Current Reviews in Musculoskeletal Medicine (2018) 11:635–642

https://doi.org/10.1007/s12178-018-9526-8

PROTEIN-RICH PLASMA: FROM BENCH TO TREATMENT OF ARTHRITIS (S CHOATE AND J TOKISH,

SECTION EDITORS)

Treatment of Muscle Injuries with Platelet-Rich Plasma: a Review

of the Literature
Kian Setayesh 1 & Arturo Villarreal 1 & Andrew Gottschalk 1 & John M. Tokish 2 & W. Stephen Choate 1

Published online: 20 October 2018

# Springer Science+Business Media, LLC, part of Springer Nature 2018

Abstract
Purpose of Review This review discusses the current literature regarding the use of platelet-rich plasma (PRP) in the treatment of
muscle strain injuries. Case series as well as experimental trials for both human and animal models are covered.
Recent Findings Multiple studies have examined outcomes for the use of PRP in the treatment of muscle strain injuries. PRP has
been shown to promote muscle recovery via anabolic growth factors released from activated platelets, and in doing so, potentially
reduces pain, swelling, and time for return to play.
Summary In vitro studies support the regenerative potential of PRP for acute soft tissue injuries. Multiple clinical case
series for PRP injections in the setting of muscle strains demonstrate imaging evidence for faster healing, less swelling,
which can decrease time for return to play. These studies, however, are retrospective in nature, and few randomized
controlled studies exist to demonstrate a clear clinical benefit. Additionally, there is tremendous heterogeneity regarding
the injectant preparation, optimum platelet concentration, presence of leukocytes, and volume of PRP which should be
administered as well as number of and timing of treatments.

Keywords Platelet-rich plasma . PRP . Sports medicine . Muscle injury . Return to play

Introduction hip flexor units, which often sustain eccentric contractile

loads [2]. Hamstring strain injuries represent 29% of all
Muscle injury is relatively common in the context of ath- injuries in sports and are seen in up to 50% of sprinters.
letic participation and can occur by a variety of mecha- Reinjury can often occur with a frequency between 12 and
nisms. Overall muscle strain prevalence in athletes is ap- 21% [3]. Opar and colleagues performed a literature re-
proximately 12–16% [1•]. Certain muscle groups are view looking at hamstring strain injuries and factors that
prone to strain and are more commonly seen on examina- lead to injury and reinjury. They collected studies from
tion. These include muscle groups that cross two joints, 1966 to 2011. Track and field hamstring injuries
such as the hamstrings, quadriceps, gastrocnemius, and accounted for 26% of all injuries, while football was
12% and rugby was 15%. Moreover, they noted that
This article is part of the Topical Collection on Protein-Rich Plasma: 27% of all hamstring injuries were recurrences of previ-
From Bench to Treatment of Arthritis ous injuries in the Australian Football League and 32% in
American Football [4]. As athletes are the main recipients
* W. Stephen Choate
of muscle strains, there are many studies evaluating return
[email protected]
to play as well as the treatment involved in expediting
Kian Setayesh return to sport. Studies demonstrate the tremendous cost
[email protected]
of lost days due to hamstring and muscle strains [5, 6].
1 With the prevalence and associated competitive and finan-
Ochsner Health System, Ochsner Sports Medicine Institute, 1201 S
Clearview Parkway, Building B, Suite 104, Jefferson, LA 70121, cial loss of acute muscle injuries, there is increased interest in
USA optimizing treatment modalities. Platelet-rich plasma (PRP)
2
Mayo Clinic Arizona, 5777 E Mayo Blvd, Scottsdale, AZ 85054, has been utilized as an adjunctive measure to possibly im-
USA prove the healing process, modulate inflammation, and
636 Curr Rev Musculoskelet Med (2018) 11:635–642

