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The Journal of EVIDENCE-BASED DENTAL PRACTICE

ORIGINAL ARTICLE

COMPARISON BETWEEN TWO DIFFERENT LOCAL

HEMOSTATIC METHODS FOR DENTAL
EXTRACTIONS IN PATIENTS ON DUAL ANTIPLATELET
THERAPY: A WITHIN-PERSON, SINGLE-BLIND,
RANDOMIZED STUDY

BRUNO GUARDIEIRO b , MARCELA ALVES SANTOS-PAUL b ,

REMO HOLANDA DE MENDONÇA FURTADO a,c , TALIA DALÇÓQUIO a , ROCÍO SALSOSO a ,
ITAMARA LÚCIA ITAGIBA NEVES b , RICARDO SIMÕES NEVES b , CYRILLO CAVALHEIRO
FILHO a , LUCIANO MOREIRA BARACIOLI a, AND JOSÉ CARLOS NICOLAU a
a
Instituto do Coracao (InCor), Unidade de Coronariopatia Aguda, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao
Paulo, SP, Brasil
b
Instituto do Coracao (InCor), Unidade de Odontologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP,
Brasil
c
Academic Research Organization, Hospital Israelita Albert Einstein, Sao Paulo, Brazil

ABSTRACT CORRESPONDING AUTHOR:

Jose C. Nicolau, MD, PhD, Rua Aureliano
Background Coutinho 355, 01224-020 Sao Paulo, Sao
Dual antiplatelet therapy (DAPT) provides additional risk reduction of ischemic Paulo, Brazil, Phone: +551126615196.
E-mail: jose.nicolau@incor.usp.br
events compared to aspirin monotherapy, at cost of higher bleeding risk. There
are few data comparing new techniques for reducing bleeding after dental ex-
tractions in these patients.
KEYWORDS
Dual Antiplatelet Therapy, Bleeding, Tooth
Purpose extraction, Surgical hemostasis, Chitosan

This study investigated the effectiveness of the HemCon Dental Dressing (HDD)
compared to oxidized cellulose gauze. POTENTIAL CONFLICTS OF INTEREST:
JCN reports research grants from Amgen,
Materials and methods Astrazeneca, Bayer, CSL Behring, Daiichi
Sankyo, Dalcor, Esperion, Janssen, Novartis,
This randomized study included 60 patients on DAPT who required at least two
NovoNordisk, Sanofi and Vifor. RHMF
dental extractions (120 procedures). Each surgical site was randomized to HDD reports research grants and personal fees
or oxidized regenerated cellulose gauze as the local hemostatic method. Intra- from AstraZeneca, Bayer, Biomm and
oral bleeding time was measured immediately after the dental extraction and Servier; and research grants from Amgen,
represents our main endpoint for comparison of both hemostatic agents. Pro- Pfizer, EMS, Aché, CytoDin, Brazilian
Ministry of Health, University Health
longed bleeding, platelet reactivity measured by Multiplate Analyser (ADPtest Network (received from his institution), and
and ASPItest) and tissue healing comparison after 7 days were also investigated. Lemann Foundation Research Fellowship.
The other authors declare that they have no
Results conflict of interest regarding this
Intra-oral bleeding time was lower in HDD compared with control (2 [2-5] vs. 5 [2- publication.
8] minutes, P=0.001). Prolonged postoperative bleeding was observed in 7 cases
Received 14 September 2022; revised 9
(11.6%), all of them successfully managed with local sterile gauze pressure. More March 2023; accepted 3 April 2023;
HDD treated sites presented better healing when compared with control sites
J Evid Base Dent Pract 2023: [101863]
[21 (36.8%) vs. 5 (8.8%), P=0.03]. There was poor correlation between platelet
1532-3382/$36.00
reactivity and intra-oral bleeding time.
© 2023 Elsevier Inc.
All rights reserved.
doi: https://doi.org/10.1016/
j.jebdp.2023.101863

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Conclusions
In patients on DAPT, HDD resulted in a lower intra-oral bleeding time compared
to oxidized cellulose gauze after dental extractions. Moreover, HDD also seems
to improve healing conditions.

