PLATELET RICH PLASMA

FOR TREATMENT OF
OSTEOARTHRITIS (AN
UPDATE)

HEALTH TECHNOLOGY ASSESSMENT SECTION

MEDICAL DEVELOPMENT DIVISION
MINISTRY OF HEALTH MALAYSIA
005/2017

i
DISCLAIMER
Technology review is a brief report, prepared on an urgent basis, which draws on
restricted reviews from analysis of pertinent literature, on expert opinion and / or
regulatory status where appropriate. It has been subjected to an external review
process. While effort has been made to do so, this document may not fully reflect all
scientific research available. Additionally, other relevant scientific findings may have
been reported since completion of this review.

Please contact: [email protected], if you would like further information.

Health Technology Assessment Section (MaHTAS),

Medical Development Division
Ministry of Health Malaysia
Level 4, Block E1, Precinct 1
Government Office Complex
62590 Putrajaya

Tel: 603 88831229

Fax: 603 8883 1230

Available at the following website: http://www.moh.gov.my

ii
Authors:

Dr. Izzuna Mudla binti Mohamed Ghazali

Public Health Physician
Senior Principal Assistant Director
Health Technology Assessment Section (MaHTAS)
Medical Development Division
Ministry of Health Malaysia

Reviewed by:
Dr. Junainah Sabirin
Public Health Physician
Deputy Director
Health Technology Assessment Section (MaHTAS)
Medical Development Division
Ministry of Health Malaysia

External Reviewer:
Dato‟ Sri Dr. Premchandran a/l P.S. Menon
Head, Orthopaedic Service, Ministry of Health Malaysia
Senior Consultant Orthopaedic Surgeon and Head of Department,
Orthopaedic Department
Hospital Tengku Ampuan Afzan,
Kuantan, Pahang

DISCLOSURE

The authors of this report have no competing interests in this subject and the
preparation of this report is totally funded by the Ministry of Health, Malaysia.

iii
EXECUTIVE SUMMARY

Introduction
Osteoarthritis(OA) is the most common articular disease globally and a leading
cause of pain and chronic disability. In the past decade, there has been increasing
interest in the use of autologous growth factors such as intra-articular platelet rich
plasma (PRP) for treatment of OA. The regenerative effect and anti-inflammatory
potential of PRP in the tissue healing process has led to extensive investigation of
PRP as a potential treatment for a variety of musculoskeletal disorders including OA.

Objective/aim
To update evidence on the efficacy, safety and cost -effectiveness of platelet rich
plasma for the treatment of osteoarthritis.

Results and conclusions

Twelve studies were included in this review. Four of the studies were systematic
reviews with meta-analysis, four systematic reviews (SR), three randomised
controlled trials (RCT) which were not included in any of the systematic reviews and
one retrospective cohort study conducted in Malaysia.

There was a reasonable amount of retrievable evidence on intraarticular PRP

treatment for OA. However, most of the studies have high risk of bias and varies in
terms of the PRP preparation and treatment frequency. The longest outcome data
available were only for 12 months.

The short term evidence consistently showed that there were no major adverse
events related to intraarticular PRP treatment for OA and there was no significant
differences in the risk of adverse events between PRP and control groups (RR, 1.40
[95% CI: 0.80, 2.45], I2 = 59%, p = 0.24). Nevertheless, minor adverse events which
were self resolved such as pain, swelling and stiffness did occur.

As for efficacy, the evidence showed that PRP significantly reduced pain in patients
with OA at six and twelve months when compared to placebo or HA. However, there
was no significant difference in pain reduction when compared to corticosteroid.
Platelet rich plasma was also shown to improve physical functions at six to twelve
months.

Methods
Literature was searched through electronic databases which included MEDLINE,
Cohrane Library via Ovid, EMBASE, PubMed and general databases such as
Google Scholar.

The search strategy used these terms either singly or in various combinations:
Platelet rich plasma, growth factors, thrombocytes rich plasma, autologous platelet
rich plasma, autologous conditioned plasma, osteoarthritis, degenerative joint
disease and osteoarthritis.

The search was limited to studies published from 2013 to current. The last search
was conducted on 3 April 2017.

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PLATELET RICH PLASMA FOR TREATMENT OF OSTEOARTHRITIS (AN UPDATE)

1. INTRODUCTION

Osteoarthritis (OA) refers to a clinical syndrome of joint pain accompanied by varying

degrees of functional limitation and reduced quality of life. It is the most common
articular disease globally and a leading cause of pain and chronic disability.1, 2 The
economic costs of OA are high, including those related to treatment, for individuals
and their families who must adapt their lives to the disease, and those due to lost
work productivity.1

The prevalence of OA increases with age and generally affects women more
frequently than men. Most of the OA disability burden is attributable to the hips and
knees.2 In the Community Oriented Program for the Control of Rheumatic Diseases
(COPCORD) study involving 2594 people in Malaysia, 14.4% complained of pain in
the joints and/or musculoskeletal pain and 11.6% had low back pain. The knee was
responsible for 64.8% of all complaints pertaining to the joints, and more than half
those examined with knee pain had clinical evidence of OA.3

The management of OA involves a multidisciplinary approach with the aim to relieve

symptoms and improve joint function. It involves nonpharmacological and
pharmacological treatment. Nonpharmacological treatment includes education,
lifestyle modification, physiotherapy, occupational therapy and orthoses.
Pharmacological treatment includes oral analgesics, topical treatments and intra-
articular injections.3

In the past decade, there has been increasing interest in the use of autologous
growth factors such as intra-articular platelet rich plasma (PRP) for treatment of OA.
The regenerative effect and anti-inflammatory potential of PRP in the tissue healing
process has led to extensive investigation of PRP as a potential treatment for a
variety of musculoskeletal disorders including OA.4

A technology review was conducted in 2013 on PRP for OA. However, there was
insufficient good level of evidence on the effectiveness of PRP for OA retrievable at
that time. This review was requested by the Deputy Director of MaHTAS to update
the evidence on PRP for OA as there were many queries from the government as
well as private sector on its effectiveness, safety and cost-effectiveness.
Furthermore, there were quite a number of studies published since the last review.

2. OBJECTIVE/AIM

To update evidence on the efficacy, safety and cost-effectiveness of PRP for the
treatment of OA.

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3. TECHNICAL FEATURES

Platelet rich plasma is defined as a volume of autologous plasma that has platelet
concentration above baseline values.5 The platelet concentrations in PRP are usually
four to five times of the baseline (1.5 – 4.5 x 105/L). Autogenous platelet gel,
platelet enriched plasma (PeRP) and platelet-rich concentrate (PRC) are the
synonyms of PRP.6

Autologous PRP was first used in 1987 by Ferrari et al. following open heart surgery.5
Since then, PRP has been used in sports medicine, orthopaedics, dentistry,
dermatology, ophthalmology, plastic, cardiothoracic and maxillofacial surgery.

Platelets have several components that may help to augment healing. Dense
granules within the platelets have compounds that influence cell migration, cell
proliferation and vascular tone. Platelet alpha granules contain and release
numerous growth factors, including hepatocyte growth factor (HGF), vascular
endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), epidermal
growth factor (EGF) and transforming growth factor beta (TGF-β).5, 6 Platelet-derived
growth factor (PDGF) and EGF are present in tendons during tendon healing process
whereas TGF-β has been shown to increase type 1 and type III collagen production
in tendon sheath cells, epitenon cells and endotenon cells.5

PRP injections are prepared from the patient‟s own blood with strict aseptic
technique. There are various methods for PRP preparation and more than 25 ready
to use kits are commercially available.6 Generally PRP can be prepared in two ways
namely “single-spinning” and “double-spinning”. Filardo et al. used double-spinning
method where the first spinning at 1480rpm for six minutes to separate erythrocytes
and the second spinning at 3400rpm for 15 minutes to concentrate platelets. 2
Double-spinning method was also used in several other studies. 7-9 Smith et al. used
single spinning method where a volume of 15 ml blood was drawn into a double
syringe system for a single spinning at 1500 rpm for 5 minutes. The PRP was
procured by pulling back on the secondary syringe to remove the leucocyte-poor
PRP layer, leaving the lower leucocyte-rich red blood cell pack behind.10 After
spinning and extraction, the activated platelets are injected into the abnormal tissue
releasing growth factors that recruit and increase the proliferation of reparative cells.
Single spinning procedure is illustrated in Figure 1 below.

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 Figure 1. Illustration of PRP preparation

4. METHODS

4.1. Searching

These scientific databases were searched such as;

 MEDLINE(R) In-process and other Non-Indexed Citations and Ovid
MEDLINE(R) 1946 to present
 Embase 1988 to 2017 Week 14
 EBM Reviews - Cochrane Central Register of Controlled Trials- December
2016
 EBM Reviews – Database of Abstracts of Review of Effects (4rd Quarter
2016)
 EBM Reviews - Cochrane Database of Systematic Reviews - 2005 to
December 2016
 EBM Reviews - Health Technology Assessment - 4th Quarter 2016
 NHS Economic Evaluation Database - 4th Quarter 2016
 PubMed

Other database or websites as below were also searched

 EuroScan
 INAHTA
 US FDA

General databases such as Google and Google Scholar were also searched. Animal
studies were excluded.

The search strategy used these terms either singly or in various combinations:
Platelet rich plasma, thrombocytes rich plasma, autologous platelet rich plasma,

3
autologous conditioned plasma, osteoarthritis, degenerative joint disease and
osteoarthritis.

The search was limited to studies published from 2013 to current. The last search
was conducted on 3 April 2017.

Appendix 1 showed the detailed search strategies.

4.2. Selection

A reviewer screened the titles and abstracts against the inclusion and exclusion
criteria and then evaluated the selected full text articles for final article selection.

The inclusion and exclusion criteria were:

Table 1. Inclusion and exclusion criteria

Inclusion criteria
Population Patients with osteoarthritis
Interventions Platelet rich plasma, autologous conditioned plasma
Comparators Hyaluronic acid, placebo, corticosteroids
Outcomes Reduction in pain, improvement in joint function, cartilage
regeneration, quality of life, cost effectiveness
Study design Systematic reviews, randomised controlled trials,
comparative studies
Exclusion criteria
Study design Animal studies

Indications PRP used for other indications, and osteoarthritis of

temporomandibular joint

Relevant articles were critically appraised using Critical Appraisal Skills Programme
(CASP) and evidence graded according to the US / Canadian Preventive Services
Task Force (see Appendix 2). Risk of bias of RCTs was assessed using Cochrane
Risk of Bias Assessment Tool.

Data were extracted and summarised in evidence table (see Appendix 4). The data
were not pooled and only qualitative analysis was carried out.

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 5. RESULTS AND DISCUSSION

Search Results

The search strategy yielded 366 titles. After removing duplicates (n=37), reviewing
the titles and abstracts, 61 full text articles were retrieved. Another 14 articles were
excluded as listed in Appendix 5.

Thirteen articles were used in Background and Technical Features sections,

whereas twelve articles were included in the Results.

