prospective No difference inflammation, MRI, or RCT with appropriate statistical power, with 1b
ACL bone- randomized clinical evaluation 2-year follow-up, single PRP application,
patellar tendon- controlled trial possible type 2 error
bone allograft (n = 50 each group)
Silva and ACL hamstring Prospective No difference in MRI evaluation Small RCT with 3-month follow-up only, single 1b
Sampaio22 allograft randomized and multiple PRP application groups, possible
controlled trial type 2 error
(N = 10 each group)
Ventura ACL hamstring Prospective No difference in clinical evaluation or Small RCT with 6-month follow-up only, single 1b
et al23 allograft randomized functional scores. Increased ACL PRP application, possible type 2 error.
controlled trial density on computed tomographic Computed tomographic scan is not commonly
(n = 10 each group) scan in PRP group, similar to used to assess ACL
density of posterior cruciate
ligament
Sanchez Acute tendon Case–control study Significant improvement in earlier Case–control study with small numbers and 3b
et al31 injury: Achilles (n = 6; control ankle range of motion, earlier 12-month follow-up (but only 6 months
tendon rupture n = 6) return to gentle running and earlier reported), single PRP application at surgery
return to sports, smaller cross- with fibrin scaffold
sectional tendon area on ultrasound
Schepull Achilles tendon Prospective No difference in functional measures RCT with 12-month follow-up. Platelet-rich 1b
et al32 rupture randomized (Achilles Tendon Total Rupture plasma–implanted bead application in depots
controlled trial Score) proximal and distal to rupture
(n = 16 PRP; n = 14
control group)
de Vos Chronic Tendon Prospective No difference in pain scores or RCT with appropriate statistical power but with 1b
et al36 Injury; Achilles randomized functional measures (VISA-A) only 6-month follow-up. Single PRP
tendinopathy controlled trial application in multiple depots under
(N = 27 each group) ultrasound guidance compared with saline
injection. Saline injection into tendon is not
commonly performed
Gaweda Achilles Case series (N = 15) Significant improvement in functional Case series only with 18-month follow-up, single 4
et al44 tendinopathy measures (VISA-A and AOFAS) or repeated ultrasound guided PRP injections
and rehabilitation
Kon et al38 Patellar Case series (N = 20) Significant improvement in quality of Case series only with 6-month follow-up, 3 PRP 4
tendinopathy life scores (EQ-VAS and SF-36) injections into depots at intervals of 15 days,
and function (Tegner score) no guidance, quality of life scores
Mishra and Elbow Case–control study Significant improvement in pain Case–control study with 24-month follow-up, 4
Pavelko40 tendinopathy (n = 15; control (VAS) and function (modified single PRP application, no guidance. Different
(wrist extensor n = 5) Mayo score) diagnoses (medial and lateral elbow
tendinopathy or tendinosis). Only 2 controls after 8 weeks and
wrist flexor not followed after this, 1 control asymptomatic
tendinopathy)
Peerbooms Elbow Prospective Significant improvement in RCT with appropriate statistical power but with 1b
et al41 tendinopathy randomized ‘‘successful outcomes’’ of decrease 12-month follow-up only, single PRP
(wrist extensor controlled trial (n = 15% in pain (VAS) and function application compared with single
tendinopathy) 51 PRP group; n = (DASH scores) corticosteroid injection, unexplained crossover
49 corticosteroid interventions, and unusual statistical analysis
injection group)
Filardo Patellar Prospective No significant improvement in PRP Small RCT with 6-month follow-up only, 3 PRP 1b
et al39 tendinopathy randomized group with pain (VAS) and injections, compared with exercise only group,
controlled trial function (Tegner score) possible type 2 error
(n = 15 PRP; n = 16
control group)
Randelli Complete rotator Case series (N = 14) Significant improvement in pain Case series with 24-month follow-up, single PRP 4
et al43 cuff tear (VAS) and function (UCLA and application at surgery. Joint-specific scores
Constant scores)
AOFAS, american orthopaedic foot and ankle society; DASH, disabilities of the arm, shoulder and hand; UCLA, UCLA shoulder rating scale; VISA-A, Victorian Institute of Sports
Assessment-Achilles.

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Clin J Sport Med  Volume 21, Number 1, January 2011 PRP Treatment for Ligament and Tendon Injuries

TABLE 3. Patellar Tendinopathy and Platelet-Rich Plasma Series of 3 Injections: Results From Case Series by Kon et al38 and Pilot
Randomized Controlled Study by Filardo et al39
Complete Recovery, Marked Improvement, Mild Improvement, No Improvement,
n (%) n (%) n (%) n (%)
PRP group (n = 20)38 6/20 (30) 8/20 (40) 2/20 (10) 4/20 (20)
PRP group (n = 15)39 5/15 (33) 6/15 (40) 2/15 (13) 2/15 (13)
Control group (exercise only) (n = 16)39 4/16 (25) 4/16 (25) 5/16 (31) 3/16 (19)
There were no significant between-group differences in pain scores, functional measures, or patient satisfaction or time-to-recovery rates in the study by Filardo et al.39