expedite return to sports and activities of daily living. We will Basic Science
review the pertinent basic science concepts and clinical out-
come studies on this topic. Basic science research has demonstrated that muscle regener-
ation and myogenesis are dependent upon paracrine healing
and growth factors, namely insulin-like growth factor-1 (IGF-
PRP Production and Usage 1), hepatocyte growth factor (HGF), fibroblast growth factor 2
(FGF-2), transforming growth factor β 1 (TGFβ-1), tumor
PRP is produced by obtaining autologous blood and centrifug- necrosis factor-α (TNF-α), platelet-derived growth factor
ing it to separate the layers based on density of the contents. (PDGF), and prostaglandins (PG). In vitro, IGF-1 has been
Platelets and leukocytes are separated from erythrocytes and shown to stimulate proliferation and differentiation of myo-
further centrifuged to increase the concentration of each com- blasts and improve muscle regeneration in mouse skeletal
ponent to a presumed therapeutic level, although there is sig- muscle [21, 22]. In vivo, FGF-2 has been shown to enhance
nificant variability between preparation methods and patients. both the diameter and number of regenerating muscle fibers.
There is also inconsistency in the desired concentrations. In animal models, HGF activates quiescent satellite cells,
Additionally, activating agents such as thrombin and calcium while TGFβ-1 supports additional growth factors such as
can be added to serum to begin the release of growth factors as PDGF which can also stimulate satellite cell activation. A
opposed to inactivated PRP, which is activated upon adminis- balance between TGFβ-1 and PG E-2 is required to prevent
tration and exposure to collagen and thromboplastin [7]. fibrosis of skeletal muscle, as TGFβ-1 has been shown to
Platelets, one of the main components in PRP, mediate the stimulate fibrotic scar tissue formation. PRP offers a concen-
release of several growth factors that are essential in the trated release of these growth factors which theoretically can
healing process. Various preparations of PRP and vendors expedite the healing process [1•]. One study demonstrated that
providing the algorithm for PRP fabrication are on the market, the addition of an antifibrotic agent, such as Losartan, can be
each with the ability to produce serum with different concen- added in with PRP to enhance muscle healing by stimulating
trations of platelets and leukocytes. Some data exists to sug- muscle regeneration and angiogenesis and preventing fibrosis
gest optimal concentrations of platelets are at four to five times [23]. Additionally, PRP releasate has been shown to promote
the normal level of serum [7]. Conversely, it has been de- skeletal muscle cell proliferation in association with the up-
scribed that concentrations greater than two times normal regulated protein expressions of PCNA, cyclin A2, cyclin B1,
may actually be catabolic and detrimental for healing. There cdk1, and cdk2 [24].
is speculation regarding the benefit of leukocyte-rich (LR) Hammond et al. investigated the healing response of 72 rats
versus leukocyte-poor (LP) PRP. It is thought that tendon to with PRP comparing maximal isometric contraction injury
bone healing would benefit from LR PRP, as inflammation is a and multiple lengthening contraction injury models [25].
required stage for tendon healing. However, recent work com- The multiple lengthening injury model paradoxically resulted
paring LR and LP formulations for tendinopathy has shown a in a longer healing time, and PRP injection resulted in signif-
better histologic healing response with LP, perhaps due to the icant functional improvement in the single lengthening injury
higher concentration of catabolic cytokine IL-6 in LR prepa- model at day 3 and the multiple lengthening protocol at days 7
rations [8]. Moreover, although the inflammatory phase of and 14. MyoD and myogenin messenger RNA transcripts,
healing is important, excessive inflammation can cause in- markers for satellite cell activation, were elevated after injury
creased pain, intramuscular fibrosis, and scar [1•]. The optimal but more so in the PRP group. Wright-Carpenter et al. looked
platelet and leukocyte concentrations for the treatment of at 108 mice with a contusion injury to the gastrocnemius mus-
acute muscle injuries remain unclear. cle treated with autologous conditioned serum injections at 2,
PRP has been used in various disciplines of medicine, from 24, and 48 h post injury compared to those in a control group
maxillofacial surgery to stimulating hair follicles. In orthope- treated with saline injection at those intervals. Histologic anal-
dics, PRP has been shown to have benefit in treating conditions ysis demonstrated that satellite cell activation between 30 and
such as lateral epicondylitis, knee osteoarthritis, rotator cuff 48 h after injury was accelerated by approximately 84% and
tendinopathy, patellar tendinopathy, Achilles tendinopathy, the diameter of the regenerating myofibers was increased in
and plantar fasciitis [9–15]. Conversely, surgical techniques the PRP group versus the controls within the first week. By
such as anterior cruciate ligament reconstruction, rotator cuff day 14, however, the difference between control and treatment
repair, Achilles tendon repair, and fracture healing have not groups was eliminated completely [26].
shown a clear benefit when augmented with PRP application In addition to tissue healing, PRP has been suggested to
[16–20]. Muscle injury is an attractive avenue for treatment play a role in the modulation of inflammatory cells and pain
with PRP because of the relatively non-invasive means in control. The mechanism is likely through regulation of inflam-
which it is administered and the potential for restoration of matory pathways. PRP does show quantifiable amounts of
muscle architecture after injury. interleukins (IL) 1, 6, 7, and 10, which can be specifically
Curr Rev Musculoskelet Med (2018) 11:635–642 637

