623994

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FAIXXX10.1177/1071100715623994Foot & Ankle InternationalSanGiovanni and Kiebzak

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Prospective Randomized Evaluation of

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DOI: 10.1177/1071100715623994

Platelet-Rich Plasma on Surgical Site fai.sagepub.com

Infection or Delayed Wound Healing

Thomas P. SanGiovanni, MD1, and Gary M. Kiebzak, PhD1

Abstract
Background: Prevention of surgical site infections and the reduction of wound-related complication rates have become
increasingly emphasized by hospital task groups and government agencies given the degree of economic burden it places
on the health care system. Platelet-rich plasma (PRP) contains growth factors and other biomolecules that promote
endogenous microbicidal activity. We hypothesized that PRP would help prevent postoperative infection and delayed
wound healing (DWH).
Methods: We randomized patients having foot or ankle surgery to the treatment group receiving intraoperative PRP
(applied to operative field) and platelet-poor plasma at closing (PPP, on the sutured skin) or the control group (no PRP/
PPP). The incidence of deep surgical site infection and DWH (collectively called endpoints) was compared between groups
(n = 250/group). PRP had a mean 5.3-fold platelet concentration compared to whole blood, with concentrated white blood
cells. Mean age (±SD) of patients was 52 years (±15), 65% were women. Minor and major operative procedures were
included. Patients were followed for 60 days. Seventy controls had PRP prepared for assay of growth factors. Procedure
mix, ASA scores, mean operative times, and comorbidity mix were similar between groups.
Results: The primary result was no difference in number of endpoints between groups: 19 patients in the PRP group (7.6%)
versus 18 controls (7.2%). Endpoints were deep surgical site infections in 2 PRP/PPP patients and 1 control, and DWH in
17 PRP/PPP patients and 17 controls. Analysis of PRP samples revealed a large variation in growth factor concentrations
between patients.
Conclusions: Intraoperative application of PRP/PPP did not reduce the incidence of postoperative infection or DWH.
Growth factor profiles varied greatly between patients, suggesting that the potentially therapeutic treatment delivered was
not consistent from patient-to-patient.
Level of Evidence: Level I, prospective randomized trial.

Keywords: platelet-rich plasma, postoperative infection, delayed wound healing

Introduction not been fully appreciated. Various studies have demon-

Wound healing complications after foot and ankle surgery
are generally considered to be more common than for other
body parts. Elimination of skin flora from the forefoot is dif-
ficult as the foot provides a unique environment for growth
of numerous bacterial species. A postoperative foot infection
can result in serious complications.5,6,8,35,36 In addition to the
discomfort and social cost to the patient for potential time
lost from normal activities and work, the associated medical
costs due to extended hospital stay, readmission, clinic visits
for wound care, etc can be considerable.6 Patients with cer-
tain risk factors such as diabetes mellitus (DM), rheumatoid
arthritis (RA), or smoking are more prone to postoperative
wound healing complications than patients without a risk
factor.11,13,14,23,26,29,37 Other risk factors may exist that have
strated the partial effectiveness of operative preparation
solutions in limiting operative wound contamination and
preventing infection.4,27 However, it is generally agreed that
use of skin-preparation solutions alone is not a sufficient tac-
tic to avoid postoperative infection. Likewise, prophylactic
antibiotic administration has not been shown to be clearly
effective at reducing postoperative infection.35,38 Theoretically,
1
Miami Orthopedics and Sports Medicine Institute (founded by UHZ
Sports Medicine), Coral Gables, FL, USA
Corresponding Author:
Gary M. Kiebzak, PhD, Brooks Rehabilitation, 3901 University Blvd, Suite
103, Jacksonville, FL 32216, USA.
Email: gary.kiebzak@brooksrehab.org