INTRODUCTION Study Design

This study was designed in a split-mouth model, where the

A ntiplatelet agents are routinely used therapeutically in

the prevention of atherothrombotic events in patients
with previous ischemic heart disease or stroke. Addition-
ally, the role of dual antiplatelet therapy (DAPT) with acetyl-
salicylic acid (ASA) and a P2Y12 receptor inhibitor (P2Y12i)
is well established in improving the outcome of patients
with acute coronary syndromes (ACS) and/or following per-
cutaneous coronary intervention (PCI).1-3 An advisory panel
consisting of both American Heart Association and Amer-
ican Dental Association recommends that, as a routine, at
least 12 months of DAPT is required after PCI.4 Although
this treatment represents a significant therapeutic advan-
tage, patients become exposed to a higher bleeding risk
posing an important clinical challenge in the perioperative
and immediate postoperative periods. It is expected that
at least 5% of all patients who have undergone PCI will be
submitted to non-cardiac surgeries within the first year af-
ter stenting.5 In this scenario, the discontinuation of DAPT
should be avoided due to the increased risk of serious is-
chemic complications6 that may greatly outweigh the bleed-
ing risk among patients undergoing invasive dental proce-
dures while on DAPT.7 Also, postponing critical invasive pro-
cedures like dental extraction may expose patients to acute
pain and bacterial infection and should be avoided. There-
fore, the use of a safe and efficient local hemostatic agent
is widely recommended in these situations, in order to keep
the patient on DAPT.8 There are few data comparing local
hemostatic agents aiming to reduce bleeding after dental
extractions in patients on DAPT.9 The HemCon Dental Dress-
ing (HDD, Tricol Biomedicals Inc, Portland, USA) is an extra-
alveolar chitosan based local hemostatic agent which usually
dissolves within 48 hours after its application.10 The main pur-
pose of this study was to investigate the efficacy of the HDD
compared to a standard local hemostatic agent, an oxidized
cellulose gauze (Surgicel, Ethicon Inc, Somerville, USA) in pa-
tients on DAPT undergoing dental extractions.
MATERIALS AND METHODS
Ethical guidelines
The study protocol was approved by our local institutional
research committee (CAPPesq SDC 3974/13/099) and regis-
tered at ClinicalTrials.gov (NCT02918045). The investigation
conforms with the principles outlined in the Declaration of
Helsinki and all participants signed an informed consent.
mouth is divided into two or more experimental segments
that are randomly assigned to different treatments. This de-
sign has the advantage of removing a lot of inter-subject
variability from the estimated treatment effect and poten-
tially requires fewer subjects than a parallel-group design
with the same power. In our study, both dental extractions
were carried out in a single session, each receiving a differ-
ent hemostatic agent (HDD or oxidized cellulose gauze) and
performed by one of the authors (BG). Both local hemostatic
agent and extraction sequence were randomly assigned by
an investigator not involved in patient enrollment from a
computer generated randomization list11 for 120 events (or
dental extractions) in 60 blocks (or patients). Although blind-
ing was not possible in this study since the hemostatic agent
is positioned over or into the extraction socket, the surgeon
had neither control over the extraction sequence nor hemo-
static agent choice for each dental extraction. All patients
were informed that different hemostatic agents would be
used, but they were unable to identify which one was the
HDD or the control.
Study population
Patients on DAPT with ASA and a P2Y12i and indication of at
least two dental extractions in different dental hemi-arches
were enrolled at Instituto do Coracao (InCor), Hospital das
Clinicas HCFMUSP, Faculdade de Medicina, Universidade
de Sao Paulo (Sao Paulo, Brazil). The main exclusion crite-
ria were presence of low platelet count (<100.000mm3 ) and
any known bleeding disorders. Patients using anticoagulant
therapy (oral or parenteral) and/or steroidal or non-steroidal
anti-inflammatory medication were also excluded.
Procedure parameters
All patients were submitted to pre-operative evaluation in-
cluding blood glucose, complete blood count and platelet
reactivity measured by Multiplate Analyzer (Roche Diagnos-
tics, Manheim, Germany) ADPtest (for P2Y12i) and ASPItest
(for cyclooxygenase dependent platelet aggregation, which
is related to ASA). A periodontal exam was carried out evalu-
ating gingival index (GI), which records gingival inflammation
as a whole, and clinical attachment level (CAL) individually
each tooth indicated for extraction.
All dental extractions were carried out under local anesthesia
using 2 cartridges of mepivacaine 3% without vasoconstric-
tor with as minimal trauma as possible using elevators and