pro or anti-inflammatory in nature. A recent laboratory study guided PRP injection and had repeat MRI at 9 and 17 days
examined the effect of PRP releasate on the treatment of gas- post treatment. MRI at 9 days after treatment initiation dem-
trocnemius muscle tears in Sprague-Dawley rats. Muscle onstrated mild resolution of edema but clinically the patient
healing was assessed at 2, 5, and 10 days. Cellular apoptosis had pain-free full range of motion. At 17 days post treatment,
was also examined following PRP treatment. The results re- the patient had no signal changes or edema on MRI and clin-
vealed that PRP can not only enhance the muscle healing ically had no pain with motion or with contraction and was
process but also decrease pro-inflammatory CD68-positive able to return to regular activities by 3 weeks. Zanon et al.
and apoptotic cells [27]. reported a case series where 57 professional European
Football players were followed for 31 months and a total of
25 grade 2 hamstring injuries were treated with autologous
Diagnosis and Imaging PRP injection [35]. They divided grade 2 injuries into groups
a, b, and c with group a having partial tear involving less than
Diagnosis of muscle injury is based on clinical exam as well as 1/3 of the muscle diameter, group b involving 1/3 to 2/3 of the
imaging. Magnetic resonance imaging (MRI) and ultrasound muscle diameter, and group c involving 2/3 but less than
(US) have become the mainstay for imaging confirmation of 100% of the muscle diameter. Group a received 2 PRP injec-
muscle injury and do an excellent job at localizing edema and tions at day 0 and day 7. Groups b and c had three injections at
structural abnormality. US is operator dependent and may be days 0, 7, and 14. US and MRI were performed within 24 to
subject to user error; however, both modalities have demon- 72 h of the initial injury. Follow-up MRI was performed at
strated good specificity and sensitivity for diagnosing injuries days 14 and 21 for group a and days 14, 21, and 28 for groups
such as tendinopathy or tendon tear [2, 28–31]. Although US b and c. Twenty-one of the 25 hamstring strains involved the
has the added benefit of a Doppler study which can demon- long head of the biceps femoris. Mean sports participation
strate neovascularization in soft tissues, MRI remains the absence (SPA) was 36.7 days overall, 31.7 days for grade
mainstay modality for the diagnosis, localization, and grading 2a, 61.3 days for grade 2b, and 49.3 days for grade 2c.
of these injuries as well as qualifying the recovery [2]. The Fifteen of 25 injuries involved the myotendinous junction.
information gleaned from this advanced imaging has been Reinjuries occurred in three players (12%). In each player,
shown to correlate with return to play and clinical outcomes. the study demonstrates minimal scarring, lack of edema,
A study looking at Australian Rules Football players with and tissue healing at the last MRI. Wright-Carpenter et al.
hamstring strains seen on MRI demonstrated a mean of performed a non-randomized, non-blinded study of 18
27 days missed from competition when edema was found professional athletes with hamstring injuries treated with
versus 16 days missed when no edematous changes were seen autologous conditioned serum (ACS) versus 11 in the
[32]. In addition to the presence of edema, injury location and control group treated with Actovegin and Traumeel,
extent of muscle volume involved are also important factors. which are a deproteinized dialysate from bovine blood
Proximal avulsion injuries and strains involving a higher and a homeopathic anti-inflammatory drug with extracts
cross-sectional area of muscle are predictive of a longer re- of arnica, calendula, and chamomile among others, re-
covery time and higher risk for recurrence [30, 32]. spectively [36]. All patients were treated within 3 days
Various studies have used longitudinal imaging to correlate of the injury and received 2.5-mL injections into the le-
with healing. A study by Bubnov et al. comparing PRP ad- sion every other day until return to play. The ACS group
ministration versus control in 30 professional athletes demon- had an accelerated return to play at 16.6 days versus
strated accelerated regenerative processes diagnosed with US 22.3 days in the control group which was statistically
in the PRP group [33]. At 7 days after treatment, 20% of the significant (p = 0.001). MRI at 14 to 16 days in each
PRP group showed a significant difference in regenerative group demonstrated nearly complete regression of edema
process on diagnosed with US compared to none in the control and bleeding in muscle with restitution of the muscle
group (p < 0.05). At 14 days after treatment, regenerative pro- structure compared to only a mild regression of the edema
cesses were seen on US in 80% of the PRP group compared to and bleeding in the control group at the same time.
20% in the control group (p < 0.01). At 3 weeks after treat-
ment, all subjects in the PRP group had imaging evidence of a
regenerative process, compared to 73% in the control group Clinical Outcome Studies
(p < 0.05). By 28 days post treatment, all patients in both
groups had regenerative healing. Findings on longitudinal PRP has been advocated as a minimally invasive intervention
MRI for hamstring strains treated with PRP have also been to facilitate healing and decrease inflammation. Multiple clin-
reported in the literature. Hamilton et al. published a case ical studies show PRP to be a potential adjunct to the conser-
report of a 42-year-old male with a grade 2 hamstring injury vative treatment of muscle injuries with regard to healing, pain
diagnosed on MRI [34]. He was treated with ultrasound- control, and return to play.
638 Curr Rev Musculoskelet Med (2018) 11:635–642

