Prp and hamstring injury

Platelet-rich plasma does not enhance return to play
in hamstring injuries: a randomised controlled trial
Bruce Hamilton,1,2
Johannes L Tol,2
Emad Almusa,3
Sirine Boukarroum,2
Cristiano Eirale,2
Abdulaziz Farooq,4
Rodney Whiteley,5
Hakim Chalabi6
▸ Additional material is
published online only. To view
please visit the journal online
(http://dx.doi.org/10.1136/
bjsports-2015-094603).
1
High Performance Sport NZ,
Millennium Institute of Sport
and Health, Auckland,
New Zealand
2
Department of Sports
Medicine, Aspetar, Doha,
Qatar
3
Department of Radiology,
Aspetar, Doha, Qatar
4
Athlete Health and
Performance Research,
5
Department of Rehabilitation,
6
Director General for
International Medical Affairs
and Programs & Centers of
Excellence, Aspetar, Doha,
Qatar
Correspondence to
Dr Bruce Hamilton,
High Performance Sport NZ,
Millennium Institute of Sport
and Health, Auckland,
New Zealand 0632; bruce.
hamilton@hpsnz.org.nz
Accepted 2 May 2015
To cite: Hamilton B, Tol JL,
Almusa E, et al. Br J Sports
Med 2015;49:943–950.
ABSTRACT
Background To evaluate the efficacy of a single
platelet-rich plasma (PRP) injection in reducing the return
to sport duration in male athletes, following an acute
hamstring injury.
Methods A randomised, three-arm (double-blind for
the injection arms), parallel-group trial, in which 90
professional athletes with MRI positive hamstring injuries
were randomised to injection with PRP-intervention,
platelet-poor plasma (PPP-control) or no injection.
All received an intensive standardised rehabilitation
programme. The primary outcome measure was time to
return to play, with secondary measures including
reinjury rate after 2 and 6 months.
Results The adjusted HR for the PRP group compared
with the PPP group was 2.29 (95% CI 1.30 to 4.04)
p=0.004; for the PRP group compared with the no
injection group 1.48 (95% CI 0.869 to 2.520) p=0.15,
and for the PPP group compared with the no injection
group 1.57 (95% CI 0.88 to −2.80) p=0.13. The
adjusted difference for time to return to sports between
the PRP and PPP groups was −5.7 days (95% CI −10.1
to −1.4) p=0.01; between the PRP and no injection
groups −2.9 days (95% CI −7.2 to 1.4) p=0.189 and
between the PPP and no injection groups 2.8 days (95%
CI −1.6 to 7.2) p=0.210. There was no significant
difference for the secondary outcome measures. No
adverse effects were reported.
Conclusions Our findings indicate that there is no
benefit of a single PRP injection over intensive
rehabilitation in athletes who have sustained acute, MRI
positive hamstring injuries. Intensive physiotherapy led
rehabilitation remains the primary means of ensuring an
optimal return to sport following muscle injury.
Trial registration number ClinicalTrials.gov
Identifier: NCT01812564.
INTRODUCTION
Hamstring muscle strain injuries are one of the
most common injuries in sport, with a significant
morbidity for elite athletes.1–3
Despite acute muscle
injuries accounting for up to one-third of all time-
loss injuries and being associated with a reinjury
rate of up to 40%, there is little evidence to
support specific management protocols.1 4–8
The time constraints implicit in professional
sport have contributed to a proliferation of injec-
tion therapies purported to enhance muscle healing
and facilitate a quicker return to competition.
Injections of platelet-rich plasma (PRP) are pro-
moted by commercial entities as appropriate for
muscle injury management.9
Animal studies, case reports, case series and a
single-blinded randomised controlled trial have
suggested a beneficial effect of PRP injections on
both healing and return to play duration following
muscle injury.10–16
However, a recent double-blind
randomised controlled trial in amateur athletes
failed to reproduce this finding, and high-quality
studies in professional athletes are lacking.17
Therefore, it remains unknown if PRP therapy is
effective in enhancing return to play in its primary
target group of professional athletes concurrently
treated with high-intensity rehabilitation in an elite
athlete setting.
The Aspetar Hamstring PRP (AHP) study was
designed to evaluate the efficacy of a single PRP
injection in reducing the return to sport (RTS) dur-
ation among male athletes, following an acute ham-
string injury.
METHODS
Study design
The AHP study was a randomised three-arm
(double-blind for the two injection arms),
parallel-group trial. We designed and conducted the
study with the assistance of staff within Aspetar,
the Qatar Orthopaedic and Sports Medicine
Hospital, and received no external funding. The
study protocol was approved by the Institutional
Medical Ethics Board.
Patient recruitment
Patients were recruited from clubs and federations
of the National Sports Medicine Program (NSMP)
to which the study centre provides sports medicine
services to athletes (professional, semiprofessional
and amateur) of Qatar. NSMP club and federation
medical staff were encouraged to contact the study
coordinator directly and/or immediately refer the
athlete to the study centre when an acute hamstring
injury was suspected.
Study patients
To be eligible for the study, patients were required
to meet the inclusion criteria of being male 18–50
years of age, being available for regular physiother-
apy and medical review, and having presented
within 5 days of having suffered the acute onset of
posterior thigh pain confirmed on MRI as a grade I
or II hamstring lesion.18
Additional eligibility cri-
teria are described in box 1. The treating sports
medicine physician (SMP) determined eligibility
and informed the patients of the study nature. All
patients provided written informed consent.
Randomisation and blinding
Eligible patients were randomised into one of three
therapy groups: PRP, platelet-poor plasma (PPP) or no
Open Access
Scan to access more
free content
Hamilton B, et al. Br J Sports Med 2015;49:943–950. doi:10.1136/bjsports-2015-094603 1 of 8
Original article
group.bmj.comon August 23, 2015 - Published byhttp://bjsm.bmj.com/Downloaded from

