Review Article
Platelet-rich Plasma in
Orthopaedic Applications:
Evidence-based
Recommendations for Treatment
Abstract
Wellington K. Hsu, MD Autologous platelet-rich plasma (PRP) therapies have seen a
dramatic increase in breadth and frequency of use for orthopaedic
Allan Mishra, MD
conditions in the past 5 years. Rich in many growth factors that
Scott R. Rodeo, MD
have important implications in healing, PRP can potentially
Freddie Fu, MD
regenerate tissue via multiple mechanisms. Proposed clinical and
Michael A. Terry, MD
surgical applications include spinal fusion, chondropathy, knee
osteoarthritis, tendinopathy, acute and chronic soft-tissue injuries,
Pietro Randelli, MD
enhancement of healing after ligament reconstruction, and muscle
S. Terry Canale, MD
strains. However, for many conditions, there is limited reliable
Frank B. Kelly, MD
clinical evidence to guide the use of PRP. Furthermore,
classification systems and identification of differences among
products are needed to understand the implications of variability.
he healthcare environment is
Pathophysiology
T
changing rapidly, and recently
JAAOS Plus Webinar
there has been increased use of
Since 1950, PRP has been used to
Join Dr. Hsu, Dr. Rodeo, and Dr. Fu
platelet-rich plasma (PRP) in ortho-
manage dermatologic and oromaxil-
for the JAAOS interactive webinar
paedic applications. However, sur-
discussing  Platelet-rich Plasma in
lofacial conditions.31,32 More re-
geons often have little guidance with
Orthopaedic Applications: Evidence-
cently, interest has grown exponen-
based Recommendations for
regard to its indications and cost-
tially in the potential use of PRP in
Treatment, on Tuesday, December
effectiveness. The continuous call for
orthopaedic applications such as
10, at 9 PM Eastern. The moderator
data in the orthopaedic community
will be William N. Levine, MD, the
bone formation and soft-tissue in-
Journal s Deputy Editor for Upper
has led to a higher quantity and
jury, and as an adjunct in surgical re-
Extremity topics.
quality of studies reporting the use of
construction procedures.
To join and to submit questions in
PRP. In February 2011, the Ameri-
PRP is defined as  a sample of au-
advance, please visit the
can Academy of Orthopaedic Sur-
tologous blood with concentrations
OrthoPortal website: http://
geons hosted a forum involving ex-
orthoportal.aaos.org/jaaos/
of platelets above baseline values. 33
pert clinicians and scientists in the
It is created through a two-phase
field of PRP therapy who presented
centrifugation process called plasma-
the best available level I through III
pheresis, in which liquid and solid
clinical studies reporting on the use
components of anticoagulated blood
J Am Acad Orthop Surg 2013;21:
739-748 of PRP in the treatment of orthopae-
are separated. The first phase con-
dic conditions.1 In this article, we ex- sists of an initial soft spin (1,200 to
http://dx.doi.org/10.5435/
JAAOS-21-12-739 amine several level I studies,2-16 level
1,500 RPM) with a relatively low
II studies,17-24 and level III studies25-30
gravitational force in which plasma
Copyright 2013 by the American
on the use of PRP in the treatment of
Academy of Orthopaedic Surgeons. and platelets are separated from red
orthopaedic conditions. blood cells and white blood cells
December 2013, Vol 21, No 12 739
Platelet-rich Plasma in Orthopaedic Applications: Evidence-based Recommendations for Treatment
platelet-rich and platelet-poor cial in conditions that require tissue
Figure 1
plasma components (Figure 1). The healing.33,36 In fact, Wasterlain et al36
necessity of this phase is controver- recently demonstrated that local in-
sial, as some commercial formula- tratendinous injection of PRP can
tions do not implement this process. lead to a systemic ergogenic effect,
Furthermore, it is unclear what po- temporarily increasing serum levels
tential benefits platelet-poor plasma of insulin-like growth factor 1, vas-
may have on tissue healing.34 cular endothelial growth factor, and
basic fibroblast growth factor. Con-
In addition to platelets, PRP con-
versely, other proteins present in PRP
tains other cell types with potentially
have demonstrated inhibitory effects,
beneficial effects in tissue healing.
such as transforming growth factor
WBCs such as monocytes and poly-
(TGF)-²1, which may lead to vari-
morphonuclear neutrophils may trig-
able clinical results in certain appli-
ger a localized inflammatory effect.
cations.37
Although some investigators believe
that this inflammatory effect is criti- The exact role of thrombin in PRP
cal to the tissue repair process, neu- has been debated. Thrombin and/or
trophils have been hypothesized to calcium chloride is necessary to cata-
impede healing.35 The inclusion of lyze the conversion of fibrinogen to
WBCs in the PRP preparation varies fibrin, but it also induces platelets to
Illustration demonstrating
depending on the particular indica- secrete growth factors. Some data,
separation of the red blood cells
tion. however, suggest that exogenous
(RBCs) and white blood cells
thrombin activation of PRP may ac-
Proteins such as platelet-derived
(WBCs) from the platelet-rich
tually diminish its ability to induce
plasma (plasma and platelets)
growth factor (PDGF), vascular en-
following the two-step
bone formation compared with non
dothelial growth factor, endothelial
centrifugation process.
thrombin-activated PRP.38
cell growth factor, and basic fibro-
blast growth factor can be detected More than 40 commercial systems
(WBCs). The second phase, or hard at high concentrations in PRP; conse- exist that claim to concentrate whole
spin (4,000 to 7,000 RPM), is per- quently, many investigators have blood into a platelet-rich substance.
formed to further concentrate the postulated that PRP may be benefi- However, many factors contribute to
From the Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL (Dr. Hsu and
Dr. Terry), the Department of Orthopaedic Surgery, Stanford University Medical Center, Stanford, CA (Dr. Mishra), the Department of
Orthopaedic Surgery and the Research Department, Hospital for Special Surgery, New York, NY (Dr. Rodeo), the Department of
Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA (Dr. Fu), the Department of Orthopaedic Surgery, University of Milan,
Milan, Italy (Dr. Randelli), the Department of Orthopaedic Surgery, University of Tennessee Campbell Clinic, Memphis, TN
(Dr. Canale), and Forsyth Street Orthopaedics, Macon, GA (Dr. Kelly).
