prp for wound healing
DESCRIPTION
TRANSCRIPT
Use of Platelet Rich Plasma Gel on Wound Healing:A Systematic Review and Meta-Analysis
Marissa J. Carter, PhD, MA,a Carelyn P. Fylling, MSN, RN, CWS, CLNC,b
and Laura K. S. Parnell, MSc, CWSc
aStrategic Solutions, Inc, Cody, WY; bCytomedix, Inc, Gaithersburg, MD; and cPrecision Consulting,Missouri City, TX
Correspondence: [email protected] September 15, 2011
Objective: Autologous platelet rich plasma is an advanced wound therapy used in hard-to-heal acute and chronic wounds. To better understand the use and clinical outcomesof the therapy, a systematic review of the published literature in cutaneous wounds wasperformed. Methods: Electronic and hand searches for randomized controlled trialsand comparative group studies using platelet rich plasma therapy in cutaneous woundsand published over the last 10 years was conducted. Eligible studies compared thetreatment to standard care or other interventions. All citations were screened and eligiblestudies were assessed for validity, quality, and bias using accepted scoring methods. Theprimary outcomes were effect of platelet rich plasma and control wound care on woundhealing and related healing measurements. Secondary outcomes related to healing suchas infection, pain, exudate, adverse events, and quality of life were also considered. Themeta-analysis utilized appropriate statistical methods to determine the overall treatmenteffect on chronic and acute wound healing and infection. Results: The search termsresulted in 8577 citations and after removing duplicates and screening for protocoleligibility, a total of 24 papers were used. The meta-analysis of chronic wound studiesrevealed platelet rich plasma therapy is significantly favored for complete healing. Themeta-analysis of acute wounds with primary closure studies demonstrated that presenceof infection was reduced in platelet rich plasma treated wounds. Conclusions: Thissystematic review and meta-analysis of platelet rich plasma therapy in cutaneous woundsshowed complete and partial wound healing was improved compared to control woundcare.
Wound healing is a complex and dynamic process.1 Once a wound begins healing,normally the process resolves with complete wound closure. However, healing of acute andchronic wounds can become impaired by patient factors (ie, comorbidities) and/or woundfactors (ie, infection).2 Restarting a wound with impaired healing is difficult because goodstandard wound care does not always provide an improved healing outcome and often moreadvanced therapies are employed.3-4
382
CARTER ET AL
Platelet rich plasma (PRP) gel is considered to be advanced wound therapy for chronicand acute wounds. For more than 20 years, PRP gel has been used to stimulate woundhealing. Autologous PRP gel consists of cytokines, growth factors, chemokines, and afibrin scaffold derived from a patient’s blood.5-6 The mechanism of action for PRP gelis thought to be the molecular and cellular induction of normal wound healing responsessimilar to that seen with platelet activation.6
Various studies evaluating PRP gel have been published over the years. Study design,study populations, clinical outcomes, and methodological quality vary widely betweencitations making concrete conclusions difficult. Currently, there are 3 systematic reviewson PRP therapy.7-9 One systematic review looked at tissue regeneration in randomizedcontrolled trials (RCTs) in maxillofacial surgery, chronic ulcers, and surgical wounds.7 An-other systematic review assessed healing of RCT diabetic ulcer studies.8 A third systematicreview was a poster presentation on the results of a systematic review of healing chronicleg ulcers.9
The systematic review described herein was performed to specifically assess studies incutaneous skin wounds treated with autologous PRP gel and standard wound care (controlgroups). Studies assessing healing information such as complete or partial wound healing,time to heal, healing trajectory, velocity or rate, and wound size reduction were consideredcritical for this systematic review.
METHODS
Selection criteria
For assessment of PRP treatment human intervention trials, only RCTs and comparativestudies (ie, treatment/intervention groups compared with controls, or a group with run-inand comparable treatment data) published in peer-reviewed journals (articles, brief articles,case studies, or letters) or presented at scientific meetings (abstracts) were considered.Literature published between March 2001 and March 2011 was reviewed. Studies wereeligible if the participants had a cutaneous ulcer or wound (including dehisced wounds,open surgical wounds, acute, or chronic wounds) that were treated with activation-processedPRP. Studies of patients with mixed origin wounds, subsets of different wound types, surgicalwounds treated with PRP prior to closure and open, surgical wounds treated with PRP forsecondary closure were included. In addition, inclusion eligibility required PRP studies tohave a control treatment group (ie, placebo, wound care treatment). Noninferiority trialsin which 2 types of PRP treatment were compared were also eligible. Studies in whichthe experimental group received other treatments were eligible provided that the controlgroup also received the same treatment or care so that confounding was avoided and thesystematic difference between the groups was only the primary intervention.
Studies focusing on burns, dental or jaw treatment, bone fractures, orthopedic injection,or plastic surgery were excluded because of the different healing characteristics of thesewounds. Studies which used homologous/allogenic PRP procedures, lysates, freezing, orfreeze-dried techniques to produce PRP, or were considered to be “fibrin glue,” were alsoexcluded.
383
ePlasty VOLUME 11
Outcome measures
Eligible studies had to report at least one wound-healing parameter as an outcome measure,and/or associated parameters such as infection rates and incidence, pain measures, exudationmanagement, quality-of-life measures, or net health benefits. Examples of wound-healingparameters included complete wound healing (proportions in each group or percentagesprovided N for each group was reported; Kaplan-Meier and Cox regressions); woundarea reduction (mean or median, relative, absolute, or percentage); wound depth or volumereduction (same parameters as for area); healing rate (change in area or wound dimensionper unit of time expressed in absolute terms or as a percentage), time to heal (mean ormedian, expressed in days or weeks), or comparison of clinical significant healing events,such as reaching a reduction of 50% or more in area using Kaplan-Meier or Cox regression.Outcomes could be unadjusted or adjusted for other covariates and factors, and comparebaseline and final outcomes, or repeated measures. Follow-up for treatment/interventiontrials had to be a minimum of 2 weeks.
Search strategy
The Cochrane Library, Scopus, CINAHL, and PubMed databases were searched usingcombinations of the following terms: platelet rich plasma, platelet rich plasma gel(s), PRP,PRP gel(s), platelet gel(s), autologous growth factors, wound(s), chronic wound(s), chronicnonhealing wound(s), open, cutaneous wound(s), dehiscence, dehisced, surgical wound(s),diabetic ulcer, venous ulcer, pressure ulcer, sternal wound(s).
The journals Wounds, Worldwide Wounds and the clinical trial database clinicaltri-als.gov were hand searched using the same terms. Identified reviews were also searched foradditional references to RCTs and comparative studies not previously captured. Narrativereviews and editorials were examined for references of potential trials. Several experts inthe field were also consulted for their knowledge of RCTs. After the initial selection ofstudy abstracts appeared to meet selection criteria, 2 reviewers (M.J.C. and C.P.F.) evaluatedeach study in full to determine whether the study met the selection criteria and outcomemeasures.
Numbers of citations for each search term entered (or combination of search terms),numbers of papers fully examined, numbers of papers eligible for review, and numbers ofpapers excluded with reasons were recorded. Duplicates were removed after confirmingidentical publication information. Papers suspected of containing the same results publishedelsewhere were reviewed to determine the originality of the results and which paper bestmet the selection criteria outlined earlier.
Initial quality assessment
The quality of each study was assessed using a method reported by Downs and Black10 andmodified by Carter et al.11 The scoring sheet comprised 5 sections: reporting (quality of howthe study data were reported), external validity (the generalizability of the study), internalvalidity (assessment of the potential for bias), internal validity (assessment of potentialconfounders that may compromise the study), and power (assessment of the power ofthe study to discriminate the effect sizes of the outcomes). Modifications of the originalmethod included replacement of the external validity module with an approach based on the
384
CARTER ET AL
number of patients who would likely have been excluded from the study.12 The section isscored according to the category of the study—satisfactory: 3 points; problematic: 2 points;unsatisfactory: 1 point. The power module was truncated with the following scoring scheme:reported sample size calculation (for RCTs): 1 point; reported more than 1 calculation: 2points; no reporting of sample size calculation: 0 points; power reported for at least 1clinically important effect (for comparative studies): 1 point; reported for all clinicallyimportant effect: 2 points; no reporting of power for clinically important effects: 0 points.The total score possible was 29 points.
Bias was summarily reported using the SIGN grade methodology, which is defined asfollows: ++ applies if all or most criteria from the checklist are fulfilled or where criteriaare not fulfilled, the conclusions of the study or review are thought very unlikely to alter;+ applies if some of the criteria from the checklist are fulfilled or where criteria are notfulfilled or are not adequately described, the conclusions of the study or review are thoughtunlikely to alter; − applies if few or no criteria from the checklist are fulfilled or wherecriteria are not fulfilled or are not adequately described, and the conclusions of the study orreview are thought likely or very likely to alter.13 The grade assignment of study bias wasaccomplished by taking the total score of the external validity and internal validity (bias andconfounding) sections of the quality assessment, and scoring as follows: 0 to 8 points (−);9 to 12 points (+); 13 to 16 points (++). Scoring was carried out independently by M.J.C.and C.P.F. who then reconciled any discrepancies in subsequent discussion. Final gradeassignments took into consideration serious flaws or inconsistencies, or other attributes thatcould decrease or increase initial grade assessment.14
Data extraction and analysis
Outcomes were categorized by type, and for each one, the pretreatment and posttreatmentnumbers, median, or mean values (SD) were extracted where possible. To ensure that correctnumbers were obtained, this process was performed by M.J.C. and checked by C.P.F. Noinvestigators were contacted for further clarification. The number needed to treat wascalculated for studies reporting complete wound healing, and where protocol analyses wereused, the data were updated to reflect an intent-to-treat analysis. Data were imported intosoftware (Revman 5.0 Information Management, Nordic Cochrane Centre, Copenhagen,Denmark) to calculate 95% confidence intervals and P values using fixed-effect modelswhere possible. The Mantel-Haenszel method was used with risk difference as the effectmeasure in the case of dichotomous events, and the inverse variance method was usedwith the weighted mean difference (WMD) as the effect measure in the case of continuous(interval) data.
Grading
After data extraction and initial quality assessment were complete, important and criticaloutcomes were agreed upon using consensus and quality assessment. Summary of findingsfor studies comparing use of PRP treatments against standard care were assessed using theGRADE system for each type of wound.14-16
385
ePlasty VOLUME 11
Meta-analysis
Meta-analysis (statistical pooling) was carried out on those studies that had the followingcompatible outcomes and reasonable clinical homogeneity: (1) complete wound healing;(2) superficial infection; and (3) pain reduction. Results from RCTs were pooled separatelyfrom other comparative studies. For dichotomous events, a fixed-effect model was em-ployed that used the Mantel-Haenszel method with risk difference as the effect measure foreasier interpretation. In the case of continuous (interval) data, a fixed-effect model was alsoemployed using the inverse variance method with the effect measure of WMD (weightedmean difference). Statistical heterogeneity was assessed using the I2 (inconsistency) statis-tic, which indicates the percentage variation between studies that is a result of heterogeneityrather than chance.17 If the I2 (inconsistency) value was 30% or higher, meta-analysis wasalso conducted using a random effects model.