injection (standard physiotherapy care). Randomisation was per-
formed in three blocks of 30 participants. To maintain the balance
among the number of patients in each group, each block consisted
of 30 labels (folded papers) prepared by the research coordinator
evenly distributed as 10 PRP, 10 PPP and 10 no injection.
Following informed consent and after blood taking, the athlete
selected one folded paper which the unblinded study coordinator
opened in order to provide the correct therapy to the unblinded
SMP. The SMP who performed the injection was not involved in
the inclusion process, or any subsequent evaluation of the patient.
To ensure the concealment of group allocation, each patient
received a unique research number and this number along with the
identifying code was stored in a secure location for the duration of
the study. The treating SMPs who assessed the outcome scores
(assessor not involved in the injection procedure), physiotherapists
and radiologists were blinded to the group allocation and specific-
ally the application of any injection. Patients were not informed
about the content of the injection to ensure a double-blind design
for the two injection arms. All three groups underwent a standar-
dised rehabilitation programme.
Intervention
Injection preparation
Both PRP and PPP were prepared for all athletes using the man-
ufacturer’s instructions from the GPS III centrifuge separation
system (Biomet Recover, GPS III Platelet Separation System)
described in detail previously.19
Briefly, in a 60 mL syringe,
54 mL of whole blood was combined with 6 mL of anticoagu-
lant citrate dextrose solution (ACD-A) anticoagulant and imme-
diately centrifuged for 15 min at 3200 rpm. The extraction of
PRP and PPP was completed by the research coordinator follow-
ing the method outlined in the commercially available separ-
ation system. No activating agent was applied to the PRP or PPP
prior to injection.
Injection procedure
During the injection preparation, all patients lay prone on the
surgical table facing away from the preparation area and
remained in this position throughout the process. Patients allo-
cated to the no injection group had the posterior thigh cleaned
with Betadine; three dressings were placed over the area of the
injury, and ice was placed on the thigh for 15 min.
In those patients allocated to an injection (PRP or PPP), the
allocated syringe with PRP or PPP was prepared and the area
for injection was dressed with Betadine. Following reference to
the MRI and after clinically confirming the location of the
injury by palpation, the unblinded SMP infiltrated into the area
of maximal tenderness corresponding to the focal region of
injury on MRI. The needle was inserted into the muscle belly, to
a depth anticipated to correspond to the depth of the injury on
MRI. Three separate depots of 1 mL (either PRP or PPP) were
infiltrated using a 25-gauge needle through three injection sites
into the site of the muscle injury (approximately 1 cm on either
side of the central injection site). After the injection procedure,
three dressings were placed over the injection site and the pos-
terior thigh was iced for 15 min.
All patients were then transferred to the physiotherapy
department where rehabilitation was started within 24 h.
Standardised rehabilitation programme
Participants underwent a daily (5 times/week) intensive, fully
supervised and standardised six-stage rehabilitation programme,
as described in detail previously.20
Rehabilitation was performed
at the study centre by three sports physical therapists and one
sports rehabilitator with 7–25 years’ experience in treating elite
level athletes, who were blinded to the intervention. As the
effect of acute injection PRP on the time course of healing for
muscle injury is unknown, functional, criteria-based progres-
sions (as opposed to time-based progressions) were utilised for
the six-stage rehabilitation protocol. The programme included
range of motion exercises, progressive strengthening exercises,
core stability training, agility exercises and sports-specific func-
tional field testing (FFT).
After successfully completing the first three stages of the
physiotherapy programme, the final stage of sports-specific FFT
was supervised by a sports rehabilitator with 11 years of prac-
tical experience in elite sports, who was also blinded to the
intervention. The programme consisted of a progression of
volume and intensity drills designed to mimic the muscle fatigue
and competitiveness which characterises training and game
situations. Successful completion of the FFT required full unre-
stricted sports-specific function without any limitation and/or
symptoms. Details of the rehabilitation are available in online
supplementary table S1.
MRI
As previously described, patients were examined on a 1.5 Tesla
Siemens Espree.21
The patients were placed in the supine pos-
ition and examined using two-phased array body matrix coils
strapped over the thigh and centred over the painful area, which
was identified by the athlete. Axial and coronal proton density
images with fat saturation (PD-FS) were obtained along the lon-
gitudinal axis of the thigh (repetition time (TR)/echo time (TE)
3490/27 and a 512×326 matrix for the coronal images and TR/
TE 3000/32 and a 512×333 matrix for the axial images) with
one signal average each. Each MRI was assessed by one radiolo-
gist with more than 9 years of experience in musculoskeletal
radiology (EA). The radiologist was blinded for the clinical
status and information on whether the MRI was of the initial
injury or at RTS. For assessment of the MRIs, we used standar-
dised scoring forms based on the literature, which included the
modification of Peetrons’ grading; grade 0: no abnormalities;
Box 1 Eligibility criteria
Inclusion criteria
▸ Age 18–50 years
▸ Available for follow-up
▸ Acute onset of posterior thigh pain
▸ Presenting an MRI within 5 days from injury
▸ MRI confirmed a grade I or II hamstring lesion
▸ Male gender
▸ Able to perform five sessions of physiotherapy a week at our
clinic
Exclusion criteria
▸ Contraindication to MRI
▸ Reinjury or chronic hamstring injury
▸ Concurrent other injury inhibiting rehabilitation
▸ Unwilling to comply with follow-up
▸ Needle phobia
▸ Overlying skin infection
▸ Diabetes, immunocompromised state
▸ Medication with increasing bleeding risk
▸ Medical contraindication to injection
2 of 8 Hamilton B, et al. Br J Sports Med 2015;49:943–950. doi:10.1136/bjsports-2015-094603
Original article

