Tautvydas Valiulis1, Andrius Ivanauskas1, Gintaras Janužis2
1 Department of Maxillofacial Surgery, Faculty of Odontology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
2 Department of Maxillofacial Surgery, Faculty of Odontology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Abstract
Background and aim. Nowadays increasing numbers of clinical trials produce evidence that PRF may indeed reduce postoperative pain, swelling and other negative outcomes of invasive tooth extractions. However, despite the evidence in the literature, controversies remain on PRF’s clinical efficiency and postextraction socket (PS) preservation in comparison with blood clots filled in PS. The aim of this study is to quantitatively evaluate the influence of platelet-rich fibrin with leukocytes in postextraction sockets on postoperative pain and swelling outcomes.
Materials and methods. The literature search was conducted in PubMed and ScienceDirect databases. Only split-mouth randomized clinical trials adhering to eligibility criteria were included. Postoperative pain and swelling data were extracted to quantitatively evaluate the effect on different periods: 1st, 3rd, 7th postoperative days.
Results. 5 studies have satisfied all eligibility criteria and been included in this study. Only 3rd postoperative day in pain evaluation statistically significant result favors PRF been noticed. Swelling evaluation could not be analyzed quantitatively because of different facial swelling measurements used between articles. Despite that, 4 of 5 articles showed statistically significant results favors PRF in the 1-4 postoperative days period.
Conclusion. Within the limitations of our study, it seems that PRF shows significant results in a reduction of postoperative pain and swelling outcomes on the most acute inflammation healing period. Despite that, to decide whether or not PRF is relevant in clinical practice, more split-mouth randomized clinical trials with low risk of bias and the same swelling evaluation approach should be done.
Keywords: platelet-rich plasma [MeSH], post-operative pain [MeSH], socket preservation, post-operative swelling.
https://doi.org/10.53453/ms.2021.06.1
Journal of Medical Sciences. Jun 30, 2021 - Volume 9 | Issue 5. Electronic - ISSN: 2345-0592
2
Medical Sciences 2021 Vol. 9 (5), p. 2-11, https://doi.org/10.53453/ms.2021.06.1
Does platelet-rich fibrin reduce negative postoperative
outcomes in postextraction sockets?
Tautvydas Valiulis
1
, Andrius Ivanauskas
1
, Gintaras Janužis
2
1
Department of Maxillofacial Surgery, Faculty of Odontology, Lithuanian University of Health
Sciences, Kaunas, Lithuania.
2
Department of Maxillofacial Surgery, Faculty of Odontology, Lithuanian University of Health
Sciences, Kaunas, Lithuania.
Abstract
Background and aim. Nowadays increasing numbers of clinical trials produce evidence that PRF may
indeed reduce postoperative pain, swelling and other negative outcomes of invasive tooth extractions.
However, despite the evidence in the literature, controversies remain on PRF’s clinical efficiency and
postextraction socket (PS) preservation in comparison with blood clots filled in PS. The aim of this study
is to quantitatively evaluate the influence of platelet-rich fibrin with leukocytes in postextraction sockets
on postoperative pain and swelling outcomes.
Materials and methods. The literature search was conducted in PubMed and ScienceDirect databases.
Only split-mouth randomized clinical trials adhering to eligibility criteria were included. Postoperative pain
and swelling data were extracted to quantitatively evaluate the effect on different periods: 1st, 3rd, 7th
postoperative days.
Results. 5 studies have satisfied all eligibility criteria and been included in this study. Only 3rd
postoperative day in pain evaluation statistically significant result favors PRF been noticed. Swelling
evaluation could not be analyzed quantitatively because of different facial swelling measurements used
between articles. Despite that, 4 of 5 articles showed statistically significant results favors PRF in the 1-4
postoperative days period.
Conclusion. Within the limitations of our study, it seems that PRF shows significant results in a reduction
of postoperative pain and swelling outcomes on the most acute inflammation healing period. Despite that,
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to decide whether or not PRF is relevant in clinical practice, more split-mouth randomized clinical trials
with low risk of bias and the same swelling evaluation approach should be done.
Keywords: platelet-rich plasma [MeSH], post-operative pain [MeSH], socket preservation, post-operative
swelling.
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1. Introduction
Platelet-rich fibrin (PRF) is one of the
available blood-derived products generally used
to promote wound healing and coagulation (1).
Ordinarily, PRF is extracted from patients’
peripheral blood and through slow centrifugation
fibrin scaffolding is created containing white
blood cells, growth factors and other proteins,
that all together promote wound healing (1,2).
PRF applications are widely used in dentistry,
especially in implant dentistry, alveolus surgery
or tooth extractions (1–3). Arguably, third molar
extractions tend to be associated with a relatively
increased risk of complications after surgery,
such as postoperative pain, trismus, swelling,
nerve injury, bleeding, alveolar osteitis and
overall compromised socket healing (4).