Number of records identified

Number of additional records
through electronic databases
identified from other sources (n=3)
searching (n=361)

Number of records after duplicates removed (n=329)

Number of records Number of records

screened (n=329) excluded (n=268)

Number of full-text Number of full-text

articles assessed articles excluded
for eligibility (n=61) (n=36) with
reasons:
- Study was already included
in systematic review and
meta-analysis (n=27)
- Irrelevant study design
(n=6)
- Irrelevant
indication/intervention (n=3)
Number of full-text articles included
in qualitative synthesis (n=12)

Articles used in Introduction and

Technical Features (n=13)

Figure 2. Flow chart of study selection

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Characteristics of included studies

Study Design
Twelve studies were included in this review. Four of the studies were systematic
review with meta-analysis, four systematic reviews (SR), three randomised controlled
trials (RCT) which were not included in any of the systematic reviews and one
retrospective cohort study conducted in Malaysia. The SR and meta-analysis were
overlapping and the studies included in the reviews were tabulated in Table 1. The
excluded studies were listed in Appendix 4.

Participants
All the studies included adult patients with OA of the knee only, except SR by Tietze
et al. which included one study on hip osteoarthritis and a RCT by Dallari et al. which
studied patients with hip OA.

Intervention
All the studies included intrarticular injection of PRP. The preparation method of the
PRP varied. Some of the studies used single spinning, some used double spinning
and few studies used triple spinning. The administration of PRP also varied in terms
of frequency and treatment interval.

Comparators
The comparator used in the studies included hyaluronic acid (HA), normal saline,
corticosteroid, placebo or different PRP preparation.

Outcome measure

a. The Western Ontario and McMaster Universities Osteoarthritis Index

(WOMAC) was the most frequently used outcome score. The Index is self-
administered and has been validated in various languages. The WOMAC
consists of 24 items divided into 3 subscales:11

 Pain (5 items): during walking, using stairs, in bed, sitting or lying,

and standing
 Stiffness (2 items): after first waking and later in the day
 Physical Function (17 items): stair use, rising from sitting, standing,
bending, walking, getting in / out of a car, shopping, putting on /
taking off socks, rising from bed, lying in bed, getting in / out of bath,
sitting, getting on / off toilet, heavy household duties, light household
duties

The WOMAC is available in 5-point Likert-type and 100mm Visual Analog

format. The Likert Scale version uses the following descriptors for all items:
none, mild moderate, severe, and extreme. These correspond to an ordinal
scale of 0-4. The 100mm Visual Analog version uses anchors of no
pain/stiffness/difficulty and extreme pain/stiffness/difficulty. 11

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 On the Likert Scale version, the scores are summed for items in each
subscale, with possible ranges as follows: pain=0-20, stiffness=0-8, physical
function=0-68. On the Visual Analog version, a ruler is used to measure the
distance (in mm) from the left end marker to the patient's mark. For each item,
the possible range of scores is therefore 0-100. Items are summed for each
subscale, resulting in possible ranges as follows: pain=0-500, stiffness=0-200,
physical function=0-1700. Most commonly, a total WOMAC score is created
by summing the items for all three subscales.11

b. The KOOS questionnaire was developed in the 1990s as an instrument to

assess the patient‟s opinion about their knee and associated problems. KOOS
is patient-administered and consists of five subscales; pain, other symptoms,
function in daily living (ADL), function in sport and recreation and knee related
Quality of life (QOL). The previous week is the time period considered when
answering the questions. Standardised answer options are given (5 Likert
boxes) and each question is assigned a score from 0 to 4. A normalized score
(100 indicating no symptoms and 0 indicating extreme symptoms) is calculated
for each subscale.12

c. The International Knee Documentation Committee (IKDC) Subjective Knee

Form is a patient-oriented questionnaire that assesses symptoms and function
in daily living activities. The instrument contains 18 selected items designed to
measure symptoms assess pain, stiffness, swelling, joint locking, and joint
instability, while other items designed to measure knee function assess the
ability to perform activities of daily living. Response types include 5-point Likert
scales, 11-point Likert scales, and dichotomous „„yes” or “no‟‟ responses.13

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Table 2. Studies included in systematic reviews on platelet rich plasma for treatment of
osteoarthritis.
Primary studies Systematic Reviews
included Shen Dai Lai Meheux Khoshbin Laudy Tietze TR
20174 201714 201515 201616 201317 201518 201419 2013
Randomised Controlled Trials
Li 2011   
Filardo 2012      
Sanchez 2012     
Cerza 2012     
Patel 2013      
Vaquerizo 2013    
Raeissadat 2015   
Gormeli 2015  
Filardo 2015  
Duymus 2016  
Smith 2016  
Paterson 2016  
Forogh 2016 
Montanez- 
Heredia 2016
Non-randomised Controlled Trials
Kon 2011      
Spakova 2012      
Filardo 2011   
Say 2013 
Comparative Observational Studies
Sanchez 2008  
Case series
Kon 2010   
Sampson 2010   
Gobbi 2012  
Gobbi 2011 
Jang 2012 
Sanchez 2012 
Napolatino 2012  
Wang 2011  

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Risk of bias assessment

All the SR with meta-analysis reported the risk of bias of the included studies. Shen
et al. reported, four studies achieved a moderate risk of bias, while the rest 10
obtained a high risk of bias.4 As for Dai et al., among the 10 studies included, two
studies were judged to be at low risk of bias, whereas eight studies were found to
have a high risk of bias.14. In Laudy et al. meta-analysis, all randomised and non-
randomised trials obtained a high risk of bias except Sánchez‟s et al. trial which
achieved a moderate risk of bias.18 Khosbin et al. included RCTs that obtained
Detsky score of 75% or more, and observational studies (prospective cohort and
case control studies) that achieved seven or greater score of the Newcastle-Ottawa
Scale (NOS).17

All the SR, did not report the risk of bias or quality assessment of the included
studies.

We used Cochrane Risk of Bias Assessment tool to assess the risk of bias of the
RCTs included in this review.20 Table 3 showed the summary of the result of risk of
bias assessment.

Table 3. Summary of risk of bias assessment of RCT included in this review.

concealment

Selective reporting (reporting

Blinding of participants and

data
Random sequence generation

personnel (performance bias)

outcome
(selection bias)

(selection bias)

(attrition bias)
Incomplete

Other bias
Allocation

bias)

Dallari 2016
+ ? + + + +

Lana 2016
+ ? + + + +

Jubert 2017
+ ? + + + +
Key: Low High Uncertain
+ risk - risk ? risk of
bias

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5.1. Safety

In our review in 2013, there was no major complications reported in the included
studies.21

A systematic review and meta-analysis by Shen et al. included 14 RCTs where a

total of 10 studies recorded adverse events. Excluding the study by Filardo et al.,
which reported adverse events in a different form, there was no statistically significant
difference in the number of patients with adverse events between PRP and HA
among the rest nine studies (RR, 1.40 [95% CI: 0.80, 2.45], I2 = 59%, p = 0.24). All
adverse events were non-specific such as pain, stiffness, syncope, dizziness,
headache, nausea, gastritis, sweating, and tachycardia. No severe complications
were recorded and all the events were self-resolved in days. 4 Filardo et al. reported
no major adverse events noted in the PRP group in their study. Platelet rich plasma
produced more post-injection swelling and pain compared to HA. However, they were
self-limiting and lasted for a few days.2 level I

Dai et al. in their meta-analysis compared the risk of adverse events in PRP versus
HA. Among the 10 studies, four studies provided the relevant data. The pooled
analysis showed that there was no significant difference between PRP and HA group
(RR 0.63, 95% CI: 0.20,1.98). Heterogeneity was significant in the pooled result (I2 =
66%).14 level I

Dallari et al. reported no complications related to the infiltrations were observed

during treatment and the follow-up period in a RCT among patients with hip
osteoarthritis , except for a transient pain reaction observed in 13 patients in the
PRP-HA group which spontaneously resolved within the treatment period.22 level I

Lana et al. in an RCT involving 105 patients found that all the patients reported mild
adverse reaction in the form of knee swelling 3-5 days after the application. 23 level I

In another RCT conducted by Jubert et al., no patient had adverse effects at injection
or follow-up. No differences were found in the use of painkillers and non-steroidal
anti-inflammatories or dose or frequency between groups at any time point.8 level I

Platelet rich plasma P was classified as biologics. However, as it was produced from
patients‟ own blood and minimally manipulated, it was not regulated by FDA.
Nevertheless, the devices used to prepare PRP were regulated and many of these
devices received FDA approval.24 level I

In summary, the evidence consistently showed that there were no major adverse
events related to intraarticular PRP treatment for OA and there was no significant
differences in the risk of adverse events between PRP and control groups.
Nevertheless, minor adverse events which were self resolved such as pain, swelling
and stiffness did occur.

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5.2 Efficacy

In our technology review report in 2013, we included two SR, two RCT, three non-
RCT, and one retrospective cohort study. We concluded that there was an
insufficient, but a good level of evidence to support the effectiveness of PRP for the
treatment of OA and the longest outcome data was 24 months. The evidence showed
that PRP may be beneficial for young patients with early OA and not overweight or
obese.21 level I

Pain Reduction

Shen et al. included 14 RCTs in their SR and meta-analysis. At three months, three
studies reported WOMAC pain subscores, and a statistically significant difference
was found in favour of PRP treatment compared with control (mean difference (MD)
−3.69 [95% CI: −6.87, −0.51], I2 = 94%, p = 0.02). At six months, the synthesis of five
studies demonstrated a statistically significant difference in favour of PRP treatment
(MD, −3. 82 [95% CI: −6.40, −1.25], I2 = 96%, p = 0.004). At 12 months, the pooled
results of four studies still favoured PRP treatment (MD, −3.76 [95% CI: −5.36,
−2.16], I2 = 86%, p < 0.001). In this study the control was not specified and included
various types of HA, saline or corticosteroids. Significant heterogeneity was observed
in the pooled results.4 level I

Dai et al. in their meta-analysis compared PRP and HA treatment. At six months, a
total of three studies (339 participants) provided relevant data on the WOMAC pain
score. The pooled analysis showed that there was no significant difference between
the PRP and HA groups (MD -1.54, 95% CI: -4.27, 1.20). Heterogeneity was
significant in the pooled result (I2= 96%). At 12 months, a total of three studies (302
participants) provided relevant data on the WOMAC pain score. The pooled analysis
showed that PRP was significantly more efficacious in pain relief compared with HA
(MD -2.83, 95% CI: -4.26, -1.39), with significant heterogeneity (I2 = 79%). For the
WOMAC pain score at six and 12 months, the overall effect sizes exceeded the
mean clinically important differences (MCID) which was set at 20% based on
previous work (-0.83 for WOMAC pain score at six months and -0.79 at 12 months).
The CI values suggested that the smallest treatment effect exceeded the MCID for
the WOMAC pain score at 12 months, whereas for WOMAC pain score at six months
the CI values encompassed the MCID.14 level I