Dr. Hsu or an immediate family member is a member of a speakers bureau or has made paid presentations on behalf of Graftys,
Medtronic Sofamor Danek, Pioneer Surgical, Stryker, Terumo Medical, and Zimmer; has received research or institutional support
from Baxter, Medtronic Sofamor Danek, and Pioneer Surgical; and serves as a board member, owner, officer, or committee member
of the American Academy of Orthopaedic Surgeons (AAOS), the Lumbar Spine Research Society, and the North American Spine
Society. Dr. Mishra or an immediate family member has received royalties from Biomet and ThermoGenesis, is an employee of
BioParadox, and has stock or stock options held in BioParadox and ThermoGenesis. Dr. Rodeo or an immediate family member
serves as a paid consultant to Smith & Nephew and has stock or stock options held in Cayenne Medical. Dr. Fu or an immediate
family member has received royalties from ArthroCare; is an employee of and has stock or stock options held in Stryker; and serves
as a board member, owner, officer, or committee member of the AAOS, the American Orthopaedic Society for Sports Medicine, the
Orthopaedic Research and Education Foundation (OREF), and the International Society of Arthroscopy, Knee Surgery, and
Orthopaedic Sports Medicine. Dr. Terry or an immediate family member has received royalties from, serves as a paid consultant to,
has received research or institutional support from, and has received nonincome support (such as equipment or services),
commercially derived honoraria, or other non-research related funding (such as paid travel) from Smith & Nephew. Dr. Randelli or an
immediate family member is a member of a speakers bureau or has made paid presentations on behalf of and has received
research or institutional support from Biomet; serves as a paid consultant to DePuy; and serves as a board member, owner, officer,
or committee member of the European Society of Sports Traumatology, Knee Surgery & Arthroscopy. Dr. Canale or an immediate
family member serves as a board member, owner, officer, or committee member of the AAOS, Bioworks, the Campbell Foundation,
and OREF. Dr. Kelly or an immediate family member serves as a board member, owner, officer, or committee member of OREF and
the Twentieth Century Orthopaedic Association.
740 Journal of the American Academy of Orthopaedic Surgeons
Wellington K. Hsu, MD, et al
Table 1
Common Platelet-rich Plasma Formulations
System Type Whole Blood Volume (mL) Centrifuge Time (min)
Cascade (Musculoskeletal P-PRF 18 6
Transplant Foundation)39
GPS III (Biomet)39 P-LRP 55 15
Magellan (Arteriocyte Medical P-LRP 26 17
Systems)39
ACP (Arthrex)40,41 P-PRP 10 5
SmartPReP (Harvest Technolo- P-LRP 60 16
gies)42
Symphony II (DePuy)43 P-LRP 54 5
P-LRP = platelet-leukocyte-rich plasma, P-PRF = pure platelet-rich fibrin, P-PRP = pure platelet-rich plasma
the variable content and, subse-
Table 2
quently, to the performance of PRP
Sports Medicine Platelet-rich Plasma Classification System
from different preparation methods
(Table 1). First, the final platelet con- PRP Typea White Blood Cells (WBCs) Activated?
centration varies not only between
1 Increased over baseline No
techniques but also within a given
2 Increased over baseline Yes
technique.39,44-46 The final platelet
3 Minimal or no WBC No
concentration of any PRP product
4 Minimal or no WBC Yes
depends on the initial volume of
whole blood, the platelet recovery ef-
PRP = platelet-rich plasma
a
Any PRP type can have an associated subtype A or subtype B. Subtype A has e"5 times
ficiency of the chosen technique, the
the concentration of platelets in the final preparation compared to baseline. Subtype B has
final volume of plasma used to sus-
<5 times the concentration of platelets in the final preparation compared to baseline.
pend concentrated platelets, the rela- Adapted with permission from Mishra A, Harmon K, Woodall J, Vieira A: Sports medicine
applications of platelet rich plasma. Curr Pharm Biotechnol 2012;13(7):1185-1195.
tive concentration of WBCs and/or
red blood cells, and the concomitant
use of thrombin. Furthermore, indi-
vidual patient factors such as comor-
bidities, age, and circulation lead to of injury, some authors have postu-
Bone Healing
differences in growth factor and cell lated that the timing of the adminis-
content.45 tration of PRP has a greater impact
PRP has demonstrated osteogenic
A higher concentration or absolute on healing than does the number of
properties in several in vitro and pre-
number of platelets within PRP does platelets.22
clinical studies;49,50 however, clinical
not necessarily lead to an enhanced The absence of a validated classifi-
reports have not been as promising.
tissue healing effect. In fact, Giusti cation system that identifies crucial
In a prospective observational study
et al47 proposed that the most effica- differences between PRP formula-
involving 123 foot and ankle fusions
cious platelet concentration for tissue tions makes it difficult to compare
in 62 patients with risk factors for
healing is 1.5 × 106 platelets per mi- studies. In an attempt to standardize
nonunion, autologous platelet con-
croliter. In addition, the dose- different PRP systems, both DeLong
centrate (APC) was used in 67 proce-
response curve is not linear, and a et al35 and Mishra et al48 have pro-
dures, and APC and bone graft were
saturation effect has been described posed systems that classify PRP sys-
used in 56 procedures.17 Because the
in which an inhibitory cascade en- tems by activation mechanism, plate-
6% nonunion rate for all patients
sues once a sufficiently high concen- let number, and/or cell content.
was below historical outcomes, the
tration of platelets is reached. Be- Although the systems have yet to be
cause platelets can exert the greatest validated in the literature, they repre- authors concluded that APC might
be beneficial in this patient popula-
influence on healing during or imme- sent an important step in furthering
tion. However, these patients under-
diately after the inflammatory phase this area of research (Table 2).