Management of these complications or
preventing them is of paramount importance in
dental practices. Increasing numbers of clinical
trials produce evidence, that PRF may indeed
reduce postoperative pain, swelling and other
negative outcomes of invasive tooth extractions
(5,6). However, despite the evidence in the
literature, controversies remain on PRF’s clinical
efficiency in reducing negative postoperative
outcomes in comparison with blood clots filled
in PS (4–7). Therefore, the aim of this study is to
quantitatively evaluate the influence of platelet-
rich fibrin (containing leukocytes) in
postextraction sockets on postoperative pain and
swelling outcomes.
2. Materials and methods
This study was conducted in accordance
with PRISMA and Cochrane methodological
recommendations for systematic reviews and
meta-analysis (8,9). A research protocol and
focus research question was developed based on
the relevant population, intervention,
comparison and outcome (PICO): does the usage
of PRF in postextraction socket enhance the
reduction of postoperative pain and swelling in
comparison with a regular blood clot? A
systematic literature search was conducted in
PubMed Medline and ScienceDirect databases
with the following keywords: “Platelet-rich
fibrin”, “PRF”, “dental extraction”, “socket
preservation”, “postextraction”, “molar
surgery”. The search was expanded by checking
for potential additional papers in the reference
lists of relevant papers. Relevant studies were
included in the analysis based upon the pre-
defined inclusion criteria: publications available
for full text and written in the English language,
(P) healthy 18-70 years old patients, (I) split-
mouth randomized controlled trial publications
comparing PRF and (C) blood clot in
postextraction sockets and (O) with at least one
of these outcomes had to be evaluated in the
article to be considered acceptable: postoperative
pain measured in Visual Analogue Scale (VAS),
postoperative facial swelling. The exclusion
criteria were as follows: patients with any
influential factors in wound healing, e. g.
smokers, animal, retrospective, non-randomized
studies, systematic reviews, case reports.
Articles identified through literature search were
subjected independently to inclusion and
exclusion criteria. The inclusion of the articles
was based on the article’s relevancy and study’s
eligibility. Each included article was
independently reviewed by two reviewers.
Disagreements in terms of publications’
eligibility for analysis, data collection process,
risk of bias were resolved by consensus with the
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expertise of the supervising experienced
researcher. Data from articles were extracted in
the form of variables according to the aim of this
systematic review. The following data was
obtained from the included articles:
• "Author(s)" – the corresponding author.
• "Year of publication" – the year in
which the study was published.
• "Patients" - describes the number of
patients who participated in the study as
a case or control group.
• “Follow-up” – describes the sequence
of post-operative follow-up dates.
• “VAS” – primary outcome measure
recorded at each follow-up according to
VAS.
• "Postoperative swelling” – describes
the postoperative swelling at each
follow-up in regards to the outcome
measurement in each study.
For randomized prospective clinical studies
quality assessment, we used a revised Cochrane
risk of bias tool (RoB 2) (10). Relevant data, as
stated previously, was collected and organized
into a Microsoft excel file. Statistical analysis
was performed using Review Manager 5.4
software to generate forest plots. Heterogeneity
between the results of the selected studies was
assessed using the I² test. Heterogeneity was
evaluated according to Cochrane Collaboration
recommendations. Since heterogeneity was
present in all studies (I² > 0), a random effect
model was used to perform a meta-analysis. Data
is presented as mean with standard deviation,
confidence interval selected at 95%.
3. Results
During the primary literature search, we
identified 615 records. 587 publications left after
duplicates were removed. During the first phase of
literature analysis, titles and abstracts were reviewed
and a total of 571 articles were excluded. The
remaining 16 full-text articles were analyzed and 11
studies were excluded, as it is showcased in Figure
1. Ultimately, 5 studies have satisfied all eligibility
criteria. 4 studies were evaluated to have an overall
high (11,12) or some concern (13,14) and only 1
article low (15) risk of bias, as shown in Table 1.
Pain evaluation results showed: (a) the 1st and 7th
postoperative days (PDs) non statistically significant
result favors PRF, respectively, mean difference = -
0.51, P 95% CI: -1.06 to 0.04 and mean difference =
-0.65, P 95% CI: -1.33 to 0.03; (b) 3rd day
statistically significant result favors PRF mean
difference = -1.05, P 95% CI: -2.01 to -0.10; (c) high
heterogeneity levels were noticed on the 1st, 3rd, 7th
PDs pain evaluations (I²=82%, 92% and 96%). All
these previous results are reflected in forest plots
(Figure 2). Swelling evaluation could not be
analyzed quantitatively because of different facial
swelling measurements used between articles.
Despite that, 4 of 5 articles showed statistically
significant results favors PRF in the 1-4 PDs period
(11–13,15) and only 1 article showed statistically
significant result favors to PRF during the 4-7 PDs
timespan (11).