Laudy et al. in their meta-analysis evaluated the efficacy of PRP in comparison to

placebo and HA. Only one study compared PRP with placebo. They reported, Patel
et al. detected a statistically significant difference on a 0–10 cm VAS in favour of the
single PRP injection and the two PRP injections compared with saline at six months
postinjection (MD −2.45; 95% CI: −2.92, −1.98; MD −2.07; 95% CI: −2.59, −1.55).
The improvement at six weeks, three and six months, was greater in the single spin
and double spin procedure compared to placebo (p<0.001) as assessed by WOMAC.
A statistically significant difference was detected in favour of the single PRP injection

11
and the two PRP injections compared with saline. RR was 8.40 (95% CI: 2.19, 32.24;
p=0.002), and 7.82 (95% CI: 2.02, 30.20; p=0.003) respectively. When compared to
HA, moderate evidence (≥75% of the studies had consistent findings, but displayed a
high risk of bias) showed PRP injections reduced pain significantly more than HA
injections.18 level I

Khoshbin et al. in their meta-analysis reported pain as measured by Visual Analog

Scale (VAS). At 24 weeks, there was no statistically significant difference in VAS
scores between the treatment (PRP) and control (HA and NS) groups (2 studies [198
patients]; MD, 0.46 [95% CI: -0.52, 1.43]; p=0.36). A random-effects model was used
(I2 =88%, p = 0.004). A separate analysis using data with LMW HA (as opposed to
HMW HA) in the study by Kon et al. did not result in a change in the observed results
(MD, 0.47 [95% CI: -0.53 , 1.48]; p = 0.36).17 level I

Lana et al. conducted an RCT involving 105 patients with mild to moderate knee OA.
Three days after the treatment, based on VAS, HA groups continued with significant
more pain than the other groups.(HA-PRP, p=0.0034; HA+PRP-PRP, p=0.0113). At
90 days, groups treated with PRP alone or in combination showed significantly less
pain than HA according to VAS score, HA -3 (-6,0), PRP -6.0 (-8,1), HA+PRP -6 (-9,-
1), HA vs. PRP p=0.0001, HA vs. HA+PRP p=0.0000, PRP vs. HA+PRP p=0.1795.
There was no significant difference in WOMAC pain score. At 180 days, significantly
less pain was observed in the groups treated with PRP alone (median change -5 (-9,-
1) vs. HA -3 (-7.4) p=0.0001) or in combination -5 (-9,-1), p=0.0000). At 360 days,
groups treated with PRP alone -5 (-9,-1) or in combination -5 (-9,-1) (p=0.0000)
showed significantly less pain in comparison to HA -2 (-7,2) according to VAS. 23 level I

Jubert et al. conducted an RCT which included 65 patients with symptomatic knee
OA (Kellgren-Lawrence grade 3 to 4), in waiting list for knee arthroplasty. One group
(n= 34) was given single leukocyte-reduced PRP prepared using a double-spin
methodology and another group was given intra-articular corticosteroid. The mean
VAS score decreased for both groups at different time points with no significant
differences between groups, at one month (PRP 35.88 ± SD 24.63, control 31.67 ±
22.14, p=0.50) , three months (PRP 33.38 ± 22.59, Control 41.00 ± 26.95, p=0.22)
and six months (PRP 38.24 ± 24.80, control 46.33 ± 29.88, p=0.29) follow-up.8 level I

The evidence showed that PRP significantly reduced pain in patients with OA at six
and twelve months when compared to placebo or HA. However, there was no
significant difference in pain reduction when compared to corticosteroid.

Physical function

Shen et al. pooled the results of three studies which reported WOMAC physical
function subscores at three months, and a statistically significant difference was
found in favour of PRP treatment compared with control (MD, −14.24 [95% CI:
−23.43, −5.05], I2 = 91%, p = 0.002). Platelet rich plasma treatment was also found to
improve physical function significantly according to the pooled analysis of five studies

12
at six months (MD, −13.51 [95% CI, −23.77, −3.26], I2 = 97%, p = 0.01) and four
studies at 12 months (MD, −13.96 [95% CI: −18.64, −9.28], I2 =84%, p < 0.001).4 level I

Dai et al. compared PRP with HA. At six months, a total of three studies (339
participants) provided relevant data on the WOMAC function score. The pooled
analysis showed that there was no significant difference between PRP and HA
groups (MD -4.39, 95% CI: -10.51, 1.74). Heterogeneity was significant in the pooled
result (I2= 87%). At 12 months, the pooled analysis of three studies (302 participants)
showed that PRP was significantly more efficacious in functional improvement
compared with HA (MD: -12.53, 95% CI: -14.58, -10.47), with moderate
heterogeneity (I2 = 31%). For the WOMAC function score at six and twelve months,
the overall effect sizes exceeded the MCID (-2.74 for WOMAC function score at six
months and -2.85 at 12 months). The CI values suggest that the smallest treatment
effect exceeded the MCID for the WOMAC function score at 12 months, whereas for
WOMAC function score at six months the CI values encompassed the MCID.14 level I

Laudy et al. in their meta-analysis reported that Vaquerizo et al. found a statistically
significant difference between PRP and HA in the number of patients reporting a 50%
decrease in the WOMAC physical function score at both six months and 48 weeks
postinjection (RR 3.80; 95% CI: 1.54, 9.35 and RR 27.20; 95% CI: 1.68, 441.24,
respectively). This trial also detected a statistically significant difference in favour of
PRP for the WOMAC physical function (0–68 Likert) at 6 months and 48 weeks
postinjection (MD −16.50; 95% CI: −22.20, −10.80, and MD −17.00; 95% CI: −22.35,
−11.65, respectively). No statistically significant differences between PRP and HA
were detected on the normalised WOMAC physical subscale (0–100) at six months
post injection in Sánchez et al. trial (MD −1.10;95% CI: −6.00, 3.80). Significant
heterogeneity was seen when pooling the data (SMD −0.41; 95% CI −0.65, −0.17; p
= 0.001, I2=94%). Function, assessed with the WOMAC total score (0–96 Likert),
showed a statistically significant difference in favour of PRP compared,with HA at
three months (pooled SMD −0.93; 95% CI −1.27, −0.59) and six months (pooled
SMD −0.81; 95% CI: −1.02, −0.61). Significant heterogeneity was observed (I²=86%
and I²=94%, respectively). At 48 weeks postinjection, the Vaquerizo et al. trial also
showed a statistically significant difference using the WOMAC total score (0–96
Likert; SMD −1.34; 95% CI −1.80, −0.88). Regarding the non-randomised trials,
Spaková et al. assessed function with the WOMAC total score at three and six
months postinjection. A statistically significant difference in favour of PRP was found
at both postinjection follow-up periods (MD −11.82; 95% CI −17.51, −6.13 and MD
−12.05; 95% CI −17.55, −6.55).18 level I

In an RCT conducted by Lana et al., at 30 days, significant improvement on WOMAC

physical subscale was observed in the group treated with HA+PRP when compared
to the other groups with a median change of -650(-1125,-75) in the HA+PRP group
compared to -362.5(-1075,200) in the HA group, p=0.001; and -375(-1050,275) in
the PRP group p=0.0004. At 90 days, improvement in WOMAC physical was
observed in the group HA+PRP when compared with other groups (HA -512.5(-
1225,500) vs HA+PRP -725(-1225,-25), p=0.0052; PRP -550(-1150,25) vs HA+PRP -

13
725(-1225,-25), p=0.0110). At 180 days, an improvement in the WOMAC physical
was observed only for the group HA+PRP in comparison with HA (p=0.0262).
Groups treated with PRP either alone or in combination showed a significant
improvement in WOMAC physical in comparison to HA -450(-1350,375) (HA+PRP -
825(-1325,-300) vs HA, p=0.0001; PRP-775(-1300,0) vs HA, p=0.0089) at 360
days.23 level I

In summary, although there were variations in the studies, the evidence consistently
showed PRP improved physical function of patients with OA at six and twelve
months.

Total Score

Shen et al. reported at three months, the pooled result of six studies on total WOMAC
scores showed a statistically significant difference in favour of PRP treatment
compared with control (MD,−14.53 [95% CI: −21.97, −7.09], I2 = 90%, p < 0.001).
PRP treatment was also found to improve total WOMAC scores significantly
according to the pooled analysis of eight studies at six months (MD, −18.21 [95% CI:
−27.84, −8.59], I2 = 97%, p < 0.001) and four studies at 12 months (MD, −19.45 [95%
CI: −26.09, −12.82], I2 = 85%, p < 0.001).4 level I

Dai et al. in their meta-analysis found at six months, four studies (459 participants)
provided relevant data on the WOMAC total score, two studies (261 participants)
provided relevant data on the IKDC score, and two studies (272 participants)
provided relevant data on the Lequesne score. The pooled analysis showed that
there was no significant difference between PRP and HA group (SMD 0.68, 95% CI:
-0.04, 1.41, I2=95%). A separate analysis using data with one PRP injection in the
study by Gormeli et al. did not result in a change in the observed results (SMD 0.43,
95% CI: -0.18, 1.04). At 12 months, three studies (302 participants) provided relevant
data on the WOMAC total score, one study (183 participants) provided relevant data
on the IKDC score, and one study (96 participants) provided relevant data on the
Lequesne score. The pooled analysis showed that PRP was associated with
significantly better outcome compared with HA (SMD 1.05, 95% CI: 0.21, 1.89, I2 =
94%).14 level I

Khoshbin et al. in their meta-analysis reported at 24 weeks, the MD in overall

WOMAC score between the treatment (PRP) and control (HA and NS) groups
favoured PRP (four studies [318 patients];MD, -18.03 [95% CI: -27.75, -8.30]; p <
0.001). There was significant heterogeneity in the data (I2 = 89%, p < 0.001). As for
the overall IKDC score at 24 weeks, the MD between the treatment (PRP) and
control (HA) groups favoured PRP (three studies [289 patients]; MD, 7.90 [95%CI:
3.72, 12.08]; p = 0.004). There was no significant statistical heterogeneity (I2= 44%, p
=0.17). A separate analysis using data with LMW HA (as opposed to HMW HA) in the
study by Kon et al. did not result in a change in the observed results (MD,8.40 [95%
CI, 2.72, 14.07]; P= 0.004).17 level I

14
Meheux et al. included six studies in their systematic review. They found, PRP
significantly improved validated patient-reported outcomes, according to WOMAC
and IKDC scores, in patients with OA of the knee at six and twelve months post
injection. According to 2-proportion z-tests, the average pretreatment WOMAC
scores for PRP and HA were 52.36 and 52.05, respectively (p = 0.420), among
studies that compared both treatments. At 12 to 26 weeks, the average WOMAC
scores for PRP and HA treatments were 28.5 and 43.4, (P=0 .0008) favouring PRP
over HA. At 26 to 52 weeks, the average WOMAC scores for PRP and HA treatments
were 22.8 and 38.1, (p=0.0062) favouring PRP over HA. All post-PRP time points up
to 12 months were significantly better than pre-PRP in WOMAC score.16 level I