RESULTS
Study selection
The protocol search terms (see “Methods”) resulted in 8577 citations, the majority ofwhich were duplicates (Fig 1). Potentially eligible studies (n = 68) were identifiedper protocol criteria.18-82 There were 44 papers excluded for one or more of the fol-lowing reasons: narrative review, noncomparative study and/or case series, confoundedwith other treatments, cost-effectiveness study, insufficient outcome data reported, non-cutaneous wounds, generic wound care research paper, reported outcomes did not in-clude protocol eligibility criteria, non-PRP systematic review, freeze-dried PRP, allo-genic PRP, frozen platelets, letter to editor discussing ineligible RCT, survey, and animalstudy.39-82
Twenty-one studies on the subject were identified and used (Fig 1).18-38 In addition,3 systematic reviews on PRP use were found and detailed in the “Discussion” section.7-9
The reviewers agreed on 95.8% of the quality analysis items scored with a kappa of 0.899.Eligible PRP publications consisted of 12 RCTs, 3 cohort studies, 5 comparative studydesigns, and 1 retrospective analysis with propensity scoring. Table 1 describes the studydesign, enrolled subjects, wounds, and wound care treatments of each. Within the eligiblestudies, 3 main types of wounds which were treated with PRP were identified: (1) open,chronic wounds,18-24 (2) acute surgical wounds with primary closure,25-35 and (3) acutesurgical wounds with secondary closure.36-38
Quality analysis
Three citations with the least bias were RCTs in primary closure acute wounds25,28,30
(Table 2). Study quality varied greatly between papers. Chronic wound studies had 2 RCTsscore − and 3 comparative studies score +. Studies in acute wounds with primary closurehad 3 RCTs score ++, 3 score − and 5 comparative studies score +. Acute woundswith secondary closure studies had 2 RCTs score + and 1 comparative study score −(Table 2).
386
CARTER ET AL
Figure 1. Systematic review of platelet rich plasma literature, March 2001to March 2011. Template from Moher D, Liberati A, Tetzlaff J, Altman DG;The PRISMA Group (2009). Preferred Reporting Items for Systematic Re-views and Meta-Analyses: The PRISMA Statement. PLoS Med. 6(6): e1000097.doi:10.1371/journal.pmed1000097
Study outcomes
Outcomes associated with wound healing directly (ie, healing, size reduction) or indirectly(healing impairments, complications) were analyzed. These outcomes were judged to becritical or important since time to heal, complications (ie, amputations or life-threateningsituations), and quality of life (QoL) can significantly impact wound healing. Data analysesfor clinical outcomes for each article are in Tables 3 to 5.
387
ePlasty VOLUME 11
Tab
le1.
Des
crip
tion
ofst
udie
s:Ty
pes
ofw
ound
san
din
terv
enti
ons
used
.In
terv
enti
ongr
oup
rece
ived
all
care
desc
ribe
dfo
rco
ntro
lgr
oup
unle
ssot
herw
ise
stat
ed∗
Stud
yD
esig
nN
Stud
yP
erio
dW
ound
Typ
eC
ontr
olG
roup
Inte
rven
tion
Gro
up
Alm
dahl
etal
25R
CT
140
6w
kL
egw
ound
sfr
omlo
ngsa
phen
ous
vein
harv
esti
ng(C
AB
G)
No
topi
calt
reat
men
t.S
tand
ard
clos
ure
(int
racu
tane
ous
poli
glec
apro
ne)
Aut
olog
ous
PR
P(G
PS
,Bio
met
Bio
logi
cs;a
ctiv
ated
wit
hau
tolo
gous
thro
mbi
n)sp
raye
dpr
ior
tocl
osur
eA
nitu
aet
al18
RC
T15
8w
kC
utan
eous
ulce
rs<
12cm
diam
eter
,≥4
-wk
old
Moi
stsa
line
gauz
edr
essi
ngs
and
clea
ning
wit
hno
rmal
sali
ne;
debr
idem
enta
ndsy
stem
ican
tibi
otic
sfo
rin
fect
ion
Aut
olog
ous
PR
P(P
RG
FS
yste
m,
BT
IB
iote
chno
logy
Inst
itut
e,V
itor
ia-G
aste
iz,S
pain
)in
ject
edon
cein
wou
ndm
argi
ns.
Buc
hwal
det
al26
RC
T70
50d
Leg
wou
nds
from
long
saph
enou
sve
inha
rves
ting
(CA
BG
)
No
topi
calt
reat
men
t.S
tand
ard
clos
ure
Aut
olog
ous
PR
P(A
ngel
;Did
eco,
Mir
ando
la,I
taly
;act
ivat
edw
ith
auto
logo
usth
rom
bin)
spra
yed
prio
rto
clos
ure
Car
ter
etal
22C
ompa
rativ
e(r
un-i
nvs
trea
tmen
tpe
riod
)
46≤8
6d
(run
-in)
;≤3
6d
(tre
atm
ent)
DF
Us,
PU
s,V
Us,
surg
ical
,de
hisc
ed,&
trau
mat
icw
ound
s,ot
her
type
s
Run
-in
peri
odre
pres
ente
dco
ntro
lgr
oup;
auth
ors
stat
eva
riet
yof
moi
stw
ound
care
dres
sing
s,dr
essi
ngch
ange
s,de
brid
emen
tas
requ
ired
;co
mpr
essi
onor
offl
oadi
ngpe
rw
ound
type
;NP
WT
for
som
ew
ound
s
Aut
olog
ous
PR
Pge
ltre
atm
ent
(Aut
oloG
el,C
ytom
edix
,G
aith
ersb
urg,
MD
,bov
ine
thro
mbi
n)ap
plie
dto
wou
ndbe
dat
leas
tonc
e.
Dri
ver
etal
19R
CT
7212
wk
DF
Us,
1A(U
Texa
s),0
.5-2
0cm
2,≥
4-w
kol
d
Cle
anin
g,dr
essi
ngch
ange
s,de
brid
emen
tas
requ
ired
;offl
oadi
ng;
sali
nege
l(M
olyn
ycke
Hea
lth
Car
e,N
orcr
oss,
GA
)an
dfo
amdr
essi
ngap
plie
daf
ter
wou
ndbe
dpr
epar
atio
nbi
wee
kly
for
12w
kor
unti
lhea
led
Aut
olog
ous
PR
Pge
l(A
utol
oGel
,C
ytom
edix
,Gai
ther
sbur
g,M
D,
bovi
neth
rom
bin)
appl
ied
afte
rw
ound
bed
prep
arat
ion
biw
eekl
yfo
r12
wk
orun
tilh
eale
d
Eng
lert
etal
27R
CT
30∼3
0d
Ste
rnal
wou
nds
(CA
BG
)N
oto
pica
ltre
atm
ent.
Con
trol
wou
ndca
reno
trep
orte
dA
utol
ogou
sP
RP
(Mag
ella
n,M
inne
apol
is,M
N)
“cau
lkin
gbe
ad”
appl
ied
tost
ernu
mw
ith
cann
ula
prio
rto
clos
ure
388
CARTER ET AL
Tab
le1.
Con
tinu
ed
Stud
yD
esig
nN
Stud
yP
erio
dW
ound
Typ
eC
ontr
olG
roup
Inte
rven
tion
Gro
up
Eve
rts
etal
31P
rosp
ectiv
eco
hort
(con
trol
sar
eco
nsec
utiv
epa
tien
tsw
hofo
llow
ed)
165
∼1w
kS
urgi
calw
ound
s(T
KA
)W
ound
drai
n,no
topi
calt
reat
men
t,w
ound
dres
sing
sno
tspe
cifi
ed,
com
pres
sion
band
age
Aut
olog
ous
PR
P(E
lect
a,S
orin
Gro
up,M
iran
dola
,Ita
ly;8
5%ac
tivat
edw
ith
auto
logo
usth
rom
bin,
rem
aini
ngac
tivat
edw
ith
bovi
neth
rom
bin)
spra
yed
inba
ckof
knee
cavi
ty,p
oste
rior
rece
ss,g
utte
rs,
etc.
)an
daf
ter
deep
clos
ure
inje
cted
onre
pair
edex
tens
orm
echa
nism
/pre
pate
llar
fat(
now
ound
drai
n)Fr
iese
etal
20R
CT
4225
wk
(12
wk
for
CW
H)
DF
Us,
Wag
ner
1-3,
>0.
7cm
2,>
6-w
kol
d
Cle
ansi
ng,d
ebri
dem
ent,
dres
sing
chan
ges
asne
eded
&of
floa
ding
.N
oto
pica
ltre
atm
ent,
wou
nddr
esse
dw
ith
poly
uret
hane
foam
Aut
olog
ous
PR
P(H
arve
stTe
chno
logi
es,P
lym
outh
,MA
)ev
ery
2w
kfo
r12
wk
Gar
dner
etal
32R
etro
spec
tive
com
pari
son
61P
RP
-tre
ated
wou
nds,
37co
ntro
lsov
ersa
me
tim
epe
riod
98∼1
wk
Sur
gica
lwou
nds
(TK
A)
No
topi
calt
reat
men
t,st
anda
rdla
yere
dcl
osur
e,dr
essi
ngs
used
butn
otsp
ecifi
edan
dus
eof
pass
ive
mot
ion
devi
ceaf
ter
24h
Aut
olog
ous
PR
P(M
edtr
onic
Seq
uest
ra10
00A
utot
rans
fusi
onS
yste
m,M
edtr
onic
,Min
neap
olis
,M
N)
inje
cted
into
post
erio
rre
cess
,gu
tter
s,ex
pose
dfe
mur
/tib
iasu
rfac
es,r
epai
red
exte
nsor
mec
hani
sm/p
repa
tell
arfa
t(no
wou
nddr
ain)
Hom
etal
38P
rosp
ectiv
eco
mpa
riso
nof
trea
ted
wou
nds
wit
hco
ntem
pora
ryow
npa
tien
tcon
trol
s
8pa
tien
ts,
80 wou
nds
6m
oP
RP
-tre
ated
skin
punc
hw
ound
s
Bac
itra
cin
topi
calt
reat
men
tand
sem
iocc
lusi
vedr
essi
ngA
utol
oGel
PR
Pge
l(M
agel
lan,
Med
tron
ic,M
inne
apol
is,M
N;
auto
logo
usth
rom
bin-
rich
seru
m)
plus
whi
tepe
trol
atum
oint
men
tap
plie
don
ceor
twic
eK
azak
oset
al36
RC
T59
3w
kT
raum
atic
wou
nds
Cle
ansi
ng,d
ebri
dem
ent,
and
Vas
elin
ega
uze
dres
sing
sA
utol
ogou
sP
RP
gel(
PR
PFa
stsy
stem
,Bio
teck
;ben
chce
ntri
fuge
;au
tolo
gous
thro
mbi
n)ap
plie
dbe
fore
oraf
ter
debr
idem
ent,
and
then
wee
kly.
Gau
zesp
onge
sap
plie
dfo
llow
ing
PR
Pge
l.
389
ePlasty VOLUME 11T
able
1.C
onti
nued
Stud
yD
esig
nN
Stud
yP
erio
dW
ound
Typ
eC
ontr
olG
roup
Inte
rven
tion
Gro
up
Kha
lafi
etal
33R
etro
spec
tive
anal
ysis
wit
hpr
open
sity
scor
ing
(PR
P/c
ontr
ols)
1,12
8∼1
wk
Ste
rnal
and
leg
wou
nds
(CA
BG
)N
oto
pica
ltre
atm
ent.
Con
trol
wou
ndca
reno
trep
orte
dA
utol
ogou
sP
RP
(GP
SII
,Bio
met
,Inc
.,W
arsa
w,I
N;a
ctiv
ated
wit
hbo
vine
thro
mbi
n)sp
raye
din
tost
erna
led
ges/
subc
utan
eous
tiss
ue&
graf
tha
rves
tsit
eM
argo
lis
etal
23R
etro
spec
tive
coho
rtst
udy
wit
hpr
open
sity
scor
ing
(PR
/con
trol
s)
26,5
9932
wk
DF
Us
(neu
ropa
thic
)N
oto
pica
ltre
atm
ent.