grade I: oedema without architectural distortion; grade II:
oedema with architectural disruption; grade III: complete
tear.18 22
When more than one muscle was involved, the muscle
with the most extensive oedema or disruption was scored. Sites
of increased T2-signal intensity were measured for the affected
hamstring muscle in craniocaudal, transverse and anteroposterior
dimensions on the fluid sensitive sequences (short T1 inversion
recovery or PD-FS). The distances from the ischial tuberosity and
longitudinal length (craniocaudal) of the lesion were recorded. In
addition, the involved cross-sectional area was calculated as a per-
centage of the total cross-sectional area of the muscle in the
transversal plane and the volume of the lesion was approximated.
Excellent intratester radiologist reliability has been previously
described.23
Isokinetic assessment protocol
After completion of the rehabilitation programme, athletes
underwent an isokinetic evaluation performed by the blinded
physical therapists of the knee flexors and extensors (System 3,
Biodex, New York, USA). Prior to testing, the athletes were
instructed as to the nature and purpose of the isokinetic testing.
The athletes performed a standardised warm-up procedure com-
prising 6 min on a stationary exercise bike (Technogym, Italy) at
a resistance (in Watts) equivalent to 1.5 times their bodyweight
(in kg) at their chosen cadence (typically, this was approximately
85 rpm).20
They were then instructed to perform a minimum of
a further 4 min warm-up of their choosing. Typically, this com-
prised dynamic running, agility drills and self-stretching. Prior to
each isokinetic test, the athlete was instructed as to the mode of
testing and given a minimum of three repetitions’ practice, and
testing was not initiated unless the athletes thought they were
ready to do so. The order (ie, left, right) was randomised, and
this was maintained for each of the three modes and speeds for
that athlete. During the testing, vigorous verbal encouragement
was provided. Testing comprised three modes and speeds. First,
the athletes were tested over five repetitions at 60°/s concentric
knee flexion and extension (concentric quadriceps (Q conc 60°/
s)|concentric hamstrings (H conc 60°/s)). This was followed by
10 repetitions at 300°/s concentric knee flexion/extension (Q
conc 300°/s|H conc 300°/s). Finally, they performed five repeti-
tions at 60°/s|180°/s eccentric knee extension/flexion (eccentric
hamstrings (H ecc)|H conc). Comparison (percentage of func-
tion) was made with the contralateral limb.
Haematological analysis
For immediate analysis of whole blood platelet and leucocyte
concentration, blood was sampled from the antecubital vein
with 10 mL drawn into an EDTA-coated tube. Analysis was
completed using the CELL-DYN 3700 SL analyser (Coulter
Count; Abbot Diagnostics, Chicago, USA).19
Outcome measures
Return to sport
The primary outcome was the time to RTS expressed as the
number of days from injury (day 0) to the completion of the
full rehabilitation programme and clearance for RTS by the
treating SMP (blinded to the intervention). The treating SMP
clinically reviewed athletes on a weekly basis and immediately
on completion of the rehabilitation programme. The guidelines
for making the final RTS decision included successful and
asymptomatic completion of the progressive criteria-based
Figure 1 Methodological flow chart (PPP, platelet-poor plasma; PRP, platelet-rich plasma).
Original article