December 2013, Vol 21, No 12 741
Platelet-rich Plasma in Orthopaedic Applications: Evidence-based Recommendations for Treatment
went a variety of procedures (ankle, such as TGF-²1, thrombospondin-1, acid (P < 0.0001). Eighty-seven per-
hindfoot, midfoot, and forefoot sur- and insulin-like growth factor.51 cent of patients enrolled in the PRP
gery), and the type of bone graft Consequently, its use has been pro- group obtained good results, which
used (ie, allograft, autograft) varied posed in patients with symptomatic led these authors to conclude that
based on surgeon choice. cartilage defects or osteochondral le- PRP should be considered as a first-
In a level III prospective study, Tsai sions. line treatment of symptomatic osteo-
et al25 reported lumbar posterolateral In a level I study in which 78 pa- chondral lesions of the talus. Al-
spine fusion rates with local bone tients with bilateral knee osteoarthri- though preliminary evidence exists,
graft in 67 consecutive patients, 34 tis were randomized to receive a sin- further study is required before con-
of whom were treated with addi- gle WBC-filtered PRP injection, two clusions can be made regarding the
tional platelet glue. At 2-year follow- PRP injections 3 weeks apart, or a efficacy of PRP in the management
up, there was no difference in non- single saline injection, both PRP of osteochondral lesions and knee
union rate (15%, platelet glue; 10%, groups were found to have signifi- osteoarthritis.
control group) as determined on cantly better outcomes than the con-
flexion-extension radiographs and trol group 6 months after treatment.2
fine-cut CT scans. Similarly, in a ret- In a separate level I randomized con- Chronic Tendinopathy
rospective cohort study of 76 consec- trolled trial (RCT) in 120 patients,
Elbow epicondylitis, which is charac-
utive patients who underwent pos- Cerza et al3 reported significantly
terized by failure of the normal ten-
terolateral lumbar fusion, the better clinical outcomes up to 24
don repair mechanism, is a common
nonunion rates at clinical follow-up weeks after a local injection of PRP
malady that leads to chronic pain
of e"24 months did not differ signifi- compared with injection of hy-
and decreased function in activities
cantly between iliac crest bone graft aluronic acid (P < 0.001). Con-
of daily living. Although treatment
plus platelet-gel preparation com- versely, in an RCT of 109 patients,
recommendations range from brac-
pared with autologous bone graft Filardo et al4 demonstrated that al-
ing, physiotherapy, and steroid injec-
alone (25% and 17%, respectively; P though intra-articular PRP injections
tions to arthroscopic or open dé-
= 0.18).26 Weiner and Walker27 dem- can offer significant clinical improve-
bridement, some investigators have
onstrated a significantly lower fusion ment up to 1 year after treatment,
indicated that the local delivery of
rate with the use of autologous these results were not better com-
humoral mediators may enhance ten-
growth factors from PRP and au- pared with hyaluronic acid injec-
don healing and lead to improved
tograft in single-level posterolateral tions. Furthermore, the authors of a
clinical outcomes.
lumbar fusion compared with iliac Clinical Practice Guideline spon-
crest bone graft alone (62% and sored by the American Academy of In a controlled trial comparing lo-
91%, respectively; P < 0.05). The ad- Orthopaedic Surgeons were  unable cal injection of either PRP formula-
dition of PRP to autograft for pos- to recommend for or against growth tion containing WBCs or bupiva-
terolateral and interbody spine fu- factor injections and/or platelet rich caine in 20 patients with chronic
sion does not appear to confer any plasma for patients with symptom- elbow epicondylar tendinosis,
benefit in fusion rates and, in fact, it atic OA of the knee. 52 Mishra and Pavelko19 demonstrated
may be detrimental. One case-control clinical study has significant improvement in clinical
been published to date on the man- outcomes in visual analog scale
Currently, limited clinical evidence
agement of cartilage defects with (VAS) and Mayo elbow scores at 8
exists demonstrating any beneficial
PRP.18 In this level II study, 32 pa- weeks after treatment with PRP (P =
effects from the use of PRP in bone
tients with symptomatic osteochon- 0.001 and P = 0.008, respectively).
healing applications. The available
evidence indicates that PRP is not ef- dral lesions of the talus classified on Patients treated with PRP had a 93%
ficacious either alone or as an ad- CT scan using the Ferkel system reduction in pain compared with
junct to local bone graft in these ap- were randomized to receive intra- baseline at an average follow-up of
articular injections of either hy- 25.6 months (P < 0.0001). Thanasas
plications.
aluronic acid or PRP. At 28-week et al5 compared clinical outcomes in
follow-up, patients who received 28 patients with the same condition
PRP demonstrated significantly who were randomized to local injec-
Cartilage Healing
greater improvements in pain, stiff- tion of either autologous whole
PRP contains factors that have been ness, and function scores compared blood or PRP in a level I study. Al-
shown to be critical in joint repair, with those treated with hyaluronic though VAS score improvements
742 Journal of the American Academy of Orthopaedic Surgeons
Wellington K. Hsu, MD, et al
were reported at every follow-up in- tients who received PRP demon- with excellent long-term results and
terval up to 6 months in the PRP strated a greater activity level; how- patient satisfaction. Maturation of
group, the only statistically signifi- ever, all other outcome measures, the tendon graft is necessary for opti-
cant difference was seen at the including VAS and pain level evalua- mal biomechanical strength and re-
6-week time point. tion, did not differ significantly from turn to activity. Graft remodeling
Using the same methodology as did the control group. Gosens et al10 may be accelerated by the actions of
Mishra and Pavelko,19 a different demonstrated that, for patients pre- PDGF, TGF-²1, and insulin-like
group of researchers compared local viously treated with cortisone, growth factor 1.29 The intra-
injection of PRP with corticosteroid ethoxysclerol, and/or surgery for pa- articular biologic environment pre-
for lateral epicondylitis in a level I tellar tendinopathy, PRP did not con- sents challenges to tissue healing that
study of 100 patients; they published fer as much improvement in VAS may lead to suboptimal results. For
one article reporting on the 1-year scores as it did in patients who had example, this anatomic area is not
follow-up results7 and a second arti- had no prior intervention. only poorly vascularized but also
cle on the 2-year follow-up results.6 Although the cost-effectiveness of produces synovial fluid containing
Significantly greater reduction in treatment is unclear, the clinical evi- proteases that prevent fibrin clot for-
VAS scores was achieved with PRP dence suggests that local injection of mation, which is normally required
measured at each time point up to 24 PRP containing WBCs may be bene- for initial wound healing.55 Further-
months after injection (P < 0.0001). ficial to patients with chronic elbow more, this contained milieu may not
Comparison of outcomes at 1- and epicondylitis refractory to standard deliver important growth factors for
2-year follow-up demonstrated that nonsurgical treatment. However, the healing.