Sta
ndar
dtr
eatm
ent(
moi
stw
ound
care
-not
spec
ified
,de
brid
emen
t,of
floa
ding
)
Aut
olog
ous
Pla
tele
tRel
easa
te(C
urat
ive
Hea
lth
Ser
vice
s,H
aupp
auge
,NY
)in
itia
ted
wit
hin
the
firs
t12
wk
ofca
re
Maz
zucc
oet
al24
Pro
spec
tive
coho
rtw
ith
hist
oric
alco
ntro
ls(d
ehis
cent
);co
hort
and
cont
rols
(ulc
ers)
2231
1y
Deh
isce
ntst
erna
lw
ound
s(C
AB
G);
necr
otic
skin
ulce
rs
Dai
lyto
pica
lwas
hing
/cle
anin
g,an
dan
tibi
otic
ther
apy
asne
eded
(deh
isce
ntw
ound
s);
clea
ning
/dre
ssin
gw
ith
hyal
uron
icac
id/s
ynth
etic
coll
agen
gauz
e(u
lcer
s)
Aut
olog
ous
PR
Pge
l(A
CD
-AV
acut
aine
rtu
bes,
Bec
ton
Dic
kins
onL
abw
are,
Fran
klin
Lak
es,N
J,an
dbe
nch
cent
rifu
ge;a
utol
ogou
sth
rom
bin)
twic
epe
rw
eek
(deh
isce
ntw
ound
s)or
once
per
wee
k(u
lcer
s)un
tilh
eale
d.C
over
edw
ith
Vas
elin
ega
uze.
Peer
boom
set
al28
RC
T10
23
mo
Sur
gica
lwou
nds
(TK
A)
No
topi
calt
reat
men
t,cl
osed
wit
hst
aple
s.W
ound
care
dres
sing
sno
tspe
cifi
ed.C
ompr
essi
onba
ndag
esan
dre
habi
lita
tion
Aut
olog
ous
PR
P(G
PS
,Bio
met
,Inc
.,W
arsa
w,I
N)
spra
yed
into
knee
cavi
ty(s
ynov
ium
+cu
tedg
esof
fem
ur/t
ibia
)an
dP
PP
spra
yed
into
subc
utan
eous
tiss
ues;
auto
logo
usth
rom
bin
Sal
dala
mac
chia
etal
21R
CT
145
wk
DF
Us
Wag
ner
2/3
&≥8
-wk
old
No
topi
calt
reat
men
t,no
nspe
cifi
cst
anda
rdca
reA
utol
ogou
sP
RP
gela
ppli
cati
onto
pica
llyfo
r5
wk,
each
wee
k.S
arat
zis
etal
34C
ompa
riso
n50
pros
pect
ivel
ytr
eate
dP
RP
-tre
ated
wou
nds
wit
h50
cont
rols
over
sam
eti
me
peri
od
100
∼30
dS
urgi
calw
ound
s(i
ngui
nal)
No
topi
calt
reat
men
t,la
yere
dcl
osur
ew
ith
sutu
res
and
stap
les.
Wou
ndca
redr
essi
ngs
nots
peci
fied
.Ant
ibio
tics
,as
piri
n,cl
opid
ogre
l,am
bula
tion
,and
docu
men
tati
onof
endo
graf
tin
tegr
ity
Aut
olog
ous
PR
P(M
agel
lan,
Min
neap
olis
,MN
;not
activ
ated
)in
ject
edsu
bcut
aneo
usly
and
perc
utan
eous
ly
390
CARTER ET AL
Tab
le1.
Con
tinu
ed
Stud
yD
esig
nN
Stud
yP
erio
dW
ound
Typ
eC
ontr
olG
roup
Inte
rven
tion
Gro
up
Spy
rida
kis
etal
37R
CT
5230
dS
urgi
calw
ound
s(p
ilon
idal
dise
ase)
No
topi
calt
reat
men
t,w
ound
care
dres
sing
sno
tspe
cifi
ed.
Aut
olog
ous
PR
P(G
PS
IIsy
stem
,B
iom
et,I
nc.,
War
saw
,IN
;au
tolo
gous
thro
mbi
n)ap
plie
din
toth
ew
ound
intr
a-op
erat
ivel
yan
dbe
fore
post
oper
ativ
ely
day
4an
d12
Tro
wbr
idge
etal
35R
etro
spec
tive
com
pari
son
PR
P-t
reat
edw
ound
sw
ith
cont
empo
rary
&hi
stor
ical
cont
rols
2,25
9N
otre
port
edS
tern
alw
ound
s(c
ardi
acsu
rger
y)
Two
cont
rolg
roup
sbo
thha
dno
topi
calt
reat
men
tand
stan
dard
care
that
was
nots
peci
fied
.One
cont
rolw
asa
hist
oric
cont
rol;
the
othe
rco
ntro
lwas
perf
orm
edat
tim
eof
stud
y.
Aut
olog
ous
PR
P(C
AT
S,T
erum
oC
ardi
ovas
cula
r,A
nnA
rbor
,MI;
Har
vest
Tech
nolo
gies
,Ply
mou
th,
MA
;Ang
el,C
OB
EC
ardi
ovas
cula
r,A
rvad
a,C
O;b
ovin
eth
rom
bin)
spra
yed
tosu
bcut
aneo
usar
eas,
asw
ella
sto
pica
lapp
lica
tion
Van
get
al29
RC
T38
∼3w
kS
tern
alw
ound
s(C
AB
G)
No
topi
calt
reat
men
t,w
ound
care
dres
sing
sno
tspe
cifi
ed.
Aut
olog
ous
PR
P(M
agel
lan,
Min
neap
olis
,MN
;bov
ine
thro
mbi
n)sp
raye
din
tode
epti
ssue
and
subc
utan
eous
laye
rsY
ooet
al30
RC
T52
∼1w
kS
urgi
calw
ound
(thy
roid
)S
alin
esp
ray
used
inst
ead
ofP
RP
(wou
ndbe
d)an
dP
PP
(und
ersk
inin
cisi
on);
Penr
ose
drai
n(5
-min
dura
tion
)an
dcl
osed
suct
ion
drai
nap
plie
dto
surg
ical
site
afte
rcl
osur
e.
Aut
olog
ous
PR
P(G
PS
,Bio
met
,Inc
.,W
arsa
w,I
N,a
utol
ogou
sth
rom
bin)
spra
yed
into
wou
ndbe
dan
dP
PP
spra
yed
unde
rsk
inin
cisi
on
∗ CA
BG
indi
cate
sco
rona
ryar
tery
bypa
ssgr
aft;
CW
H,c
ompl
ete
wou
ndhe
alin
g;D
FU
,dia
beti
cfo
otul
cer;
NP
WT,
nega
tive
pres
sure
wou
ndth
erap
y;P
U,p
ress
ure
ulce
r;P
PP,
plat
elet
-poo
rpl
asm
a;P
RP,
plat
elet
-ric
hpl
asm
a;P
U,p
ress
ure
ulce
r;R
CT,
rand
omiz
edco
ntro
lled
tria
l;T
KA
,tot
alkn
eear
thro
plas
ty;V
U,v
enou
sul
cer.
391
ePlasty VOLUME 11
Tab
le2.
Qua
lity
revi
ewof
stud
ies:
Scor
esh
eet.
SIG
Ngr
ade
was
esti
mat
edus
ing
the
gene
ralm
etho
dolo
gyof
Har
bour
and
Mil
ler,
assi
gnin
ga
grad
eba
sed
onth
eto
tals
core
ofex
tern
alva
lidi
ty,i
nter
nalv
alid
ity
(bia
san
dco
nfou
ndin
g)as
foll
ows:
0-8
(−);
9-12
(+);
13-1
6(+
+)D
owns
and
Bla
ck,C
arte
r,C
arte
rH
arbo
uran
dM
iller
Aut
hor
Com
men
tsSt
udy
Qua
lity
Ext
erna
lIn
tern
alIn
tern
alV
alid
ity
Scor
eR
easo
nfo
rU
pgra
deA
sses
sed
Rep
orti
ngV
alid
ity
Val
idit
y(B
ias)
(Con
foun
ding
)P
ower
(of
29)
SIG
Nor
Dow
ngra
de
Ani
tua
etal
189
13
30
16−
Dri
ver
etal
1910
26
11
20−
Dow
ngra
de-
Effi
cacy
anal
ysis
:dr
opou
tshi
gh;m
any
trea
tmen
tvi
olat
ions
Frie
seet
al20
∗
Sal
dala
mac
chia
etal
21∗
Car
ter
etal
228
35
31
20+
Maz
zucc
oet
al24
103
52
222
+M
argo
lis
etal
238
33
40
18+
Alm
dahl
etal
2511
37
51
27++
Buc
hwal
det
al26
90
72
018
−D
owng
rade
-N
otcl
ear
wha
ttr
eatm
entc
ontr
ols
got
Eng
lert
etal
277
35
30
18−
Dow
ngra
de-
Not
clea
rw
hat
trea
tmen
tcon
trol
sgo
tPe
erbo
oms
etal
289
27
31
22++
Upg
rade
-IT
Tan
alys
issh
owed
bett
erre
sult
sth
anP
PV
ang
etal
2910
24
12
19−
Yoo
etal
309
26
50
22++
Eve
rts
etal
318
35
20
18+
Gar
dner
etal
325
34
20
14+
Kha
lafi
etal
337
33
20
15+
Upg
rade
-L
arge
N,p
rope
nsit
ysc
orin
gte
chni
ques
used
Sar
atzi
set
al34
102
64
022
+T
row
brid
geet
al35
93
44
020
+K
azak
oset
al36
103
52
020
+S
pyri
daki
set
al37
83
53
019
+H
omet
al38
102
42
018
−∗ Fr
iese
cita
tion
was
aR
CT
abst
ract
and
the
Sal
dala
mac
chia
cita
tion
was
are
sear
chle
tter
.N
eith
erof
thes
etw
oci
tati
ons
coul
dbe
scor
ed.
Bot
hci
tati
ons
are
incl
uded
beca
use
Coc
hran
ew
ould
have
incl
uded
them
inth
eir
anal
ysis
.
392
CARTER ET AL
Tab
le3.
Det
aile
dou
tcom
esre
port
edfo
rth
est
udy
peri
od.
Num
ber
need
edto
trea
t(N
NT
)w
asca
lcul
ated
base
don
com
plet
ew
ound
heal
ing
info
rmat
ion
prov
ided
inth
epu
blic
atio
n∗
Stud
yO
utco
me
Cri
teri
aO
utco
mes
95%
CI†
P†
NN
T
Chr
onic
wou
nds
(RC
Ts)
Ani
tua
etal
181.
Wou
ndar
eare
duct
ion
(%)
2.C
ompl
ete
wou
ndhe
alin
g3.
AE
s
1.E
:72.
9;C
:21.
5(8
wk)
(n=
5;n
=4)§
2.E
:1/8
;C:0
/7(8
wk)‡
3.E
:1/8
;C:3
/7
1.13
.22-
89.7
01.
.008
2.N
S3.
NS
Dri
ver
etal
191.
Com
plet
ew
ound
heal
ing
2.C
ompl
ete
wou
ndhe
alin
g3.
Com
plet
ew
ound
heal
ing
4.T
ime
tohe
al(K
M)
(d)
5.A
Es
6.D
evic
ere
late
dA
Es
7.S
erio
usA
Es
8.D
evic
ere
late
dse
riou
sA
Es
1.E
:13/
40;C
:9/3
2(1
2w
k)‡
2.E
:13/
19;C
:9/2
1(P
P1,
12w
k)§
3.E
:13/
16;C
:8/1
9(P
P2,
12w
k)§
4.E
:42.