rehabilitation programme, clinical evaluation and interpretation
of the results of isokinetic assessment.20
Secondary outcome scores, compliance and adverse effects
Patients were monitored by telephone on a monthly basis for
6 months following RTS, and in the event of any clinical suspi-
cion of reinjury, the player was advised to immediately consult
the hospital and/or study coordinator. Acute hamstring strain
injuries at the same site, occurring within either 2 or 6 months
from RTS, were classiﬁed as reinjuries. Other secondary
outcome scores included isokinetic strength testing at RTS and
alteration of T2-signal intensity on MRI at 3 weeks follow-up
compared with the baseline MRI assessments. Both assessments
have been described in detail previously.20 23
Adverse effects were recorded during the weekly clinical
follow-up with the treating SMP and at the ﬁnal telephone
Table 1 Baseline characteristics of patients*
Platelet-rich plasma group
(n=30)
Platelet-poor plasma group
(n=30)
No injection group
(n=30)
Age (years) 26.6±5.9
26.3 (21.2–31.4)
25.6±5.8
24.9 (22.1–29.3)
25.5±5.7
24.3 (20.7–29.4)
Male gender 30 (100.0) 30 (100.0) 30 (100.0)
Sports category
Athletics 0 (0.0) 2 (6.7) 2 (6.7)
Basketball 1 (3.3) 1 (3.3) 0 (0.0)
Decathlon 1 (3.3) 0 (0.0) 0 (0.0)
Football 22 (73.3) 22 (73.3) 22 (73.3)
Futsal 3 (10.0) 3 (10.0) 2 (6.7)
Handball 1 (3.3) 1 (3.3) 1 (3.3)
Hockey 1 (3.3) 0 (0.0) 1 (3.3)
Physical coach football 0 (0.0) 0 (0.0) 1 (3.3)
Squash 0 (0.0) 1 (3.3) 0 (0.0)
Volleyball 0 (0.0) 0 (0.0) 1 (3.3)
Weightlifting and bodybuilding 1 (3.3) 0 (0.0) 0 (0.0)
Level of sports
Professional 30 (100) 28 (93.3) 29 (96.7)
Competitive 0 (0) 2 (6.7) 1 (3.3)
Sprinting type of injury 14 (46.7) 20 (66.7) 22 (73.3)
Previous hamstring injuries 19 (63.3) 15 (50.0) 15 (50.0)
Previous ipsilateral hamstring injuries 10 (33.3) 10 (33.3) 8 (26.7)
Maximum pain score with the injury 6.8±2.2
7 (5.0–8.0)
6.6±1.8
7 (5.0–8.0)
6.9±1.7
7 (6.0–8.0)
Length of the pain palpation (cm) 6.7±3.7
5 (4.0–9.5)
7.6±3.9
7.75 (4.5–10.0)
6.5±3.3
6 (4.0–8.0)
Width of the pain palpation (cm) 3.4±1.7
3 (2.0–4.5)
4.4±2.9
3.5 (3.0–6.0)
3.7±1.9
3.5 (2.5–4.5)
No full knee extension deficit at rest 2 (6.7) 1 (3.3) 0 (0.0)
Painful passive straight leg raise (yes only) 30 (100.0) 29 (96.7) 25 (83.3)
Days between injury and intervention (days) 1.8±0.9
2 (1.0–3.0)
1.8±1.1
1 (1.0–3.0)
2.3±1.1
2 (1.0–3.0)
MRI characteristics of oedema
Anteroposterior (cm) 2.3±1.4
2 (1.4–2.9)
2.5±1.5
2.2 (1.4–3.0)
2.7±1.7
2.25 (1.2–4.1)
Anteroposterior (%) 43.0±25.0
36 (24.0–52.0)
41.0±25.0
38 (26.0–51.0)
46.0±28.0
41 (22.0–66.0)
Mediolateral (cm) 2.4±1.3
2.4 (1.2–3.2)
2.1±1.2
1.8 (1.4–2.8)
2.3±1.3
2.4 (1.1–3.3)
Mediolateral (%) 53.0±28.0
47 (29.0–73.0)
48.0±24.0
43 (31.0–69.0)
50.0±24.0
51 (31.0–63.0)
Craniocaudal (cm) 15.8±8.2
14.05 (9.1–23.0)
14.6±7.4
14.4 (9.2–20.2)
15.5±6.1
15.8 (10.6–20.0)
Volume (cm3
) 77.6±108.5
29.21 (9.9–82.0)
61.9±83.4
33.41 (7.4–64.6)
75.8±74.6
62.83 (10.0–135.7)
Cross-sectional area (%) 28.0±28.0
17 (8.0–39.0)
24.0±23.0
15 (8.0–33.0)
29.0±24.0
23 (9.0–51.0)
Distance from most caudal ischial tuberosity (cm) 9.6±7.7
9.4 (2.3–16.6)
12.0±8.3
11.9 (3.3–19.5)
9.5±7.0
8.7 (4.5–13.0)
Grade I 17 (56.7) 16 (55.2) 13 (43.3)
Grade II 13 (43.3) 13 (44.8) 17 (56.7)
*Data are either shown as mean±SD and median (IQR) for continuous variables or frequency and valid column percentage (%) for categorical variables.
Original article

follow-up. Sports physical therapists were instructed to report
adverse effects that influenced the rehabilitation programme.
Daily adherence to the rehabilitation programme was recorded
by the treating physical therapist.
Power and statistical analysis
On the basis of previous studies, our alternative hypothesis was
that in the group of patients who received PRP injection (active
comparator), the RTS would be 25% (6.75 days; practical impli-
cation would be 1 week) quicker in comparison with the PPP
(placebo comparator) and/or no injection group (usual care/no
intervention). The SD was estimated at 8.75 days.24 25
We calculated that a sample of 30 was required in each group
to detect this difference, with a power of 80% with two-sided
testing at a significance of 0.05, and assuming that 10% would
be lost to follow-up.
All randomised patients received the allocated intervention.
All statistical analyses were performed with SPSS V.21.0
software. To determine if the variables of interest were balanced
between the randomised arms, we performed Pearson χ2
test
or exact tests for categorical data and one-way analysis of vari-
ance between the three groups for continuous data. Where
there was deviation from normality, non-parametric equivalent
Kruskal-Wallis tests were used. For the primary end point (RTS
in days), Kaplan-Meier curves with cumulative survival curves in
three groups were plotted. To determine the treatment effect of
intervention on the time to RTS, a Cox proportional-hazards
model and a generalised linear model were performed to
compute hazard ratios (HR) and mean RTS, respectively.
Adjustments were made for baseline variables that influenced
the primary outcome with p<0.10. Patients sustaining a non-
hamstring injury before RTS, which was assumed to be unre-
lated to the injection intervention, were censored in the analysis
at the time of this injury (non-informative censoring). The
assumption of proportional hazard for three treatment groups
was met. Patients lost to follow-up before RTS were censored at
the time of the last available follow-up. All primary analyses per-
formed were based on the intention-to-treat principle. In add-
ition, we performed imputation analysis on the missing data on
RTS and the sensitivity analysis showed no difference from the
initial analysis.
RESULTS
Study patients and follow-up
From November 2009 to October 2013, 357 athletes were
screened for eligibility and a total of 90 athletes were randomly
assigned to one of the three groups (figure 1). The baseline
characteristics are shown in table 1. For the primary outcome,
analysis adjustments were made for the baseline variables
maximum pain score and MRI volume of oedema. Five patients
(2 patients in the PRP group and 3 in the no injection group)
were lost to follow-up before RTS and were censored at the latest
follow-up for the primary outcome (see online supplementary
table S2). Seven of the 90 patients had data on reinjury missing at
6 months follow-up (see online supplementary table S3).
Nineteen SMPs were involved in the allocation process and nine
SMPs in the injection procedure; all had 7–22 years’ experience
in working with elite and recreational athletes.
Primary outcome: time to RTS
The median duration of RTS was 21 days (95% CI 17.9 to
24.1) in the PRP group, 27 days (95% CI 20.6 to 33.4) in the
PPP group and 25 days (95% CI 21.5 to 28.5) in the no injec-
tion group (figure 2). On the basis of Cox regression, the
adjusted HR for the PRP group compared with the PPP group
was 2.29 (95% CI 1.30 to 4.04) p=0.004; for the PRP group
compared with the no injection group, 1.48 (95% CI 0.869 to
2.520) p=0.15, and for the PPP group compared with the
no injection group 1.57 (95% CI 0.88 to −2.80) p=0.13
(figure 3). This HR may be interpreted as meaning that at any
given point in time, a patient infiltrated with PRP has a 2.29
times greater chance of return to play compared with a patient
given PPP.
Figure 2 Box plot showing median and IQR for number of days to
return to play in the three groups. Closed circles represent individual
outliers (PPP, platelet-poor plasma; PRP, platelet-rich plasma).
Figure 3 Kaplan–Meier curves showing the cumulative incidence of
return to play (PPP, platelet-poor plasma; PRP, platelet-rich plasma).
Original article