Tietze et al. conducted a systematic review which included 13 studies (one RCT, two
NRCT, one cohort and nine case series). The results was not pooled. All studies
showed statistically significant improvement in patient outcome scores with PRP.
PRP has statistically significant benefit in knee OA when compared with HA. The
benefit of PRP appears to last between six and 12 months. Younger patients with
less of a disease burden tend to have the most improvement.19 level I

Dallari et al. in their RCT involving 111 patients with hip OA conducted multivariate
generalized linear model repeated measures which showed significant improvement
in VAS, HHS and WOMAC scores during the time. At two-months, PRP group
showed higher values in terms of the WOMAC score (mean 73;95% CI: 68,78) and
lower values in VAS score (mean 23; 95% CI: 16,29) compared with HA (mean
WOMAC: 59 (95% CI: 53,65); mean VAS 38 (95% CI: 30,46) and PRP+HA (mean
WOMAC: 59 (95% CI: 52,64), mean VAS: 35(95% CI: 26,45). At the six-months
follow-up, similar trend was observed, PRP group had higher values in terms of the
WOMAC score (mean, 72; 95% CI, 67, 76) and lower values in terms of the VAS
score (mean, 21; 95% CI, 15, 28) compared with the HA (mean WOMAC: 59 [95%
CI, 54, 65], mean VAS: 44 [95% CI, 36, 52;]) and PRP+HA (mean WOMAC: 59 [95%
CI, 54,66], mean VAS: 35 [95% CI: 26,45]) groups. At 12 months follow up, there
was no significant difference in the WOMAC score among groups maintaining a
meaningful trend only for the VAS score: PRP (mean 24; 95% CI: 17, 30) versus HA
(mean 42; 95% CI: 34,50) and PRP+HA (mean 38; 95% CI: 28,47).22 level I

Jubert et al. in their RCT comparing PRP and corticosteroid found KOOS Quality of
Life scores between baseline, three and six months increased significantly more in
the PRP than in the control group ( mean 17.77 versus 4.91 at three months and
16.88 versus 3.56 at six months; p=0.05 and 0.03 respectively). The improvement in
SF-36 general health perception score between baseline and six months was greater
in the PRP group than in the control group (4.25 vs -4.92; p=0.018)..8 level I

Saturveithan et al. conducted a retrospective study among 64 patients with Grade III
and IV primary knee OA based on Kellgren Lawrence classification who received 4
ml high molecular weight HA with concentration of 22 mg/ml alone or with
combination of PRP. At two months post injection, the IKDC score for HA group was
7.0 (SD 7.8), HA + PRP 16.3 (SD 11.9). Mean Diff (95% CI): -9.3 (-13.2, -5.4). At six

15
months post injection HA 12.1 (SD 8.2), HA + PRP : 24.3 (SD 13.7) with mean
difference of -12.1 (95% CI: -16.6, -7.7).25 level II-2

For WOMAC total score, PRP showed better outcome when compared to HA at 12
months. The results were not consistent at six months or earlier.

Patient Satisfaction

Khosbin et al. in their review, reported at 24 weeks, there was no difference in patient
satisfaction between PRP treatment and the control (HA and NS) groups (2 studies
[198 patients]; OR, 8.97 [95% CI 0.54, 149.25]). Heterogeneity assessment I2 = 90%,
p=0 .002, and a random effects model was used. A separate analysis using data with
LMW HA (as opposed to HMW HA) in the study by Kon et al. did not result in a
change in the observed results (OR, 9.35 [95% CI: 0.62, 142.1]).17 level I

Jubert et al. in their study found no significant difference in satisfaction between

groups.8 level I

5.3 Cost-effectiveness

There was no retrievable evidence on cost-effectiveness of PRP. The fee per session
of treatment ranged from USD 500 to USD 1200. 26

5.4 Limitations

There were several limitations in this review. The selection of the studies was done
by one reviewer and checked by another reviewer. Although there was no restriction
in language during the search but finally, only English full text articles were included
in this report. None of the studies reported long term outcome.

6. CONCLUSION

There was a reasonable amount of retrievable evidence of intraarticular PRP

treatment for OA. However, most of the studies have a high risk of bias and varies in
terms of the PRP preparation and treatment frequency. The longest outcome data
available were only for 12 months.

The short term evidence consistently showed that there were no major adverse
events related to intraarticular PRP treatment for OA and there was no significant
differences in the risk of adverse events between PRP and control groups.
Nevertheless, minor adverse events which were self resolved such as pain, swelling
and stiffness did occur.

Compared to HA and placebo, intraarticular PRP showed better outcome in pain

reduction and functional improvement in patients with OA.

16
7. REFERENCES

1. Plotnikoff R, Karunamuni N, Lytvyak E et al. Osteoarthritis prevalence and

modifiable factors: a population study. BMC Public Health. 2015;15(1):1195.

2. Filardo G, Di Matteo B, Di Martino A et al. Platelet-Rich Plasma Intra-articular

Knee Injections Show No Superiority Versus Viscosupplementation: A
Randomized Controlled Trial. Am J Sports Med. 2015;43(7):1575-1582.

3. Guidelines Development Group. Management of Osteoarthritis. Putrajaya:

Ministry of Health Malaysia, 2013.

4. Shen L, Yuan T, Chen S et al. The temporal effect of platelet-rich plasma on

pain and physical function in the treatment of knee osteoarthritis: systematic
review and meta-analysis of randomized controlled trials. J Orthop Surg Res.
2017;12(1)

5. Malanga GA, Goldin M. PRP: review of the current evidence for

musculoskeletal conditions. Curr Phys Med Rehabil Rep. 2014;2(1):1-15.

6. Dhillon MS, Patel S, John R. PRP in OA knee-update, current confusions and

future options. SICOT-J. 2017;3(27):6 pgs.

7. Montañez-Heredia E, Irízar S, Huertas P et al. Intra-Articular Injections of

Platelet-Rich Plasma versus Hyaluronic Acid in the Treatment of Osteoarthritic
Knee Pain: A Randomized Clinical Trial in the Context of the Spanish National
Health Care System. Int J Mol Sci. 2016;17(7):1064.

8. Joshi Jubert N, Rodríguez L, Reverté-Vinaixa MM et al. Platelet-Rich Plasma

Injections for Advanced Knee Osteoarthritis: A Prospective, Randomized,
Double-Blinded Clinical Trial. Orthop J Sports Med.
2017;5(2):2325967116689386.

9. Paterson KL, Nicholls M, Bennell KL et al. Intra-articular injection of photo-

activated platelet-rich plasma in patients with knee osteoarthritis: a double-
blind, randomized controlled pilot study. BMC Musculoskelet Disord.
2016;17:67.

10. Smith PA. Intra-articular Autologous Conditioned Plasma Injections Provide

Safe and Efficacious Treatment for Knee Osteoarthritis: An FDA-Sanctioned,
Randomized, Double-blind, Placebo-controlled Clinical Trial. Am J Sports Med.
2016;44(4):884-891.

11. American College of Rheumatology. Western Ontario and McMaster

Universities Osteoarthritis Index (WOMAC) c2015 [cited 2017 22 March ];
Available from: https://www.rheumatology.org/I-Am-

17
 A/Rheumatologist/Research/Clinician-Researchers/Western-Ontario-
McMaster-Universities-Osteoarthritis-Index-WOMAC.

12. Roos E. What is the KOOS? c2016 [cited 2017 22 March]; Available from:
http://www.koos.nu/.

13. Higgins LD, Taylor MK, Park D et al. Reliability and validity of the International
Knee Documentation Committee (IKDC) Subjective Knee Form. Joint Bone
Spine. 2007;74(6):594-599.

14. Dai W-L, Zhou A-G, Zhang H et al. Efficacy of Platelet-Rich Plasma in the
Treatment of Knee Osteoarthritis: A Meta-analysis of Randomized Controlled
Trials. Arthroscopy. 2017;33(3):659-670.e651.

15. Lai LP, Stitik TP, Foye PM et al. Use of Platelet-Rich Plasma in Intra-Articular
Knee Injections for Osteoarthritis: A Systematic Review. Pm & R.
2015;7(6):637-648.

16. Meheux CJ, McCulloch PC, Lintner DM et al. Efficacy of Intra-articular Platelet-
Rich Plasma Injections in Knee Osteoarthritis: A Systematic Review.
Arthroscopy. 2016;32(3):495-505.

17. Khoshbin A, Leroux T, Wasserstein D et al. The efficacy of platelet-rich plasma

in the treatment of symptomatic knee osteoarthritis: a systematic review with
quantitative synthesis. Arthroscopy. 2013;29(12):2037-2048.

18. Laudy ABM, Bakker EWP, Rekers M et al. Efficacy of platelet-rich plasma
injections in osteoarthritis of the knee: a systematic review and meta-analysis.
Br J Sports Med. 2015;49(10):657-672.

19. Tietze DC, Geissler K, Borchers J. The effects of platelet-rich plasma in the
treatment of large-joint osteoarthritis: a systematic review. Physician &
Sportsmedicine. 2014;42(2):27-37.

20. Higgins JPT, Altman DG, Gøtzsche PC et al. The Cochrane Collaboration‟s
tool for assessing risk of bias in randomised trials. BMJ. 2011;343(d5928)

21. Izzuna MMG, Thye SL, Rugayah Bakri. Platelet-rich plasma for treatment of
osteoarthritis. Putrajaya: Ministry of Health Malaysia, 2013.

22. Dallari D, Stagni C, Rani N et al. Ultrasound-Guided Injection of Platelet-Rich

Plasma and Hyaluronic Acid, Separately and in Combination, for Hip
Osteoarthritis: A Randomized Controlled Study. Am J Sports Med.
2016;44(3):664-671.

23. Lana JFSD, Weglein A, Sampson SE et al. Randomized controlled trial

comparing hyaluronic acid, platelet-rich plasma and the combination of both in

18
 the treatment of mild and moderate osteoarthritis of the knee. J Stem Cells
Regen Med. 2016;12(2):69-78.

24. Beitzel K, Allen D, Apostolakos J et al. US Definitions, Current Use, and FDA
Stance on Use of Platelet-Rich Plasma in Sports Medicine. J Knee Surg.
2015;28(01):029-034.

25. Saturveithan C, Premganesh G, Fakhrizzaki S et al. Intra-articular Hyaluronic

Acid (HA) and Platelet Rich Plasma (PRP) injection versus Hyaluronic acid
(HA) injection alone in Patients with Grade III and IV Knee Osteoarthritis (OA):
A Retrospective Study on Functional Outcome. Malays Orthop J.
2016;10(2):35-40.

26. Aschwanden C. Platelet-rich plasma treatment is popular for sports injuries,

whether it works or not. The Washington Post. 2014.