clinical scores in the corticosteroid results of PRP treatment of other In vitro studies have demonstrated
group steadily declined, whereas chronic tendinopathies are not as the ability of PRP to improve ACL
those of the PRP group were main- clear. cell viability and function.43 Thus,
tained.6 These studies suggest that treatments have been proposed to in-
PRP formulations containing WBCs crease both histologic metrics in re-
Surgical Repair of Acute
improve patient outcomes compared pair and remodeling at the midsub-
Soft-tissue Injuries
with local injection of anesthetic, stance of the reconstructed ACL as
whole blood, or corticosteroid. well as within the patellar tendon
Because of the rich source of growth
The results have not been as prom- harvest site in patients treated with
factors in PRP, it has been suggested
ising for other tendinopathies. In a bone patellar tendon bone au-
that administering PRP in the setting
level I RCT comparing local injec- tografts.56 Early administration of
of acute soft-tissue injuries could
tion of PRP to saline for Achilles ten- PRP during the inflammatory pro-
provide enhanced healing, thus facil-
dinopathy in conjunction with eccen- cess may lead to an accelerated heal-
itating an early return to sports.20,29
tric exercises, de Vos et al8 reported ing cascade that is shorter than the
Tendon healing is typically character-
no difference in the improvement of typical 1-year period expected for
ized by an initial inflammatory re-
clinical outcome up to a 24-week full graft maturation.56
sponse that is associated with the in-
follow-up. In a follow-up study, Radice et al29 conducted a prospec-
flux of factors such as PDGF and
members of the same research group tive single-blind study of 50 patients
TGF-² (within 2 days), resulting in
randomized 54 patients diagnosed who were treated with either ACL
angiogenesis (2 to 3 days), and colla-
with chronic Achilles tendinopathy autograft alone or ACL autograft
gen synthesis (3 to 5 days).53 Because
to blinded injections containing ei- with application of PRP gel at the
PRP contains these critical growth
ther PRP or saline in addition to a time of surgery. At 1-year follow-up,
factors that can aid in the inflamma-
training program.9 Although patients it was found that application of PRP
tory response, its utility may be
in both groups had improved clinical gel resulted in significantly faster bi-
greatest when administered early in
outcomes 1 year after injection, there ologic maturation than did autograft
the healing period.54
was no significant difference in bene- alone as measured on MRI (177 and
fit. In a prospective level III study, Fi- 369 days, respectively; P < 0.001)
Anterior Cruciate Ligament
lardo et al28 studied the utility of (Figure 2). Similarly, in an RCT with
Reconstruction
PRP injection for refractory jumper s 108 patients, Orrego et al21 demon-
knee in 31 patients who were treated Anterior cruciate ligament (ACL) re- strated that the addition of platelet
with either local injection of PRP or construction has traditionally been concentrate to a semitendinosus-
exercise. At 6-month follow-up, pa- considered a successful procedure gracilis graft and to the femoral tun-
December 2013, Vol 21, No 12 743
Platelet-rich Plasma in Orthopaedic Applications: Evidence-based Recommendations for Treatment
platelet-enriched gel. In the investiga-
Figure 2
tional group, gel was sutured into
the allograft and applied in the tibial
tunnel. At a mean follow-up of 2
years and based on clinical and ra-
diographic outcomes according to
the International Knee Documenta-
tion Committee score, KT-1000 ar-
thrometer (MEDmetric), plain radi-
ography, and MRI, the authors
concluded that there were no signifi-
cant differences in any parameter.
The variability in clinical outcomes
could be attributed to several factors,
including PRP preparation/centri-
fugation, graft choice, rehabilitation
protocols, and application technique.
These findings were supported by
Magnussen et al,58 who demon-
strated that the use of PRP in al-
Sagittal T2-weighted magnetic resonance images of the knee obtained 6
months after anterior cruciate ligament reconstruction with bone patellar
lograft ACL reconstructions did not
tendon bone graft without platelet-rich plasma (PRP) (A) and 5 months after
lead to differences in patient-
reconstruction with PRP (B). A more homogeneous signal was demonstrated
reported outcomes at 2-year follow-
in grafts with PRP, which suggests a quicker maturation rate. (Reproduced
with permission from Radice F, Yánez R, Gutiérrez V, Rosales J, Pinedo M, up.
Coda S: Comparison of magnetic resonance imaging findings in anterior
More than 40% of patients who
cruciate ligament grafts with and without autologous platelet-derived growth
undergo ACL reconstruction with a
factors. Arthroscopy 2010;26[1]:50-57.)