The generalised linear model showed that the adjusted differ-
ence for time to RTS between the PRP and PPP groups was
−5.7 days (95% CI −10.1 to −1.4) p=0.01; between the PRP
and no injection groups, it was −2.9 days (95% CI −7.2 to 1.4)
p=0.189, and between the PPP and no injection groups it was
2.8 days (95% CI −1.6 to 7.2) p=0.210.
Secondary outcome measures
Reinjuries within 6 months occurred in 2 of the 26 patients
(7.7%) of the PRP group, in 3 of the 28 patients (10.7%) of the
PPP group and in 3 of the 29 patients (10.3%) of the no injec-
tion group (table 2). There was no significant difference in the
reinjury rate at either 2 months (p=0.999) or 6 months
(p=0.905) between the study groups. The odds of reinjury
within 2 months in the PPP group were OR=0.821 95% CI
(0.107 to 6.293) p=0.850 compared with the PRP group; the
odds of reinjury within 2 months in the no injection group were
OR=0.958 (95% CI 0.124 to 7.383) p=0.967 compared with
the PRP group. The 6 month odds of reinjury in the PPP group
were OR=1.44 (0.221 to 9.388) p=0.703 compared with the
PRP group; the odds of reinjury within 6 months in the no
injection group were OR=1.385 (95% CI 0.213 to 9.013),
p=0.733 compared with the PRP group.
There were no significant between-group differences for the
secondary outcome scores of isokinetic strength testing and
MRI alterations in signal intensity (tables 3 and 4).
Adherence to the rehabilitation programme
The median adherence to the scheduled rehabilitation sessions
was 85.5% (IQR 75.0–100.0%) in the PRP group, 92.3% (IQR
84.8–100%) in the PPP group and 87.5% (IQR 68.7–86.7%) in
the no injection group. There were no significant differences in
adherence to the rehabilitation programme between the study
groups (p=0.234).
Whole blood, PRP and PPP analysis
Compared with the whole blood platelet concentration
increased by a factor or 3.2 in PRP and decreased by a factor
8.5 in the PPP (table 5).
Adverse events
There were no serious adverse events reported.
DISCUSSION
In our randomised controlled trial involving predominantly pro-
fessional football athletes suffering an acute hamstring injury,
we found that a single PRP injection in combination with an
intensive rehabilitation programme did not reduce the RTS dur-
ation when compared with rehabilitation only. In contrast, a
single PRP injection in combination with intensive rehabilitation
reduced the RTS duration when compared with a single PPP
injection and rehabilitation.
This study has some strengths and limitations. A strength is
that predominantly professional athletes undergoing a daily
intensive rehabilitation programme were included, as these are
currently the primary target group for PRP injections.
Moreover, with our single-centre rehabilitation programme in
an elite athlete medical setting with rehabilitation supervision by
three highly experienced sports physical therapists, we were able
to control the content, utilisation and daily compliance with the
rehabilitation programme, resulting in a quick RTS and a rela-
tively low reinjury rate. Our standardised imaging, assessment
and follow-up regimen with blinded sports physicians ensured a
comprehensive approach to injury management and data collec-
tion. The double-blind design of the two injection arms mini-
mised the risk of bias and our imputation and sensitivity
analysis showed robustness of results. All attempts were made to
ensure blinding of the therapist to injection or no injection, but
this cannot be completely guaranteed, and it was not monitored
if there was information revealed by the patient to the therapist.
Therapists did not actively seek this information. As the treating
physical therapist was responsible for the decision to progress
through the six-phase criteria-based rehabilitation process, there
is a risk of bias when comparing with the no injection group.
With the objective criteria-based progression criteria, we have
tried to minimise this potential bias. Our study patients were
predominantly male professional football players, which may
limit generalisability to other athletes. Furthermore, where the
area of injury was determined by reference to the ultrasound
Table 2 Cumulative reinjury at 2 and 6 months after return to sport
2 months 6 months
Platelet-rich plasma
(n=25)
Platelet-poor plasma
(n=30)
No intervention
(n=26)
(n=26)
(n=28)
No intervention
(n=29)
Reinjury number (%) 2 (8.0%) 2 (6.7%) 2 (7.7%) 2 (7.7%) 3 (10.7%) 3 (10.3%)
Table 3 Percentage difference in isokinetic strength assessment at return to sport in the injured compared with the uninjured leg
n=24
n=29
No injection
n=26
Mean±SD 95% CI Mean±SD 95% CI Mean±SD 95% CI
Q conc 60°/s (%) 0.7±13.7 −5.1 to 6.5 −3.8±17.9 −10.6 to 3.0 −6.6±17.4 −13.7 to 0.4
H conc 60°/s (%) −6.8±13.2 −12.4 to −1.2 −7.1±12.6 −11.8 to −2.3 −9.2±16.0 −15.7 to −2.8
Q conc 300°/s (%) −0.9±14.0 −6.8 to 5.1 −1.9±17.8 −8.8 to 5.1 −3.1±14.3 −8.9 to 2.6
H conc 300°/s (%) 0.5±12.5 −4.7 to 5.8 3.7±18.7* −3.6 to 10.9 −5.8±18.4 −13.2 to 1.6
H ecc 60°/s (%) −5.2±18.7 −13.5 to 3.1 −7.9±14.4*† −13.6 to −2.2 2.5±17.1 −4.8 to 9.7
*Significantly higher compared with the physiotherapy group.
†p Values based on non-parametric test.
H conc, concentric hamstrings; H ecc, eccentric hamstrings; Q conc, concentric quadriceps.
Original article