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Figure 1. HDD positioned over the extraction socket
and stabilized by figure-of-eight suture.
forceps. Vertical incisions and osteotomies were performed
only when strictly necessary. Careful curettage, debridement
and irrigation with normal saline were performed to avoid
any granulation tissue leftover. Dental extractions random-
ized to the test group received one unit of HDD cut to ex-
actly fit over the postextraction socket and positioned with-
out pressure; dental extractions randomized to the control
group received one unit of oxidized cellulose gauze posi-
tioned inside the postextraction socket (in case of multiple
roots the hemostatic agent was cut in equal sizes, one for
each root cavity). Both groups received figure-of-eight su-
ture (4-0 resorbable sutures) over the postextraction socket
to stabilize the hemostatic agent (Figure 1).
Following the procedure, all patients received written and
verbal instructions on recommended postoperative care in-
cluding pressure with sterile gauze in case of bleeding from
the postextraction socket. Sodium dipyrone (500mg tablets)
was prescribed for pain management every 6 hours for at
least two days.
Primary endpoint
Our primary endpoint was the comparison of immediate
bleeding after dental extractions as measured by the intra-
oral bleeding time proposed by Brennan et al.12 , 13 The intra-
oral bleeding time was recorded immediately after apply-
ing each hemostatic agent. The test consists of verifying the
presence of blood extending beyond the alveolar crest at
the end of predefined intervals (2, 5, 8, 11, 14 and 20 min-
utes). At the end of each interval, if blood was present ex-
tending beyond the alveolar crest, sterile gauze would re-
move the excess bleeding and the site was observed until
the end of the next predefined interval when another check
was performed. If no blood was found extending beyond the
alveolar crest at the end of any predefined interval, the test
recording was concluded and the intra-oral bleeding time
was defined as the time of the last observed interval. There-
[mNS;July 7, 2023;11:8]
The Journal of EVIDENCE-BASED DENTAL PRACTICE
fore, intra-oral bleeding time was defined as the length of
time for bleeding to cease to extend beyond the alveolar
crest.
Secondary endpoints
1. To compare tissue healing between HDD and control
groups. All patients were scheduled for a follow-up ap-
pointment 7 days after the procedure. Tissue healing was
assessed by visually comparing both surgical sites consid-
ering the following aspects: redness in surrounding tis-
sues, presence of granulation tissue, degree of epithe-
lization, active bleeding and pain on palpation. The result
of this evaluation would classify tissue healing in one sur-
gical site as better, worst or equal compared to the other.
At this moment it was not possible to identify which surgi-
cal site received each hemostatic material, since the HDD
dissolves in saliva after approximately 48 hours and the
control hemostatic was placed inside the postextraction
socket. Only after this comparison was complete the re-
sult would be transferred to the clinical record and the
randomization would be revealed.
2. To assess the correlation between intra-oral bleeding
time from both groups with platelet reactivity and lo-
cal periodontal markers. Both platelet reactivity and peri-
odontal exams were carried out preoperatively as previ-
ously described.
3. To assess the correlation between prolonged bleeding
in the whole population with platelet reactivity and local
periodontal markers. Prolonged bleeding was defined as
clinically significant when it extended beyond 12 hours,
made the patient call or return to the dental office or to
an emergency service, resulted in a hematoma or ecchy-
mosis within the oral soft tissues or required blood trans-
fusion.14 All patients received two phone calls routinely,
12 and 48 hours after surgery, to answer the following
questions: 1) did you observe any bleeding during this
time period (y/n), 2) was it necessary to bite sterile gauze
due to the bleeding (y/n) and 3) was it necessary to seek
an emergency service of dental office due to the bleed-
ing (y/n). Therefore, prolonged bleeding was confirmed
when patients reported bleeding at both phone calls or
reported calls and/or returns to the dental office or emer-
gency service. The presence of hematoma or ecchymosis
was evaluated at the follow-up appointment.
4. To compare operative time and surgical trauma between
both groups. The operative time was defined as the con-
tinuous time measure between incision and hemostatic
application for each dental extraction and was recorded
by an investigator unaware of the hemostatic technique.
Surgical trauma was determined according to the dif-
ficulty of extraction and recorded for each surgery as:
1 (forceps extraction of a tooth with a single root), 2
(forceps extraction of a tooth with 2 roots), 3 (forceps
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extraction of a tooth with 3 roots) or 4 (surgical extraction