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2 Foot & Ankle International 
application of growth factors to wounds should promote
wound healing, and although the concept has gained consid-
erable attention in recent years, study outcomes have not
been consistent and growth factor efficacy is still controver-
sial.2,20,21,30,33 An easy-to-access source of a large variety of
growth factors is autologous platelet-rich plasma (PRP).
Depending on the cell mix, PRP may also contain other bio-
molecules that directly or indirectly promote endogenous
microbicidal activity.3,9,19,25,34 Platelet-poor plasma (PPP)
may also be isolated from the PRP preparation, and when
applied to the skin over sutures, may further help in preven-
tion of infection by serving as physical barrier, like a fibrin
sealant material.18
Although to date there is a general lack of double-blind
randomized controlled studies evaluating the healing capa-
bilities of PRP, there are numerous case series and uncon-
trolled studies strongly suggesting a positive effect of PRP
in a variety of orthopedic conditions.2,15,20,21,24,28,30,33 Several
periodontal studies have shown efficacy of PRP treatment
in conjunction with an operative procedure.1,10 Although
not a consistent finding in all studies, some reports have
described a positive effect of PRP treatment on promoting
healing of cutaneous wounds.12,18,21,32
We hypothesized that increasing the localized concentra-
tion of growth factors via intraoperative application of PRP
and fibrin sealant capabilities of PPP would reduce rates of
postoperative infection and delayed wound healing seen in
foot and ankle procedures. Herein, we report the results of a
comparison of outcomes between patients receiving intra-
operative PRP/PPP and untreated controls.
Methods
Study Design and Cohort  losporin (ie, 2 g Ancef). Alternatively, clindamycin 600 to
We prospectively enrolled men and women aged 18 to 80
years of age who were scheduled for foot or ankle surgery
regardless of procedure (other than diagnostic arthroscopy
with no anticipated corrective procedure). All operative
procedures were performed by the same surgeon at a single
institution. The study was approved by the hospital’s insti-
tutional review board and all patients signed an informed
consent form. Patients were randomized to the group receiv-
ing intraoperative PRP/PPP or the control group not receiv-
ing PRP/PPP. A stratified adaptive randomization process
was used to balance the number and age of men and women
in each study group (PRP/PPP vs control) and the number
of patients with risk factors. Treatment assignment was
done using the random number tables in GraphPad
QuickCalcs (GraphPad Software, San Diego, CA). Patients
were blinded to the group in which they were randomized.
Postoperative exclusion criteria included patients with
active infection, immunosuppression, thrombocytopenia or
severe anemia with abnormal blood count profiles of
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hemoglobin levels <6.5 mmol/L, platelet count <100 × 109/L
(these data were sometimes not available immediately
before surgery when patients were often consented). In addi-
tion, minimally invasive procedures, ankle arthroscopies,
and minor hardware removal procedures or unexpected
short procedure times concluding with skin closure within
20 minutes of incision were excluded postoperatively.
A total of 515 patients were consented; 2 patients with-
drew consent prior to surgery, 2 patients were withdrawn
due to abnormal complete blood count (the PRP composi-
tion was not expected to be typical of the rest of the cohort),
4 patients canceled surgery after consenting, 7 patients were
dropped because their operative time was very short (<20
minutes) or had arthroscopy only, with no operative proce-
dure and met the postoperative exclusion criterion.
Enrollment continued until there was a final sample size of
250 in each study group, with 70 patients in the control
group having blood drawn and PRP prepared for later assay
of growth factors. The stratified adaptive randomization
process resulted in a similar mix of patients in each study
group, with no statistically significant differences in age,
sex, numbers of patients with known risk factors for wound
healing complications, ASA scores, operative times, and
overall procedure mix as summarized in Table 1.
Perioperative Procedures for Limiting Operative
Wound Contamination and Preventing Infection
Foot and ankle operative field preparation included initial
cleansing with alcohol followed by application of either
chloraprep or betadine scrub. Per the hospital’s protocol for
orthopedic procedures, patients were administered a single
dose of intravenous antibiotic with a first generation cepha-
900 mg was administered for patients reporting penicillin
allergy. At the time of wound closure, the operative field
was irrigated with normal saline containing combined baci-
tracin/polymyxin.
Blood Collection and Preparation of PRP/PPP
Following induction of anesthesia, 20 mL of whole blood
was drawn into a syringe from a vein in the cubital fossa
(separate from the vein used to deliver anesthetics) for prep-
aration of PRP. The Harvest SmartPrep II platelet concen-
trate system (Harvest Technologies Corporation, Plymouth,
MA) was used, which consisted of a microprocessor-con-
trolled centrifuge with automated decanting. This prepara-
tion purportedly produced a type A2 PRP, meaning activated
platelets were concentrated at least 5-fold compared to
whole blood, and the PRP contained concentrated white
blood cells.24 During processing, the 20 mL of anticoagu-
lated autologous whole blood was automatically separated
into red blood cells and plasma. The plasma and upper
SanGiovanni and Kiebzak 3

Table 1.  Entire Cohort Demographics, Procedure Mix and Case Severity.