pain to decrease from baseline by 18 to 48 on VAS at 4 to mention that this is a common reaction, but patient numbers are
8 weeks and possibly up to 20 to 65 on VAS by 6 months. not specified, nor is the severity of the pain response.
One study suggests that the improvement from PRP may be
sustained for 12 months.40
DISCUSSION
Despite worldwide interest from the medical commu-
SIDE EFFECTS nity, athletes, and the media45 concerning PRP and the
In all human clinical studies on PRP in ligament and possibility of enhanced healing and earlier return to sport,
tendon injuries, there were a total of only 248 patients (70 ACL there is no evidence in human clinical trails of the efficacy of
injury, 22 Achilles tendon rupture, and 156 chronic tendino- PRP in treating ligament and tendon injuries. There is certainly
pathies in multiple sites, including Achilles tendinopathy, a lack of scientific evidence of earlier, or more effective,
patellar tendinopathy, wrist flexor tendinopathy, wrist extensor return-to-sport rates with PRP injections compared with other
tendinopathy, and rotator cuff tendinopathy) who were treated inert injections. In fact, few randomized controlled clinical
with PRP application/injection. In these studies, it was reported trials have found significant differences in clinical measures of
that there was 1 patient who had ACL graft hypertrophy with efficacy, or MRI appearance of ligament healing in the short
synovial reaction around the treated ACL,23 1 patient who had term, with the use of PRP in treating ligament and tendon
a marked pain response that lasted 3 weeks to PRP injected injuries (see Tables 2–4).
into patellar tendon,38 and common but unspecified numbers of It has been suggested that patients with refractory
patients with local inflammation causing pain for 3 to 4 weeks conditions, such as Achilles tendinopathy, who have failed
after PRP injection for lateral epicondylosis.41 In pooled studies physiotherapy and multiple nonsurgical modalities may be
of PRP use in ACL reconstruction, this represents a side effect candidates for PRP injections.7,46 However, there is currently
rate of 1.4%, although there was a 10% rate in the study by no reason to consider PRP a more efficacious injection option
Ventura et al.23 In pooled studies of PRP injection for chronic than many other treatments, including polidocanol, autolo-
tendinopathy, there is a side effect rate of at least 1.3%, although gous blood, normal saline, or glucose prolotherapy. These
there was a 5% rate of side effects in the study by Kon et al.38 treatments are also often less expensive than PRP and may
Interestingly, only the study by Kon et al measured increased also be considered in the treatment algorithm, especially given
pain and stiffness after PRP injection; this was present in all the lack of efficacy in the only RCT on PRP in Achilles
subjects with a mean intensity of 6.1 of 10 for both pain and tendinopathy.36 At best, in this setting, we may expect pain to
stiffness, and lasted between 1.5 and 2.1 days. Peerbooms et al41 decrease from baseline by 18 to 48 on VAS at 4 to 8 weeks and

TABLE 4. Tendinopathy at the Elbow and Platelet-Rich Plasma: Results From a Randomized Controlled Study on Wrist Extensor
Tendinopathy by Peerbooms et al41 Using 1-mL Peppering Technique Injection and a Case–Control Study on Combined Group of
Wrist Extensor Tendinopathy and Wrist Flexor Tendinopathy Patients by Mishra et al40 Using 3-mL Peppering Technique Injection
Baseline VAS Decrease
VAS 4 Weeks (%) 8 Weeks (%) 12 Weeks (%) 26 Weeks (%) 52 Weeks (%)
PRP group (N = 51)41 70.1 (100%) 14.7 (21%) 23.2 (33.1%) 31.4 (44.8%) 37.5 (53%) 44.8 (63.9%)
Control group (cortisone 65.8 (100%) 21.6 (32.8%) 22.9 (34.8%) 21.6 (32.8%) 9.2 (14%) 15.7 (24%)
injection) (N = 49)41
PRP group (N = 15)40 80.3 (100%) 33.9 (46%) 48.3 (60%) — — 74.6 (93%)
Control group (bupivicaine 86 (100%) 15 (17%) 3 patients withdrew; — — —
injection) (N = 5)40 1 of 2 remaining
patients showed
nil symptoms
There were no reported significant between-group differences in pain scores in the study by Peerbooms et al, but there was a significant difference in the number of PRP-treated
patients who achieved .25% reduction in visual analog pain scores at 1 year (primary outcome measure with a ‘‘pre-established analysis plan’’).

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Paoloni et al Clin J Sport Med  Volume 21, Number 1, January 2011

possibly up to 20 to 65 on VAS by 6 months. It is interesting, theoretical considerations, the potential risks involved with
but not altogether surprising, that the better clinical studies, PRP are fortunately very low. However, benefits have not been
including RCTs, often fail to detect significant differences proven to date, particularly when comparing PRP injections
with PRP use, whereas uncontrolled studies consistently with other more inert substances, such as glucose or normal
detect significant differences. Although it is possible that saline. Commercially available kits may be able to increase
there are no significant differences on RCTs due to type 2 the concentration of PRP injections and therefore may be
error from underpowered studies, and there are few noted side somewhat more likely to subsequently show benefits, but the
effects from PRP use, this cannot be a justification for the use cost of a specific kit may not be able to be justified currently in
of PRP in ligament and tendon injuries. Evidence of efficacy the absence of such studies. Although taking PRP from a
and safety of PRP are lacking, and currently, PRP is on the simple centrifugation process is also not proven as a treatment
World Anti-Doping Authority prohibited list 2010. Having to date, at least it can be undertaken as a low-cost and low-risk
stated this, there is no reason to completely discount PRP treatment option.
injections because some elements of PRP may have clinically
useful effects on healing when delivered in the correct
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