9;C
:47.
4(P
P2,
12w
k)§
5.E
:60/
40;C
:62/
326.
E:1
;C:1
7.E
:6/4
0;C
:17/
328.
E:0
;C:0
3.0.
10-0
.68
4.−1
7.00
-8.0
0
1.N
S‖
2.N
S‖
3..0
36‖
4..0
18‖
3
Frie
seet
al20
1.C
ompl
ete
wou
ndhe
alin
g2.
Com
plet
ew
ound
heal
ing
3.A
Es
4.T
ime
tohe
al(w
k)
1.E
:11/
21;C
:5/2
1(1
2w
k)‡
2.E
:11/
20;C
:5/2
1(P
P,12
wk)§
3.E
:2/2
0;C
:9/2
14.
E:9
.2;C
:12.
0
2.1.
03-1
4.87
1.N
S2.
.05
3..0
2‖
Sal
dala
mac
chia
etal
211.
Com
plet
ew
ound
heal
ing
2.W
ound
area
redu
ctio
n(%
)1.
E:2
/7;C
:1/7
(5w
k)‡
2.E
:71.
9;C
:9.2
(5w
k)1.
NS
2..0
39‖
Chr
onic
wou
nds
(com
para
tive
desi
gns;
non-
RC
Ts)
Car
ter
etal
221.
Wou
ndde
pth
(%)
2.W
ound
area
(%)
3.M
ean
tim
eto
reac
h50
%de
pth
redu
ctio
n(K
M)
4.M
ean
tim
eto
reac
h50
%ar
eare
duct
ion
(KM
)
1.E
:65.
9;C
:100
¶2.
E:6
1.8;
C:1
00¶
3.E
:22.
3;C
:72.
9(d
)¶4.
E:2
5.1;
C:6
6.0
(d)¶
1.12
.86-
55.3
5#2.
10.6
4-65
.69#
3.−3
6.29
to−6
3.71
4.−4
1.92
to−6
6.66
‖
1..0
0037
‖, #2.
.002
‖, #3.
.000
34‖
4..0
28‖
Mar
goli
set
al23
1.C
ompl
ete
wou
ndhe
alin
g1.
Pro
pens
ity
scor
equ
inti
les:
Gro
up1:
RR
(hea
ling
wit
hP
R):
1.14
Gro
up2:
RR
(hea
ling
wit
hP
R):
1.24
Gro
up3:
RR
(hea
ling
wit
hP
R):
1.29
Gro
up4:
RR
(hea
ling
wit
hP
R):
1.43
Gro
up5:
RR
(hea
ling
wit
hP
R):
1.59
Ove
rall
:1.3
8
1.03
-1.2
7‖1.
16-1
.34‖
1.20
-1.3
8‖1.
33-1
.52‖
1.49
-1.7
0‖1.
33-1
.42‖
19 12 11 7 6 11
393
ePlasty VOLUME 11
Tab
le3.
Con
tinu
ed
Stud
yO
utco
me
Cri
teri
aO
utco
mes
95%
CI†
P†
NN
T
Maz
zucc
oet
al24
1.T
ime
tohe
al(m
edia
n;K
M):
Deh
isce
dst
erna
lw
ound
s2.
Hos
pita
liza
tion
tim
ere
quir
edto
achi
eve
com
plet
ehe
alin
g:st
erna
l3.
Tim
ere
quir
edbe
fore
surg
ery
(med
ian;
KM
):ne
crot
icsk
inul
cers
1.E
:3.5
;C:6
.0(w
k)
2.E
:31.
5;C
:52.
5(d
)
3.E
:15.
0;C
:35.
5(w
k)
1..0
002‖
2.<
.000
1‖
3.<
.000
1‖
Acu
tew
ound
spr
imar
ycl
osur
e(R
CT
s)
Alm
dahl
etal
251.
Har
vest
site
infe
ctio
n2.
AE
s1.
E:9
/70;
C:8
/70
(6w
k)2.
Non
ein
eith
ergr
oup
1.N
S
Buc
hwal
det
al26
1.N
orm
alw
ound
heal
ing
2.A
bnor
mal
wou
ndhe
alin
g3.
Wou
ndhe
alin
gim
pair
men
t4.
Lar
ge-a
rea
hem
atom
as5.
Post
oppa
inle
vel(
mea
n)
1.E
:22/
35;C
:16/
35(b
yda
y50
)‡2.
E:6
/35;
C:5
/35
(by
day
50)‡
3.E
:6/3
5;11
/35
(by
day
50)‡
4.E
:10/
35;C
:21/
35(b
yda
y50
)‡5.
E:0
.083
;C:0
.11‖
0.10
-0.7
21.
NS
2.N
S3.
NS
4..0
095.
NS
3
Eng
lert
etal
271.
Post
opch
estp
ain
(mea
n)
2.Po
stop
leg
pain
(mea
n)
1.E
:1.4
7;C
:4.4
7(d
ay1)‡
E:1
.40;
C:4
.53
(day
3)‡
E:0
.53;
C:2
.27
(day
30)‡
2.E
:1.3
3;C
:3.0
6(d
ay1)‡
E:1
.46;
C:2
.80
(day
3)‡
E:0
.53;
C:2
.33
(day
30)‡
<.0
01‖∗
∗
<.0
01‖,¶
Peer
boom
set
al28
1.W
ound
clos
ure
2.Pa
inat
rest
(med
ian)
3.Pa
in,w
alki
ng(m
edia
n)
1.E
:4/5
0;C
:16/
52(2
wk)‡
E:4
/36;
C:1
6/46
(2w
k)§
2.E
:2;C
:2(6
wk)‡
3.E
:2;C
:2(6
wk)‡
−41
to−7
(%)‖
1.N
S†
.02‖
2.N
S‖
3.N
S‖
Van
get
al29
1.S
tern
umpa
in(y
es)
2.L
egpa
in(y
es)
1.E
:7/1
5;C
:7/1
5(d
ay2)§
E:2
/14;
4/15
(3w
k)§
2.E
:0/1
5:C
:0/1
5(d
ay2)§
E:3
/14;
C:5
/15
(3w
k)§
1.N
S‖
NS‖
2.N
S‖
NS‖
Yoo
etal
301.
Cum
ulat
ive
drai
nage
(mea
n)2.
Pain
(mea
n)1.
E:4
4.9;
C:6
3.5
(mL
;24
h)‡
2.E
:2.1
;C:2
.0(1
2h)§
1..0
394
2.N
S
394
CARTER ET AL
Tab
le3.
Con
tinu
ed
Stud
yO
utco
me
Cri
teri
aO
utco
mes
95%
CI†
P†
NN
T
Acu
tew
ound
spr
imar
ycl
osur
e(c
ompa
rativ
ede
sign
s;no
n-R
CT
s)
Eve
rts
etal
311.
Wou
ndex
udat
ele
akag
e2.
Wou
ndhe
alin
gdi
stur
banc
es3.
Sup
erfi
cial
infe
ctio
ns4.
Hos
pita
lsta
y(m
ean
days
)
1.E
:2/8
5;C
:12/
802.
E:0
/85;
C:9
/80
3.E
:0/8
5;C
:4/8
04.
E:6
.4;C
:8.3
1.<
.001
‖2.
.001
‖3.
<.0
5‖4.
<.0
01‖
8 9 20
Gar
dner
etal
321.
Mea
nin
trav
enou
sna
rcot
icus
e2.
Fun
ctio
nalR
OM
atdi
scha
rge
(◦)
3.H
ospi
tals
tay
(mea
nda
ys)
1.E
:17.
0;C
:36.
3(m
g/d)
2.E
:78.
2;C
:71.
93.
E:4
.04;
C:5
.29
1..0
24‖
2..0
52‖
3..0
02‖
Kha
lafi
etal
331.
Che
stin
fect
ion
2.C
hest
drai
nage
(not
able
)3.
Leg
infe
ctio
n4.
Leg
drai
nage
(not
able
)
1.0.
074
(OR
for
Eco
mpa
red
toC
)2.
0.04
2(O
Rfo
rE
com
pare
dto
C)
3.0/
560;
3/45
64.
0.12
0(O
Rfo
rE
com
pare
dto
C)
0.00
32-1
.753
‖0.
0085
-0.2
10‖
0.07
14-0
.200
‖
1.<
.05‖
2.<
.001
‖3.
NS‖
4.<
.001
‖S
arat
zis
etal
341.
Post
oper
ativ
eco
mpl
icat
ions
(pat
ient
basi
s)2.
Post
oper
ativ
eco
mpl
icat
ions
(wou
ndba
sis)
3.H
ospi
tals
tay
(pos
tope
rativ
eda
ys)
1.E
:2/5
0;C
:9/5
0(<
30d)
2.E
:3/5
0;C
:12/
50(<
30d)
3.E
:4.4
8;C
:6.1
4
1..0
4†
2..0
2†
.026
‖3.
.001
‖
7 6
Tro
wbr
idge
etal
351.
Sup
erfi
cial
infe
ctio
n2.
Dee
pst
erna
linf
ecti
on1.
E:1
/382
;17/
948
2.E
:0/3
82;1
4/94
81.
<.0
5‖2.
<.0
29‖
65 68
Acu
tew
ound
sse
cond
ary
clos
ure
(RC
Ts)
Kaz
akos
etal
361.
Mea
nti
me
requ
ired
tohe
alto
unde
rgo
reco
nstr
uctiv
esu
rger
y2.
Sur
face
area
redu
ctio
n(%
)
3.Pa
in(V
AS
scal
e)
1.E
:21.
3;C
:40.
6(d
)
2.E
:12.
2;C
:8.3
(1w
k)E
:24.
2;C
:16.
0(2
wk)
E:3
6.4;
C:2
3.1
(3w
k)3.
E:5
7.6;
C:7
9.8
(3w
k)
1.<
.001
‖
2..0
03‖
<.0
01‖
<.0
01‖
3.<
.001
Spy
rida
kis
etal
371.
Mea
nw
ound
volu
me
redu
ctio
n2.
Tim
eto
com
plet
ew
ound
heal
ing
3.S
F-3
6sc
ores
(3w
k)4.
Pati
entd
istr
ess
(day
sof
med
ical
serv
ice)
1.E
:11.
6;C
:6.7
(mL
;day
s10
-15)
2.E
:24;
C:3
0(d
)3.
E:7
5;C
:62
4.E
:24;
C:3
0
1.<
.01‖
2.<
.01‖
3.<
.03‖
4.<
.01‖
395
ePlasty VOLUME 11
Tab
le3.
Con
tinu
ed
Stud
yO
utco
me
Cri
teri
aO
utco
mes
95%
CI†
P†
NN
T
Acu
tew
ound
sse
cond
ary
clos
ure
(com
para
tive
desi
gns;
non-
RC
Ts)
Hom
etal
381.
Perc
enta
geof
clos
ure
2.F
ullc
losu
re
3.W
ound
heal
ing
velo
city
E:8
1.1;
C:5
7.2
(day
17)
E:1
3/16
;C:7
/16
(day
24)
Sum
mat
ion
ofhe
alin
gve
loci
tyat
allt
ime
poin
tsbe
twee
ngr
oups
(det
aile
dda
tano
trep
orte
d)
2.13
-27.
521.