and MRI examinations and confirmed with palpation, our injec-
tion protocol did not include standardised ultrasonographic
guidance, which may have influenced the accuracy of the injec-
tion technique. The optimal location for any injection is not
known, and our injection technique allows for a pragmatic and
generalised distribution of the injectate to the area of injury.
Similarly, while not observed by Reurink et al,17
the sequential
application of further PRP or PPP injections could potentially
result in a different outcome. This question was beyond the
scope of this research to evaluate.
Two recently published randomised controlled trials evalu-
ated the efficacy of PRP injections in acute hamstring injuries
in a non-professional setting. In a double-blind RCT involving
80 non-professional athletes, Reurink et al17
found no benefit
of PRP compared with saline injection when both were com-
bined with a mixed home and clinic-based rehabilitation pro-
gramme. In contrast, a single-blinded RCT with a smaller
sample size found that PRP injection in combination with a
home-based rehabilitation programme significantly reduced the
RTS duration in non-professional athletes.16
In the latter study,
unblinded patients, caregivers and the absence of a placebo
injection may have introduced bias. While Reurink used saline
as a placebo, the present study used PPP. Since the alleged
benefits of PRP are suggested to be the result of elevated con-
centrations of growth factors (GF), PPP was chosen as a
placebo in this study due to the reduced platelet count and
growth factor concentrations relative to PRP. Both groups still
received both an injection and a fluid bolus in the area of the
injury. That the PRP injection resulted in a reduced RTS dur-
ation when compared with PPP suggests a physiological dis-
tinction between the two injectates.
The RTS duration achieved in this study is comparable to that
seen in previous studies involving professional athletes22 26 27
but faster than that seen in recreational athletes.17
Hamid
et al16
reviewed their athletes weekly and found an RTS of
42 days for the control group and 26 days for the PRP injection.
In contrast to the RCT involving recreational athletes,16 17
in
this study athletes participated in a daily (5 days/week) high-
intensity rehabilitation programme with a high level of compli-
ance. In this study, the RTS duration for the PRP, PPP and
physiotherapy only (no injection) groups compare favourably
with both these studies. Furthermore, the observed reinjury
rate (8%) at 2 months is lower than previously reported in pro-
fessional European football players (16%)1
and in the study
population of Reurink et al17
(16%), suggesting an effective
rehabilitation and RTS protocol. Taken together, these findings
suggest that intensive rehabilitation is a critical element in a suc-
cessful RTS.
While the current blinded study design with two injection
arms was comparable to that of Reurink et al,17
our observed
difference between PRP and PPP is in contrast to the lack of dif-
ference observed between PRP and saline injection. Advocates
of PRP may argue that our detected difference between PRP
and PPP was due to the positive regenerative effect of PRP,
while others might propose a negative effect of PPP. In the
absence of any difference between either PRP or PPP compared
with no injection, this question remains unresolved. Our find-
ings indicate that there is no benefit, in regard to either RTS
duration or reinjury risk, of adding a single PRP injection to the
intensive rehabilitation of professional (predominantly football)
athletes with a grade I or II hamstring injury. PPP may result in
a slightly slower RTS than PRP when both are combined with
rehabilitation.
There remain many unanswered questions when considering
the use of PRP for muscle injuries in athletes. While this study
fails to show any benefit of a single injection of PRP, it remains
Table 4 Percentage decrease (mean±SD and median (IQR)) in oedema on MRI at follow-up, compared with the baseline measurements*
n=26
n=27
No injection
n=26
Mean±SD Median (IQR) Mean±SD Median (IQR) Mean±SD Median (IQR)
Delay in days† 9.7±16.7 4 (1–13) 7.6±9.6 5 (2–9) 12.5±18.4 7 (3–14)
Craniocaudal (cm) 35.4±60.5 41 (15–65) 18.5±107.6 41 (13–72) 42.7±47.5 54 (23–69)
Anteroposterior (cm) 35.1±62.0 48 (15–64) 10.7±108.1 36 (12–66) 38.7±50.0 52 (12–66)
Mediolateral (cm) 45.2±37.4 43 (13–67) 14.9±73.2 43 (-6–58) 39.2±37.2 34 (20–69)
Volume (cm3
) 62.1±66.4 81 (59–93) 9.6±217.6 84 (56–91) 63.5±64.2 78 (58–94)
Cross-sectional area (%) 46.8±74.7 69 (21–87) −10.4±206.1 70 (15–83) 49.0±68.8 71 (35–86)
*No statistical significance was found between the three groups.
†As per protocol, MRI was planned at third week postinjury. Number of days delayed in MRI is presented.
What are the new findings?
▸ Our findings indicate that there is no benefit of a single
platelet-rich plasma (PRP) injection over intensive
rehabilitation in professional athletes who have sustained
acute, MRI positive hamstring injuries.
▸ A single PRP injection in combination with intensive
rehabilitation reduced the return to sport duration when
compared with a single platelet-poor plasma injection and
rehabilitation.
Table 5 Platelets, leucocytes and RBCs (×109
/L) in whole blood,
PRP or PPP (for groups injected)*
PRP
n=30
PPP
n=30
No injection
n=30 p Value
Whole blood
Platelets 237.2±50.2 256.2±57.1 247.9±40.9 0.338
Leucocytes 5.9±2.2 6.0±1.5 5.7±1.5 0.730†
RBC count 5.2±0.4 5.2±0.4 5.3±0.4 0.245
Injection
Platelets 765.8±423.6 30.3±23.0 NA
Leucocytes 26.1±13.7 0.03±0.03 NA
RBC count 1.0±0.9 0.001±0.001 NA
*Plus–minus values are mean±SD.
†p Value calculated based on a non-parametric test.
NA, not applicable; PPP, platelet-poor plasma; PRP, platelet-rich plasma; RBC, red
blood cell.
Original article