single-bundle patellar tendon au-
tograft report residual symptoms (eg,
nel led to a significantly higher rate et al56 reported results in 37 patients pain, sensory problems) at the donor
of graft maturation 6 months after who had second-look arthroscopies site.59 In an RCT involving 40 pa-
reconstruction, signified by low- after ACL reconstruction with autog- tients, Cervellin et al12 studied the ef-
intensity signal on MRI (P = 0.036). enous hamstring grafts with and fect of the addition of autologous
In contrast, Silva and Sampaio20 ap- without injection of a PRP prepara- PRP gel sutured into the patellar and
plied PRP in the femoral tunnels in tion rich in growth factors. Both tibial bone plug harvest site. Al-
30 patients and found no difference gross morphology and histologic though VAS scores were not signifi-
in MRI findings of the signal inten- evaluation of graft biopsies demon- cantly different at 12-month follow-
sity of fibrous interzone in the tun- strated improvements in graft re- up, Victorian Institute of Sport
nels 3 months after surgery. The dif- modeling and the amount of new Assessment questionnaire scores,
ferences in this study20 may be connective tissue enveloping the which have been validated to quan-
partially explained by the shorter graft, as well as a higher graft thick- tify knee function in subjects with
time point of radiographic imaging ness and synovial coverage rating for patellar tendinopathy,60 were signifi-
and smaller number of patients than patients treated with PRP. Although cantly higher in patients treated with
in either of the other two studies.21,29 the period of time from index ACL PRP (P = 0.041), suggesting greater
A systematic review of eight con- surgery to second-look arthroscopy satisfaction with knee function. In a
trolled clinical trials concluded that varied widely, the authors concluded separate level I randomized study, 12
the addition of platelet concentrates that use of PRP in vivo may enhance patients who received 20 to 40 mL
to ACL reconstruction may have a the ligamentization process in ten- of PRP gel at the patellar tendon de-
20% to 30% beneficial effect on don grafts. fect were compared with 15 patients
graft maturation.57 In a level I study, Nin et al11 ran- who did not receive PRP.13 At
Histologic analysis of ACL grafts domized 100 patients with ACL re- 6-month follow-up MRI examina-
following PRP application also sug- construction with patellar tendon al- tion, the patellar tendon gap area
gests enhanced maturation. Sánchez lograft to receive or not receive was found to be significantly smaller
744 Journal of the American Academy of Orthopaedic Surgeons
Wellington K. Hsu, MD, et al
in the PRP group (P = 0.046) (Figure
Figure 3
3). Furthermore, immediate postop-
erative VAS scores were lower in the
investigational group than in the
control group (P = 0.02). Based on
these findings, the authors concluded
that PRP can both enhance tendon
healing within the patellar tendon
defect and contribute anti-inflam-
matory effects that may modulate
pain after surgery.
Rotator Cuff Repair
Five level I and II controlled studies
have compared results after surgical
repair of rotator cuff injuries with
Axial magnetic resonance images of the gap area (dotted line near the top of
and without the adjunctive use of
panel A; arrow, panel B) of the patellar tendon harvest site in a patient who
PRP. Castricini et al14 reported no
did not receive platelet-rich plasma (PRP) (A) and a patient who did receive
PRP (B). The gap is smaller in panel B than in panel A. (Adapted with
significant difference in Constant
permission from de Almeida AM, Demange MK, Sobrado MF, Rodrigues MB,
scores and tendon scores graded on
Pedrinelli A, Hernandez AJ: Patellar tendon healing with platelet-rich plasma:
MRI up to 16 months after primary
A prospective randomized controlled trial. Am J Sports Med
arthroscopic rotator cuff repair with 2012;40[6]:1282-1288.)
or without the use of autologous
platelet-rich fibrin matrix (PRFM).
These authors concluded that PRP to arthroscopic rotator cuff repairs did different from that used by Castricini
had no demonstrable benefit for
not accelerate recovery with respect to et al14 and Rodeo et al.22
small to medium-size rotator cuff pain, motion, strength, or overall pa- In a randomized trial involving 40
tears.
tient satisfaction at any time point up
patients with subacromial decom-
Similarly, in a level II study involv- to a minimum of 16 months postoper-
pression, the use of PRP led to signif-
ing 79 patients in whom reattach- atively. The difference in re-tear rate
icantly decreased pain scores and im-
ment of the rotator cuff was per- between the groups at 9-month
proved shoulder range of motion
formed with suture anchors, the follow-up was not statistically signifi-
postoperatively compared with that
clinical scores in the group with
cant.
of control patients (P < 0.001).16 De-
PRFM sutured in the tendon-bone Conversely, in a double-blind RCT
spite this, a systematic review per-
interface were no different from of 53 patients, intraoperative appli-
formed by Chahal et al61 concluded
those of the control group at a mini- cation of PRP with an autologous
that PRP does not have an effect on
mum 1-year follow-up.22 In fact, lo- thrombin component during arthro-
re-tear rates or clinical outcomes af-
gistic regression analysis of both
scopic rotator cuff repair led to sig-
ter arthroscopic repair. Although
groups demonstrated that the use of nificantly higher Constant and Uni-
there is some evidence demonstrating
PRFM was a significant predictor of
versity of California, Los Angeles
potential benefit, further study is re-
tendon defect at 12-week follow-up scores and strength in external rota-
quired before the routine use of ad-
(P = 0.037), suggesting that it may tion 3 months after surgery but not
junctive PRP during shoulder surgery
have a negative effect on healing.
at 6, 12, and 24 months compared
can be recommended.
The authors postulated that the vari- with control subjects.15 In grade 1
ability in the composition and qual- and 2 tears, the use of PRP led to sig-
Achilles Tendon Repair
ity of PRP for each patient likely led nificantly higher strength in external
Achilles tendon ruptures can be asso-
to variability in the capacity for ten- rotation scores at 3, 6, 12, and 24
don repair. In a prospective cohort ciated with prolonged recovery and
months postoperatively (P < 0.05)
postoperative complications such as
study involving 42 patients, Jo et al23 and a lower rate of re-rupture (P =
demonstrated that, compared with the re-rupture because of the poor vascu-
0.08). Notably, Randelli et al15 used
lar environment surrounding the re-
control group, application of PRP gel a commercial preparation of PRP
December 2013, Vol 21, No 12 745
Platelet-rich Plasma in Orthopaedic Applications: Evidence-based Recommendations for Treatment
pair. In a case-control study involv- adequate cost-benefit analysis. PRP suggests that success varies depend-
ing 12 athletes who had acute therapy is not covered by many in- ing on the preparation method and
Achilles tendon repair, patients who surance plans in the United States,
composition, medical condition of
were injected with a preparation rich and until appropriate data are avail-
the patient, anatomic location, and
in growth factors around the tendon able, this situation may not change.
tissue type. In response to a growing
fibers demonstrated significantly In a study involving diabetic wound
interest among both patients and sur-
faster recovery of range of motion (P ulcers, the cost of PRP treatment in
geons in the use of PRP, recent stud-
= 0.025) and time to running (P = 2006 was estimated to be $450 per
ies have reported outcomes in a vari-
0.042).30 However, a level II study of treatment, for a monthly cost of
ety of conditions. Further critical
30 patients who underwent Achilles $3,600 for an uncomplicated ulcer.63
review and rigorous clinical studies
tendon repair with or without PRP Dougherty63 concluded that PRP gel
are required to formulate a cost-
administration demonstrated no sig- was more cost-effective than wet-to-
effective, efficacious algorithm for
nificant difference between the two dry saline dressings in managing
the use of PRP in patients with or-
groups in heel raise index or elastic- nonhealing diabetic foot ulcers over
thopaedic conditions.
