Cirugía - 01 - Hemorragia Complicaciones Exodoncia

DENTOALVEOLAR SURGERY
Hemorrhagic Complications of Dental

Extractions in 181 Patients Undergoing
Double Antiplatelet Therapy
Olga Olmos-Carrasco, MD, FP,* Victoria Pastor-Ramos, MD, PhD, DDS,y
Rafael Espinilla-Blanco, MD, DMD,z Ana Ortiz-Z arate, MD, DMD,x

Irene Garcıa-Avila, DMD, PhD,k Elıas Rodrıguez-Alonso, MD, DMD,{
Rosario Herrero-Sanju an, MD, DMD,# Marıa-Magdalena Ruiz-Garcıa, DMD,**
Paloma Gallego-Beuter, MD, DMD,yy Marıa-Paz S anchez-Salgado, MD, DMD,zz
an-Agustın, MD, DMD,xx Milagros Fern
Ana-Isabel Ter andez-Behar, MD, DMD,kk
and Inmaculada Pe~ na-Sainz, MD, FP{{
Purpose: There is limited information on hemorrhagic complications during invasive dental procedures
in patients treated with double antiplatelet therapy. The objective of this study is to assess the frequency of
hemorrhagic complications of patients taking dual antiplatelet medication undergoing dental extractions.
Patients and Methods: An observational, multicenter, prospective, cohort study was performed in 11
oral and dental care units of primary care. The study sample was derived from the population of patients
aged 18 years or older who were undergoing double antiplatelet therapy and presented to the oral and
dental care units requiring dental extraction. Double antiplatelet therapy is the combination of 100 mg
per day of acetylsalicylic acid and a second antiplatelet agent. The predictor variables were type of extrac-
tion performed, number of extracted teeth, number of extracted roots, and presence of inflammation. The
primary outcome variable was intraoperative hemorrhage, and the secondary outcome variables were
hemorrhage at 24 hours and hemorrhage at 10 days. First, a univariate analysis that considered all studied
variables was performed. All variables with P < .25 in the univariate analysis were included in a multivariate
analysis. The association between hemorrhage severity and its relevant factors was evaluated using logistic
regression analysis.
Results: The study included 181 patients. Light hemorrhage (<30 minutes) was observed in 165 patients
(91.2%). Intraoperative hemorrhage lasted more than 30 minutes in 15 patients (8.3%) and more than 60
*Specialized in Family and Community Medicine, Health Center yySpecialized in Stomatology, Oral and Dental Care Unit Silvano I,
Jazmın, Servicio Madrile~
no de Salud, Madrid, Spain. Servicio Madrile~
no de Salud, Madrid, Spain.
ySpecialized in Stomatology and Maxillofacial Surgery, Oral and zzSpecialized in Stomatology, Oral and Dental Care Unit Jazmın,
Dental Care Unit Alpes, Servicio Madrile~
zSpecialized in Stomatology, Oral and Dental Care Unit San xxSpecialized in Stomatology, Oral and Dental Care Unit Alameda,
Fermın, Servicio Madrile~
xSpecialized in Stomatology, Oral and Dental Care Unit Benita de kkSpecialized in Stomatology, Oral and Dental Care Unit Canal de
vila, Servicio Madrile~
A no de Salud, Madrid, Spain. Panama, Servicio Madrile~
kUniversity degree in Odontology, Oral and Dental Care Unit {{Specialized in Family and Community Medicine, Health Center
Silvano II, Servicio Madrile~
no de Salud, and Assistant Professor, Jazmın, Servicio Madrile~
University Dentistry Clinic, ‘Alfonso X El Sabio’’ University of Conflict of Interest Disclosures: None of the authors reported any
Madrid, Madrid, Spain. disclosures.