Rossi et al. compared the time for return to play and risk for analysis specific to hamstring strains did not show this
recurrence after acute grade 2 muscle injuries in recreational reduced time to play [40•].
and competitive athletes who were treated with conservative Although some of the aforementioned studies suggest
measures with or without PRP. The PRP group contained 34 a healing benefit to PRP, there are additional studies
patients and the control group had 38, and all athletes subse- which challenge the clinical utility of this treatment
quently had progressive rehab consisting of agility and trunk [41]. Hamilton and colleagues reported on the results of
stabilization. Mean time to play was 21.1 days for PRP and three treatment groups for hamstring injuries—PRP in-
25 days for the control group, which was found to be signif- jection, PPP (platelet poor plasma) injection, and no in-
icant (p = 0.001). Pain, as assessed with the VAS, improved jection [42•]. They found that the median time of return
for both treatment regimens, without a significant difference to sport was 21 days in PRP group, 27 days in PPP
between the two. While PRP shortened time to sports after group, and 25 days in the no injection group. In compar-
acute grade 2 muscle injury versus control, the rate of recur- ing the PRP and PPP groups, there was a significant
rence was not significantly different between the groups [1•]. difference in favor of PRP (p = .01); however, in compar-
Conversely, Delos et al. described in their study the results of ing the PRP and no injection groups, there was no sig-
PRP injections with US guidance for muscle injuries. They nificant difference (p = .210). Reinjury rate at 6 months
reported no complications from PRP injections and stated that post treatment was 2 of 26 in the PRP group, 3 of 28 in
their athletes had full functional recovery in half the time the PPP group, and 3 of 29 in the no injection group,
compared to athletes not treated with PRP; however, no con- without a difference between the groups. There was also
trol group was available for comparison [37]. A single-blinded no difference in isokinetic strength testing at 6 months.
randomized controlled trial by Hamid and colleagues in 2014 Rettig et al. published a case control retrospective study
examined outcomes for the use of PRP in the treatment of where 10 NFL players with grade 1 or 2 hamstring
acute grade 2 hamstring injuries [38]. Twenty-eight patients strains were treated with PRP and rehabilitation versus
with hamstring injuries were included in the study. Return to rehabilitation alone [43]. Median return to play was
play was 26.7 days for the PRP group and 42.5 days for the 20 days in the treatment group and 17 days in the con-
control groups, which was found to be statistically significant. trol group, which was not shown to be significantly dif-
There were also lower overall VAS pain scores in the PRP ferent. They speculated that the degree of strain and ede-
group; however, this did not reach statistical significance. ma on MRI cross section were the strongest predictors of
Several studies have looked at PRP for the treatment of ham- recovery time. There were no injury recurrences at
string injuries in NFL players. Mejia and Bradley reported on 6 months in either group. A meta-analysis by Grassi
a case series of PRP injections given to National Football et al. looked at six studies, two of which were random-
League (NFL) players with acute hamstring injuries within ized control trials, and analyzed the effect of PRP for the
24–48 h of injury [39]. They noted that there was an earlier treatment of acute muscle injuries versus at least one
return to play by 3 days for grade 1 hamstring strains and control group including patients treated with placebo in-
5 days for grade 2 hamstring strains, which was equivalent jection or physical therapy. The outcomes evaluated were
to a one game difference. They also noted that there was a 0% time to return to sport, reinjuries, complications, pain,
recurrence rate in this population. A recent systematic review muscle strength, range of motion and flexibility, muscle
looked at return to play for conservative treatment with or function, and imaging [44•]. The time to return to sport
without PRP as an adjunctive modality for acute muscle inju- evaluated in all six studies was significantly shorter in pa-
ries in athletes across different sports. The study collected 268 tients treated with PRP with a mean difference of −
participants with muscle injuries in five studies with the mean 7.17 days (p < 0.05). Looking at only the double-blind
age 25 years old and follow-up 12 months. They noted that studies (n = 2) or studies including only hamstring injuries
soccer was the most common sport for acute muscle injury at (n = 3), there were no significant differences however.
69.2%. The difference in time to return to sport with the PRP Reinjury and post treatment complications demonstrated
versus control groups favored PRP by 6 days. However, a relative risk of − 0.03 and 0.01, respectively, and were also
subgroup analysis of PRP in acute grade 1 or 2 hamstring statistically not significant between the two groups
strains revealed no difference in return to sport with PRP ver- (p > 0.05). Nor were any substantial differences found re-
sus control. Moreover, there was no difference in return to garding pain, muscle strength, ROM and flexibility, muscle
sport between PRP and control groups for all acute grade 2 function, and tissue integrity on imaging. The performance
muscle strains. The overall pooled reinjury rate was 14.3% bias was high due to the lack of patient blinding in four
and 17.1% with PRP and control, which was not significant. studies. One of the additional theoretical clinical benefits
The authors found that PRP may reduce time for return to of PRP for muscle injury is improved healing and reduced
sport with all types of grade 1 or 2 muscle strains without risk for subsequent reinjury. Reurink et al. reported on 42
increase risk of rerupture at 6 months, but subgroup patients who underwent PRP injection for acute muscle
Curr Rev Musculoskelet Med (2018) 11:635–642 639