a possibility that further injections, or injections delivered at a
different time period or location, may have had some impact.
Furthermore, there is a known variation in the white cell
and red cell concentrations in different PRP formulations,
which could potentially impact on the outcome. All of these
elements require further evaluation before PRP can be rou-
tinely recommended for use in acute muscle strain injuries. In
the interim, intensive physiotherapy led rehabilitation remains
the primary means of ensuring an optimal RTS following
muscle injury.
Collaborators The Aspetar Hamstring PRP (AHP) study group: Dr Mohammed
Ghanem, Dr Khalifa Alkuwari, Director General Aspetar Orthopaedic and Sports
Medicine Hospital; Dr Justin Paoloni, Dr Claude Tremblay, Dr Massimiliano Sala,
Dr Eduardo Mauri, Dr Celeste Geertsema, Dr Robbart van Linschoten, Dr Aston
Ngai, Dr Stephen Targett, Dr Adam Weir, Dr Frank van Hellmondt, Dr Liesel
Geertsema, Dr Massimo Manara, Dr Paul Dijkstra, Dr Juan Manuel Alonso,
Dr. York Schumacher; Riadh Miladi, Philipp Jacobsen, Patrice Muxart, Roald Otten,
Mohsen Abassi, Polyvios Kyritsis; Justin Grantham, Wade Knez, Faten Smiley,
Arnlaug Wangensteen, Andreas Serner, Rima Tabanji; Dr Nabil Jomaah, Dr Bernard
Roger, Clubs and federations of the National Sports Medicine Program (NSMP); Al
Ahli Sports Club, Al Arabi Sports club, Al Gharafa Sports Club, Al jaish team, Al
kharitiyath Sports Club, Al Khor Sports Club, Al Markhiya Sports Club, Al Rayyan
Sports Club, Al Sadd Sports Club, Al Sailiya Sports Club, Al Shahaniya Sports Club,
Al Shamal Sports Club, Al Wakrah Sports Club, Mesaimeer Sports Club, Military
Sports Association, Moaither Sports Club, Lakhwaya Sports Club, Qatar Hockey
Federation, Qatar Sports Club, Qatar Armed Forces, Qatar Basketball Federation,
Qatar Football Association, Qatar Taekwondo & Karate Federation, Qatar
Weightlifting and Bodybuilding Federation, Qatar National team, Um Salal Sports
Club, Ziyad R Mahfoudour, Weil Cornell Medical College Qatar.
Contributors BH contributed in the concept and design of the study, acquisition
and interpretation of the data, and in drafting and revising of the manuscript. JLT
was involved in the acquisition and interpretation of the data, and in drafting and
revising of the manuscript. EA and RW participated in the acquisition and
interpretation of the data, and in revising of the manuscript. SB participated in the
acquisition of the data, and in drafting and revising of the manuscript. CE
contributed in the concept of the study, acquisition and interpretation of the data,
and in revising of the manuscript. AF contributed in the design of the study,
interpretation of the data, and in drafting and revising of the manuscript. HC
contributed in the concept and design of the study, acquisition and interpretation of
the data, and in revising of the manuscript. All the authors gave their approval for
the final version of the manuscript.
Funding Internally funded by Aspetar; Qatar Orthopaedic and Sports Medicine
Hospital.
Competing interests None declared.
Ethics approval The study protocol was approved by the Institutional Medical
Ethics Board of Aspetar/Aspire Zone.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Patient level data and/or full data set and/or technical
appendix and/or statistical code are available from the corresponding author at
bruce.hamilton@hpsnz.org.nz.
Open Access This is an Open Access article distributed in accordance with the
Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which
permits others to distribute, remix, adapt, build upon this work non-commercially,
and license their derivative works on different terms, provided the original work is
properly cited and the use is non-commercial. See: http://creativecommons.org/
licenses/by-nc/4.0/
REFERENCES
1 Ekstrand J, Hagglund M, Walden M. Epidemiology of muscle injuries in professional
football (soccer). Am J Sports Med 2011;39:1226–32.
2 Orchard J, Seward H. Epidemiology of injuries in the Australian Football League,
seasons 1997–2000. Br J Sports Med 2002;36:39–44.
3 Feeley BT, Kennelly S, Barnes R, et al. Epidemiology of National Football League
training camp injuries from 1998 to 2007. Am J Sports Med 2008;36:1597–603.
4 Hamilton B. Hamstring muscle strain injuries: what can we learn from history? Br J
Sports Med 2012;46:900–3.
5 Verrall GM, Slavotinek JP, Barnes PG, et al. Assessment of physical examination and
magnetic resonance imaging findings of hamstring injury as predictors for recurrent
injury. J Orthop Sports Phys Ther 2006;36:215–24.
6 Ekstrand J, Hagglund M, Walden M. Injury incidence and injury patterns in
professional football: the UEFA injury study. Br J Sports Med 2011;45:553–8.
7 Eirale C, Farroq A, Smiley FA, et al. Epidemiology of football injuries in Asia:
a prospective study in Qatar. J Sci Med Sport 2013;16:113–17.
8 Orchard J. The management of muscle strain injuries: an early return versus the risk
of recurrence. Clin J Sport Med 2002;12:3–5.
9 Maffulli N. Autologous blood products in musculoskeletal medicine. BMJ 2013;346:
f2979.
10 Hamilton B, Knez W, Eirale C, et al. Platelet enriched plasma for acute muscle
injury. Acta Orthopaedica Belgica 2010;76:443–8.
11 Hammond J, Hinton RY, Curl LA, et al. Use of autologous platelet-rich plasma to
treat muscle strain injuries. Am J Sports Med 2009;37:1135–42.
12 Loo W, Lee D, Soon M. Plasma rich in growth factors to treat adductor longus tear.
Ann Acad Med 2009;38:733–4.
13 Rettig AC, Meyer S, Bhadra A. Platelet-rich plasma in addition to rehabilitation for
acute hamstring injuries in NFL players. Orthop J Sports Med 2013;1:1–5.
14 Wright-Carpenter T, Klein P, Schaferhoff P, et al. Treatment of muscle injuries by
local administration of autologous conditioned serum: a pilot study on sportsmen
with muscle strains. Int J Sports Med 2004;25:588–93.
15 Wright-Carpenter T, Opolon P, Appell HJ, et al. Treatment of muscle injuries by local
administration of autologous conditioned serum: animal experiments using a muscle
contusion model. Int J Sports Med 2004;25:582–7.
16 Hamid MS, Mohamed Ali MR, Yusof A, et al. Platelet-rich plasma injections for the
treatment of hamstring injuries: a randomized controlled trial. Am J Sports Med
2014:42:2410–18.
17 Reurink G, Goudswaard GJ, Moen MH, et al. Platelet-rich plasma injections in acute
muscle injury. N Engl J Med 2014;370:2546–7.
18 Peetrons P. Ultrasound of muscles. Eur Radiol 2002;12:35–43.
19 Hamilton B, Tol JL, Knez W, et al. Exercise and the platelet activator calcium
chloride both influence the growth factor content of platelet-rich plasma (PRP):
overlooked biochemical factors that could influence PRP treatment. Br J Sports Med
2015;49:956–9.
20 Tol JL, Hamilton B, Eirale C, et al. At return to play following hamstring injury the
majority of professional football players have residual isokinetic deficits. Br J Sports
Med 2014;48:1364–9.
21 Hamilton B, Whiteley R, Farooq A, et al. Vitamin D concentration in 342
professional football players and association with lower limb isokinetic function.
J Sci Med Sport 2014;17:139–43.
22 Ekstrand J, Healy JC, Walden M, et al. Hamstring muscle injuries in professional
football: the correlation of MRI findings with return to play. Br J Sports Med
2012;46:112–17.
23 Hamilton B, Whiteley R, Almusa E, et al. Excellent reliability for MRI grading and
prognostic parameters in acute hamstring injuries. Br J Sports Med
2014;48:1385–7.
24 Slavotinek JP, Verrall GM, Fon GT. Hamstring injury in athletes: using MR imaging
measurements to compare extent of muscle injury with amount of time lost from
competition. Am J Radiol 2002;179:1621–8.
25 Verrall GM, Slavotinek JP, Barnes PG, et al. Diagnostic and prognostic value of
clinical findings in 83 athletes with posterior thigh injury: comparison of clinical
findings with magnetic resonance imaging documentation of hamstring muscle
strain. Am J Sports Med 2003;31:969–73.
26 Askling C, Karlsson J, Thorstensson A. Hamstring injury occurrence in elite soccer
players after preseason strength training with eccentric overload. Scand J Med Sci
Sports 2003;13:244–50.
27 Ekstrand J, Askling C, Magnusson H, et al. Return to play after thigh muscle injury
in elite football players: implementation and validation of the Munich muscle
injury classification. Br J Sports Med 2013;47:769–74.
How might it impact on clinical practice in the near
future?
▸ Intensive physiotherapy led rehabilitation remains the
primary means of ensuring an optimal return to sport
following muscle injury.
▸ Single injections of platelet-rich plasma are not indicated in
professional athletes who have sustained acute, MRI-positive
hamstring injuries.
Original article