ity modulus at 1-year follow-up.24 In a 5-year period.
fact, the Achilles Tendon Total Rup- In the Netherlands, PRP treatment
ture Score was lower in the PRP costs approximately twice as much
References
group, which suggests that intraoper- as corticosteroid treatment but just
ative use of PRP may be detrimental. half that of surgical débridement.6 Evidence-based Medicine: Levels of
Because the formulation of PRP used Although the short-term costs of
evidence are described in the table of
in this study was 17 times that of PRP are greater than those of stan-
contents. In this article, references
baseline platelets without WBCs, the dard steroid injections, if the inci-
2-16 are level I studies. References
difference in preparations could have dence of further intervention (ie, sur-
17-24 are level II studies. References
contributed to the conflicting results. gery, re-injection) is decreased at
25-30 are level III studies.
Although no significant difference in long-term follow-up or if satisfaction
References printed in bold type are
clinical outcomes has been found, pre- is significantly greater with PRP, then
those published within the past 5
liminary clinical evidence suggests that an overall cost savings can be real-
years.
PRP may be beneficial during the lig- ized. Gosens et al6 suggested that
1. PRP an Unproven Option, Say Experts.
amentization and maturation processes PRP may be less expensive than cor-
Available at: http://www.aaos.org/news/
of graft healing as well as that of the ticosteroids at 2-year follow-up in
acadnews/2011/AAOS1_2_16.asp.
patellar tendon graft harvest sites in the management of lateral epicondy- Accessed September 23, 2013.
ACL reconstruction. For rotator cuff litis.
2. Patel S, Dhillon MS, Aggarwal S,
Marwaha N, Jain A: Treatment with
and Achilles tendon repairs, the results
In the orthopaedic literature, fu-
platelet-rich plasma is more effective
of clinical studies are equivocal, and
ture research with data from
than placebo for knee osteoarthritis: A
further study is needed before definitive prospective, double-blind, randomized
EuroQol-5D measures would greatly
trial. Am J Sports Med 2013;41(2):356-
conclusions can be drawn and recom- enhance the ability to implement a
364.
mendations made.
cost-benefit analysis. More impor-
3. Cerza F, Carnì S, Carcangiu A, et al:
tantly, comparison groups would
Comparison between hyaluronic acid
and platelet-rich plasma, intra-articular
have to be properly chosen in such a
infiltration in the treatment of
Cost-benefit study. Cost analysis would have to
gonarthrosis. Am J Sports Med 2012;
Considerations be compared with a surgical inter- 40(12):2822-2827.
vention. Proper economic evaluation
4. Filardo G, Kon E, Di Martino A, et al:
As the quality of investigational
must take into account reported suc- Platelet-rich plasma vs hyaluronic acid to
treat knee degenerative pathology: Study
studies regarding PRP increases, so
cess rates, timing of treatment, and
design and preliminary results of a
too will the demand for its clinical
the patient population.
randomized controlled trial. BMC
Musculoskelet Disord 2012;13:229.
use. The market for PRP, valued at
$45 million in 2009, is expected to
5. Thanasas C, Papadimitriou G,
Charalambidis C, Paraskevopoulos I,
grow to $126 million by 2016.62
Summary
Papanikolaou A: Platelet-rich plasma
Although the body of evidence for
versus autologous whole blood for the
treatment of chronic lateral elbow
the use of PRP in orthopaedic condi- Although PRP has a theoretic benefit
epicondylitis: A randomized controlled
tions is rapidly expanding, insuffi- in the augmentation of tissue heal-
clinical trial. Am J Sports Med 2011;
cient evidence exists to perform an ing, the evidence-based literature 39(10):2130-2134.
746 Journal of the American Academy of Orthopaedic Surgeons
Wellington K. Hsu, MD, et al
6. Gosens T, Peerbooms JC, van Laar W, 16. Everts PA, Devilee RJ, Brown Mahoney 28. Filardo G, Kon E, Della Villa S,
den Oudsten BL: Ongoing positive effect C, et al: Exogenous application of Vincentelli F, Fornasari PM, Marcacci
of platelet-rich plasma versus platelet-leukocyte gel during open M: Use of platelet-rich plasma for the
corticosteroid injection in lateral subacromial decompression contributes treatment of refractory jumper s knee.
epicondylitis: A double-blind
to improved patient outcome: A Int Orthop 2010;34(6):909-915.
randomized controlled trial with 2-year
prospective randomized double-blind
29. Radice F, Yánez R, Gutiérrez V, Rosales
follow-up. Am J Sports Med 2011;39(6):
study. Eur Surg Res 2008;40(2):203-210.
J, Pinedo M, Coda S: Comparison of
1200-1208.
17. Bibbo C, Bono CM, Lin SS: Union rates magnetic resonance imaging findings in
7. Peerbooms JC, Sluimer J, Bruijn DJ,
using autologous platelet concentrate anterior cruciate ligament grafts with
Gosens T: Positive effect of an
alone and with bone graft in high-risk and without autologous platelet-derived
autologous platelet concentrate in lateral
foot and ankle surgery patients. J Surg growth factors. Arthroscopy 2010;26(1):
epicondylitis in a double-blind
Orthop Adv 2005;14(1):17-22. 50-57.
randomized controlled trial: Platelet-rich
plasma versus corticosteroid injection
18. Mei-Dan O, Carmont MR, Laver L, 30. Sánchez M, Anitua E, Azofra J, Andía I,
with a 1-year follow-up. Am J Sports
Mann G, Maffulli N, Nyska M: Platelet- Padilla S, Mujika I: Comparison of
Med 2010;38(2):255-262.
rich plasma or hyaluronate in the surgically repaired Achilles tendon tears
management of osteochondral lesions of using platelet-rich fibrin matrices. Am J
8. de Vos RJ, Weir A, van Schie HT, et al:
the talus. Am J Sports Med 2012;40(3): Sports Med 2007;35(2):245-251.
Platelet-rich plasma injection for chronic
534-541.