Control With PRP for

Characteristic PRP/PPP (n = 250) Control (n = 250) Growth Factor Assay (n = 70)
Age (y), mean ± SD 52.8 ± 15.1 51.9 ± 16.6 52.9 ± 17.9
Age ≥60 y, % 39.2 36.4 37.1
Sex, n (%)
 Men 89 (36) 87 (35) 26 (37)
 Women 161 (64) 163 (65) 44 (63)
Preoperative platelet count, 103/uL 248 ± 57 246 ± 60 253 ± 63
Diabetes mellitus,a n (%) 15 (6.0) 14 (5.6) 8 (11.4)
Rheumatoid arthritis,a n (%) 9 (3.6) 11 (4.4) 3 (5.7)
Current smoker,a n (%) 12 (4.8) 12 (4.8) 6 (8.6)
Combinations of above, n (%) 4 DM + smoker (1.6) 2 DM + smoker (0.8) 1 (1.4)
  1 RA + smoker (0.4) DM + RA
  2 DM + RA (0.8)  
ASA scores, n (%)
 1 47 (18) 37 (15) 12 (17.4)
 2 167 (67) 168 (67) 45 (64.3)
 3 36 (15) 45 (18) 13 (18.6)
Mean operative time, min 119 ± 82 107 ± 62 98.0 ± 50
Procedure mix, n (%)
 Forefoot 106 (42.4) 102 (40.8) 33 (47)
 Midfoot 10 (4.0) 16 (6.4) 7 (10)
 Hindfoot 134 (53.6) 132 (52.8) 30 (43)
  Arthrodesis, any type 63 (25.2)b 42 (16.8)  
  Tendon or ligament repair/transfer 54 (21.6) 45 (18.0)  
 Bunionectomy 41 (16.4) 49 (19.6)  
  Fracture repair 26(10.4) 25 (10.0)  
  Hammertoe repair 10 (4.0) 15 (6.0)  
  Total ankle 11 (4.4) 8 (3.2)  

Abbreviations: ASA, American Society of Anesthesiologists; PRP, platelet-rich plasma; PPP, platelet-poor plasma; SD, standard deviation.
a
Diabetes mellitus (DM), rheumatoid arthritis (RA), smoker only.
b
The only statistically significant difference between study groups was for the number of cases of arthrodesis, with more cases of any type (not
weighted by complexity) in the PRP/PPP group compared to controls, P = .028.

portion of the buffy coat layer was decanted into a second
chamber of the centrifugal bowl. The platelets were then
separated from the plasma, producing PPP and unactivated
PRP. The double-barreled Harvest SmartJet Applicator in
pistol-like configuration was used to draw up the PPP or
PRP into one barrel and a thrombin/calcium chloride activa-
tor solution into the second barrel. PRP was sprayed within
the depths of the wound, PRP and PPP were applied to the
subcutaneous layer, and PPP applied to the surface skin
incisional layer. As the pistol applicator was depressed,
both PRP and activator solution were mixed and dispensed
simultaneously. Either an interrupted horizontal or vertical
mattress suture technique using 4-0 nylon was used for skin
closure. Incisions were dressed with a nonadhesive
Xeroform gauze.
Processing of PRP for Growth Factor Assay.  To assess the vari-
ability of growth factor concentrations between samples,
we assayed PRP for insulin-like growth factor 1 (IGF-1),
platelet-derived growth factor, isoform AB (PDGF-AB);
vascular endothelial growth factor, isoform A (VEGF-A);
and fibroblast growth factor (FGF). No particular criteria
were used to select these 4 growth factors other than their
assay, which was the most accessible to us.
Approximately 3 mL of unactivated PRP from control
patients was transferred from the vacutainer collection tube
to a polypropylene 15-mL tube and immediately processed
for growth factor assays. After gentle mixing, a small ali-
quot (approximately 0.5 mL) was used to perform a com-
plete blood count using an automated cell counter in the
hospital clinical chemistry laboratory. Concurrently, the
remainder of the PRP was transferred to an Eppendorf DNA
lo-bind 2.0 mL polypropylene tube and frozen at minus 30
°C until assayed. Prior to assay, the PRP was put through 3
freeze-thaw cycles to lyse the platelets and release growth
factors into the solution. After the third cycle, samples were
refrozen and shipped on dry-ice for assay at Cytonics
Corporation (Jupiter, FL).