<.0
01‖,†
†
2..0
4† NS‖
3..0
01‖
∗ Wou
ndsi
zere
duct
ions
are
repo
rted
asm
ean
redu
ctio
nsun
less
othe
rwis
est
ated
;C
Isar
eca
lcul
ated
for
risk
diff
eren
cein
dich
otom
ous
outc
omes
and
for
wei
ghte
dm
ean
diff
eren
cein
cont
inuo
usou
tcom
esun
less
othe
rwis
est
ated
.A
Ein
dica
tes
adve
rse
even
t;C
,co
ntro
lgr
oup
(com
pari
son)
;C
I,co
nfide
nce
inte
rval
s;E
,ex
peri
men
tal
grou
p(P
RP
);K
M,
Kap
lan-
Mei
er;
NN
T,nu
mbe
rne
eded
totr
eat(
base
don
com
plet
ew
ound
heal
ing)
;NS
,not
sign
ifica
nt;O
R,o
dds
rati
o;P
RP,
plat
elet
rich
plas
ma;
PR
,pla
tele
trel
easa
te;R
R,r
elat
ive
risk
.†
Val
ues
calc
ulat
edus
ing
the
Zte
st(fi
xed
effe
cts)
whe
nsi
gnifi
cant
unle
ssot
herw
ise
indi
cate
d(i
e,au
thor
valu
es).
‡Int
enti
on-t
o-tr
eat(
ITT
)an
alys
is.
§Per
prot
ocol
(PP
)an
alys
is.
‖Aut
hor
valu
es.
¶Cre
pres
ents
wou
nds
duri
nga
run-
inpe
riod
and
Ere
pres
ents
sam
ew
ound
sdu
ring
trea
tmen
tper
iod.
#M
ultiv
aria
tere
peat
edm
easu
res
gene
rall
inea
rm
odel
inw
hich
95%
CI
isfo
rm
ean
diff
eren
ce;v
alue
sfo
rC
repr
esen
tare
aor
dept
hat
firs
tpre
trea
tmen
tval
uean
dfo
rE
repr
esen
tper
cent
area
orde
pth
atla
sttr
eatm
entt
ime.
∗∗R
epea
ted-
mea
sure
sA
NO
VA
:mul
tivar
iate
for
ches
tpai
n(W
ilk’
sλ
=0.
43)
and
univ
aria
tefo
rle
gpa
in.
††R
epea
ted-
mea
sure
sA
NO
VA
,42
days
.
396
CARTER ET AL
Tab
le4.
Qua
lity
asse
ssm
enta
ndsu
mm
ary
offin
ding
sfo
rst
udie
sco
mpa
ring
use
ofpl
atel
et-r
ich
plas
ma
trea
tmen
tsag
ains
tsta
ndar
dca
refo
rch
roni
cw
ound
s
Qua
lity
Ass
essm
ent
Sum
mar
yof
Fin
ding
s
No
ofP
atie
nts
Eff
ect
No
ofO
ther
Mod
ifyi
ngR
elat
ive
Stud
ies
Des
ign
Qua
lity
Con
sist
ency
Dir
ectn
ess
Fac
tors
PR
PC
ontr
ols
(95%
CI)
Abs
olut
eQ
ualit
yIm
port
ance
Com
plet
eW
ound
heal
ing
4R
CT
Ser
ious
lim
-it
atio
nsS
ome
inco
nsis
-te
ncy
No
unce
r-ta
inty
Sm
allt
rial
s(p
ower
issu
es)
7667
RD
:0.2
4(0
.07-
0.40
)*22
/100
Low
Cri
tica
l
1C
ompa
rativ
eN
ose
riou
sli
mit
a-ti
ons
No
inco
n-si
sten
cyN
oun
cer-
tain
tyL
arge
N,w
ell-
done
anal
ysis
,evi
denc
eof
bett
erhe
alin
gfo
rse
vere
wou
nds
6,25
220
,347
RR
:1.3
8(1
.33-
1.42
)9/
100
Mod
Cri
tica
l
Tim
eto
heal
(day
s)1
RC
TS
erio
usli
m-
itat
ions
Som
ein
cons
is-
tenc
y
No
unce
r-ta
inty
Num
erou
spr
otoc
olvi
olat
ions
1921
WM
D:−
4.50
(–17
.0to
8.0)
−4.5
dL
owC
riti
cal
1C
ompa
rativ
eN
ose
riou
sli
mit
a-ti
ons
No
inco
n-si
sten
cyN
oun
cer-
tain
tyS
mal
lN10
12—
−17.
5d
Low
Cri
tica
l
Mea
nti
me
tore
ach
50%
dept
hor
area
redu
ctio
n1
Com
para
tive
No
seri
ous
lim
ita-
tion
s
No
inco
n-si
sten
cyN
oun
cer-
tain
tyR
elat
ivel
ysm
allN
41 39
46 46
Dep
th:W
MD
:−5
0.6
(–37
.56
to−6
3.64
)A
rea:
WM
D:
−40.
9(–
26.1
9to
−55.
61)
Dep
th:
3.3-
fold
Are
a:2.
6-fo
ld
Mod
Cri
tica
l
Adv
erse
even
ts3
RC
TS
ome
lim
i-ta
tion
sN
oin
con-
sist
ency
No
unce
r-ta
inty
Sm
alla
ggre
gate
N63
74—
NN
H:1
1L
owIm
port
ant
∗ Dat
afr
omon
eR
CT
uses
inte
rmed
iate
PP
resu
lts
(N=
19/2
1);
mod
indi
cate
sm
oder
ate;
NN
H,
num
ber
need
edto
harm
;R
CT,
rand
omiz
edco
ntro
lled
tria
l;R
D,
risk
diff
eren
ce;
RR
,re
lativ
eri
sk;W
MD
,wei
ghte
dm
ean
diff
eren
ce.
397
ePlasty VOLUME 11
Tab
le5.
Qua
lity
asse
ssm
enta
ndsu
mm
ary
offin
ding
sfo
rst
udie
sco
mpa
ring
use
ofpl
atel
et-r
ich
plas
ma
trea
tmen
tsag
ains
tsta
ndar
dca
refo
rac
ute
wou
nds∗
Qua
lity
Ass
essm
ent
Sum
mar
yof
Fin
ding
s
No
ofP
atie
nts
Eff
ect
No
ofO
ther
Mod
ifyi
ngR
elat
ive
Stud
ies
Des
ign
Qua
lity
Con
sist
ency
Dir
ectn
ess
Fac
tors
PR
PC
ontr
ols
(95%
CI)
Abs
olut
eQ
ualit
yIm
port
ance
Acu
tew
ound
s(p
rim
ary
clos
ure)
Com
plet
ew
ound
heal
ing
1R
CT
No
lim
ita-
tion
sN
oin
con-
sist
ency
No
unce
r-ta
inty
Sho
rtfo
llow
-up
5052
RD
:−0.
23(−
0.37
to−0
.08)
−23/
100
Mod
Cri
tica
l
Infe
ctio
n1
RC
TN
oli
mit
a-ti
ons
No
inco
n-si
sten
cyN
oun
cer-
tain
tyL
egin
fect
ion
7070
RD
:0.0
1(−
0.09
to0.
12)
1.4/
100
Hig
hIm
port
ant
1C
ompa
rativ
eN
ose
riou
sli
mit
a-ti
ons
No
inco
n-si
sten
cyN
oun
cer-
tain
tyL
egin
fect
ion;
larg
eN
560
546
RD
:−0.
01(−
0.01
to0)
−5.5
/100
0M
odIm
port
ant
2C
ompa
rativ
eN
ose
riou
sli
mit
a-ti
ons
No
inco
n-si
sten
cyN
oun
cer-
tain
tyS
uper
fici
alin
fect
ion
467
1028
RD
:−0.
02(−
0.06
to0.
01)
−22/
1000
Mod
Impo
rtan
t
1C
ompa
rativ
eN
ose
riou
sli
mit
a-ti
ons
No
inco
n-si
sten
cyN
oun
cer-
tain
tyC
hest
infe
ctio
n;la
rge
N;p
rope
nsit
ysc
orin
g
571
557
OR
:0.0
743
(0.0
032-
1.75
35)
—M
odIm
port
ant
1C
ompa
rativ
eN
ose
riou
sli
mit
a-ti
ons
No
inco
n-si
sten
cyN
oun
cer-
tain
tyC
hest
infe
ctio
n38
294
8R
D:−
0.01
(−0.
02to
−0.0
1)
14.8
/100
0M
odIm
port
ant
Pain
redu
ctio
n3
RC
TS
ome
seri
ous
lim
ita-
tion
s
Inco
nsis
tenc
ybe
twee
nst
udie
s
Som
eun
-ce
rtai
nty
(ove
rall
vs.c
hest
pain
)
Sm
allN
6361
WM
D:−
0.75
(−2.
38to
0.89
)
−0.7
5/10
Ver
y low
Impo
rtan
t
1R
CT
No
seri
ous
lim
ita-
tion
s
No
inco
n-si
sten
cyS
ome
un-
cert
aint
y50
52—
No di
ffer
-en
ce
Mod
Impo
rtan
t
398
CARTER ET AL
Tab
le5.
Con
tinu
ed
Qua
lity
Ass
essm
ent
Sum
mar
yof
Fin
ding
s
No
ofP
atie
nts
Eff
ect
No
ofO
ther
Mod
ifyi
ngR
elat
ive
Stud
ies
Des
ign
Qua
lity
Con
sist
ency
Dir
ectn
ess
Fac
tors
PR
PC
ontr
ols
(95%
CI)
Abs
olut
eQ
ualit
yIm
port
ance
1R
CT
Ser
ious
lim
i-ta
tion
sN
oin
cons
is-
tenc
yS
ome
unce
rtai
nty
Dic
hoto
mou
sou
tcom
es15
15R
D:0
(−0.
36to
0.36
)N
odi
ffer
-en
ceV
ery low
Impo
rtan
t
Wou
nddr
aina
ge/e
xuda
te1
RC
TN
ose
riou
sli
mit
a-ti
ons
No
inco
nsis
-te
ncy
No
unce
rtai
nty
Sm
allN
2626
WM
D:1
8.6
(36.
92to
0.28
)
18.6
mL
Low
Impo
rtan
t
1C
ompa
rativ
eN
ose
riou
sli
mit
a-ti
ons
No
inco
nsis
-te
ncy
No
unce
rtai
nty
Lar
geN
;pro
pens
ity
scor
ing
571
557
OR
:0.0
42—
Mod
Impo
rtan
t
1C
ompa
rativ
eN
ose
riou
sli
mit
a-ti
ons
No
inco
nsis
-te
ncy
Som
eun
cert
aint
y85
80R
D:−
0.13
(−0.
21to
−0.0
4)
−13/
100
Mod
Impo
rtan
t
Acu
tew
ound
s(s
econ
dary
clos
ure)
Com
plet
ew
ound
heal
ing
1C
ompa
rativ
eS
erio
usli
mi-
tati
ons
No
inco
nsis
-te
ncy
No
unce
rtai
nty
Sm
allN
1616
RD
:0.3
1(−
0.02
to0.
64)
31/1
00V
ery low
Cri
tica
l
Tim
eto
com
plet
ew
ound
heal
ing
1R
CT
No
seri
ous
lim
ita-
tion
s
No
inco
nsis
-te
ncy
No
unce
rtai
nty
Sm
allN
3022
—6
dL
owC
riti
cal
Wou
ndvo
lum
ere
duct
ion
1R
CT
No
seri
ous
lim
ita-
tion
s
No
inco
nsis
-te
ncy
No
unce
rtai
nty
Sm
allN
3022
WM
D:4
.9(3
.79-
6.01
)4.