of any tooth).15 Figure 2. Participant flow diagram.

Statistical analysis
Categorical variables are reported as numbers and percent-
ages. Continuous variables with normal distribution are pre-
sented as mean ± standard deviation; those with non-normal
distribution are reported as median [25th-75th percentile].
The normality of distribution of continuous variables was
tested by one-sample Kolmogorov-Smirnov test. The pri-
mary endpoint was compared between the two hemostatic
techniques groups with a Wilcoxon signed rank test due to
the non-independence of observations (dental extractions)
from the same patient. The 95% confidence interval for the
difference in medians of our primary endpoint was gener-
ated by quantile regression and bootstrap resampling with
1000 replications. MacNemar’s or Wilcoxon signed rank test
were applied when categorical variables were involved. Cor-
relation between intra-oral bleeding time and platelet reac-
tivity or other biomarkers of coagulation was assessed by
Pearson correlation test, or Spearman’s correlation test when
variables were not normally distributed.
The sample size calculation utilized the t-Student for paired
samples and considered a median intra-oral bleeding time myocardial infarction (with or without ST-segment elevation)
of 5.2 ± 4.37 in the control group, based on our first 10 in- within the previous 2 months before enrolment. The remain-
clusions, and a 30% intra-oral bleeding time reduction in the ing 39 patients had chronic coronary syndromes, of which
HDD group. For an 89% statistical power and alpha<0.05, 60 92% (n=34) had been submitted to angioplasty for no longer
patients needed to be included. than 6 months. All patients were on DAPT with ASA plus
No carry-across effect between both groups was expected, clopidogrel (57 patients) or ticagrelor (3 patients).
since the primary objective was measured immediately af- A total of 124 dental extractions were performed, 57 being
ter each dental extraction. A value of P<0.05 was consid- maxillary teeth and 67 mandibular. Two surgical procedures
ered significant. P-values and 95% confidence intervals for involved the extraction of two adjacent single rooted teeth
secondary endpoints have not been adjusted for multiplicity and were included in the same group, being described as 2
and should be regarded as exploratory. Only cases with com- rooted teeth and receiving one unit of the hemostatic agent.
plete data were considered in the analysis and no method for Both groups presented balanced dental characteristic such
imputing missing data was needed. as positioning (maxillary or mandibular), number of roots and
The data were analyzed by IBM SPSS Statistics for Mac ver- CAL (P=0.648, P=0.904 and P=0.952, respectively) (Table 2).
sion 26 (IBM Corp., Armonk, USA), Stata version 13 (Stata- GI classification of our sample were as follows: 12 (20%) as
Corp LLC, College Station, USA) and R version 4.0.3 (R Foun- severe inflammation, 24 (40%) as moderate inflammation, 23
dation for Statistical Computing, Vienna, Austria) including (38,3%) as mild inflammation and 1 (1,7%) as normal. There
ggplot2 package. were no withdrawals due to any adverse events related to
the procedure. One patient returned to office after 6 hours
of surgery due to bleeding, which was controlled by ster-
RESULTS ile gauze compression for 30 minutes and the patient was
A total of 60 patients (48 men, mean age 59.6 years) were discharged after observation for 30 more minutes without
included in the study from April 2017 to July 2019. Following bleeding. Prolonged bleeding was observed in 7 patients
the study design, participants were actively recruited until (11.6%): 6 due bleeding reported exceeding 12 hours after
the target sample of 60 participants had been fulfilled, on an dental extraction and 1 due to ecchymosis in oral soft tissues.
intention-to-treat basis (Figure 2).
Table 1 shows the baseline characteristics of the population. Primary endpoint
Twenty-one patients (35%) had recent ACS, which for the pur- Our primary endpoint results are summarized in Figure 3.
pose of this study was defined as unstable angina or acute The intra-oral bleeding time obtained after using HDD was