Achilles tendinopathy: A randomized
31. Marx RE: Platelet-rich plasma: Evidence
controlled trial. JAMA 2010;303(2):144-
19. Mishra A, Pavelko T: Treatment of to support its use. J Oral Maxillofac
149.
chronic elbow tendinosis with buffered Surg 2004;62(4):489-496.
platelet-rich plasma. Am J Sports Med
9. de Jonge S, de Vos RJ, Weir A, et al:
32. Tayapongsak P, O Brien DA, Monteiro
2006;34(11):1774-1778.
One-year follow-up of platelet-rich
CB, Arceo-Diaz LY: Autologous fibrin
plasma treatment in chronic Achilles
20. Silva A, Sampaio R: Anatomic ACL adhesive in mandibular reconstruction
tendinopathy: A double-blind
reconstruction: Does the platelet-rich with particulate cancellous bone and
randomized placebo-controlled trial. Am
plasma accelerate tendon healing? Knee marrow. J Oral Maxillofac Surg 1994;
J Sports Med 2011;39(8):1623-1629.
Surg Sports Traumatol Arthrosc 2009; 52(2):161-165, discussion 166.
17(6):676-682.
10. Gosens T, Den Oudsten BL, Fievez E,
33. Hall MP, Band PA, Meislin RJ, Jazrawi
van  t Spijker P, Fievez A: Pain and
21. Orrego M, Larrain C, Rosales J, et al: LM, Cardone DA: Platelet-rich plasma:
activity levels before and after platelet-
Effects of platelet concentrate and a bone Current concepts and application in
rich plasma injection treatment of
plug on the healing of hamstring tendons sports medicine. J Am Acad Orthop Surg
patellar tendinopathy: A prospective
in a bone tunnel. Arthroscopy 2008; 2009;17(10):602-608.
cohort study and the influence of
24(12):1373-1380.
previous treatments. Int Orthop 2012; 34. Mazzocca AD, McCarthy MB,
36(9):1941-1946. 22. Rodeo SA, Delos D, Williams RJ, Adler Chowaniec DM, et al: Platelet-rich
RS, Pearle A, Warren RF: The effect of plasma differs according to preparation
11. Nin JR, Gasque GM, Azcárate AV, Beola
platelet-rich fibrin matrix on rotator cuff method and human variability. J Bone
JD, Gonzalez MH: Has platelet-rich
tendon healing: A prospective, Joint Surg Am 2012;94(4):308-316.
plasma any role in anterior cruciate
randomized clinical study. Am J Sports
ligament allograft healing? Arthroscopy 35. DeLong JM, Russell RP, Mazzocca AD:
Med 2012;40(6):1234-1241.
2009;25(11):1206-1213. Platelet-rich plasma: The PAW
23. Jo CH, Kim JE, Yoon KS, et al: Does classification system. Arthroscopy 2012;
12. Cervellin M, de Girolamo L, Bait C,
platelet-rich plasma accelerate recovery 28(7):998-1009.
Denti M, Volpi P: Autologous platelet-
after rotator cuff repair? A prospective
rich plasma gel to reduce donor-site 36. Wasterlain AS, Braun HJ, Harris AH,
cohort study. Am J Sports Med 2011;
morbidity after patellar tendon graft Kim HJ, Dragoo JL: The systemic effects
39(10):2082-2090.
harvesting for anterior cruciate ligament of platelet-rich plasma injection. Am J
reconstruction: A randomized, controlled 24. Schepull T, Kvist J, Norrman H, Trinks Sports Med 2013;41(1):186-193.
clinical study. Knee Surg Sports M, Berlin G, Aspenberg P: Autologous
37. Harris SE, Bonewald LF, Harris MA,
Traumatol Arthrosc 2012;20(1):114- platelets have no effect on the healing of
et al: Effects of transforming growth
120. human achilles tendon ruptures: A
factor beta on bone nodule formation
randomized single-blind study. Am J
13. de Almeida AM, Demange MK, Sobrado and expression of bone morphogenetic
Sports Med 2011;39(1):38-47.
MF, Rodrigues MB, Pedrinelli A, protein 2, osteocalcin, osteopontin,
Hernandez AJ: Patellar tendon healing 25. Tsai CH, Hsu HC, Chen YJ, Lin MJ, alkaline phosphatase, and type I collagen
with platelet-rich plasma: A prospective Chen HT: Using the growth factors- mRNA in long-term cultures of fetal rat
randomized controlled trial. Am J Sports enriched platelet glue in spinal fusion calvarial osteoblasts. J Bone Miner Res
Med 2012;40(6):1282-1288. and its efficiency. J Spinal Disord Tech 1994;9(6):855-863.
2009;22(4):246-250.
14. Castricini R, Longo UG, De Benedetto 38. Han B, Woodell-May J, Ponticiello M,
M, et al: Platelet-rich plasma 26. Carreon LY, Glassman SD, Anekstein Y, Yang Z, Nimni M: The effect of
augmentation for arthroscopic rotator Puno RM: Platelet gel (AGF) fails to thrombin activation of platelet-rich
cuff repair: A randomized controlled increase fusion rates in instrumented plasma on demineralized bone matrix
trial. Am J Sports Med 2011;39(2):258- posterolateral fusions. Spine (Phila Pa osteoinductivity. J Bone Joint Surg Am
265. 1976) 2005;30(9):E243-E246, discussion 2009;91(6):1459-1470.
E247.
15. Randelli P, Arrigoni P, Ragone V, 39. Castillo TN, Pouliot MA, Kim HJ,
Aliprandi A, Cabitza P: Platelet rich 27. Weiner BK, Walker M: Efficacy of Dragoo JL: Comparison of growth factor
plasma in arthroscopic rotator cuff autologous growth factors in lumbar and platelet concentration from
repair: A prospective RCT study, 2-year intertransverse fusions. Spine (Phila Pa commercial platelet-rich plasma
follow-up. J Shoulder Elbow Surg 2011; 1976) 2003;28(17):1968-1970, discus- separation systems. Am J Sports Med
20(4):518-528. sion 1971. 2011;39(2):266-271.