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4 Foot & Ankle International 
Postoperative Follow-up
Standard follow-up protocol was followed consisting of the
first visit within 15 days after surgery, then additional visits
as required (all follow-up visits were standard of care; there
were no visits strictly for the purposes of this study).
Patients remained in the study for 60 days depending on
scheduling of appointments.
Study Endpoints (Outcome Variables)
DWH was defined as lack of primary healing of skin edges
(any degree) with wound secretion but without signs of
infection or necrosis 14 to 60 days after surgery.16 We
planned to include difficult-to-classify possible “superficial
infection” as being DWH with the rationale that even if a
true superficial infection, it would lead to DWH.
Postoperative deep surgical site infection occurring
within 30 days after surgery was defined as involving fas-
cial and muscle layers requiring intravenous antibiotics
with or without operative debridement.17 All deep infec-
tions were culture confirmed. The determination of the
presence of DWH and deep surgical site infection was made
by consensus of the research team consisting of the surgeon,
fellow, physician assistant, and sports medicine trainer.
Growth Factor Assays
Quantitative measurement of IGF-1 and PDGF-AB in PRP
was done using enzyme-linked immunosorbent assays
(ELISAs) using commercially available kits (R&D Systems,
Inc, Minneapolis, MN, and Sigma-Aldrich, St Louis, MO,
respectively). VEGF-A and FGF were quantified using a
multiplex immunoassay (Bio-Rad Laboratories, Berkeley,
CA). Individual protocols for the various growth factor
assays were strictly followed to ensure accuracy of the mea-
sured values.
Statistical Analyses
Based on a retrospective review of previous cases (encom-
passing the past 8 years prior to starting the study), we esti-
mated the combined incidence of endpoints to be 12.2%
without the intraoperative use of PRP/PPP. We hypothe-
sized that use of PRP/PPP would reduce endpoints by at
least 50% to 6.1%. However, because we suspected that the
current incidence of infection and DWH was actually lower
than in the past, we adjusted the endpoint incidence down-
ward 1% and rounded to an expected endpoint incidence of
5% when using PRP/PPP. We performed a proportion dif-
ference power analysis (using Interactive Statistics web
application, www.statpages.org) with power at 80%, alpha
= 0.05, and estimated sample size (to detect a proportional
difference between PRP/PPP and control groups of 0.072 or
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7.2%) to be 237 per group. We conservatively set a target of
n = 250 per group.
Descriptive statistics are presented to summarize patient
age, operative times, growth factor concentrations, etc.
Simple comparisons between 2 groups was done using
2-tailed unpaired t tests. Percentages (ratios) of patients in
each group with endpoints and other ratio comparisons
were analyzed using the Fisher exact test and relative risk
calculated. Correlation assuming Gaussian distributions
were done using the Pearson r test.
Significance was defined as P < .05. All statistics were
calculated using GraphPad InStat, version 3.00, for
Windows 95, GraphPad Software.
Results
Primary Outcome
Table 2 summarizes the occurrence of endpoints (infections
and DWH) in each of the 2 study groups. The number of com-
bined endpoints between groups was not statistically signifi-
cantly different: 19 patients in the PRP group (7.6%) versus
18 patients in controls (7.2%). There were 3 deep surgical site
infections, 2 in PRP/PPP group, and 1 in the control group.
DWH was documented in 17 patients in each study group.
Endpoint Details
DWH events were not graded or categorized by severity.
Most cases were very minor, consisting of small focal areas
<1 to 2 cm with dehiscence or serosanguineous discharge.
These were treated with topical antibiotics. The mean extra
visits to monitor the DWH was 2.2 ± 2.0 in both study
groups (range, 0 to 7 extra visits in both groups). Wound
vacuum-assisted closure (negative-pressure wound ther-
apy) was needed for 1 PRP/PPP and 2 control patients;
home care treatment for 2 PRP/PPP patients and 3 controls;
in-office minor debridement in 4 PRP/PPP patients and 3
controls. Of the 3 patients with deep surgical site infections,
2 required readmission to the hospital for debridement and
one had intravenous antibiotic treatment. Each infection
case required 8 extra visits to monitor healing. Each required
wound vacuum-assisted closure and home care treatment
until healing was documented.
Considering the possibility that more stringent criteria
for defining DWH would reveal a difference between treat-
ment groups, we subtracted out very minor DWH cases
(which comprised 18 of the 34 DWH cases, 53%) and tal-
lied only patients who required wound vacuum-assisted
closure, home-care treatment, or in-office minor debride-
ment, resulting in 7 DWH cases in the PRP/PPP group and
8 in the control group. Adding the deep surgical site infec-
tions brought the combined endpoint numbers in each group
to 9 (3.6% in each study group).
SanGiovanni and Kiebzak 5

Table 2.  Patients With Postoperative Infection or Delayed Wound Healing: Demographics, Procedure Mix, and Case Severity.