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Table 1. Baseline clinical and laboratory characteristics of Figure 3. Box-and-whisker plot of the intra-oral bleed-
the population. ing time results from HDD and control groups. Patient
Characteristic (n=60) dispersion is also represented in points.

Age - yr 59.6 ± 1.17

Male sex 48 (80%)

Hypertension 55 (91.70%)

Dyslipidemia 56 (93.30%)

Diabetes 22 (36.70%)

Current smoking 29 (48%)

Acute coronary syndromesa 21 (35%)

Chronic coronary syndromes 39 (65%)

Dual antiplatelet therapy

ASA + Clopidogrel 57 (95%)

ASA + Ticagrelor 3 (5%)

Hb (g/dL) 13.70 ± 1.70

Ht (%) 41 ± 5

Neutrophils (mil/mm3 ) 4595 [3739-5605] Secondary endpoints

Platelet count (103 /mm3 ) 228.50 [196.75-272.5]

1. Tissue healing comparison between groups: Approx-
imately half of our patients evaluated for tissue heal-
HbA1C (%) 5.90 [5.68-7.08] ing presented HDD and control with similar character-
istics (n=31, 54%), although the incidence of improved
PT (seconds) 11.41 ± 0.82
HDD postextraction healing over control was higher
PTT (seconds) 28.35 ± 3.44 (P=0.003) (Figure 4). Three patients did not return for
the 7-day follow-up and thus were excluded from tis-
INR 0.90 [0.9-1.0] sue healing comparison; however, these patients were
Multiple electrode aggregometry (AUC) contacted by phone and answered the 12- and 48-
hours follow-up questionnaires.
ASPItest 19 [13-34] 2. Intra-oral bleeding time comparison with platelet re-
activity and local periodontal markers: We did not find
ADPtest 38 [27-52]
any significant correlation between intra-oral bleeding
time obtained from both groups and platelet reactivity
Abbreviations: ASA: acetylsalicylic acid; Hb: hemoglobin; Ht: hemat-
ocrit; HbA1C: glycated hemoglobin; PT: prothrombin time; PTT: partial
(r=-0.707, P=0.085 and -0.600, P=0.148 for Multiplate
thromboplastin time; INR: international normalized ratio; AUC: area un- ADPtest in HDD and control groups respectively, and
der the curve; ASPItest: aspirin test; ADPtest: adenosine diphosphate -0.327, P=0.110 and -0.640, P=0.121 for Multiplate AS-
test.
Data are presented as n (%), mean ± standard deviation or median PItest, respectively). Furthermore, when compared to
[25th-75th percentile] GI and CAL, intra-oral bleeding time from HDD and
a
Within 2 months from an ACS episode
control groups also did not show significant correla-
tion (P=0.169, P=0.343, P=0.169 and P=0.167 respec-
tively).
3. Prolonged bleeding comparison platelet reactivity and
local periodontal markers: As can be seen in Figure 5,
2 [2-5] minutes, and after oxidized cellulose gauze (control the median platelet reactivity in patients with or with-
group) was 5 [2-8] minutes (P=0.001). The difference in me- out prolonged bleeding did not show significant differ-
dians between groups was -3.0, 95% CI [-5.91, -0.09] favoring ences between the groups considering both platelet
HDD. reactivity methods utilized. Both periodontal markers

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Table 2. Baseline dental characteristics of the population.