December 2013, Vol 21, No 12 747
Platelet-rich Plasma in Orthopaedic Applications: Evidence-based Recommendations for Treatment
40. Sundman EA, Cole BJ, Fortier LA: 48. Mishra A, Harmon K, Woodall J, Vieira endogenous preparation rich in growth
Growth factor and catabolic cytokine A: Sports medicine applications of factors: Gross morphology and histology.
platelet rich plasma. Curr Pharm
concentrations are influenced by the Arthroscopy 2010;26(4):470-480.
Biotechnol 2012;13(7):1185-1195.
cellular composition of platelet-rich
57. Vavken P, Sadoghi P, Murray MM: The
plasma. Am J Sports Med 2011;39(10):
49. Okamoto S, Ikeda T, Sawamura K, et al:
effect of platelet concentrates on graft
2135-2140.
Positive effect on bone fusion by the
maturation and graft-bone interface
combination of platelet-rich plasma and
41. Metcalf KB, Mandelbaum BR, healing in anterior cruciate ligament
a gelatin ²-tricalcium phosphate sponge:
McIlwraith CW: Application of platelet- reconstruction in human patients: A
A study using a posterolateral fusion
rich plasma to disorders of the knee systematic review of controlled trials.
model of lumbar vertebrae in rats. Tissue
joint. Cartilage 2013;4(4):295-312. Arthroscopy 2011;27(11):1573-1583.
Eng Part A 2012;18(1-2):157-166.
42. Harvest Terumo: SmartPrep2: The 58. Magnussen RA, Flanigan DC, Pedroza
50. Iqbal J, Pepkowitz SH, Klapper E:
Optimal Platelet Rich Plasma AD, Heinlein KA, Kaeding CC: Platelet
Platelet-rich plasma for the
Composition. Available at: http:// rich plasma use in allograft ACL
replenishment of bone. Curr Osteoporos
www.harvesttech.com/pdf/SL-021-0961- reconstructions: Two-year clinical results
Rep 2011;9(4):258-263.
PRPCorporateBrochure.pdf. Accessed of a MOON cohort study. Knee 2013;
October 3, 2013. 51. Leitner GC, Gruber R, Neumüller J, 20(4):277-280.
et al: Platelet content and growth factor
43. Fallouh L, Nakagawa K, Sasho T, et al: 59. Kartus J, Magnusson L, Stener S,
release in platelet-rich plasma: A
Effects of autologous platelet-rich Brandsson S, Eriksson BI, Karlsson J:
comparison of four different systems.
plasma on cell viability and collagen Complications following arthroscopic
Vox Sang 2006;91(2):135-139.
synthesis in injured human anterior anterior cruciate ligament
cruciate ligament. J Bone Joint Surg Am 52. American Academy of Orthopaedic reconstruction: A 2-5-year follow-up of
2010;92(18):2909-2916. Surgeons: Treatment of Osteoarthritis of 604 patients with special emphasis on
the Knee: Evidence-Based Guideline, 2nd anterior knee pain. Knee Surg Sports
44. Leitner GC, Koszik F, Rudnicki T, et al:
Edition. Available at: http:// Traumatol Arthrosc 1999;7(1):2-8.
Apheresis products of the Amicus and
www.aaos.org/research/guidelines/
the AS.TEC 204 cell separators are 60. Visentini PJ, Khan KM, Cook JL, Kiss
TreatmentofOsteoarthritisoftheKnee
comparable with regard to dendritic cells ZS, Harcourt PR, Wark JD; Victorian
Guideline.pdf. Accessed October 3,
derived from the mononuclear cell Institute of Sport Tendon Study Group:
2013.
collection. Vox Sang 2007;92(1):37-41. The VISA score: An index of severity of
53. Pierce GF, Mustoe TA, Lingelbach J, symptoms in patients with jumper s knee
45. Mazzucco L, Balbo V, Cattana E,
Masakowski VR, Gramates P, Deuel TF: (patellar tendinosis). J Sci Med Sport
Guaschino R, Borzini P: Not every PRP-
Transforming growth factor beta 1998;1(1):22-28.
gel is born equal: Evaluation of growth
reverses the glucocorticoid-induced
factor availability for tissues through 61. Chahal J, Van Thiel GS, Mall N, et al:
wound-healing deficit in rats: Possible
four PRP-gel preparations. Fibrinet, The role of platelet-rich plasma in
regulation in macrophages by platelet-
RegenPRP-Kit, Plateltex and one manual arthroscopic rotator cuff repair: A
derived growth factor. Proc Natl Acad
procedure. Vox Sang 2009;97(2):110- systematic review with quantitative
Sci US A1989;86(7):2229-2233.
118. synthesis. Arthroscopy 2012;28(11):
54. Marx RE: Platelet-rich plasma (PRP): 1718-1727.
46. Weibrich G, Kleis WK, Hitzler WE,
What is PRP and what is not PRP?
Hafner G: Comparison of the platelet 62. GlobalData: Platelet Rich Plasma: A
Implant Dent 2001;10(4):225-228.
concentrate collection system with the Market Snapshot. Available at: http://
plasma-rich-in-growth-factors kit to 55. Murray MM, Spindler KP, Ballard P, www.docstoc.com/docs/47503668/
produce platelet-rich plasma: A technical Welch TP, Zurakowski D, Nanney LB: Platelet-Rich-Plasma-A-Market-
report. Int J Oral Maxillofac Implants Enhanced histologic repair in a central Snapshot. Accessed September 17, 2013.
2005;20(1):118-123. wound in the anterior cruciate ligament
63. Dougherty EJ: An evidence-based model
with a collagen-platelet-rich plasma
47. Giusti I, Rughetti A, D Ascenzo S, et al: comparing the cost-effectiveness of
scaffold. J Orthop Res 2007;25(8):1007-
Identification of an optimal platelet-rich plasma gel to alternative
1017.
concentration of platelet gel for therapies for patients with nonhealing
promoting angiogenesis in human 56. Sánchez M, Anitua E, Azofra J, Prado R, diabetic foot ulcers. Adv Skin Wound
endothelial cells. Transfusion 2009; Muruzabal F, Andia I: Ligamentization Care 2008;21(12):568-575.
49(4):771-778. of tendon grafts treated with an
748 Journal of the American Academy of Orthopaedic Surgeons