injury versus 42 patients with placebo. No significant dif- groups, which followed the same rehabilitation program
ference in reinjury rate was noted with 16% reinjury in the consisting of isometric exercises for the gastrocnemius/
PRP group and 14% in the placebo group [45]. soleus complex, ankle muscles, biking, and eccentric mus-
The published outcomes of PRP in the treatment of cle strengthening. Control groups started the second phase
acute muscle injuries, not including the hamstring, are few- of exercise in delayed fashion compared to the PRP group
er in number. Loo et al. reported on a case of a 35-year-old at 17 days versus 9 days, respectively. This was mainly due
male body builder with an ultrasound confirmed adductor to pain. VAS decreased for the PRP group from 7.8 to 2.3
longus strain [46]. Autologous PRP with calcium was ad- after 1 week, 1.2 at the end of active exercise therapy, and
ministered each week for 3 weeks. The patient was able to 0.38 after 3 months. The control group started with pain at
return to competitive training 1 week after the last injec- 8.2 and decreased to 5.1 after 1 week, 2.8 at the end of
tion. Important to note, the authors did not disclose the active exercise therapy, and 1.95 after 3 months.
injury grade, timing of the injection, or if rehabilitation Progression to the third phase of exercise rehabilitation
treatment was also provided. Borrione et al. conducted a was delayed in control group versus PRP at 43 days and
retrospective observational study to evaluate functional re- 27 days respectively. Time to walk without pain was
covery following exercise following PRP for muscular le- 24 days in the PRP group and 52 days in the control group.
sions of the distal musculotendinous junction of the medial Time to return to sport was 53 days in the PRP group and
gastrocnemius head [22]. All lesions were grade 2 or 3 of 119 in the control group.
distal junction medial gastrocnemius head, and patients A summary of conclusions from the available level I and II
received three ultrasound-guided PRP injections. There studies on the use of PRP in the treatment of acute muscle
were 31 total patients in both the treatment and control injuries is included in Table 1.

Table 1 A summarized review of level I and II clinical studies on the outcomes of PRP for the treatment of muscle injuries

Authors Summary Conclusion Level of

evidence

Grassi et al. Sports Med, • Meta-analysis of randomized controlled trials and PRP shortened return to play by over 7 days; Level I
2018 [44•] prospective studies assessing functional outcomes however, subgroup analysis of randomized
after PRP injection vs placebo or control control trials showed no difference as did
isolated hamstring injuries.
Rossi et al. Knee Surg • Randomized controlled trial comparing effect of PRP shortened time to return to sports after acute Level I
Sports Traumatol PRP and rehabilitation versus rehabilitation alone grade 2 muscle injury vs control, but the rate of
Arthrosc, 2017 [1•] after acute grade 2 muscle injury with a 2-year recurrence at 1 year was not significantly different.
follow-up
Hamilton et al. Br J Sports • Randomized three-arm double-blinded parallel There was no benefit of a single PRP injection over Level I
Med, 2015 [21] group trial consisting of 90 professional athletes intensive rehabilitation in athletes who sustained
with MRI positive hamstring injuries acute hamstring injuries. There was a statistically
significant difference between PRP and PPP
regarding return to play.
Reurink et al. N Engl J • Randomized double-blind, placebo controlled 3 Median time for return to sports was not different Level I
Med, 2014 [24] center clinical trials of 80 recreational athletes in between the groups (42 days)
the Netherlands with acute muscle injuries
diagnosed with MRI. Compared a PRP group
which received 2 injections (first within 5 days of
injury and second 5–7 days after the first) versus a
placebo group which received an isotonic saline
injection
Sheth et al. Arthroscopy, • Meta-analysis of 5 studies including 268 PRP may reduce time to return to sport for acute grade Level II
2018 [19] participants comparing return to sport with PRP 1 or 2 muscle injuries; however, subgroup analysis
versus control did not demonstrate a significant return to sport
with acute grade 1 or 2 hamstring injuries.
Hamid et al. Am J Sports • Single-blinded randomized controlled trial Single autologous PRP injection combined with Level II
Med, 2014 [17] investigating time to return to sport after acute rehabilitation program was significantly more
grade 2 hamstring injuries. effective in treating hamstring injuries than a
rehabilitation program alone.
Bubnov et al. Med • Randomized prospective trial assessing outcomes in The PRP group demonstrated a significantly higher Level II
Ultrasound, 2013 [26] 30 consecutive professional athletes with acute level of pain relief, quicker return to sport by a
muscle injury for single PRP injection under mean difference of 12 days and faster muscle
ultrasound guidance combined with a conservative strength recovery compared to the control group
rehab program versus rehab only
640 Curr Rev Musculoskelet Med (2018) 11:635–642

