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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
Allan Mishra, MD dramatic increase in breadth and frequency of use for orthopaedic
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
Pietro Randelli, MD osteoarthritis, tendinopathy, acute and chronic soft-tissue injuries,
S. Terry Canale, MD enhancement of healing after ligament reconstruction, and muscle
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.

JAAOS Plus Webinar


T he healthcare environment is
changing rapidly, and recently
there has been increased use of
Pathophysiology

Join Dr. Hsu, Dr. Rodeo, and Dr. Fu


Since 1950, PRP has been used to
platelet-rich plasma (PRP) in ortho-
for the JAAOS interactive webinar manage dermatologic and oromaxil-
paedic applications. However, sur-
discussing “Platelet-rich Plasma in lofacial conditions.31,32 More re-
Orthopaedic Applications: Evidence- geons often have little guidance with
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
will be William N. Levine, MD, the data in the orthopaedic community 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://
orthoportal.aaos.org/jaaos/ geons hosted a forum involving ex- 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
J Am Acad Orthop Surg 2013;21: clinical studies reporting on the use components of anticoagulated blood
739-748 of PRP in the treatment of orthopae- are separated. The first phase con-
http://dx.doi.org/10.5435/ dic conditions.1 In this article, we ex- sists of an initial soft spin (1,200 to
JAAOS-21-12-739 amine several level I studies,2-16 level 1,500 RPM) with a relatively low
Copyright 2013 by the American II studies,17-24 and level III studies25-30 gravitational force in which plasma
Academy of Orthopaedic Surgeons. on the use of PRP in the treatment of 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

Figure 1 platelet-rich and platelet-poor cial in conditions that require tissue


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
In addition to platelets, PRP con- basic fibroblast growth factor. Con-
tains other cell types with potentially versely, other proteins present in PRP
beneficial effects in tissue healing. have demonstrated inhibitory effects,
WBCs such as monocytes and poly- such as transforming growth factor
morphonuclear neutrophils may trig- (TGF)-β1, which may lead to vari-
ger a localized inflammatory effect. able clinical results in certain appli-
Although some investigators believe cations.37
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
(WBCs) from the platelet-rich Proteins such as platelet-derived thrombin activation of PRP may ac-
plasma (plasma and platelets) growth factor (PDGF), vascular en- tually diminish its ability to induce
following the two-step dothelial growth factor, endothelial bone formation compared with non–
centrifugation process.
cell growth factor, and basic fibro- thrombin-activated PRP.38
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
from different preparation methods Sports Medicine Platelet-rich Plasma Classification System
(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
ficiency of the chosen technique, the Any PRP type can have an associated subtype A or subtype B. Subtype A has ≥5 times
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-
differences in growth factor and cell lated that the timing of the adminis- Bone Healing
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
et al47 proposed that the most effica- differences between PRP formula- In a prospective observational study
cious platelet concentration for tissue tions makes it difficult to compare involving 123 foot and ankle fusions
healing is 1.5 × 106 platelets per mi- studies. In an attempt to standardize in 62 patients with risk factors for
croliter. In addition, the dose- different PRP systems, both DeLong nonunion, autologous platelet con-
response curve is not linear, and a et al35 and Mishra et al48 have pro- centrate (APC) was used in 67 proce-
saturation effect has been described posed systems that classify PRP sys- dures, and APC and bone graft were
in which an inhibitory cascade en- tems by activation mechanism, plate- used in 56 procedures.17 Because the
sues once a sufficiently high concen- let number, and/or cell content. 6% nonunion rate for all patients
tration of platelets is reached. Be- Although the systems have yet to be was below historical outcomes, the
cause platelets can exert the greatest validated in the literature, they repre- authors concluded that APC might
influence on healing during or imme- sent an important step in furthering be beneficial in this patient popula-
diately after the inflammatory phase this area of research (Table 2). tion. However, these patients under-