{Specialized in Stomatology, Oral and Dental Care Unit Dr. Cirajas Address correspondence and reprint requests to Dr Olmos-
I, Servicio Madrile~
no de Salud, and Associated Professor, Department Carrasco: Calle de Belice 52, 28027 Madrid, Spain; e-mail: olga.
of Stomatology, Faculty of Health Sciences, ‘ Rey Juan Carlos’’ olmos@salud.madrid.org
University of Madrid, Madrid, Spain. Received June 4 2014
#Specialized in Stomatology, Oral and Dental Care Unit Luis Vives, Accepted August 5 2014
Servicio Madrile~
no de Salud, Madrid, Spain. Ó 2015 American Association of Oral and Maxillofacial Surgeons
**University degree in Odontology, Oral and Dental Care Unit 0278-2391/14/01318-4
Daroca, Servicio Madrile~
no de Salud, Madrid, Spain. http://dx.doi.org/10.1016/j.joms.2014.08.011
203
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204 HEMORRHAGIC COMPLICATIONS OF DENTAL EXTRACTIONS
minutes in only 1 patient, whose hemorrhage was controlled by local hemostatic measures. The presence
of inflammation and 3-root extractions increased the probability of hemorrhage persisting for more than
30 minutes by factors of 10 and 7.3, respectively.
Conclusions: In 8.3% of patients treated with dual antiplatelet therapy, dental extractions cause hemor-
rhagic complications lasting more than 30 minutes are resolved using local hemostatic measures. The re-
sults of this study support the safety of dental extraction without withdrawal double antiplatelet therapy.
Ó 2015 American Association of Oral and Maxillofacial Surgeons
J Oral Maxillofac Surg 73:203-210, 2015
Double antiplatelet therapy should not be prematurely was performed in accordance with the Declaration
stopped after an acute coronary syndrome or a stent of Helsinki. Written informed consent was obtained
implant because of the risk of myocardial infarction from all patients before enrollment in the study.
and death.1 Numerous studies have assessed the
frequency and severity of hemorrhagic complications STUDY SAMPLE
of dental interventions in patients undergoing
The scope of the study included 11 oral and dental
anticoagulant treatment, antiplatelet monotherapy,
care units of primary care in the community of Madrid
and anticoagulant-antiplatelet combination therapy.2-13
that serve a population of 561,603 persons aged older
However, information on these complications in
than 14 years. Of these, 2,170 persons (0.39%) were
patients with double antiplatelet therapy is scarce.
undergoing double antiplatelet therapy at the begin-
Few studies include patients with double
ning of the study. The study sample was derived from
antiaggregant therapy, and some have methodologic
the population of patients who were undergoing dou-
deficiencies regarding their small sample size and the
ble antiplatelet therapy and presented to the oral and
bias inherent to retrospective data collection.5,14-16
dental care units needing dental extraction between
Despite this paucity of information, the American
October 1, 2011 and December 31, 2013. Double anti-
Heart Association, American College of Cardiology, So-
platelet therapy is the combination of 100 mg per day
ciety for Cardiovascular Angiography and Interven-
of acetylsalicylic acid and a second antiplatelet agent
tions, American College of Physicians, American
(clopidogrel, ticlopidine, prasugrel, or ticagrelor).
College of Surgeons, American Dental Association, Na-
To be included in the study sample, patients must
tional Health Service, and numerous authors recom-
have been aged 18 years or older, been treated at least
mend either maintaining double antiplatelet therapy
in the last 7 days, and consented to participate in the
in dental interventions and applying the necessary
study. Patients were excluded as study patients if they
local hemostatic measures to control the hemorrhage
were aged younger than 18 years, had stopped the sin-
or delaying the intervention until the dual therapy
gle or double antiplatelet treatment for more than 48
can be withdrawn without risk.1,17-26
hours before extraction, or refused study enrollment.
The purpose of this study was to address the
following question: Among patients with double anti-
platelet therapy, can dental extractions be carried STUDY VARIABLES
out safely? We hypothesized that dental extractions The primary outcome variable was intraoperative
have a low frequency of hemorrhagic complications hemorrhage. The secondary outcome variables were
that are resolved using local hemostatic measures. hemorrhage at 24 hours and hemorrhage at 10 days.