Conclusions 35 initially treated in the PRP group had recurrence of muscle

strain (5.7%) versus 4 of 40 in the control group (10%) but was
not found to be statistically significant. This study ultimately
PRP has been suggested as a treatment adjunct for muscle showed that a single injection of autologous PRP with a reha-
injuries; however, few level one studies exist demonstrating bilitation program significantly shortened time to return to
a clear benefit. Outcome comparisons between studies are sports after and acute grade 2 muscle injury when compared
with control group; however, the rate of recurrence was not
limited due to significantly variability in study design and
significant between the two groups.
PRP preparation and application techniques. Additional study 2. Connell DA, Schneider-Kolsky ME, Hoving JL, Malara F,
is needed to identify and standardize the optimal PRP prepa- Buchbinder R, Koulouris G, et al. Longitudinal study comparing
ration and content for the treatment of acute muscle injuries. A sonographic and MRI assessments of acute and healing hamstring
injuries. AJR Am J Roentgenol. 2004;183(4):975–84.
large proportion of studies mentioned in this review are nei-
3. Ahmad CS, Redler LH, Ciccotti MG, Maffulli N, Longo UG,
ther blinded nor randomized controlled trials. The majority of Bradley J. Evaluation and management of hamstring injuries. Am
studies included in this review report main outcomes as return J Sports Med. 2013;41(12):2933–47.
to play and pain scores, and they do not report on muscle 4. Opar DA, Williams MD, Shield AJ. Hamstring strain injuries: factors
that lead to injury and re-injury. Sports Med. 2012;42(3):209–26.
strength or flexibility. Reinjury rates are reported in some
5. Woods C, Hawkins R, Hulse M, Hodson A. The football associa-
studies but the main objective outcome scores are return to tion medical research program: an audit of injuries in professional
play and days until return to play. Follow-up imaging studies football-analysis of preseason injuries. Br J Sports Med.
are evaluated qualitatively looking at edema, scar formation, 2002;36(6):436–41.
6. Verrall GM, Kalairajah Y, Slavotinek JP, Spriggins AJ. Assessment
and muscle architecture. High-quality randomized controlled
of player performance following return to sport after hamstring
studies are also necessary to determine the clinical efficacy of muscle strain injury. J Sci Med Sport. 2006;9(1–2):87–90.
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Compliance with Ethical Standards
8. Yan R, Gu Y, Ran J, Hu Y, Zheng Z, Zeng M, et al. Intratendon
delivery of leukocyte-poor platelet-rich plasma improves
Conflict of Interest The authors declare that they have no conflict of healing compared with leukocyte-rich platelet-rich plasma in a
interest. rabbit Achilles tendinopathy model. Am J Sports Med.
2017;45(8):1909–20.
Human and Animal Rights and Informed Consent This article does not 9. Mishra AK, Skrepnik NV, Edwards SG, Jones GL, Sampson S,
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Curr Rev Musculoskelet Med (2018) 11:635–642 641