Characteristic PRP/PPP (n = 19) Control (n = 18)

Age (y), mean ± SD 58.9 ± 14.8 57.8 ± 14.2
Sex, n (%)
 Men  7 10
 Women 12  8
Preoperative platelet count, 103/uL 238 ± 84 246 ± 76
Diabetes mellitis,a n (%) 5 (26.3) 1 (5.6)
Rheumatoid arthritis,a n (%)  0 3 (16.7)
Current smoker,a n (%) 1 (5.6) 1 (5.6)
Combination of above, n (%)  0 1 RA + smoker (5.6)
ASA scores, n (%)
 1 2 (10.5)  0
 2 8 (42.1) 12 (66.7)
 3 9 (47.4) 6 (33.3)
Mean operative time, min 140 ± 56 135 ± 49
Procedure mix, n (%)
 Forefoot 7 (36.8) 7 (38.9)
 Midfoot  0 2 (11.1)
 Hindfoot 12 (63.2) 9 (50.0)
  Arthrodesis, any type 12 (63.1) 7 (44.4)
  Tendon or ligament repair/transfer 3 (15.8) 2 (10.5)
 Bunionectomy 2 (10.5) 5 (27.8)
  Fracture repair 1 (5.3) 0 
  Hammertoe repair 1 (5.3) 1(5.6)
  Total ankle  0 1 (5.6)
 Other  0 2 (11.1)

Abbreviations: ASA, American Society of Anesthesiologists; PRP, platelet-rich plasma; PPP, platelet-poor plasma; RA, rheumatoid arthritis; SD, standard
deviation.
a
Diabetes mellitus, rheumatoid arthritis, smoker only.

Characteristics of Endpoint Patients (Table 2)
Patients with endpoint events were significantly older than
patients without wound healing complications, 58.4 ± 14.3
versus 51.7± 15.8 years (P = .013), with 13 in the PRP/PPP
group and 8 in the control group being >60 years old. The
percentage of endpoint patients with ASA score 3 was sig-
nificantly greater compared to patients without endpoints,
41% versus 14.5% (Fisher exact test, P = .0002). The per-
centage of patients with endpoints who had known risk fac-
tors for wound complications (12 of 37 patients, 32.4%)
was significantly greater than the percentage of patients
with risk factors in the total cohort (minus those with end-
points; 75 of 463, 16.1%) (Fisher exact test, P = .022).
PRP Assessment
Seventy patients from the control group had blood collected
intraoperatively for the assessment of cell content and measure-
ment of growth factors. Six of the samples were used for valida-
tion tests, and in 3 patients, the platelets were clumped (verified
by histologic examination) and the samples were not usable for
measuring cell counts or growth factors. The mean age was 52
± 19 years (range, 19-78 years), with the group composed of 21
men and 44 women, of which 13 had DM or RA, and 4 were
smokers (one had diabetes and was a smoker). For the 61 sam-
ples used for assessment of cell content and growth factors, the
PRP had a mean increase in platelet concentration from whole
blood of 5.3-fold ± 1.4-fold (mean concentration, 1141 ± 349 ×
106/mL). However, the range was large, with the actual increase
varying from 2.8- to 7.4-fold (45 to- 1231 × 106/µL). Table 3
summarizes the cell composition of the PRP.
Table 4 summarizes the mean growth factor concentra-
tions in the PRP preparations. Large variation was seen in the
growth factor concentrations between patients (even after
adjusting for platelet count, data not shown). Cluster analyses
revealed no pattern of growth factor profiles that could be
associated with any demographic or outcome event. There
was no difference in mean growth factor concentrations com-
paring men to women, patients <60 years old to those >60
years old, patients with known risk factors (DM, RA, or
smoking) to those without risk factors, or patients with
wound healing complication endpoints to those without
wound healing complications (data not shown).