19
9. APPENDIX

9.1. Appendix 1: LITERATURE SEARCH STRATEGY

Ovid MEDLINE® In-process & other Non-Indexed citations and OvidMEDLINE®

1948 to present

1. Platelet-Rich Plasma/
2. Platelet rich plasma.tw.
3. Platelet-rich plasma.tw.
4. autologous conditioned plasma.tw.
5. thrombocytes rich plasma.tw
6. 1 or 2 or 3 or 4 or 5
7. Osteoarthritis/th [Therapy]
8. osteoarthritis.tw.
9. degenerative disease$.tw
10. 7 or 8 or 9
11. 6 AND 10

OTHER DATABASES
EBM Reviews - Cochrane Same MeSH, keywords, limits used as per MEDLINE
Central Register of search
Controlled Trials
EBM Reviews - Database
of Abstracts of Review of
Effects
EBM Reviews - Cochrane
Database of Systematic
Reviews
EBM Reviews - Health
Technology Assessment
PubMed

NHS Economic
Evaluation Database
INAHTA
FDA
Horizon Scanning
Database
Others

20
9.2. Appendix 2

HIERARCHY OF EVIDENCE FOR EFFECTIVENESS STUDIES

DESIGNATION OF LEVELS OF EVIDENCE

I Evidence obtained from at least one properly designed randomised controlled

trial.

II-I Evidence obtained from well-designed controlled trials without

randomisation.

II-2 Evidence obtained from well-designed cohort or case-control analytic studies,

preferably from more than one centre or research group.

II-3 Evidence obtained from multiple time series with or without the intervention.
Dramatic results in uncontrolled experiments (such as the results of the
introduction of penicillin treatment in the 1940s) could also be regarded as this
type of evidence.

III Opinions or respected authorities, based on clinical experience; descriptive

studies and case reports; or reports of expert committees.

SOURCE: US/CANADIAN PREVENTIVE SERVICES TASK FORCE (Harris 2001)

21
9.3 Appendix 3

Abbreviation

BMI Body Mass Index

HA Hyaluronic Acid
ICRS International Cartilage Research Society Visual
Assessment Scale
KOOS knee injury and osteoarthritis outcome score
IKDC International Knee Documentation Committee
MRI Magnetic Resonance Imaging
MSC Mesenchymal stem cell
PBPC Peripheral Blood Progenitor Cell
PBSC Peripheral Blood Stem Cell
PRGF Platelet Rich in Growth Factors
PRP Platelet Rich Plasma
RCT Randomised Controlled Trial
US FDA United States of America Food and Drug Administration
VAS Visual Analogue Scale
WOMAC Western Ontario and McMaster Universities Arthritis
Index

22
9.4 Appendix 4
EVIDENCE TABLE : SAFETY AND EFFECTIVENESS
QUESTION : IS PLATELET RICH PLASMA SAFE AND EFFECTIVE FOR OSTEOARTHRITIS TREATMENT?

Bibliographic Study type LE Num. of pts and Intervention Comparison Follow Outcome measures General
citation and methods Pt up comments
characteristics
1.Shen L, Yuan Sytematic I Fourteen RCTs PRP HA Minim Total WOMAC scores Four
T, Chen S et al. Review and comprising 1423 Placebo um of At 3 months, 6 studies reported total WOMAC studies
The temporal meta-analysis participants Ozone 12 scores and a statistically significant difference achieved a
effect of platelet- aged 18 years or weeks was found in favor of PRP treatment compared moderate
rich plasma on older with with control (MD,−14.53 [95% CI, −21.97 to risk of bias,
2
pain and symptomatic −7.09], I = 90%, p < 0.001). PRP treatment was while the
physical function knee OA and also found to improve total WOMAC scores rest 10
in the treatment had a minimum significantly according to the pooling analysis of obtained a
of knee follow-up of 12 8 studies at 6 months (MD, −18.21 [95% high risk of
2
osteoarthritis: weeks were CI,−27.84 to −8.59], I = 97%, p < 0.001) and 4 bias
systematic included. All studies at 12 months (MD, −19.45 [95% CI,
2
review and studies had to −26.09 to −12.82], I = 85%, p < 0.001)
meta-analysis of include at least 1
randomized control group Knee Pain
controlled trials. treated by intra- At 3 months, 3 studies reported WOMAC pain
Journal of articular agents subscores,and a statistically significant
Orthopaedic other than PRP. difference was found in favor of PRP treatment
Surgery and The studies that compared with control (MD, −3.69 [95% CI,
2
Research. PRP was used in −6.87 to −0.51], I = 94%,p = 0.02).
2017;12(1) combination with At 6 months, the synthesis of 5 studies
operations were demonstrated a statistically significant difference
excluded. in favor of PRP treatment (MD, −3.82 [95% CI,
−6.40 to −1.25], I2 = 96%, p = 0.004).
Li 2011 At 12 months, the pooling results of 4 studies
Sanchez 2012 still favoured PRP treatment (MD, −3.76 [95%
2
Cerza 2012 CI, −5.36 to −2.16], I = 86%, p < 0.001)
Patel 2013
Vaquerizo 2013 Physical function
Raeissadat 2015 At 3 months, 3 studies reported WOMAC
Gormeli 2015 physical function subscores, and a statistically
Filardo 2015 significant difference was found in favor of PRP
Duymus 2016 treatment compared with control (MD, −14.24
Smith 2016 [95% CI, −23.43 to −5.05], I2 = 91%,p = 0.002).
Paterson 2016 PRP treatment was also found to improve
Forogh 2016 physical function significantly according to the
Montanez- pooling analysis of 5 studies at 6 months (MD,

23
Bibliographic Study type LE Num. of pts and Intervention Comparison Follow Outcome measures General
citation and methods Pt up comments
characteristics
2
Heredia 2016 −13.51 [95% CI, −23.77 to −3.26], I = 97%, p =
Spakova 2012 0.01) and 4 studies at 12 months (MD, −13.96
2
[95% CI, −18.64 to −9.28], I =84%, p < 0.001)

Adverse events
A total of 10 studies recorded adverse events.
Excluding the study by Filardo et al., which
reported adverse events in a different form,
there was no statistically significant difference in
the number of patients with adverse events
between PRP and HA among the rest 9 studies
2
(RR, 1.40 [95% CI,0.80, 2.45], I = 59%, p =
0.24).
All adverse events were non-specific, the
symptoms including pain, stiffness, syncope,
dizziness, headache, nausea, gastritis,
sweating, and tachycardia. No severe
complications were recorded and all the events
were self-resolved in days.

24
EVIDENCE TABLE : SAFETY AND EFFECTIVENESS
QUESTION : IS PLATELET RICH PLASMA SAFE AND EFFECTIVE FOR OSTEOARTHRITIS TREATMENT?

Bibliographic Study type LE Num. of pts and Intervention Comparison Follow Outcome measures General
citation and methods Pt up comments
characteristics
2. Dai W-L, Systematic I 10 RCTs Intra-articular Intra- Minimu WOMAC Pain Score (PRP vs HA) Among the
Zhou A-G, Review and (n=1069) PRP articular HA, m of 12 At 6 months, a total of 3 studies (339 10 studies,
Zhang H et al. meta-analysis saline, weeks participants) provided relevant data on the 2 studies
Efficacy of Li 2011 Corticosteroi WOMAC pain score. The pooled analysis were
Platelet-Rich Sanchez 2012 d, exercise showed that there was no significant difference judged to
Plasma in the Cerza 2012 or no between the PRP and HA groups (MD -1.54, be at low
Treatment of Patel 2013 treatment 95% CI -4.27 to 1.20, P = 0 .27). Heterogeneity risk of bias,
2
Knee Vaquerizo 2013 was significant in the pooled result (I = 96%). whereas 8
Osteoarthritis: A Raeissadat 2015 At 12 months, a total of 3 studies (302 studies
Meta-analysis of Gormeli 2015 participants) provided relevant data on the were found
Randomized Filardo 2015 WOMAC pain score. The pooled analysis to have a
Controlled Duymus 2016 showed that PRP was significantly more high risk of
Trials. Smith 2016 efficacious in pain relief compared with HA (MD bias
Arthroscopy: Paterson 2016 -2.83, 95% CI -4.26 to -1.39, P .0001), with
2
The Journal of Forogh 2016 significant heterogeneity (I = 79%). Last search
Arthroscopic & Montanez- For the WOMAC pain score at 6 and 12 April 2016
Related Heredia 2016 months, the
Surgery. Spakova 2012 overall effect sizes exceeded the MCID (-0.83
2017;33(3):659- for
670.e651. Patients WOMAC pain score at 6 months and -0.79 at
diagnosed with 12 months). CI values suggest that the smallest
knee OA based treatment effect exceeded the MCID for the
on the criteria WOMAC pain score at 12 months, whereas for
described by the WOMAC pain score at 6 months the CI values
American encompassed the MCID.
College of
Rheumatology WOMAC Function Score (PRP vs HA)
At 6 months, a total of 3 studies (339
participants)
provided relevant data on the WOMAC function
score. The pooled analysis showed that there
was
no significant difference between PRP and HA
groups
(MD -4.39, 95% CI -10.51 to 1.74, P= .16).
Heterogeneity was significant in the pooled
result
2
(I = 87%).
At 12 months, a total of 3 studies (302

25
Bibliographic Study type LE Num. of pts and Intervention Comparison Follow Outcome measures General
citation and methods Pt up comments
characteristics
participants) provided relevant data on the
WOMAC function score. The pooled analysis
showed that PRP was significantly more
efficacious in functional improvement compared
with HA (MD: -12.53, 95%
CI: -14.58 to -10.47, P < .00001), with moderate
2
heterogeneity (I = 31%).

For the WOMAC function score at 6 and 12

months,
the overall effect sizes exceeded the MCID (-
2.74 for
WOMAC function score at 6 months and -2.85
at
12 months). CI values suggest that the smallest
treatment effect exceeded the MCID for the
WOMAC
function score at 12 months, whereas for
WOMAC
function score at 6 months the CI values
encompassed the MCID.

WOMAC Total Score, IKDC Score, and

Lequesne
Score (PRP vs HA)
At 6 months, 4 studies (459 participants)
provided relevant data on the WOMAC total
score, 2 studies (261 participants) provided
relevant data on the IKDC score, and 2 studies
(272 participants) provided relevant data on the
Lequesne score.
The pooled analysis showed that there was no
significant difference between PRP and HA
group (SMD 0.68, 95% C: 0.04, 1.41, P = 0.06,
2
I =95%). A separate analysis using data with 1
PRP injection in the study by Gormeli et al did
not result in a change in the observed results
(SMD 0.43, 95% CI: 0.18, 1.04, P=0.17).
At 12 months, 3 studies (302 participants)
provided relevant data on the WOMAC total
score, 1
study (183 participants) provided relevant data

26
Bibliographic Study type LE Num. of pts and Intervention Comparison Follow Outcome measures General
citation and methods Pt up comments
characteristics
on the
IKDC score, and 1 study (96 participants)
provided
relevant data on the Lequesne score. The
pooled analysis showed that PRP was
associated with significantly better outcome
compared with HA (SMD 1.05, 95% CI: 0.21,
1.89, P= 0.01). Again heterogeneity was
2
significant in the pooled result (I = 94%).