18. De Carli A, Lanzetti RM, Ciompi A, Lupariello D, Vadala A, autologous conditioned serum: a pilot study on sportsmen with
Argento G, et al. Can platelet-rich plasma have a role in Achilles muscle strains. Int J Sports Med. 2004;25:588–93.
tendon surgical repair? Knee Surg Sports Traumatol Arthrosc. 37. Delos D, Maak TG, Rodeo SA. Muscle injuries in athletes: enhanc-
2016;24:2231–7. ing recovery through scientific understanding and novel therapies.
19. Mirzatolooei F, Alamdari MT, Khalkhali HR. The impact of Sports Health. 2013;5(4):346–52.
platelet-rich plasma on the prevention of tunnel widening in ante- 38. Hamid MSA, Ali MRMA, Yusof A, Lee LPC. Platelet-rich plasma
rior cruciate ligament reconstruction using quadrupled autologous injections for the treatment of hamstring injections. Am J Sports
hamstring tendon. Bone Joint J. 2013;95-B:65–9. Med. 2014;42(10):2410–8.
20. Guzel Y, Karalezli N, Bilge O, Kacira BK, Esen H, Karadag H, 39. Mejia HA, Bradley JP. The effects of platelet-rich plasma on mus-
et al. The biomechanical and histological effects of platelet-rich cle: basic science and clinical application. Oper Tech Sports Med.
plasma on fracture healing. Knee Surg Sports Traumatol Arthrosc. 2011;19:149–53.
2015;23:1378–83. 40.• Sheth U, Dwyer T, Smith I, Wasserstein D, Theodoropoulos J,
21. Cole BJ, Seroyer ST, Filardo G, Bajaj S, Fortier LA. Platelet-rich Takhar S, et al. Does platelet-rich plasma lead to earlier return to
plasma: where are we now and where are we going. Sports Health. sport when compared with conservative treatment in acute muscle
2010;2(3):203–10. injuries? a systematic review and meta-analysis. Arthroscopy.
22. Borrione P, Fossati C, Pereira MT, Giannini S, Davico M, Minganti 2018;34(1):281–8. This study aimed to compare the time to re-
C, et al. The use of platelet-rich plasma (PRP) in the treatment of turn to sport and reinjury rate after PRP injection versus con-
gastrocnemius strains: a retrospective observational study. Platelets. trol in patients with acute grade I or II muscle strains. The
2018;29(6):596–601. primary outcome was time to return to play while the second-
23. Terada S, Ota S, Kobayashi T, Mifune Y, Takayama K, Witt M, ary outcome was the rate of reinjury at a minimum of 6 months.
et al. Use of an antifibrotic agent improves the effect of platelet-rich Subgroup analysis was performed to examine efficacy of PRP
plasma on muscle healing after injury. J Bone Joint Surg Am. in hamstring muscle strain individually. Five randomized con-
2013;95(11):980–8. trolled trials which included a total of 268 patients with grade I
24. Tsai WC, Yu TY, Lin LP, Lin MS, Wu YC, Liao CH, et al. Platelet and II acute muscle injuries were eligible review. Two-hundred
rich plasma releasate promoted proliferation of skeletal muscle cells twenty-two of 268 patients were reported to be competitive
in association with upregulation of PCNA, cyclins, and cyclin de- athletes. Two studies described PRP usage with the GPSIII
pendent kinases. Platelets. 2017;28(5):491–7. system (Biomet Biologics), whereas one study used the autolo-
25. Hammond JW, Hinton RY, Curl LA, Muriel JM, Loverin RM. Use gous conditioned plasma (Arthrex), and the remaining two
of autologous platelet-rich plasma to treat muscle strain injuries. studies did not report which system was used. Platelet concen-
Am J Sports Med. 2009;37(6):1135–42. tration ranged from 443 to 1297 × 103/μL and there was con-
26. Wright-Carpenter T, Opolon P, Appell HJ, Meijer H, Wehling P, siderable variability in injection protocols, ranging from a sin-
Mir LM. Treatment of muscle injuries by local administration of gle 3-mL injection to 5-mL injection to a multiple 3-mL injec-
autologous conditioned serum: animal experiments using a muscle tion protocol. Control groups were treated with a daily home
contusion model. Int J Sports Med. 2004;25(8):582–7. exercise program with progressive agility and trunk stabiliza-
27. Tsai WC, Yu TY, Chang GJ, Lin LP, Lin MS, Pang JS. Platelet-rich tion in conjunction with 1, 2, or 3 physiotherapy sessions, while
plasma releasate promotes regeneration and decreases inflammation one study had a control group with blinded placebo (normal
and apoptosis of injured skeletal muscle. Am J Sports Med. saline) injection. The pooled results demonstrated a significant-
2018;46(8):1980–6. ly earlier return to sport for the PRP group when compared to
28. De Jesus JO, Parker L, Frangos AJ, Nazarian LN. Accuracy of control with a mean difference of 5.57 days earlier return to
MRI, MR arthrography, and ultrasound in the diagnosis of rotator play with PRP. Subgroup analysis showed no difference in time
cuff tears: a meta-analysis. AJR. 2009;192(6):1701–7. to return to sport when comparing PRP and control for treat-
29. Warden SJ, Kiss ZS, Malara FA. Comparative accuracy of mag- ment of grade I and II hamstring muscle strains alone. No
netic resonance imaging and ultrasonography in confirming significant reinjury rate was found between two groups at a
clinically diagnosed patellar tendinopathy. Am J Sports Med. 6-month follow-up. The study suggested that the use of PRP
2007;35(3):427–36. for acute grade I and II muscle strains may result in faster
30. Askling CM, Tengvar M, Saartok T, Thorstensson A. Acute first- return to sport without increasing the rate of reinjury; however,
time hamstring strains during high-speed running: a longitudinal no difference was noted in time to return to sport looking at
study including clinical and magnetic resonance imaging findings. acute grade I and II hamstring strains specifically.
Am J Sports Med. 2007;35(2):197–206. 41. Mosca M, Rodeo S. Platelet rich plasma for muscle injuries: game
31. Koulouris G, Connell D. Imaging of hamstring injuries: therapeutic over or time out? Curr Rev Musculoskelet Med. 2015;8:145–53.
implications. Eur Radiol. 2006;16:1478–87. 42.• Hamilton B, Tol JL, Almusa E, Boukarroum S, Eirale C, Farooq A,
32. Verrall GM, Slavotinek JP, Barnes PG, Fon GT. Diagnostic and et al. Platelet-rich plasma does not enhance return to play in ham-
prognostic value of clinical findings in 83 athletes with posterior string injuries: a randomized controlled trial. Br J Sports Med.
thigh injury: comparison of clinical findings with magnetic reso- 2015;49:943–50. This study looked at the efficacy of a single
nance imaging documentation of hamstring muscle strain. Am J PRP injection in reducing the return to sport duration in male
Sports Med. 2003;31(6):969–73. athletes after acute hamstring injury. The study is a random-
33. Bubnov R, Yevseenko V, Semeniv I. Ultrasound guided injections ized, three-arm, double-blind, parallel-group trial including 90
of platelets rich in plasma for muscle injury in professional athletes: professional athletes with hamstring injuries confirmed on
comparative study. Med Ultrasound. 2013;15(2):101–5. MRI. Patients were randomized to PRP, PPP (platelet-poor
34. Hamilton B, Knez W, Eirale C, Chalabi H. Platelet enriched plasma plasma) or control (no injection) groups. All patients received
for acute muscle injury. Acta Orthop Belg. 2010;76(4):443–8. intensive standardized rehabilitation and the primary outcome
35. Zanon G, Combi F, Combi A, Perticarini L, Sammarchi L, Benazzo measure was return to play, with secondary outcome measures
F. Platelet-rich plasma in the treatment of acute hamstring injuries in including reinjury rate after 2 and 6 months. The adjusted time
professional football players. Joints. 2016;4(1):17–23. to return to sport was − 5.7 days between PRP and PPP which
36. Wright-Carpenter T, Klein P, Schaferhoff P, Appell HK, Mir LM, was significant (p = 0.01); however, the adjusted time to return
Wehling P. Treatment of muscle injuries by local administration of to sport between PRP and control was − 2.9 days, which was
642 Curr Rev Musculoskelet Med (2018) 11:635–642