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Tables
Table 1. Clinical studies quality assessment (RoB 2).
Risk of bias domains
D1
D2
D3
D4
D5
Overall
Study
Ozgul 2015
-
-
-
+
+
-
Asutay 2016
-
+
+
+
+
-
Daugela 2018
+
+
+
+
+
+
Kapse 2018
-
-
X
+
+
X
Gupta 2020
-
-
X
-
-
X
Judgement:
X High
- Some concerns
+ Low
Domains:
D1: Bias arising from the randomization process.
D2: Bias due to deviations from intended
intervention.
D3: Bias due to missing outcome data.
D4: Bias in measurement of the outcome.
D5: Bias in selection of the reported result.
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Figures
Figure 1. Prisma flow diagram.
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Figure 2. Random effects forest plots. Comparison of pain levels 1st, 3rd, 7th postoperative days between
PRF versus blood clot filled postextraction sockets.
4. Discussion
In this systematic review we have found
that PRF has a positive influence on
postoperative pain reduction in postextraction
sockets on the most acute inflammation healing
period. Although the clinical efficacy of PRF is
still a topic of controversy in dentistry, more
evidence is emerging supporting the PRF use in
third molar extraction surgeries.
PRF use in the context of tooth extraction is
thought to generate a network of fibrin similar
that of blood clot. PRF generally consists of
platelets and growth factors that are enmeshed
into the fibrin matrix through slow centrifugation
(16–18). This fibrin matrix creates a scaffolding
to enhance cell migration and differentiation
(19,20). It is also known that the fibrin matrix
releases growth factors over a period of 7-14
days to promote angiogenesis, these growth
factors include transforming growth factor
(TGF-b), vascular endothelial growth factor
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(VEGF) and many other growth factors: platelet-
derived growth factor (PDGF), and insulin-like
growth factor (16–20). Furthermore, PRF also
contains leukocytes and cytokines (such as
interleukin (IL-4; IL-6; IL-1A), tumor necrosis
factor), which tend to contribute to anti-
infectious and tissue healing properties of the
PRF (16–20). Therefore, PRF generally is
thought to contribute to angiogenesis, tissue
healing and wound cicatrization; and it can be
hypothesized that PRF may reduce negative
postoperative complications or outcomes.
In this study, quantitative analysis of
postoperative swelling could not be performed
due to methodological differences between the
studies. However, qualitative analysis revealed
that PRF does reduce swelling during the first 4
PDs of the third molar extraction healing process
(11–13,15). Only one study stated otherwise
(14), however, a recent systematic review also
concluded that PRF had a positive effect on
reducing postoperative swelling (5) but
conclusions remain contradictory in other
reviews and meta-analyses (4,6,7). On the other
hand, it should be noted, that same as in our
study, evidence could not be summarized
decisively due to lack of methodologically
homogeneous studies for meta-analysis,
indicating the need for high-quality studies (5,7).
Regarding quantitative pain evaluation, our
results indicate that the use of PRF reduce
postoperative pain, however a significant result
was detected only on the third day after surgery.
Similar results were observed in other systematic
reviews, in which pain reduction was detected
when PRF had been used (4–7), although authors
agreed that more studies were needed to reach a
definitive conclusion.
Therefore, it is difficult to accurately estimate
PRF efficiency in pain reduction, as results seem
to be inconclusive. This may be related to several
factors. Firstly, pain reporting may be influenced
by the split-mouth evaluation, patients may have
had difficulty in accurately distinguishing pain
from site to site, also pain expression is the
entirely subjective parameter. Another point to
consider is the presence of leukocytes in the PRF.
The statement that leukocytes included in
platelet concentrate could negatively affect the
healing process could be found in the scientific
literature (21). Therefore, as an alternative for
platelet-rich fibrin, PRGF (platelet concentrate
without leukocytes) should be investigated in
future studies for the purpose to expect a better
outcome.
There are some limitations in this study. Firstly,
merely one of five studies have been evaluated as
low risk of bias. Secondly, postoperative
swelling evaluation could not be assessed
quantitatively due to different facial swelling
measurements between included studies.
Thirdly, a high heterogeneity level between
studies been noted. Lastly, this systematic
review would have qualified for highest
standards of systematic reviews if it had been
registered in the international register of
systematic reviews and meta-analyses
(PROSPERO).
Despite that, this article has some strengths as
well. Firstly, inclusion criteria strictness - only
split-mouth, randomized clinical trials have been
included, thus, high-quality evidence is
presented in this article. Secondly, patients with
any influential factors in wound healing were
excluded, Figure 1 shows that 3 articles had been
excluded for the reason of included patients who
were smokers and 2 articles had been excluded
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due to the patients receiving anticoagulant
therapy.
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