HDD Control P value

Number of roots

1 rooted 33 (55%) 31 (51.7%) 0.667a

2 rooted 17 (28.3%) 22 (36.7%)

3 rooted 10 (16.7%) 7 (11.6%)

Maxillary teeth 27 (43.5%) 30 (48.4%) 0.648b

Mandibular teeth 35 (56.5%) 32 (51.6%)

Clinical attachment level (CAL) (mm) 5 [3-10] 6 [3-9] 0.952a

Data are presented as n (%) or median [25th-75th percentile]

a
Wilcoxon signed rank
b
McNemar’s test

Figure 4. Comparison of tissue healing between HDD Figure 5. Comparison of platelet reactivity with Multi-
and control group seven days after dental extractions. plate ADPtest and ASPItest with the incidence of pro-
longed bleeding.

not statistically significant between groups (P=0.727)

(Figure 6).

evaluated were also compared to the incidence of pro- DISCUSSION

longed bleeding after dental extractions and, again,
no significant correlation was observed between them
(P=0.749 for GI and 0.862 and 0.494 for CAL from HDD
and control groups, respectively).
4. Operative time was considerably shorter in control
sites (581.18 ± 176.96 seconds vs. 455.46 ± 161.35
seconds, P<0.001) and the difference between the
surgical trauma required for dental extractions was
The present study demonstrated that HDD reduces the intra-
oral bleeding time after dental extractions in patients on
DAPT when compared to the standard of care oxidized cellu-
lose gauze. Similar results have been published previously in
different populations.10 , 16 , 17 The efficacy of local hemostat-
ics in patients on DAPT has not been established due to lack
of controlled randomized studies, since most published pa-
pers are based on retrospective observational studies.18-22 To