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6 Foot & Ankle International 

Table 3.  PRP Cell Composition.

White Red Blood Mean Neutrophils Lymphocytes Monocytes

Blood Cells, Cells, 106/ Platelet
  103/µL µL Hematocrit Volume 103/µL % 103/µL % 103/µL %
PRP 18.9 ± 7.0 4.5 ± 1.1 40.4 ± 8.5 10.2 ± 0.8 5.1 ± 2.7 27.3 ± 10.2 10.9 ± 4.5 56.8 ± 12.6 2.7 ± 0.4 14.1 ± 2.0
Fold change +3.1 +1.2 +1.1 0 +1.8 −2.2 +6.5 +1.9 +5.6 +1.8
from whole
blood

Abbreviation: PRP, platelet-rich plasma.

Table 4.  Growth Factor Concentrations in PRP.

IGF-1, ng/mL PDGF-AB, ng/mL FGF, pg/mL VEGF-A, pg/mL

Mean 69 62 21 75
SD 18 23 19 51
Minimum 39 20 0.7 10
Maximum 147 104 78 218
CV, % 26 37 99 68

Abbreviations: CV, coefficient of variation; FGF, fibroblast growth factor; IGF-1, insulin-like growth factor 1; PDGF-AB, platelet-derived growth factor,
isoform AB; PRP, platelet-rich plasma; SD, standard deviation; VEGF-A, vascular endothelial growth factor, isoform A.

There was no difference in PRP platelet count between
men and women or patients <60 years old to those >60
years old, although PRP platelet count was negatively cor-
related with age, r = −0.283 (P = .027), for the entire group
of patients who had growth factors measured. Concentrations
of PDGF-AB and IGF-1 were statistically significantly pos-
itively correlated with platelet count in the PRP preparation,
with correlation coefficients (r’s) of +0.789 (P < .0001) and
+0.277 (P = .031), respectively (for FGF, r = +0.249 which
was nearly significant with P = .053). Concentrations of
PDGF-AB and IGF-1 were negatively correlated with age,
with correlation coefficients (r’s) of −0.347 (P = .006) and
−0.520 (P < .0001), respectively, whereas concentrations of
FGF were positively correlated with age, r = +0.288 (P =
.024). Concentrations of PDGF-AB, FGF, and VEGF-A
were statistically significantly positively correlated with the
white blood cell count in the PRP preparation, with correla-
tion coefficients (r’s) of +0.344 (P = .007), +0.305 (P = .018),
and +0.256 (P = .048), respectively.
Discussion
In this randomized prospective study, we observed no ben-
eficial effect of a type A2 PRP preparation (activated plate-
lets concentrated >5 times and having concentrated white
blood cells) and PPP used intraoperatively to prevent post-
operative infection or DWH complications (the endpoints).
The explanation for the lack of effect of PRP/PPP is elusive
but may be related to the type of PRP used (ie, cell composi-
tion), timing of administration, or the concentration and
mix of growth factors and microbicidal agents achieved. It
is also possible that a beneficial effect of PRP/PPP is only
evident in a select (and as-yet undefined) subgroup of
patients, which would have been masked when studying a
heterogeneous cohort. Finally, the incidence of combined
wound healing complications was 7.4% (3.6%, considering
only higher-grade complications); it is possible that there is
simply a floor limit for the ability to minimize wound heal-
ing complications to a significantly lower level as there are
uncontrollable variables impacting the course of healing,
such as the unknown effect of concurrent medications and
comorbidities, and occasional lack of patient compliance
with wound care instructions.
The rationale for the use of autologous PRP/PPP is that
the platelets produce a variety of growth factors that are
essential for growth and repair of tissue (once applied to the
surgical site, the platelets become activated, alpha-granules
degranulate, and locally acting growth factors are
released).20,21,30 These growth factors aid healing in a variety
of ways such as by attracting undifferentiated cells to the
surgical site, promoting new capillary growth, accelerating
epithelialization, etc. However, perhaps most important in
the application we have described in this study (intraopera-
tive use of PRP to help prevent postoperative infection) is
that platelets and white blood cells directly and indirectly
promote the upregulation of endogenous microbicidal activ-
ity.3,9,19,25,34 Platelets can bind and internalize pathogens and
release microbicidal proteins that kill certain bacteria and
fungi.19 Neutrophils produce microbicidal hypochlorous
acid as well as secreting microbicidal proteins. An increas-
ing number of studies are reporting microbicidal activity of
PRP against bacteria such as Escherichia coli, Staphylococcus