The specific aims of this study were to estimate the fre- Intraoperative hemorrhage was defined as hemor-
quency of hemorrhagic complications in dental extrac- rhage occurring either during the intervention or the
tions of patients undergoing double antiplatelet subsequent time the patient spent under observation
therapy and to identify factors associated with an during the consultation. The severity of the hemor-
increased risk of intraoperative hemorrhage. rhage was classified as a function of its duration and
the measures needed to control it as follows: light
Patients and Methods hemorrhage if hemostasis was achieved in less than
30 minutes using the aforementioned protocol, mod-
STUDY DESIGN erate hemorrhage if the bleeding continued for more
To address the research purpose, we designed and than 30 minutes but less than 60 minutes, intense hem-
implemented an observational, multicenter, prospec- orrhage if bleeding continued for more than 60 mi-
tive, cohort study. This project was approved by the nutes, and severe hemorrhage when it required
Ethics and Clinical Research Board of Hospital Ram
on general measures and referral to a hospital. Thus hem-
y Cajal and by the Central Research Committee of orrhage at 24 hours and hemorrhage at 10 days were
Primary Care of the Community of Madrid. The study classified as absent, light, moderate, intense, or severe.
OLMOS-CARRASCO ET AL 205
We defined the following as predictor variables: type mouth washing with a 500-mg ampule of tranexamic
of extraction performed, number of extracted teeth, acid for 2 minutes, starting 2 hours after the interven-
number of extracted roots, presence of inflammation. tion, with repeated washings every 6 hours during the
Both simple and complex exodontias were per- initial 48 hours after the extraction. In the case of a hem-
formed. The extraction of the tooth from its socket orrhagic episode, the patient was instructed to record
without damaging it was considered a simple exodontia, its duration to communicate it at the following consulta-
and the procedures in which an osteotomy, odontosec- tion. The patient was scheduled for a clinical consulta-
tion, or elevation of the mucoperiosteal flap was neces- tion at 24 hours and 10 days after the intervention, or
sary were considered complex. a phone inquiry was made to determine whether any
Inflammation was considered to exist if signs or hemorrhagic complications had occurred.
symptoms of periodontitis or purulent discharge,
swelling, or erythema of soft tissues were present close DATA COLLECTION, MANAGEMENT, AND
to the tooth. Other patient variables collected included ANALYSES
age, gender, anesthetic technique (infiltration, nerve A specific protocol was designed to collect data and
block, or both techniques), number of anesthetic car- included in the electronic clinical record. All data
tridges, combination of antiaggregant drugs (acetylsali- handling and analysis were performed by the first
cylic acid plus clopidogrel, ticlopidine, prasugrel, or author and were analyzed using SPSS statistical soft-
ticagrelor), anticoagulant drugs (yes or no), and intake ware for Microsoft Windows, version 18 (SPSS, Chi-
of nonsteroidal anti-inflammatory drugs (NSAIDs). cago, IL).
Information collected from patients’ family doctor clin- Previous research has found a high rate of bleeding
ical file included data regarding excessive alcohol con- complications that seems far higher than the rates pro-
sumption (yes or no), hepatopathology (yes or no), duced in our area.5,14,15 Therefore the sample size
kidney failure (yes or no), poorly controlled arterial hy- calculation was based on our previous experience,
pertension (yes or no), coagulopathies (yes or no), and a value of approximately 8% was estimated for
chemotherapy (yes or no), and long-term steroid treat- hemorrhagic complications lasting more than 30
ment (yes or no). Patients were considered to have un- minutes. The necessary sample size was 164 patients
dergone NSAID treatment if they had taken the dosage (a error, 5%; b error, 20%; precision, 4%).
indicated in the drug technical file during the 24 hours Data are presented as mean standard deviation for
before the intervention. Each health professional’s total quantitative variables and as percentage and frequency
work experience was recorded as well. distribution for qualitative variables. Age was evalu-
ated as a categorical variable by splitting the patients
into 2 groups: less than 65 years and 65 years or older.
INTERVENTION
First, a univariate analysis that considered all studied
The extractions were performed by the 11 dentists variables was performed. All variables with P < .25 in
of the oral and dental care units, who followed their the univariate analysis were included in a multivariate
usual dental extraction procedures in patients under- analysis. Possible interactions were considered and
going treatments that interfered with hemostasis. In added to the initial model. The results of the logistic
all cases 3% mepivacaine without a vasoconstrictor regression analysis are presented as the odds ratio
was the anesthetic used. and 95% confidence interval.