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-β1, 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,
utive patients who underwent pos- Cerza et al3 reported significantly Elbow epicondylitis, which is charac-
terolateral lumbar fusion, the better clinical outcomes up to 24 terized by failure of the normal ten-
nonunion rates at clinical follow-up weeks after a local injection of PRP don repair mechanism, is a common
of ≥24 months did not differ signifi- compared with injection of hy- malady that leads to chronic pain
cantly between iliac crest bone graft aluronic acid (P < 0.001). Con- and decreased function in activities
plus platelet-gel preparation com- versely, in an RCT of 109 patients, of daily living. Although treatment
pared with autologous bone graft Filardo et al4 demonstrated that al- recommendations range from brac-
alone (25% and 17%, respectively; P though intra-articular PRP injections ing, physiotherapy, and steroid injec-
= 0.18).26 Weiner and Walker27 dem- can offer significant clinical improve- tions to arthroscopic or open dé-
onstrated a significantly lower fusion ment up to 1 year after treatment, bridement, some investigators have
rate with the use of autologous these results were not better com- indicated that the local delivery of
growth factors from PRP and au- pared with hyaluronic acid injec- humoral mediators may enhance ten-
tograft in single-level posterolateral tions. Furthermore, the authors of a don healing and lead to improved
lumbar fusion compared with iliac Clinical Practice Guideline spon- clinical outcomes.
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,
19
benefit in fusion rates and, in fact, it atic OA of the knee.”52 Mishra and Pavelko demonstrated
may be detrimental. One case-control clinical study has significant improvement in clinical
Currently, limited clinical evidence been published to date on the man- outcomes in visual analog scale
exists demonstrating any beneficial agement of cartilage defects with (VAS) and Mayo elbow scores at 8
effects from the use of PRP in bone PRP.18 In this level II study, 32 pa- weeks after treatment with PRP (P =
healing applications. The available tients with symptomatic osteochon- 0.001 and P = 0.008, respectively).
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
plications. articular injections of either hy- 25.6 months (P < 0.0001). Thanasas
aluronic acid or PRP. At 28-week et al5 compared clinical outcomes in
follow-up, patients who received 28 patients with the same condition
Cartilage Healing PRP demonstrated significantly who were randomized to local injec-
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-β1, 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-
improve patient outcomes compared Surgical Repair of Acute pair and remodeling at the midsub-
with local injection of anesthetic, Soft-tissue Injuries stance of the reconstructed ACL as
whole blood, or corticosteroid. well as within the patellar tendon
The results have not been as prom- Because of the rich source of growth harvest site in patients treated with
ising for other tendinopathies. In a factors in PRP, it has been suggested bone–patellar tendon–bone au-
level I RCT comparing local injec- that administering PRP in the setting 56
tografts. Early administration of
tion of PRP to saline for Achilles ten- of acute soft-tissue injuries could PRP during the inflammatory pro-
dinopathy in conjunction with eccen- provide enhanced healing, thus facil- cess may lead to an accelerated heal-
tric exercises, de Vos et al8 reported itating an early return to sports.20,29 ing cascade that is shorter than the
no difference in the improvement of Tendon healing is typically character- typical 1-year period expected for
clinical outcome up to a 24-week ized by an initial inflammatory re- full graft maturation.56
follow-up. In a follow-up study, sponse that is associated with the in- Radice et al29 conducted a prospec-
members of the same research group flux of factors such as PDGF and tive single-blind study of 50 patients
randomized 54 patients diagnosed TGF-β (within 2 days), resulting in who were treated with either ACL
with chronic Achilles tendinopathy angiogenesis (2 to 3 days), and colla- autograft alone or ACL autograft
to blinded injections containing ei- gen synthesis (3 to 5 days).53 Because with application of PRP gel at the
ther PRP or saline in addition to a PRP contains these critical growth time of surgery. At 1-year follow-up,
training program.9 Although patients factors that can aid in the inflamma- it was found that application of PRP
in both groups had improved clinical tory response, its utility may be gel resulted in significantly faster bi-
outcomes 1 year after injection, there greatest when administered early in ologic maturation than did autograft
was no significant difference in bene- the healing period.54 alone as measured on MRI (177 and
fit. In a prospective level III study, Fi- 369 days, respectively; P < 0.001)
lardo et al28 studied the utility of Anterior Cruciate Ligament (Figure 2). Similarly, in an RCT with
PRP injection for refractory jumper’s Reconstruction 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

Figure 2 platelet-enriched gel. In the investiga-


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-
Sagittal T2-weighted magnetic resonance images of the knee obtained 6 strated that the use of PRP in al-
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
in grafts with PRP, which suggests a quicker maturation rate. (Reproduced reported outcomes at 2-year follow-
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
significant difference in Constant PRP (B). The gap is smaller in panel B than in panel A. (Adapted with
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
tendon defect at 12-week follow-up potential benefit, further study is re-
scores and strength in external rota-
(P = 0.037), suggesting that it may tion 3 months after surgery but not quired before the routine use of ad-
have a negative effect on healing. at 6, 12, and 24 months compared junctive PRP during shoulder surgery
The authors postulated that the vari- with control subjects.15 In grade 1 can be recommended.
ability in the composition and qual- and 2 tears, the use of PRP led to sig-
ity of PRP for each patient likely led nificantly higher strength in external Achilles Tendon Repair
to variability in the capacity for ten- rotation scores at 3, 6, 12, and 24 Achilles tendon ruptures can be asso-
don repair. In a prospective cohort months postoperatively (P < 0.05) ciated with prolonged recovery and
study involving 42 patients, Jo et al23 and a lower rate of re-rupture (P = postoperative complications such as
demonstrated that, compared with the 0.08). Notably, Randelli et al15 used re-rupture because of the poor vascu-
control group, application of PRP gel a commercial preparation of PRP lar environment surrounding the re-

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
amentization and maturation processes PRP may be less expensive than cor- 1. PRP an Unproven Option, Say Experts.
Available at: http://www.aaos.org/news/
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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 EuroQol-5D measures would greatly prospective, double-blind, randomized
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mendations made. cost-benefit analysis. More impor-
3. Cerza F, Carnì S, Carcangiu A, et al:
tantly, comparison groups would Comparison between hyaluronic acid
have to be properly chosen in such a and platelet-rich plasma, intra-articular
infiltration in the treatment of
Cost-benefit study. Cost analysis would have to gonarthrosis. Am J Sports Med 2012;
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As the quality of investigational must take into account reported suc- Platelet-rich plasma vs hyaluronic acid to
studies regarding PRP increases, so treat knee degenerative pathology: Study
cess rates, timing of treatment, and design and preliminary results of a
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Papanikolaou A: Platelet-rich plasma
Although the body of evidence for versus autologous whole blood for the
the use of PRP in orthopaedic condi- Although PRP has a theoretic benefit treatment of chronic lateral elbow
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

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Platelet-rich Plasma in Orthopaedic Applications: Evidence-based Recommendations for Treatment

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748 Journal of the American Academy of Orthopaedic Surgeons