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Figure 6. (a) Operative time comparison between HDD and control groups recorded from incision until hemostatic
application. (b) Distribution of surgical trauma related to dental extractions across HDD and control groups.
the best of our knowledge, this is the first randomized con-
trolled trial analyzing specifically patients on DAPT submit-
ted to dental extractions and comparing HDD to a standard
hemostatic method. The maintenance of DAPT with the use
of an efficient local hemostatic method with favorable safety
profile is highly desirable in this high-risk population and pre-
ferred over the discontinuation of one or both antiplatelet
drugs due to the increased risk of mortality, stent throm-
bosis and re-hospitalization with medication withdrawal.5
In this context, our results are particularly relevant as they
show that the use of HDD as a local hemostatic allows
a safer performance of dental extractions in patients on
DAPT.
Several studies evaluated the immediate bleeding after den-
tal extractions by continuously measuring time until the
bleeding from the postextraction socket stops.7 , 10 , 17 , 23-25
However, the hemostatic process is dynamic and the exact
amount of time from hemostatic application to complete
hemostasis is subjective. Thus, we chose the intra-oral bleed-
ing time proposed by Brennan et al. (2008)12 as a reliable
method to verify the immediate hemostatic time after a den-
tal extraction without the bias of subjective assessment, re-
sulting in better reproducibility.
Puppi et al. demonstrated a longer time to achieve hemosta-
sis after dental extractions with HDD when compared to
other hemostatic techniques (P=0.0452). In their study, su-
tures were used only in the control group and the authors
suggested that it may have exerted pressure on the gingi-
val tissues around the extraction socket and influenced the
results.25 It is important to recognize the controversy regard-
ing suture (use and technique) in patients submitted to den-
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The Journal of EVIDENCE-BASED DENTAL PRACTICE
tal extractions, especially in those with higher bleeding risk.
For some authors26 , 27 the use of sutures should be avoided
and, if necessary, non-resorbable sutures should be utilized
to avoid increasing the inflammatory response which could
result in an antifibrinolytic effect that could destabilize the
blood clot.28 On the other hand, it has been proposed that
the use of resorbable and non-resorbable sutures is based
on the surgeon’s judgment and ability.29 The only inconve-
nience could be the need of suture removal after 4-7 days
which could lead to minor bleeding. The present study stan-
dardized the use of sutures in both groups, using resorbable
material with the same synthesis technique for both extrac-
tion sockets. The figure-of-eight or criss-cross suture is com-
monly used to contain the hemostatic material inside the ex-
traction socket and, in the case of HDD, stabilize the mate-
rial on the borders without pushing it into the postextrac-
tion socket. Using a standardized suture technique for both
groups reduce bias when comparing immediate bleeding
outcomes.
Tissue healing was significantly better in the HDD sites (37%
of cases) when compared to control sites (9%). Other stud-
ies demonstrated similar results when comparing HDD ver-
sus other hemostatic agents.10 , 17 , 24 , 25 This finding may be
related to specific chitosan characteristics such as biocom-
patibility, biodegradability and antimicrobial properties,30-32
which improves the healing process by promoting and main-
taining the clot.25 Moreover, the fact that the control hemo-
static is placed inside the extraction socket may be related
to disturbances in the healing process such as alveolitis as
suggested by some studies.33 , 34 To the best of our knowl-
edge there is no other standard extra-alveolar hemostatic
that could be used for direct comparison and the oxidized
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cellulose gauze is widely known and used for hemostatic
matters.
No statistically significant correlation was found between
bleeding results from dental extractions and platelet reac-
tivity, in accordance with previous publication.35 Our find-
ings are probably mainly related to the small bleeding vol-
ume observed in dental extractions. Nagao et al.36 reported
a correlation between what the authors considered a diffi-
cult hemostasis (10 or more minutes for achieving hemosta-
sis) and platelet reactivity as categorical variable considering
cutoffs of 6.5 AUC for ASPItest and 21 AUC for ADPtest. Us-
ing the same cutoffs in the present material did not change
our main results. It should be mentioned that the association
between low platelet reactivity and major bleeding in stud-
ies among patients on DAPT submitted to PCI has been con-
troversial, with some studies37 suggesting that platelet reac-
tivity did not identify patients at risk of bleeding. Whether
these tests may identify patients at risk of dental bleeding,
which are usually mild, rather than major or fatal bleeding,
remains to be assessed in future studies.
Although acute inflammation such as gingivitis and pe-
riodontitis have been reported as a contributing factor
in increasing post-extraction bleeding in patients under
DAPT,38 , 39 our results did not show significant correlation be-
tween local markers such as CAL and GI and intra-oral bleed-
ing time or the incidence of prolonged bleeding. Since our
focus was the comparison of two distinct hemostatic agents
in a split-mouth design, differences in inflammation levels
and its influence on immediate or prolonged bleeding might
need a specific criteria and sample size. Additionally, no sig-
nificant differences in CAL measures were observed between