Adverse Events (PRP vs HA)

Among the 10 studies, 4 studies compared the
risk of adverse events in PRP versus HA. The
pooled analysis showed that there was no
significant difference between PRP and HA
group (RR 0.63, 95% CI: 0.20,1.98, P= 0.43,).
Heterogeneity was significant in the pooled
2
result (I = 66%).

27
EVIDENCE TABLE : SAFETY AND EFFECTIVENESS
QUESTION : IS PLATELET RICH PLASMA SAFE AND EFFECTIVE FOR OSTEOARTHRITIS TREATMENT?

Bibliographic Study type LE Num. of pts and Intervention Comparison Follow Outcome measures General
citation and methods Pt up comments
characteristics
3. Laudy ABM, Meta-analysis I Patients PRP Placebo (one The PRP versus placebo All randomised
Bakker EWP, Of RCT n (>18 years) study) total Patel et al detected a statistically and non-
Rekers M et al. NRCT diagnosed with (5 of 10 follow- significant difference on a 0–10 randomised trials
Efficacy of monolateral or studies used Hyaluronic up of cm VAS in favour of the single obtained a
platelet-rich bilateral OA of the single spin Acid (8 seven PRP injection and the two PRP high risk of bias
plasma knee based on the procedure, studies) trials injections compared with saline except Sánchez‟s
injections in criteria described whereas 3 was 6 at 6 months postinjection et al trial which
osteoarthritis of by the ACR, studies months (MD −2.45; 95% CI: −2.92, achieved a
the knee: a Altman et al‟s reported and −1.98; p <0.00001, MD −2.07; moderate risk of
systematic classification double spin that of 95% CI: −2.59, −1.55; p bias,
review and criteria and procedure. three <0.00001). As for both pain and
meta-analysis. clinical and One study trials physical function, as assessed
British Journal radiological compared both had a by WOMAC, the improvement at
of Sports information. The techniques duratio 6 weeks, 3 and 6 months, was
Medicine. mean number of and another n of greater in the single spin and
2015;49(10):657 patients study used 12 double spin procedure
-672. randomised was three spinning months compared to placebo (p<0.001).
102 and ranged technique)
from 30 to 176. A statistically significant
difference was detected in
10 studies favour of the single PRP
included injection and the two PRP
(6 RCT) injections compared with saline.
PRP-Placebo – RR was 8.40 (95% CI: 2.19,
Patel S 2013 32.24; p=0.002), RR was 7.82
PRP-HA – (95% CI: 2.02, 30.20; p=0.003).
Vaquerizo V 2013
Cerza F 2012 PRP vs HA
Sanchez M 2012 Moderate evidence (≥75% of the
Li M 2011 studies had consistent findings
Filardo G 2012 but displayed a high risk of bias)
is available that PRP injections
4 NRCT reduce pain significantly more
Say F 2013 than do HA injections.
Spakova T 2012
Kon E 2011 Regarding physical function,
Filardo G 2012 Vaquerizo et al reported a
statistically significant difference
between PRP and HA in the

28
Bibliographic Study type LE Num. of pts and Intervention Comparison Follow Outcome measures General
citation and methods Pt up comments
characteristics
number of patients reporting a
50% decrease in the WOMAC
physical function score at both 6
months and 48 weeks
postinjection
(RR 3.80; 95% CI: 1.54, 9.35;
p=0.004 and RR 27.20; 95% CI:
1.68, 441.24; p=0.02,
respectively). This trial also
detected a statistically significant
difference in favour of PRP for
the WOMAC physical function
(0–68 Likert) at 6 months and 48
weeks postinjection (MD −16.50;
95% CI: −22.20, −10.80; p
<0.00001, MD −17.00; 95% CI:
−22.35 to −11.65; p <0.00001,
respectively). No statistically
significant differences between
PRP and HA were detected on
the normalised WOMAC
physical subscale (0–100) at 6
months post injection in
Sánchez et al‟s trial (MD
−1.10;95% CI: −6.00, 3.80; p=
0.66). Pooled data (SMD −0.41;
95% CI −0.65, −0.17; p = 0.001,
2
I =94%).

Function, assessed with the

WOMAC total score (0–96
Likert), showed a statistically
significant difference in favour of
PRP compared,with HA at 3
months (pooled SMD −0.93;
95% CI −1.27, −0.59; p=
0.00001) and 6 months (pooled
SMD −0.81; 95% CI: −1.02,
−0.61; p<0.00001)
Heterogeneity: (I²=86% and
I²=94%, respectively)

29
EVIDENCE TABLE : SAFETY AND EFFECTIVENESS
QUESTION : IS PLATELET RICH PLASMA SAFE AND EFFECTIVE FOR OSTEOARTHRITIS TREATMENT?

Bibliographic Study type LE Num. of pts and Intervention Comparison Follow Outcome measures General
citation and methods Pt up comments
characteristics
4. Meheux CJ, Systematic 1 6 RCTsincluded Autologous PRP HA Minimu PRP significantly improved Data was
McCulloch PC, Review PRP-Placebo – vixcosupplement m of 6 validated patient-reported not pooled
Lintner DM et al. Patel S 2013 ation, months outcomes, according to Search
Efficacy of Intra- PRP-HA – corticosteroid, WOMAC and IKDC scores, in conducted
articular Vaquerizo V placebo, or other patients with OA of the knee at on 12
Platelet-Rich 2013 intraarticular 6 and 12 months postinjection. February
Plasma Cerza F 2012 injections PRP was also shown to be 2015
Injections in Sanchez M 2012 better than HA at improving
Knee Li M 2011 patient outcomes such as pain,
Osteoarthritis: A Filardo G 2012 physical function, and stiffness.
Systematic According to 2-proportion z-
Review. (739 patients, tests, the average pretreatment
Arthroscopy. 817 knees) WOMAC scores for PRP and
2016;32(3):495- HA were 52.36 and 52.05,
505 respectively (P=0 .420), among
studies that compared both
treatments. At 12 to 26 weeks,
the average WOMAC scores for
PRP and HA treatments were
28.5 and 43.4, (P=0 .0008)
favouring PRP over HA. At 26
to 52 weeks, the average
WOMAC scores for PRP and
HA treatments were 22.8 and
38.1, (P=0.0062) favouring PRP
over HA. All post-PRP time
points up to 12 months were
significantly better than pre-
PRP in WOMAC score

30
EVIDENCE TABLE : SAFETY AND EFFECTIVENESS
QUESTION : IS PLATELET RICH PLASMA SAFE AND EFFECTIVE FOR OSTEOARTHRITIS TREATMENT?

Bibliographic Study type LE Num. of pts and Intervention Comparison Follow Outcome measures General
citation and methods Pt up comments
characteristics
5. Khoshbin A, Systematic I 6 studies were Intra-articular HA or placebo Minimu WOMAC score Last search
Leroux T, Review and included Platelet-rich (normal saline) m of 24 At 24 weeks, the MD in overall ~week 6
Wasserstein D Meta-analysis plasma months WOMAC score between the 2013
et al. The of RCT and PRP-Placebo – treatment (PRP) and control (HA and
efficacy of prospective Patel S 2013 NS)groups favored PRP (4 studies
platelet-rich cohort study PRP-HA – [318 patients];MD, -18.03 [95% CI, -
plasma in the Cerza F 2012 27.75, -8.30]; P < 0.001).
treatment of Li M 2011 There was significant heterogeneity
2
symptomatic Filardo G 2012 in the data(I = 89%, P < .001), and
knee as such, a random-effects
osteoarthritis: a Cohort
systematic Spakova T 2012 IKDC Score
review with Kon E 2011 At 24 weeks, the MD in overall IKDC
quantitative score between the treatment (PRP)
synthesis. - Adults aged and control (HA) groups favored
Arthroscopy. >18 year s PRP (3 studies [289 patients]; MD,
2013;29(12):203 7.90 [95%CI, 3.72, 12.08]; P=
7-2048 0.004). There was no
significant statistical heterogeneity
2
(I = 44%, P =0.17). A separate
analysis using data with LMW HA
(as opposed to HMW HA) in the
study by Kon et al. did not result in a
change in the observed results
(MD,8.40 [95% CI, 2.72, 14.07]; P=
0.004).

Visual Analog Scale (Pain)

At 24 weeks, there was no statistical
difference in VAS scores between
the treatment (PRP) and control (HA
and NS) groups (2 studies
[198 patients]; MD, 0.46 [95% CI, -
0.52, 1.43]; P=0.36). A random-
2
effects model was used (I =88%,
P=0 .004). A separate analysis using
data with LMW HA (as opposed to
HMW HA) in the study by Kon et al.
did not result in a change in the

31
Bibliographic Study type LE Num. of pts and Intervention Comparison Follow Outcome measures General
citation and methods Pt up comments
characteristics
observed results (MD, 0.47 [95%CI, -
0.53 , 1.48]; P=0.36).

Patient Satisfaction
At 24 weeks, there was no difference
in patient satisfaction between PRP
treatment and the control (HA and
NS) groups (2 studies [198 patients];
OR, 8.97 [95% CI 0.54, 149.25]; P=0
2
.13). (I = 90%, P=0 .002), and a
random effects model was used. A
separate analysis using data with
LMW HA (as opposed to HMW HA)
in the study by Kon et al. did not
result in a change in the observed
results (OR, 9.35 [95% CI, 0.62,
142.1];
P=0 .11).

Adverse Events.
No AEs related to treatment
injections were observed in 2
studies. One study reported 19 AEs
over the course of PRP treatment.
Nonspecific AEs reported were pain,
stiffness, syncope, dizziness,
headache, nausea, gastritis,
sweating, and tachycardia, and all
complications were self-limited.
Another study reported 31 AEs in the
PRP group and 30 AEs in the control
group.In this study AEs reported
were post-injection pain, swelling of
the injection site, and activity
limitations. All AEsreported resolved
in all patients within 4 days. One
study was not included in the pooled
study for AE rates because the
number of patients with AEs was not
reported.In this study a higher post-
injection length of pain in the PRP
group versus the control group

32
Bibliographic Study type LE Num. of pts and Intervention Comparison Follow Outcome measures General
citation and methods Pt up comments
characteristics
(16.7days v 9.2 days, P=0.039) was
reported. This pain reaction was self-
limited in all patients. Similarly,
another study reported that 6
patients had worsening of pain after
PRP treatment, which resolved in all
patients within 2 days. With respect
to AEs, PRP treatment had a higher
incidence of AEs when compared
with control treatments (8.4% v
3.8%, P=0 .002).

33
EVIDENCE TABLE : SAFETY AND EFFECTIVENESS
QUESTION : IS PLATELET RICH PLASMA SAFE AND EFFECTIVE FOR OSTEOARTHRITIS TREATMENT?