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SanGiovanni and Kiebzak 7
aureus, and Cryptococcus neoformans.3,9,19,25,34 After clos-
ing the operative field, the application of PPP on the surface
of skin over the sutures theoretically serves to improve
hemostasis and to act as a physical barrier to provide addi-
tional protection against infection.
Although the above potential benefits of PRP/PPP are
well appreciated in addition to the low risk of adverse
events because the PRP preparation is autologous, there
may be substantial limitations to the practical application of
PRP in operative and clinical practice. Perhaps most impor-
tantly, we observed a striking inconsistency in the cell com-
position and growth factor concentrations in PRP from
patient to patient. First, the ability to concentrate the plate-
lets greater than 5-fold was variable. This obviously would
lead to large variation in growth factor concentrations
between patients because the growth factor concentrations
tended to be correlated with platelet count. This variability
may be explained to a degree by the patient’s baseline plate-
let count, or by partial clumping of platelets during PRP
preparation; we had 3 cases in which the platelets were
clumped and thus the PRP, if used as a treatment, would
likely not have had the full complement of platelets acti-
vated, thus limiting the expression of growth factors and
final concentration delivered to the wound surface. The
importance of the large variability in the growth factor con-
centrations observed is that the actual treatment delivered to
each patient was therefore unique, a fact that obviously has
ramifications on the overall effectiveness of PRP as a treat-
ment modality. Further, the optimal profile of growth fac-
tors (ie, the concentration of one growth factor in relation to
another) or the minimally effective concentrations needed
to promote tissue healing are not known. Though obviously
important considerations, these issues have in general been
poorly studied or even discussed when interpreting the
effectiveness (or lack thereof) of PRP treatments. Large
variability in the PRP preparation with large variability in
growth factor concentrations and profiles has been reported
by others and may partly explain the inconsistent reports in
the literature regarding PRP treatment efficacy.7,22,31
In this study, we carefully evaluated the final mix of pro-
cedures and patient characteristics in each study group. The
study groups were evenly matched overall with respect to
known risk factors, ASA scores, operative times, etc. Thus,
inequity in the characteristics of each study group (eg, many
more DM patients in one group than the other) could not have
biased the results. Although it perhaps would have been pref-
erable to have included only one type of procedure, that
would have been impractical given the sample size targets
needed to complete this study with adequate power. Further,
we believe that having only one type of procedure included
would have severely biased the generalizability of the study
results; the purpose of this study was to provide evidence that
use of PRP/PPP treatment for all patients would impact the
overall incidence of wound healing complications.
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Studies of low-occurring endpoints are difficult to exe-
cute because of the large sample sizes needed to achieve
adequate power to avoid type I or II statistical errors. The
total combined incidence of endpoints observed in this
study, 7.4%, was lower than expected when we calculated
the sample sizes needed when planning the study. Using the
actual observed incidence to calculate power would result
in much larger sample sizes needed per group. However,
given the equivalence of results with near identical numbers
of endpoints per group, we declared futility of effort and
terminated the study. Even if a marginal level of signifi-
cance was achieved favoring PRP/PPP treatment, the cost
effectiveness of treating a large number of patients to pre-
vent a small number of adverse events (mostly DWH)
would be suspect as the PRP/PPP treatment is expensive
and not reimbursed by insurance.
In conclusion, the results of our study showed that intra-
operative application of PRP and PPP did not reduce the
incidence of postoperative infection or DWH, and that
growth factor profiles varied greatly between patients, sug-
gesting that the potentially therapeutic treatment delivered
was not consistent from patient to patient. It remains possi-
ble that future study could identify a select subgroup of
patients who could benefit from PRP/PPP treatment or that
another type of PRP or treatment regimen (eg, multiple
doses) could be effective.
Acknowledgments
We thank the patients who volunteered to participate in this study,
the nursing staff in the Doctors Hospital Ambulatory unit who
were graciously supportive as we spoke with and consented
patients prior to surgery, and especially Yvette Hernandez, CCRP,
for her work enrolling study participants and maintaining study
documentation.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.
Funding
The author(s) disclosed receipt of the following financial support
for the research, authorship, and/or publication of this article: This
study was supported by the Doctors Hospital Foundation, Baptist
Health South Florida.
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