groups (Table 2). Also, any leftover granulation tissue, which
is often a common cause of prolonged bleeding,40 was care-
fully removed from postextraction sites in both groups.
The time elapsed to position the hemostatic agent after
dental extractions have been reported in two different stud-
ies.24 , 25 In both, the HDD application time was significantly
lower than the control (P<0.01 and P=0.002, respectively).
Contrary to these findings, our results demonstrated a sig-
nificant lower operative time favoring the oxidized cellulose
gauze, although it included not only the time to apply the
hemostatic agent but the whole dental extraction proce-
dure. Since all procedures were performed by the same op-
erator without statistically significant difference in surgical
trauma, we believe that this significant difference in oper-
ative time might be due to the hemostatic application itself
and not to the dental extraction. HDD seems to require addi-
tional training and practice to use compared to the insertion
of a hemostatic agent inside the postextraction socket, as it
is for the oxidized cellulose gauze.
Surgical splints can be used as physical barriers to preserve
the blood clot in its position and reduce bleeding.41 Since it
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[mNS;July 7, 2023;11:8]
is recommended that HDD is kept in contact with the oral en-
vironment for normal dissolution, the use of a surgical splint
was not considered in our study. In addition, primary closure
of the extraction socket is not indicated when using HDD
as a hemostatic method. According to the manufacturer, the
HDD usually dissolves within 48 hours, but may take up to
seven days and any residual material should be washed away
with irrigation. Also, the use of grafting material is not con-
traindicated when using the HDD to seal the wound.
There are several other hemostatic methods that can be ap-
plied after dental extractions with different presentations.
An extensive systematic review42 demonstrated that many
hemostatic methods were effective reducing or limiting pos-
textraction bleeding in different scenarios, mostly on antico-
agulated patients. However, it is difficult to compare stud-
ies due to the large number of different hemostatic meth-
ods, antithrombotic regimens and study designs. Additional
clinical studies comparing these methods in specific patient
populations are recommended, using a standardized ap-
proach.
Adequate postoperative recommendations and patient
compliance are also important aspects when considering
dental extractions in patients on DAPT. In the present study,
more than half of our patients (n=33, 55%) reported bleeding
within the first 12 hours after the surgical procedure and the
majority of them (n=27, 81%) also reported that the bleed-
ing was controlled by sterile gauze compression. The same
occurred with patients who reported any bleeding that ex-
tended beyond 12 hours after dental extractions (n=6, 10%).
Thus, careful counseling on managing minor bleedings after
dental extractions is recommended and effective for patients
on DAPT, avoiding unnecessary returns to the dental office,
as mentioned by other authors.12 , 43
LIMITATIONS
The present study has several limitations that should be
mentioned. First, considering the specificity of our inclu-
sion criteria, it was not always possible to include contralat-
eral teeth with exact same characteristics (size or number of
roots). Although this could have impacted the bleeding com-
parisons, the differences in surgical trauma between dental
extractions were not statistically significant. Second, another
limitation was related to prolonged bleeding evaluation. As
in split-mouth designs both procedures are performed in the
same surgical time, it was not possible to determine post-
operatively by phone inquire exactly from which postextrac-
tion socket the bleeding was originated. For this matter, all
prolonged bleeding analyses considered the incidence of
bleeding as the whole patient and not each postextraction
socket. Finally, our study was open label and endpoints were
not blindly assessed, thus raising the possibility of ascertain-
ment bias. However, this issue may have been mitigated by
JID: YMED
ARTICLE IN PRESS
the objectiveness of the measurements and following stan-
dardized techniques of assessment.
CONCLUSIONS
In patients submitted to dental extractions in use of dual
antiplatelet therapy, HDD is superior to oxidized cellulose
gauze regarding intra-oral bleeding time up to 20 minutes
after dental extractions, with good safety profile overall for
both techniques, supporting the recommendation of not
withdraw antiplatelet drugs before dental extractions. Ad-
ditionally, there is a suggestion of improved healing process
in favor of HDD, at the cost of a higher operation time.
ACKNOWLEDGMENTS
This research was supported by The São Paulo Research
Foundation (Fundacao de Amparo a Pesquisa do Estado de
Sao Paulo - FAPESP) grant #2014/01021-4. JCN is recipient
of a Scholarship from National Council of Scientific and Tech-
nological Development (Conselho Nacional de Desenvolvi-
mento Cientifico e Tecnologico – CNPq) #301242/2017-8.
CREDIT AUTHORSHIP CONTRIBUTION
STATEMENT
Bruno Guardieiro: Project administration, Concep-
tualization, Methodology, Writing – original draft.
Marcela Alves Santos-Paul: Writing – review & editing.
Remo Holanda de Mendonça Furtado: Writing – review &
editing. Talia Dalçóquio: Writing – review & editing. Rocío
Salsoso: Writing – review & editing. Itamara Lúcia Itagiba
Neves: Writing – review & editing. Ricardo Simões Neves:
Writing – review & editing. Cyrillo Cavalheiro Filho: Writing
– review & editing. José Carlos Nicolau: Supervision, Fund-
ing acquisition, Conceptualization, Methodology, Writing –
original draft.
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