controlled trial
to play in hamstring injuries: a randomised
Platelet-rich plasma does not enhance return
Cristiano Eirale, Abdulaziz Farooq, Rodney Whiteley and Hakim Chalabi
Bruce Hamilton, Johannes L Tol, Emad Almusa, Sirine Boukarroum,
doi: 10.1136/bjsports-2015-094603
2015 49: 943-950Br J Sports Med
http://bjsm.bmj.com/content/49/14/943
Updated information and services can be found at:
These include:
Material
Supplementary
http://bjsm.bmj.com/content/suppl/2015/06/29/49.14.943.DC1.html
Supplementary material can be found at:
References
#BIBLhttp://bjsm.bmj.com/content/49/14/943
This article cites 27 articles, 13 of which you can access for free at:
Open Access
http://creativecommons.org/licenses/by-nc/4.0/non-commercial. See:
provided the original work is properly cited and the use is
non-commercially, and license their derivative works on different terms,
permits others to distribute, remix, adapt, build upon this work
Commons Attribution Non Commercial (CC BY-NC 4.0) license, which
This is an Open Access article distributed in accordance with the Creative
service
Email alerting
box at the top right corner of the online article.
Receive free email alerts when new articles cite this article. Sign up in the
Collections
Topic Articles on similar topics can be found in the following collections
(200)Physiotherapy
(147)Physiotherapy
(184)Open access
Notes
http://group.bmj.com/group/rights-licensing/permissions
To request permissions go to:
http://journals.bmj.com/cgi/reprintform
To order reprints go to:
http://group.bmj.com/subscribe/
To subscribe to BMJ go to:

Prp and hamstring injury

More Related Content

What's hot (20)

Viewers also liked (20)

Similar to Prp and hamstring injury (20)

More from Satoshi Kajiyama (20)

Recently uploaded (20)

Prp and hamstring injury