9m
LM
odIm
port
ant
Are
are
duct
ion
(quo
tien
tmet
hod)
1R
CT
No
seri
ous
lim
ita-
tion
s
No
inco
nsis
-te
ncy
No
unce
rtai
nty
Sm
allN
3227
WM
D:0
.13
(0.0
8-0.
18)
0.13
cm2
Mod
Impo
rtan
t
Pain
1R
CT
No
seri
ous
lim
ita-
tion
s
Som
ein
con-
sist
ency
No
unce
rtai
nty
Sm
allN
3227
WM
D:−
22.2
(−31
.16
to−1
3.28
)
−22.
2/10
0L
owIm
port
ant
∗ Mod
indi
cate
sm
oder
ate;
OR
,odd
sra
tio;
RC
T,ra
ndom
ized
cont
roll
edtr
ial;
RD
,ris
kdi
ffer
ence
;RR
,rel
ativ
eri
sk;W
MD
,wei
ghte
dm
ean
diff
eren
ce.
399
ePlasty VOLUME 11
Chronic wounds
Of 4 RCTs, 2 were statistically significant for complete wound healing compared to salinegel or no topical treatment.19-20 It should be noted that the 2 studies that did not detectsignificance at weeks 5 and 8 did have statistically significant wound area reductionscompared to saline gauze or no topical treatment suggesting that a longer study period wouldhave detected complete healing18,21 (Table 3). A non-RCT, comparative designed studyshowed consistently higher significant relative risks for complete wound healing in favorof platelet releasate compared to no topical treatment based on 26,599 subjects23 (Table 3).Two RCT studies evaluated time to heal and both showed significant improvements in PRP-treated subjects versus saline gel or no topical treatment19-20 (Table 3). Platelet rich plasmasubjects in a historical cohort study required significantly fewer days to complete healingcompared to hyaluronic acid–dressed wounds24 (Tables 3 and 4). Two RCT studies showedstatistically significant differences in wound area reduction compared to saline gauze or notopical treatment controls.18,21 Similarly, a non-RCT, comparative study showed significantarea and depth reductions with 2.5- to 3.5-fold decrease in time to reach 50% compared topretreatment moist wound care controls.22 Adverse events were consistently lower for PRPgroups than for controls of saline gauze, saline gel or no topical treatment.18-20
Acute primary closure wounds
Only 2 RCT and 2 non-RCT comparative studies specifically looked at wound-healingoutcomes (Tables 3 and 5).26,28,31,34 One RCT detected a statistically significant differencein complete wound healing for PRP compared to no topical treatment during a short 2-weekfollow-up28 (Tables 3 and 5). The other RCT study evaluated wounds with impaired woundhealing at day 50 and found no difference between no treatment and PRP gel suggesting thatPRP therapy does not impede wound healing.26 In all studies, PRP therapy had statisticallyfewer wound-healing disturbances and wound postoperative complications than the notreatment control counterparts26,31,34 (Table 3).
Six different infection sites and postoperative complications were considered espe-cially important criteria and were addressed in 1 RCT and 4 comparative studies.25,31,33-35
Two studies found infection rates that were not significantly different compared to no topicaltreatment,25,33 however, chest, superficial and deep infections and postoperative complica-tions were significantly lower in PRP-treated study subjects than in no topical treatmentcontrols25,31,33-35 (Tables 3 and 5). Infection was significantly increased in control groupsthan that in PRP groups in all but 1 study (Tables 3 and 5).
Exudate, drainage, and hematomas were evaluated in 2 RCT and 2 compara-tive studies.26,30-31,33 In 1 RCT, PRP-treated wounds had significantly fewer large areahematomas than no topical treatment control wounds, thus reducing a potential source forinfection.26 The amount and presence of drainage was statistically significantly reduced inthe PRP-treated wounds in all studies compared to controls of saline spray or no topicaltreatment30-31,33 (see Tables 3 and 5).
Postoperative, general, resting, and active pain, as well as narcotic use was assessed in 5RCT studies and 1 comparative study.26-30,32 Although 4 RCT studies did not show statisticaldifferences in mean postoperative pain, 1 study did27 (Tables 3 and 5). Postoperative painfor both leg and chest were significantly reduced for the PRP-treated wounds for 30 days,
400
CARTER ET AL
but not for no topical treatment control wounds27 (Table 3). A comparative study alsoshowed intravenous narcotic use was statistically lower in PRP-treated subjects than in notopical treatment controls indicating less pain was present32 (Table 3).
Acute secondary closure wounds
Complete wound closure was found to be statistically faster in PRP treated wounds com-pared to Bacitracin or no topical treatment in both a RCT and comparative study37-38
(Tables 3 and 5). The healing velocity of PRP-treated wounds was significantly greaterthan Bacitracin control.38 In 1 RCT, the mean time PRP-treated wounds required topartially heal in preparation for definitive surgery was not only significant, but almosthalf of that of Vaseline gauze controls36 (Tables 3 and 5). The PRP group healing ratesand wound area and volume reductions were statistically significant in all studies36-38
(Tables 3 and 5). One RCT study assessed VAS pain scores at 3 weeks and foundPRP-treated wounds had significantly less pain than Vaseline gauze controls36 (Tables 3and 5). One RCT administered the SF-36 tool at week 3 to evaluate wound treatment effecton patient QoL and showed PRP-treated subjects had significantly better QoL scores thansubjects with no topical treatment37 (Table 3).
Meta-analysis
A meta-analysis was performed on chronic wound RCTs studies using PRP and standardwound care to analyze the impact of the therapies on complete wound healing.18-21 Usingthe fixed-effect model for complete wound healing, the results were significantly in favor ofthe PRP therapy with no significant heterogeneity compared to control therapies of salinegauze, saline gel, or no topical treatment (Fig 2). A meta-analysis for RCTs in acute woundswith primary closure was not undertaken because there were only 2 studies and their definedoutcomes for complete closure were incompatible. A meta-analysis of infection and for painreduction, however, could be performed. Acute wounds with primary closure comparativestudies evaluating superficial infection were modeled using random effects.31,35 The resultswere in favor of the PRP therapy to reduce infection but not significant compared to notopical treatment (Fig 3). For the acute wound with primary closure, RCT studies evaluatingpostoperative pain were modeled using random effects.26-27,30 The results were in favor ofthe PRP therapy to reduce pain but not significant compared to saline spray or no topicaltreatment (Fig 4).
DISCUSSION
There were 21 publications that were RCT or comparative non-RCT designs in this sys-tematic review. Given the physiological and healing differences between acute and chronicwounds, the citations were divided by study design and by type of wound prior to reviewand meta-analysis. The primary outcome assessed in this systematic review was completehealing. In both chronic and acute wound studies, complete wound closure was more likelyin wounds treated with PRP therapy. Similar partial healing and wound area/volume re-duction outcomes were noted more frequently with the PRP-treated wounds likely because
401
ePlasty VOLUME 11
Stud
y or
Su
bgro
up
Wou
nd
Type
Co
ntro
l Ag
ent
PRP
Even
ts
Tota
l Co
ntro
l Ev
ents
To
tal
Wei
ght
Risk
Diff
eren
ce
M-H
, Fix
ed, 9
5% C
I
Anitu
a et
al42
Cu
tane
ous
ulce
rs
Salin
e ga
uze
dres
sings
1
8 1
7 13
.5%
−0
.02
[−0.
36, 0
.33]
Driv
er e
t al19
DF
Us
Salin
e ge
l 13
19
9
21
36.0
%
0.26
[−0.
04, 0
.55]
Frie
se e
t al20
DF
Us
No
topi
cal
trea
tmen
t 11
21
5
21
37.9
%
0.29
[0.0
0, 0
.57]
Sald
alam
acch
ia
et a
l21
DFU
s N
o to
pica
l tr
eatm
ent
2 7
1 7
12.6
%
0.14
[−0.
28, 0
.57]
To
tal (
95%
CI)
55
56
100%
0.
22 [0
.05,
0.3
8]
Tota
l eve
nts
27
16
Hete
roge
neity
: χ2 =
2.1
7, df =
3 (P
= .5
4); I
2 =
0%
Test
for o
vera
ll eff
ect:
Z =
2.54
(P =
.01)
Fig
ure
2.M
eta-
anal
ysis
:For
estp
loto
fch
roni
cw
ound
com
plet
ew
ound
heal
ing
stud
ies
trea
ted
wit
hst
anda
rdw
ound
care
and
eith
erP
RP
orco
ntro
lag
ent.
Thi
san
alys
isus
edth
ele
ast
cons
erva
tive
PP
anal
ysis
for
Dri
ver
etal
.19C
Iin
dica
tes
confi
denc
ein
terv
al;
df,
degr
ees
offr
eedo
m;
M-H
,M
ante
l-H
aens
zel;
PR
P,pl
atel
et-r
ich
plas
ma.
402
CARTER ET AL
Stud
y or
Su
bgro
up
Wou
nd
Type
Co
ntro
l Ag
ent
PRP
Even
ts
Tota
l Co
ntro
l Ev
ents
To
tal
Wei
ght
Risk
Diff
eren
ce
M-H
, Fix
ed, 9
5% C
I
Ever
ts 2
006
Surg
ical
w
ound
s N
o to
pica
l tr
eatm
ent
0 85
4
80
27.7
%
−0.0
5 [−
0.10
, 0.0
0]
Trow
brid
ge
2005
St
erna
l w
ound
s N
o to
pica
l tr
eatm
ent
1 38
2 17
94
8 72
.3%
−0
.02
[−0.
03, −
0.01
]
To
tal (
95%
CI)
46
7
1028
10
0.0%
− −0
.02
[−−0.
06, 0
.01]
Tota
l eve
nts
1
21
He
tero
gene
ity: τ
2 = 0.
00; χ2 =
2.0
9, df =
1 (P
= .1
5); I
2 =52
%
Test
for o
vera
ll eff
ect:
Z= 1
.42
(P =
.16)
Fig
ure
3.M
eta-
anal
ysis
:For
estp
loto
fac
ute
wou
nds
wit
hpr
imar
ycl
osur
efo
rsu
perfi
cial
infe
ctio
ntr
eate
dw
ith
stan
dard
wou
ndca
rean
dei
ther
PR
Por
cont
rola
gent
.CI
indi
cate
sco
nfide
nce
inte
rval
;df,
degr
ees
offr
eedo
m;M
-H,M
ante
l-H
aens
zel;
PR
P,pl
atel
et-r
ich
plas
ma.
403
ePlasty VOLUME 11
Stud
y or
Su
bgro
up
Wou
nd
Type
Co
ntro
l Ag
ent
PRP
Mea
n PR
P SD
Tota
l Co
ntro
l M
ean
Cont
rol
SD
Tota
l W
eigh
t Ri
sk
Diffe
renc
e M
-H, F
ixed
, 95
% C
I
Buch
wal
d et
al26
Su
rgic
al
wou
nds
No
topi
cal
trea
tmen
t 0.
083
0.69
35
0.
11
0.59
34
36
.0%
−0
.03
[−
0.33
, 0.2
8]
Engl
ert
et a
l52
Ster
nal
wou
nds
No
topi
cal
trea
tmen
t 1.
47
0.83
15
4.
47
2.06
15
31
.1%
−3
.00
[−
4.12
, −1.
88]
Yoo
et a
l30
Surg
ical
w
ound
s Sa
line
spra
y 1.
2 1.
2 13
0.
6 1.
1 12
32
.8%
0.
60
[−0.
30, 1
.50]
Tota
l (9
5% C
I)
63
61
10
0.0%
−0
.75
[−
2.38
, 0.8
9]
He
tero
gene
ity: τ
2=
1.90
; χ2 =
27.