not significant (p = 0.189). The time to return to sport between muscle strength, range of motion and flexibility, muscle func-
PPP and control was 2.8 days, which was not significant (p = tion, and imaging. Six studies were included with a total of 374
0.210). There was no difference in reinjury rate between any patients. Time to return to sport was significantly shorter in
groups. In conclusion, this study found that there was no benefit patients treated with PRP (mean difference − 7.17 days), but
of a single PRP injection over rehabilitation program in athletes if only double-blind studies or studies or studies involving only
who have sustained acute MRI positive hamstring injuries. hamstring injuries were analyzed, non-significant differences
43. Rettig AC, Meyer S, Bhadra AK. Platelet-rich plasma in addition to were found. The rate of reinjury and complications was similar
rehabilitation for acute hamstring injuries in NFL players: clinical ef- between the two groups (p > 0.05), nor was any differences in
fects and time to return to play. Orthop J Sports Med. 2013;1(1):1–5. pain, muscle strength, flexibility muscle function, and imaging.
44.• Grassi A, Napoli F, Romandini I, Samuelsson K, Zaffagnini S, The authors did note that the performance bias was a high risk
Candrian C, et al. Platelet-rich plasma (PRP) effective in the treat- due to lack of blinding in four studies. Due to the bias in the
ment of acute muscle injuries? a systematic review and meta-anal- studies, heterogeneity of the findings, and limited sample size,
ysis. Sports Med. 2018;48(4):971–89. This study was a meta- the authors found that the evidence should be considered a low
analysis of randomized controlled trials looking to evaluate quality despite promising biological rationale, positive preclin-
the effect of PRP injections on outcomes following acute muscle ical findings, and early successful clinical experience of PRP.
injuries. They included randomized controlled trials which in- 45. Reurink G, Goudswaard GJ, Moen MH, Weir A, Verhaar JAN,
vestigated the effect of PRP for the treatment of acute muscle Bierma-Zeinstra SMA, et al. Platelet-rich plasma injections in acute
injuries against at least one control group, encompassing pla- muscle injury. N Engl J Med. 2014;370(26):2546–7.
cebo injection or physical therapy. The outcomes evaluated 46. Loo W, Lee D, Soon M. Plasma rich in growth factors to treat
were time to return to sport, reinjuries, complications, pain, adductor longus tear. Ann Acad Med. 2009;38:733–4.