Bibliographic Study type LE Num. of pts and Intervention Comparison Follow Outcome measures General
citation and methods Pt up comments
characteristics
6. Tietze DC, Systematic I Total 13 studies PRP HA, PRGF Maximu The results was not pooled. Last search
Geissler K, Review m 24 23 October
Borchers J. The 1 RCT months All studies showed statistically 2012
effects of Filardo 2012 significant improvement in
platelet-rich single vs double patient outcome scores with
plasma in the spinning PRP. PRP has statistically
treatment of significant benefit in knee OA
large-joint 2 NRCT when compared with hyaluronic
osteoarthritis: a Kon 2011 acid. The benefit of PRP
systematic Spakova 2012 appears to last between 6 and
review. 12 months. Younger patients
Physician & 1 retrospective with less of a disease burden
Sportsmedicine. cohort tend to have the most
2014;42(2):27- Sanchez 2008 improvement .
37.
9 Case Series
Filardo 2011
Gobbi 2012
Gobbi 2011
Jang 2012
Kon 2010
Napolatino 2012
Sampson 2010
Sanchez 2012
Wang 2011

34
EVIDENCE TABLE : SAFETY AND EFFECTIVENESS
QUESTION : IS PLATELET RICH PLASMA SAFE AND EFFECTIVE FOR OSTEOARTHRITIS TREATMENT?

Bibliographic Study type LE Num. of pts and Intervention Comparison Follow Outcome measures General
citation and methods Pt up comments
characteristics
7. Lai LP, Stitik Systematic I 8 relevant journal PRP HA or placebo 6 Regardless of the outcome
TP, Foye PM et Review articles were months measures, all studies
al. Use of identified, all of – 2 consistently have demonstrated
Platelet-Rich which were years the efficacy of PRP in improving
Plasma in Intra- published function and quality of life and
Articular Knee between 2010 reducing pain
Injections for and 2013 among patients with knee OA.
Osteoarthritis: A The onset of treatment effects
Systematic appeared fairly early in the
Review. Pm & treatment (within 2 months of
R. treatment initiation) however, it
2015;7(6):637- seemed that the effects were
648. only stable in the short term. In
multiple studies, numerically
worse outcomes were observed
when a longer follow-up period
was studied. For example,
some studies showed that
Western Ontario and McMaster
Universities Arthritis Index, pain
VAS, and EQ VAS were slightly
worse at 6 months compared
with the outcomes measured at
2 and 3 months. Only 2 studies
demonstrated that improved
outcomes were maintained up
to 12 months. The only study
with a follow-up time beyond
1year showed clearly worse
outcomes at 2 years compared
with those at 1 year, although
the outcomes were still better
compared at baseline. The
median duration of clinical
improvement was only 9
months.

35
EVIDENCE TABLE : SAFETY AND EFFECTIVENESS
QUESTION : IS PLATELET RICH PLASMA SAFE AND EFFECTIVE FOR OSTEOARTHRITIS TREATMENT?

Bibliographic Study L No. of pts and Pt Intervention Comparison Follo Outcome measures General
citation type and E characteristics w up comments
methods
8. Dallari D, RCT I 111 patients aged 3 weekly IA PRP 3 weekly IA 2, 6, Safety +randomis
Stagni C, Rani between 18 and 65 (n=44) HA (n=36) 12 No complications related to the ation,
N et al. 3 arms years old who were mont infiltrations were observed during computer
Ultrasound- treated with 3 weekly hs treatment and the follow-up period, generated
Guided Injection outpatient surgery PRP+HA (n=31) after except for a transient pain reaction +blinding
of Platelet-Rich and who had hip OA treat observed in 13 patients in the PRP-HA of outcome
Plasma and and pain intensity at ment group which spontaneously resolved assessmen
Hyaluronic Acid, baseline of >20 on a Ultrasound- within the treatment period. t
Separately and 100-mm Hg visual guided +intention
in Combination, analog scale (VAS), Efficacy to treat
for Hip Kellgren 1-4 Multivariate generalized linear model analyses
Osteoarthritis: A repeated measures showed significant
Randomized improvement in VAS, HHS and WOMAC
Controlled scores during time.
Study. American At 2-months, PRP group showed higher
Journal of values in terms of the WOMAC score
Sports (mean 73;95% CI: 68,78) and lower
Medicine. values in VAS score (mean 23; 95% CI:
2016;44(3):664- 16,29) compared with HA (mean
671. WOMAC: 59 (95% CI: 53,65); mean VAS
38 (95% CI: 30,46) and PRP+HA (mean
WOMAC: 59 (95% CI: 52,64), mean
VAS: 35(95% CI: 26,45)
At the 6-month follow-up, similar trend
observed, PRP group had higher values
in terms of the WOMAC score (mean, 72;
95% CI, 67, 76) and lower values in
terms of the VAS score (mean, 21; 95%
CI, 15, 28) compared with the HA (mean
WOMAC: 59 [95% CI, 54, 65], P = 0.009;
mean VAS: 44 [95% CI, 36, 52], P
<0.0005) and PRP+HA (mean WOMAC:
59 [95% CI, 54,66], P =0.005; mean VAS:
35 [95% CI, 26,45], P = .007) groups.
AT 12 months follow up, there was no
significant difference in the WOMAc
score among groups maintaining a
meaningful trend only for the VAS score:

36
Bibliographic Study L No. of pts and Pt Intervention Comparison Follo Outcome measures General
citation type and E characteristics w up comments
methods
PRP (mean 24; 95% CI 17, 30) versus
HA (mean 42; 95% CI: 34,50; p=0.002)
and PRP+HA(mean 38; 95% CI: 28,47;
p=0.017)

37
 EVIDENCE TABLE : SAFETY AND EFFECTIVENESS
QUESTION : IS PLATELET RICH PLASMA SAFE AND EFFECTIVE FOR OSTEOARTHRITIS TREATMENT?

Bibliographic Study LE Num. of pts and Pt Intervention Comparison Follo Outcome measures General
citation type and characteristics w up comments
methods

9. Lana JFSD, RCT I 105 patients aged PRP (n=36) HA (n=36) 1 Safety ?
Weglein A, between 40 and 70 year All patients reported mild adverse reaction in the randomisat
Sampson SE years old, history of HA+ form of knee swelling 2-5 days after the ion by lot
et al. chronic pain, for at PRP(n=33) application. +double
Randomized least 4 months 3 days after the treatment, based on VAS, HA blind
controlled trial and/or joint oedema groups continued with significant more pain than
comparing and radiographic the other groups.(HA-PRP, p=0.0034; HA+PRP-
hyaluronic evidence of mild to PRP, p=0.0113)
acid, platelet- moderate OA
rich plasma according to Efficacy
and the Kellgren-Lawrence At 30 days, significant improvement on WOMAC
combination classification. physical in the group treated with HA+PRP when
of both in the compared to the other groups median change
treatment of HA+PRP -650(-1125,-75) vs HA -362.5(-
mild and 1075,200), p=0.001; HA +PRP 650(-1125,-75) vs
moderate PRP -375(-1050,275), p=0.0004).
osteoarthritis
of the knee. At 90 days, groups treated with PRP alone or in
Journal of combination showed significant less pain than HA
Stem Cells & according to VAS score, HA -3 (-6,0), PRP -6.0 (-
Regenerative 8,1), HA+PRP -6 (-9,-1), HA vs PRP p=0.0001, HA
Medicine. vs HA+PRP p=0.0000, PRP vs HA+PRP p=0.1795
2016;12(2):69 There was no significant difference in WOMAC
-78. pain score. Improvement in WOMAC physical was
observed in the group HA+PRP when compared
with other groups (HA -512.5(-1225,500) vs
HA+PRP -725(-1225,-25), p=0.0052; PRP -550(-
1150,25) vs HA+PRP -725(-1225,-25), p=0.0110)

At 180 days,significantly less pain was observed in

the groups treated with PRP alone (Median
change -5(-9,-1) vs HA -3(-7.4) p=0.0001) or in
combination -5(-9,-1), p=0.0000) and an
improvement in the WOMAC physical was
observed only for the group HA+PRP in
comparison with HA (p=0.0262)

At 360 days, groups treated with PRP alone -5(-9,-

38
Bibliographic Study LE Num. of pts and Pt Intervention Comparison Follo Outcome measures General
citation type and characteristics w up comments
methods

1) or in combination -5(-9,-1) (p=0.0000) showed

significant less pain in comparison to HA -2(-7,2)
according to VAS. Also these groups showed a
significant improvement in WOMAC physical in
comparison to HA -450(-1350,375) (HA+PRP -
825(-1325,-300) vs HA, p=0.0001; PRP-775(-
1300,0) vs HA, p=0.0089).

39
EVIDENCE TABLE : SAFETY AND EFFECTIVENESS
QUESTION : IS PLATELET RICH PLASMA SAFE AND EFFECTIVE FOR OSTEOARTHRITIS TREATMENT?

Bibliographic Study type LE Num. of pts Intervention Comparison Follow Outcome measures General
citation and methods and Pt up comments
characteristic
s
10.Joshi Jubert RCT I 65 patients Single leucocyte- Intra-articular 6 Primary outcome- Pain VAS Unclear
N, Rodríguez L, with reduced PRP corticosteroid months Scores at 1-month randomisati
Reverté-Vinaixa symptomatic VAS score decreased for both on method,
MM et al. knee OA Prepared using a (n=30) groups with no significant unclear
Platelet-Rich (Kellgren- double-spin differences between groups at allocation
Plasma Lawrence methodology different time points ( 1, 3 and 6 concealme
Injections for grade 3 to 4), months) nt,
Advanced Knee in waiting list (n= 34) +Blinding
Osteoarthritis: A for knee
Prospective, arthroplasty 1 lost to follow-up KOOS Quality of Life scores
Randomized, between baseline, 3,and 6
Double-Blinded months increased significantly
Clinical Trial. more in the PRP than in the
Orthopaedic control group ( mean 17.77 vs
Journal of 4.91 at 3 months and 16.88 vs
Sports 3.56 at 6 months; p=0.05 and
Medicine. 0.03 respectively)
2017;5(2):23259
67116689386. The improvement in SF-36
general health perception score
between baseline and 6 months
was greater in the PRP group
than in control group (4.25 vs -
4.92 ; p=0.018)
No significant difference in
satisfaction between groups.

Safety
No patient had adverse effects
at injection or follow-up. No
differences were found in the
use of painkillers and non-
steroidal anti-inflammatories or
dose or frequency between
groups at any time point.

40
EVIDENCE TABLE : SAFETY AND EFFECTIVENESS
QUESTION : IS PLATELET RICH PLASMA SAFE AND EFFECTIVE FOR OSTEOARTHRITIS TREATMENT?