99, df =
2 (P
< .0
0001
); I2 =9
3%
Te
st fo
r ove
rall
effec
t: Z=
0.9
0 (P
= .3
7)
Fig
ure
4.M
eta-
anal
ysis
:Fo
rest
plot
ofac
ute
wou
nds
wit
hpr
imar
ycl
osur
efo
rpa
inre
duct
ion
trea
ted
wit
hst
anda
rdw
ound
care
and
eith
erP
RP
orco
ntro
lage
nt.C
Iin
dica
tes
confi
denc
ein
terv
al;d
f,de
gree
sof
free
dom
;M-H
,Man
tel-
Hae
nsze
l;P
RP,
plat
elet
-ric
h.
404
CARTER ET AL
the therapy is discontinued once the wound begins healing. This meta-analysis and othersystematic reviews show PRP has sufficient efficacy to stimulate healing in stalled wounds.One systematic review concluded that the percentage of total healing in PRP-treated skinulcers consistently increased compared to controls.7 The meta-analysis of chronic woundstudies confirmed the use of PRP treatment favored complete healing compared to controlcare. Other systematic reviews on PRP therapy reached the same conclusions.7-9 One sys-tematic review went so far as to conclude that based on the meta-analysis and scientificevidence regarding consistent favorable outcomes, PRP is a treatment of choice for thetopical care of wounds.9
Because nonhealing wounds incur expenses as well as run a higher risk of complica-tions, the sooner a wound can heal or be ready for surgery, the less likely the wound willbecome more problematic.83 The data suggest that PRP therapy can be extremely cost-effective in chronic wounds and it may also be effective in certain acute wounds. A recentstudy found that a specific PRP gel was the most cost-effective over a 5-year period of timecompared to other advanced wound therapies in the treatment of diabetic foot ulcers.84
From a clinical point of view, the decrease in complication risks and expenses with healingimpacts patient health, finances, and QoL. From a payor’s perspective, achieving closure at25% to 50% faster rate than control care treatment alleviates the expenses of a longer andmore problematic treatment course resulting in a benefit for both patient and payor.
Infection and exudate were evaluated in many acute primary closure wound studiesbecause both can delay healing. Overall, infection rates appear to be lower in PRP-treatedsubjects. The meta-analysis of the RCT studies confirmed the infection rates were lowerwhen PRP treatment was used compared to control care although not significantly so.Because increased exudate in wounds can be a precursor to infection, the presence ofthe exudate is closely documented. As seen in this review, in both RCT and non-RCTcomparative studies, the amount and presence of drainage was statistically significantlyreduced in the PRP-treated wounds suggesting potentially fewer infectious complications.Decreasing exudate and infection risks are beneficial for the patient, the wound, and theclinician and should improve the healing rate. Obvious benefits of no or reduced topicaland systemic antimicrobials are limiting exposure to microorganisms, reduction in ex-penses and improved patient QoL. Payors know that wounds that are infected or heavilycolonized do not heal as quickly as wounds that are not contaminated, saving costs andtime.2
Pain is often associated with wounds, but because of the subjective nature of the sen-sation, determining the impact of wound care therapies on different types of pain, levels ofpain, and when pain is assessed can be difficult. Pain outcomes appeared mixed with somestudies reporting no difference between treatments and others showing significantly statisti-cal differences favoring PRP treatment. Objective use of measured intravenous narcotic useand SF-36 tool for QoL more clearly demonstrate PRP-treated subjects had significantlybetter QoL scores and fewer required narcotic medication. This suggests the therapy mayresult in less wound pain. The meta-analysis suggests PRP therapy may positively impactthe patient by reducing pain. Presence of persistent pain can impair healing as well as affectpatient QoL.85 Reduction in pain allows clinicians to prescribe less addictive and lowerrisk analgesics as well as fewer drug interactions. While payors sometime underestimatethe impact pain has on healing and QoL, the expense of high level pain medication adds upquickly.
405
ePlasty VOLUME 11
The quality of the eligible studies varied widely as shown through multiple scoringmethods. Using several methods together allowed the authors to quickly and consistentlyevaluate the strengths and weaknesses of each paper. Many RCTs were lower in quality,higher in bias, and had more serious limitations than many comparative or cohort studies.This emphasizes the need to evaluate the quality and bias of published studies in additionto the study design.
One limitation of this systematic review was that while many citations evaluated theimpact of PRP treatment on wound healing, there are many methods and definitions fordetermining and measuring wound healing. As the literature pool grows, more subcategories(ie, by PRP product type) can be assessed.
On the basis of the last 10 years of research, the results of this systematic review andmeta-analysis suggest that PRP therapy can positively impact wound healing and associatedfactors such as pain and infection in both chronic and acute cutaneous wounds.
Acknowledgments
The authors wish to thank their colleagues for their expert opinions in seeking out availablestudies for the systematic review. The funding for the systematic review was provided byCytomedix, Inc (Gaithersburg, MD). Carelyn Fylling is an employee of Cytomedix, Inc,and publication of this review was not required as part of her duties. Marissa J. Carter andLaura K. S. Parnell are independent research consultants.
REFERENCES
1. Mast BA. The skin. In: Cohen IK, Diegelmann RF, Lindblad WJ, eds. Wound Healing, Biochemical andClinical Aspects. Philadelphia, PA: W.B. Saunders; 1992:344-55.
2. Lawrence WT. Clinical management of nonhealing wounds. In: Cohen IK, Diegelmann RF, Lindblad WJ,eds. Wound Healing: Biochemical and Clinical Aspects. Philadelphia, PA: W.B. Saunders; 1992:541-61.
3. Steed DL, Attinger C, Colaizzi T, et al. Guidelines for the treatment of diabetic ulcers. Wound Repair Regen.2006;14(6):680-92.
4. Bolton LL, van Rijswijk L, Shaffer FA. Quality wound care equals cost-effective wound care: a clinicalmodel. Adv Wound Care. 1997;10(4):33-8.
5. Frykberg RG, Driver VR, Carman D, et al. Chronic wounds treated with a physiologically relevant concen-tration of platelet-rich plasma gel: a prospective case series. Ostomy Wound Manage. 2010;56(6):36-44.
6. Reese RJ. Autologous platelet rich plasma (PRP): what do we know? Important concepts relevant to hairrestoration surgery. Hair Transplant Forum Int. 2010:14-7.
7. Martinez-Zapata MJ, Marti-Carvajal A, Sola I, et al. Efficacy and safety of the use of autologous plasmarich in platelets for tissue regeneration: a systematic review. Transfusion. 2009;49(1):44-56.
8. Villela DL, Santos VL. Evidence on the use of platelet-rich plasma for diabetic ulcer: a systematic review.Growth Factors. 2010;28(2):111-6.
9. Villela DL, Santos VL. Topical therapy of chronic leg ulcers with platelet-rich plasma: a systematic reviewof the literature. Paper presented at: WOCN 2010 Conference of the Wound Ostomy Continence NurseSociety; June 12-16, 2010; St Louis, MO.
10. Downs SH, Black N. The feasibility of creating a checklist for the assessment of the methodological qualityboth of randomized and non-randomized studies of health care interventions. J Epidemiol CommunityHealth. 1998;52:377-84.
11. Carter MJ, Tingley-Kelley K, Warriner RA III. Silver treatments and silver-impregnated dressings forthe healing of leg wounds and ulcers: a systematic review and meta-analysis. Am Acad Dermatol.2010;63(4):668-79.
406
CARTER ET AL
12. Carter MJ, Fife CE, Walker D, Thomson B. Estimating the applicability of wound-care randomized con-trolled trials to general wound care populations by estimating the percentage of individuals excluded froma typical wound care population in such trials. Adv Skin Wound Care. 2009;22:316-24.
13. Harbour R, Miller J. A new system for grading recommendations in evidence-based guidelines. BMJ.2001;323:334-6.
14. Atkins D, Best D, Briss PA, et al; GRADE Working Group. Grading quality of evidence and strength ofrecommendations. BMJ. 2004;328(7454):1490.
15. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Schunemann HJ. GRADE: What is “quality ofevidence” and why is it important to clinicians? BMJ. 2008;336:995-8.
16. Guyatt GH, Oxman AD, Kunz R, et al. GRADE: going from evidence to recommendations. BMJ.2008;336:1049-51.
17. Higgins JB, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539-58.
18. Anitua E, Aguirre JJ, Algorta J, et al. Effectiveness of autologous preparation rich in growth fac-tors for the treatment of chronic cutaneous ulcers. J Biomed Mater Res B Appl Biomater. 2008;84(2):415-21.
19. Driver VR, Hanft J, Fylling CP, Beriou JM; Autologel Diabetic Foot Ulcer Study Group. A prospective,randomized, controlled trial of autologous platelet-rich plasma gel for the treatment of diabetic foot ulcers.Ostomy Wound Manage. 2006;52(6):68-87.
20. Friese G, Herten M, Scherbaum WA. The use of autologous platelet concentrate activated by autologousthrombin (APC+) is effective and safe in the treatment of chronic diabetic foot ulcers: a randomizedcontrolled trial. Paper presented at: Fifth International Symposium on the Diabetic Foot; May 9-12, 2007;Noordwijkerhout, The Netherlands.
21. Saldalamacchia G, Lapice E, Cuomo V, et al. A controlled study of the use of autologous platelet gel forthe treatment of diabetic foot ulcers. Nutr Metab Cardiovasc Dis. 2004;14:395-6.
22. Carter M, Fylling C, Li W, et al. A statistical analysis of a wound outcomes registry using run-in data:clinical impact of platelet rich plasma gel on healing trajectory. Int Wound J.; In Press.
23. Margolis DJ, Kantor J, Santanna J, Strom BL, Berlin JA. Effectiveness of platelet releasate for the treatmentof diabetic neuropathic foot ulcers. Diabetes Care. 2001;24(3):483-8.
24. Mazzucco L, Medici D, Serra M, et al. The use of autologous platelet gel to treat difficult-to-heal wounds:a pilot study. Transfusion. 2004;44(7):1013-8.
25. Almdahl SM, Veel T, Halvorsen P, Vold MB, Molstad P. Randomized prospective trial of saphenous veinharvest site infection after wound closure with and without topical application of autologous platelet-richplasma. Eur J Cardiothorac Surg. 2011;39(1):44-8.
26. Buchwald D, Kaltschmidt C, Haardt H, Laczkovics A, Reber D. Autologous platelet gel fails to showbeneficial effects on wound healing after saphenectomy in CABG patients. J Extra Corpor Technol.2008;40(3):196-202.
27. Englert SJ, Estep TH, Ellis-Stoll CC. Postoperative surgical chest and leg incision sites using platelet gel:a retrospective study. J Extra Corpor Technol. 2008;40(4):225-8.
28. Peerbooms JC, de Wolf GS, Colaris JW, Bruijn DJ, Verhaar JA. No positive effect of autologous plateletgel after total knee arthroplasty. Acta Orthop. 2009;80(5):557-62.
29. Vang SN, Brady CP, Christensen KA, et al. Autologous platelet gel in coronary artery bypass grafting:effects on surgical wound healing. J Extra Corpor Technol. 2007;39(1):31-8.
30. Yoo J, Roth K, Hughes B, et al. Evaluation of postoperative drainage with application of platelet-richand platelet-poor plasma following hemithyroidectomy: a randomized controlled clinical trial. Head Neck.2008;30(12):1552-8.
31. Everts PA, Devilee RJ, Brown Mahoney C, et al. Platelet gel and fibrin sealant reduce allogeneic bloodtransfusions in total knee arthroplasty. Acta Anaesthesiol Scand. 2006;50(5):593-9.