Bibliographic Study type LE Num. of pts and Intervention Comparison Follow Outcome measures General
citation and methods Pt up comments
characteristics
11.Saturveithan Retrospective II- 64 patients with PRP+HA HA only 6 IKDC score
C, Premganesh cohort 2 Grade III and IV months
G, Fakhrizzaki S primary knee OA At 2 months post injection
et al. Intra- based on HA (SD) : 7.0 (7.8)
articular Kellgren HA + PRP (SD) : 16.3 (11.9)
Hyaluronic Acid Lawrence Mean Diff (95% CI): -9.3 (-13.2,
(HA) and classification -5.4), p<0.05
Platelet Rich who received 4
Plasma (PRP) ml High At 6 months post injection
injection versus Molecular HA (SD) : 12.1 (8.2)
Hyaluronic acid Weight HA + PRP (SD) : 24.3 (13.7)
(HA) injection Hyaluronic Acid Mean Diff (95% CI): -12.1 (-
alone in Patients with 16.6, -7.7), p<0.05
with Grade III concentration of
and IV Knee 22 mg/ml alone
Osteoarthritis or with
(OA): A combination of
Retrospective PRP.
Study on
Functional
Outcome.
Malaysian
Orthopaedic
Journal.
2016;10(2):35-
40

41
EXCLUDED STUDIES

1. Chang K-V, Hung C-Y, Aliwarga F et al. Comparative effectiveness of

platelet-rich plasma injections for treating knee joint cartilage degenerative
pathology: a systematic review and meta-analysis. Archives of Physical
Medicine & Rehabilitation. 2014;95(3):562-575. – results from different study
designs pooled together

2. Yilmaz I, Akkaya S, Isyar M et al. Is there a treatment protocol in which

platelet-rich plasma is effective? Journal of Orthopaedics. 2016;13(4):316-
321. – different research question

3. Al-Ajlouni J, Awidi A, Samara O et al. Safety and Efficacy of Autologous Intra-

articular Platelet Lysates in Early and Intermediate Knee Osteoarthrosis in
Humans: A Prospective Open-Label Study. Clinical Journal of Sport Medicine.
2015;25(6):524-528.- not PRP

4. Richards MM, Maxwell JS, Weng L et al. Intra-articular treatment of knee

osteoarthritis: from anti-inflammatories to products of regenerative medicine.
Physician & Sportsmedicine. 2016;44(2):101-108. – narrative review

5. Halpern B, Chaudhury S, Rodeo SA et al. Clinical and MRI outcomes after

platelet-rich plasma treatment for knee osteoarthritis. Clinical Journal of Sport
Medicine. 2013;23(3):238-239. – case report

6. van Drumpt RAM, van der Weegen W, King W et al. Safety and Treatment
Effectiveness of a Single Autologous Protein Solution Injection in Patients
with Knee Osteoarthritis. BioResearch Open Access. 2016;5(1):261-268. Not
PRP

7. Cömert Kiliç S, Güngörmüş M. Is arthrocentesis plus platelet-rich plasma

superior to arthrocentesis plus hyaluronic acid for the treatment of
temporomandibular joint osteoarthritis: a randomized clinical trial.
International Journal of Oral and Maxillofacial Surgery. 2016;45(12):1538-
1544. – PRP for TMJ

8. Campbell KA, Saltzman BM, Mascarenhas R et al. Does Intra-articular

Platelet-Rich Plasma Injection Provide Clinically Superior Outcomes
Compared With Other Therapies in the Treatment of Knee Osteoarthritis? A
Systematic Review of Overlapping Meta-analyses. Arthroscopy.
2015;31(11):2213-2221 - Overview of meta-analysis

9. Malanga GA, Goldin M. PRP: review of the current evidence for

musculoskeletal conditions. Current Physical Medicine and Rehabilitation
Reports. 2014;2(1):1-15. Narrative review

10. Paterson KL, Nicholls M, Bennell KL et al. Intra-articular injection of photo-

activated platelet-rich plasma in patients with knee osteoarthritis: a double-
42
 blind, randomized controlled pilot study. BMC Musculoskeletal Disorders.
2016;17:67. – already included in one of the SR

11. Montañez-Heredia E, Irízar S, Huertas P et al. Intra-Articular Injections of

Platelet-Rich Plasma versus Hyaluronic Acid in the Treatment of
Osteoarthritic Knee Pain: A Randomized Clinical Trial in the Context of the
Spanish National Health Care System. International Journal of Molecular
Sciences. 2016;17(7):1064. . – already included in one of the SR

12. Smith PA. Intra-articular Autologous Conditioned Plasma Injections Provide

Safe and Efficacious Treatment for Knee Osteoarthritis: An FDA-Sanctioned,
Randomized, Double-blind, Placebo-controlled Clinical Trial. American
Journal of Sports Medicine. 2016;44(4):884-891.– already included in one of
the SR. – already included in one of the SR

13. Filardo G, Di Matteo B, Di Martino A et al. Platelet-Rich Plasma Intra-articular

Knee Injections Show No Superiority Versus Viscosupplementation: A
Randomized Controlled Trial. American Journal of Sports Medicine.
2015;43(7):1575-1582. – already included in one of the SR

14. Rahimzadeh P, Imani F, Seyed-Hamid-Reza-Faiz et al. Adding Intra-articular

Frowth Hormone to Platelet Rich Plasma under Ultrasound Guidance in Knee
Osteoarthritis: A Comparative Double-Blind Clinical Trial. Anest Pain Med.
2016;6(6):e41719. – already included in one of the SR

15. Li M, Zhang C, Ai Z et al. [Therapeutic effectiveness of intra-knee-articular

injection of platelet-rich plasma on knee articular cartilage degeneration].
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2011;25(10):1192-1196.-
already included in one of the SR

16. Filardo G, Kon E, Di Martino A et al. Platelet-rich plasma vs hyaluronic acid to

treat knee degenerative pathology: study design and preliminary results of a
randomized controlled trial. BMC Musculoskelet Disord. 2012;13(1):229.-
already included in one of the SR

17. Sánchez M, Fiz N, Azofra J et al. A randomized clinical trial evaluating

plasma rich in growth factors (PRGF-Endoret) versus hyaluronic acid in the
short-term treatment of symptomatic knee osteoarthritis. Arthroscopy.
2012;28(8):1070-1078.- already included in one of the SR

18. Cerza F, Carni S, Carcangiu A et al. Comparison between hyaluronic acid

and platelet-rich plasma, intra-articular infiltration in the treatment of
gonarthrosis. Am J Sports Med. 2012;40(12):2822-2827.- already included in
one of the SR

43
19. Patel S, Dhillon MS, Aggarwal S et al. Treatment with platelet-rich plasma is
more effective than placebo for knee osteoarthritis: a prospective, double-
blind, randomized trial. Am J Sports Med. 2013;41(2):356-364.- already
included in one of the SR

20. Vaquerizo V, Plasencia MA, Arribas I et al. Comparison of intra-articular

injections of plasma rich in growth factors (PRGF-Endoret) versus Durolane
hyaluronic acid in the treatment of patients with symptomatic osteoarthritis: a
randomized controlled trial. Arthroscopy. 2013;29(10):1635-1643.- already
included in one of the SR

21. Raeissadat SA, Rayegani SM, Hassanabadi H et al. Knee Osteoarthritis

Injection Choices: Platelet- Rich Plasma (PRP) Versus Hyaluronic Acid (A
one-year randomized clinical trial). Clin Med Insights Arthritis Musculoskelet
Disord. 2015;8:1-8. - already included in one of the SR

22. Görmeli G, Görmeli CA, Ataoglu B et al. Multiple PRP injections are more
effective than single injections and hyaluronic acid in knees with early
osteoarthritis: a randomized, double-blind, placebo-controlled trial. Knee Surg
Sports Traumatol Arthrosc. 2015;25(3):958-965.- already included in one of
the SR

23. Duymus TM, Mutlu S, Dernek B et al. Choice of intra-articular injection in

treatment of knee osteoarthritis: platelet-rich plasma, hyaluronic acid or ozone
options. Knee Surg Sports Traumatol Arthrosc. 2017;25(2):485-492.- already
included in one of the SR

24. Forogh B, Mianehsaz E, Shoaee S et al. Effect of single injection of platelet-

rich plasma in comparison with corticosteroid on knee osteoarthritis: a double-
blind randomized clinical trial. J Sports Med Phys Fitness. 2016;56(7-8):901-
908.- already included in one of the SR

25. Kon E, Mandelbaum B, Buda R et al. Platelet-rich plasma intra-articular

injection versus hyaluronic acid viscosupplementation as treatments for
cartilage pathology: from early degeneration to osteoarthritis. Arthroscopy.
2011;27(11):1490-1501.- already included in one of the SR

26. Spaková T, Rosocha J, Lacko M et al. Treatment of knee joint osteoarthritis

with autologous platelet-rich plasma in comparison with hyaluronic acid. Am J
Phys Med Rehabil. 2012;91(5):411-417.- already included in one of the SR

27. Filardo G, Kon E, Buda R et al. Platelet-rich plasma intra-articular knee

injections for the treatment of degenerative cartilage lesions and
osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2011;19:528-535.-
already included in one of the SR

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28. Say F, Gurler D, Yener K et al. Platelet-rich plasma injection is more effective
than hyaluronic acid in the treatment of knee osteoarthritis. Acta Chir Orthop
Traumatol Cech. 2013;80(4):278-283.- already included in one of the SR

29. Sánchez M, Anitua E, Azofra J et al. Intra-articular injection of an autologous

preparation rich in growth factors for the treatment of knee OA: a
retrospective cohort study. Clin Exp Rheumatol. 2008;26:910-913.- already
included in one of the SR

30. Sampson S, Reed M, Silvers H et al. Injection of platelet-rich plasma in

patients with primary and secondary knee osteoarthritis: a pilot study. Am J
Phys Med Rehabil. 2010;89(12):961-969.- already included in one of the SR

31. Gobbi A, Karnatzikos G, Mahajan V et al. Platelet-Rich Plasma Treatment in

Symptomatic Patients With Knee Osteoarthritis: Preliminary Results in a
Group of Active Patients. Sports Health. 2012;4(2):162-172.- already included
in one of the SR

32. Gobbi A., Malchira S., Karnatzikos G. Platelet rich plasma in osteoarthritis.
Minerva Ortopedica e Traumatologica. 2011;62(5):331-336.- already included
in one of the SR

33. Jang SJ, Kim JD, Cha SS. Platelet-rich plasma (PRP) injections as an
effective treatment for early osteoarthritis. Eur J Orthop Surg Traumatol.
2013;23(5):573-580.- already included in one of the SR

34. Sanchez M, Guadilla J, Fiz N et al. Ultrasound-guided platelet-rich plasma

injections for the treatment of osteoarthritis of the hip. Rheumatology
(Oxford). 2012;51(1):144-150.- already included in one of the SR

35. Napolitano M, Matera S, Bossio M et al. Autologous platelet gel for tissue
regeneration in degenerative disorders of the knee. Blood Transfus.
2012;10:72-77.- already included in one of the SR

36. Wang-Saegusa A, Cugat R, Ares O et al. Infiltration of plasma rich in growth

factors for osteoarthritis of the knee short-term effects on function and quality
of life. Arch Orthop Trauma Surg. 2011;131(3):311-317.- already included in
one of the SR

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