32. Gardner MJ, Demetrakopoulos D, Klepchick PR, Mooar PA. The efficacy of autologous platelet gel in paincontrol and blood loss in total knee arthroplasty. An analysis of the haemoglobin, narcotic requirement andrange of motion. Int Orthop. 2007;31(3):309-13.
33. Khalafi RS, Bradford DW, Wilson MG. Topical application of autologous blood products during surgicalclosure following a coronary artery bypass graft. Eur J Cardiothorac Surg. 2008;34(2):360-4.
407
ePlasty VOLUME 11
34. Saratzis N, Saratzis A, Melas N, Kiskinis D. Non-activated autologous platelet-rich plasma for the preventionof inguinal wound-related complications after endovascular repair of abdominal aortic aneurysms. J ExtraCorpor Technol. 2008;40(1):52-6.
35. Trowbridge CC, Stammers AH, Woods E, Yen BR, Klayman M, Gilbert C. Use of platelet gel and its effectson infection in cardiac surgery. J Extra Corpor Technol. 2005;37(4):381-6.
36. Kazakos K, Lyras DN, Verettas D, Tilkeridis K, Tryfonidis M. The use of autologous PRP gel as an aid inthe management of acute trauma wounds. Injury. 2009;40(8):801-5.
37. Spyridakis M, Christodoulidis G, Chatzitheofilou C, Symeonidis D, Tepetes K. The role of the platelet-richplasma in accelerating the wound-healing process and recovery in patients being operated for pilonidalsinus disease: preliminary results. World Journal of Surgery. 2009;33(8):1764-9.
38. Hom DB, Linzie BM, Huang TC. The healing effects of autologous platelet gel on acute human skinwounds. Arch Facial Plast Surg. 2007;9:174-83.
39. Akingboye AA, Giddins S, Gamston P, Tucker A, Navsaria H, Kyriakides C. Application of autologousderived-platelet rich plasma gel in the treatment of chronic wound ulcer: diabetic foot ulcer. J Extra CorporTechnol. 2010;42(1):20-9.
40. Alsousou J, Thompson M, Hulley P, Noble A, Willett K. The biology of platelet-rich plasma and itsapplication in trauma and orthopaedic surgery: a review of the literature. J Bone Joint Surg Br. 2009;91(8):987-96.
41. Anitua E, Andia I, Ardanza B, Nurden P, Nurden AT. Autologous platelets as a source of proteins for healingand tissue regeneration. Thromb Haemost. 2004;91(1):4-15.
42. Anitua E, Sanchez M, Orive G, Andia I. The potential impact of the preparation rich in growth factors(PRGF) in different medical fields. Biomaterials. 2007;28(31):4551-60.
43. Arora NS, Ramanayake T, Ren YF, Romanos GE. Platelet-rich plasma: a literature review. Implant Dent.2009;18(4):303-10.
44. Balbo R, Avonto I, Marenchino D, Maddalena L, Menardi G, Peano G. Platelet gel for the treatment oftraumatic loss of finger substance. Blood Transfus. 2010;8(4):255-9.
45. Bernuzzi G, Tardito S, Bussolati O, et al. Platelet gel in the treatment of cutaneous ulcers: the experienceof the Immunohaematology and Transfusion Centre of Parma. Blood Transfus. 2010;8(4):237-47.
46. Braund R, Hook S, Medlicott NJ. The role of topical growth factors in chronic wounds. Curr Drug Deliv.2007;4(3):195-204.
47. Cervelli V, De Angelis B, Lucarini L, et al. Tissue regeneration in loss of substance on the lower limbsthrough use of platelet-rich plasma, stem cells from adipose tissue, and hyaluronic acid. Adv Skin WoundCare. 2010;23(6):262-72.
48. Cervelli V, Gentile P, De Angelis B, et al. Application of enhanced stromal vascular fraction and fat graftingmixed with PRP in post-traumatic lower extremity ulcers. Stem Cell Res. 2011;6(2):103-11.
49. Cervelli V, Gentile P, Scioli MG, et al. Application of platelet-rich plasma in plastic surgery: clinical and invitro evaluation. Tissue Eng Part C Methods. 2009;15(4):625-34.
50. Crovetti G, Martinelli G, Issi M, et al. Platelet gel for healing cutaneous chronic wounds. Transfus ApherSci. 2004;30(2):145-51.
51. Dougherty EJ. An evidence-based model comparing the cost-effectiveness of platelet-rich plasma gel to al-ternative therapies for patients with nonhealing diabetic foot ulcers. Adv Skin Wound Care. 2008;21(12):568-75.
52. Englert SJ, Estep TH, Ellis-Stoll CC. Autologous platelet gel applications during cardiovascular surgery:effect on wound healing. J Extra Corpor Technol. 2005;37(2):148-52.
53. Everts PA, Knape JT, Weibrich G, et al. Platelet-rich plasma and platelet gel: a review. J Extra CorporTechnol. 2006;38(2):174-87.
54. Fanning J, Murrain L, Flora R, Hutchings T, Johnson JM, Fenton BW. Phase I/II prospective trial of autolo-gous platelet tissue graft in gynecologic surgery. Journal of Minimally Invasive Gynecology. 2007;14(5):633-7.
55. Ficarelli E, Bernuzzi G, Tognetti E, et al. Treatment of chronic venous leg ulcers by platelet gel. DermatolTher. 2008;21(suppl 1):S13-7.
56. Frechette JP, Martineau I, Gagnon G. Platelet-rich plasmas: growth factor content and roles in woundhealing. J Dent Res. 2005;84(5):434-9.
408
CARTER ET AL
57. Frykberg RG, Driver VR, Carman D, et al. Chronic wounds treated with a physiologically relevant concen-tration of platelet-rich plasma gel: a prospective case series. Ostomy Wound Manage. 2010;56(6):36-44.
58. Gottrup F, Apelqvist J, Price P. Outcomes in controlled and comparative studies on non-healing wounds:recommendations to improve the quality of evidence in wound management. J Wound Care. 2010;19(6):237-68.
59. Grant WP, Jerlin EA, Pietrzak WS, Tam HS. The utilization of autologous growth factors for the fa-cilitation of fusion in complex neuropathic fractures in the diabetic population. Clin Podiatr Med Surg.2005;22(4):561-84, vi.
60. Gunaydin S, McCusker K, Sari T, et al. Clinical impact and biomaterial evaluation of autologous plateletgel in cardiac surgery. Perfusion. 2008;23(3):179-86.
61. Gurgen M. Treatment of chronic wounds with autologous platelet-rich plasma. EWMA Journal. 2008;8(2):5-11.
62. Gurvich L. Synergism in using negative pressure wound therapy with alternated applications of autologousplatelet-derived growth factors in treating post-acute surgical wounds. Wounds A Compend Clin Res Pract.2009;21(5):134-40.
63. Kakagia DD, Kazakos KJ, Xarchas KC, et al. Synergistic action of protease-modulating matrix and au-tologous growth factors in healing of diabetic foot ulcers: a prospective randomized trial. J DiabetesComplications. 2007;21(6):387-91.
64. Klayman MH, Trowbridge CC, Stammers AH, Wolfgang GL, Zijerdi DA, Bitterly TJ. Autologous plateletconcentrate and vacuum-assisted closure device use in a nonhealing total knee replacement. J Extra CorporTechnol. 2006;38(1):44-47.
65. Lacci KM, Dardik A. Platelet-rich plasma: support for its use in wound healing. Yale J Biol Med.2010;83(1):1-9.
66. Langer A, Rogowski W. Systematic review of economic evaluations of human cell-derived wound careproducts for the treatment of venous leg and diabetic foot ulcers. BMC Health Serv Res. 2009;9:115.
67. McAleer JP, Kaplan E, Persich G. Efficacy of concentrated autologous platelet-derived growth factors inchronic lower-extremity wounds. J Am Podiatr Med Assoc. 2006;96(6):482-8.
68. O’Connell SM, Impeduglia T, Hessler K, Wang XJ, Carroll RJ, Dardik H. Autologous platelet-rich fibrinmatrix as cell therapy in the healing of chronic lower-extremity ulcers. Wound Repair Regen. 2008;16(6):749-56.
69. Pietramaggiori G, Kaipainen A, Czeczuga JM, Wagner CT, Orgill DP. Freeze-dried platelet-rich plasmashows beneficial healing properties in chronic wounds. Wound Repair Regen. 2006;14(5):573-80.
70. Roukis TS, Zgonis T, Tiernan B. Autologous platelet-rich plasma for wound and osseous healing: a reviewof the literature and commercially available products. Adv Ther. 2006;23(2):218-37.
71. Rozman P, Bolta Z. Use of platelet growth factors in treating wounds and soft-tissue injuries. Acta Derma-tovenerol Alp Panonica Adriat. 2007;16(4):156-65.
72. Scevola S, Nicoletti G, Brenta F, Isernia P, Maestri M, Faga A. Allogenic platelet gel in the treatment ofpressure sores: a pilot study. Int Wound J. 2010;7(3):184-90.
73. Schade VL, Roukis TS. Use of platelet-rich plasma with split-thickness skin grafts in the high-risk patient.Foot Ankle Spec. 2008;1(3):155-59.
74. Senet P, Bon FX, Benbunan M, et al. Randomized trial and local biological effect of autologous plateletsused as adjuvant therapy for chronic venous leg ulcers. J Vasc Surg. 2003;38(6):1342-8.
75. Senet P, Kellouche S, Benbunan M, Calvo F, Dosquet C. Letter to the editor regarding Borzini et al letter tothe editor regarding Randomized trial and local biological effect of autologous platelets used as adjuvanttherapy for chronic venous leg ulcers. J Vasc Surg. 2004;39(5):1146-7.
76. Smith SE, Roukis TS. Bone and wound healing augmentation with platelet-rich plasma. Clin Podiatr MedSurg. 2009;26(4):559-88.
77. Soomekh DJ. Current concepts for the use of platelet-rich plasma in the foot and ankle. Clin Podiatr MedSurg. 2011;28(1):155-70.
78. Stammers AH, Trowbridge CC, Marko M, et al. Autologous platelet gel: fad or savoir? Do we really know?J Extra Corpor Technol. 2009;41(4):P25-P30.
79. Steenvoorde P, van Doorn L, Naves C, Oskam J. Use of autologous platelet-rich fibrin on hard-to-healwounds. J Wound Care. 2008;17(2):60-3.
409
ePlasty VOLUME 11
80. van der Hagen SJ, Baeten CG, Soeters PB, van Gemert WG. Autologous platelet-derived growth factors(platelet-rich plasma) as an adjunct to mucosal advancement flap in high cryptoglandular perianal fistulae:a pilot study. Colorectal Dis. 2011;13(2):215-8.
81. Whitlow J, Shackelford A, Sievert A, Sistino J. Barriers to the acceptance and use of autologous plateletgel. Perfusion. 2008;23(5):283-9.
82. Yol S, Tekin A, Yilmaz H, et al. Effects of platelet rich plasma on colonic anastomosis. J Surg Res.2008;146(2):190-4.
83. Donohue K, Falanga V. Healing rate as a prognostic indicator of complete healing: a reappraisal. Wounds.2003;15(3):71-6.
84. Dougherty EJ. An evidence-based model comparing the cost-effectiveness of platelet-rich plasma gel to al-ternative therapies for patients with nonhealing diabetic foot ulcers. Adv Skin Wound Care. 2008;21(12):568-75.
85. Krull EA. Chronic cutaneous ulcerations and impaired healing in human skin. J Am Acad Dermatol.1985;12(2, pt 2):394-401.
410