Regarding the hemostatic technique, the patient un-
derwent 30 minutes of compression with gauze Results
impregnated with a 500-mg ampule of tranexamic
acid. If the hemorrhage continued beyond 30 minutes, One hundred eighty-one patients with a mean age of
the gauze compression with tranexamic acid was 66.98 12.8 years were included in the study. Most
repeated for an additional 30 minutes. The aim of the were male: 139 (76.8%). A total of 217 teeth were ex-
application of tranexamic acid is to locally stabilize tracted, with a mean of 1.2 0.4 teeth per patient. The
the clot formed once the hemostasis phase has ended. most common antiplatelet combination was acetylsali-
Tranexamic acid forms a reversible complex that dis- cylic acid, 100 mg per day, and clopidogrel, 75 mg per
places plasminogen from fibrin, resulting in inhibition day (97.2%). Only 5 patients were treated with 100 mg
of fibrinolysis; it also inhibits the proteolytic activity of per day of acetylsalicylic acid and 10 mg of prasugrel.
plasmin. This technique is part of our usual protocol to
prevent postoperative bleeding in patients undergoing INTRAOPERATIVE HEMORRHAGE
anticoagulant and antiplatelet therapy requiring dental During the course of extraction, 165 patients
extractions.27 (91.2%) had light hemorrhage, defined as hemorrhage
After the procedure, the patient received written in- lasting less than 30 minutes. In 15 instances (8.3%) the
structions on recommended home care that included hemorrhage continued for more than 30 minutes, and
1 patient had a hemorrhagic episode exceeding 60 mi- dental extractions can be carried out safely without
nutes. Hence, intraoperative hemorrhage was classi- stopping dual antiplatelet therapy.
fied according to its duration as less than 30 minutes There is no standard definition for hemorrhage
or more than 30 minutes. Table 1 shows the results severity after dental extractions. In the existing litera-
of the descriptive analysis. The single patient with ture, the method used to measure the severity of hem-
hemorrhage persisting more than 60 minutes had a orrhagic complications is frequently not described,
vertical fracture of the extracted tooth, which was a and there is substantial heterogeneity in the defini-
mandibular molar; granulation tissue had replaced tions of those that do describe it,3-5,9-16,27 which
the bone and vestibular table, and it was necessary complicates the comparison of studies.26 The classifi-
to perform an extensive curettage. cation used in this study was based on the duration
The logistic regression model included the of the hemorrhage, which appears to be appropriate
following variables: years of working experience, because of its ease of use and adaptation to our
number of anesthetic cartridges, number of extracted usual protocol.
roots, presence of inflammation, and excessive alcohol In a study by Lillis et al,15 66.7% of 33 patients under-
consumption. The final model results are shown in going double antiplatelet therapy had hemorrhage last-
Table 2. Only the presence of inflammation and the ing more than 30 minutes. In a study by Ca~ nigral and
presence of 3-root extractions were found to be risk Silvestre,5 4 of the 9 patients (44.4%) receiving dual
factors for intraoperative hemorrhage. Neither work- therapy had moderate hemorrhage that was defined
ing experience time nor excessive alcohol consump- as hemorrhage lasting more than 10 minutes and was
tion was related to the severity of the hemorrhage. stopped using local hemostatic measures in less than
60 minutes in all cases. A study from the University
HEMORRHAGE AT 24 HOURS of Korea, by Park et al,16 with all dental extractions
performed in the hospital by the same dentist,
At 24 hours, 162 patients (89.5%) reported an
included 100 patients with double and triple antiplate-
absence of bleeding, 15 (8.3%) had light hemorrhage,
let therapy, and only 2 cases of excessive hemorrhage
and 4 (2.2%) recounted a bleeding episode lasting
(lasting 4 and 5 hours) were found; however, the au-
more than 30 minutes that was self-controlled using
thors did not discuss the number of patients with hem-
the recommended local hemostatic measures. No rele-
orrhage of shorter duration.
vant statistical association was found between hemor-
In our study there were several circumstances that
rhage severity at 24 hours and the studied factors.
may have increased the duration of the bleeding:
HEMORRHAGE AT 10 DAYS Contrary to the procedure of other

At 10 days, 174 patients (96.1%) reported an authors,4,9-11,15,16,18,23,25 we used anesthesia
absence of bleeding and 7 (3.9%) had light hemor- without a vasoconstrictor to avoid adverse
rhage that was controlled with local hemostatic mea- reactions in patients with coronary disease,
sures. No significant statistical association was found whose epinephrine dosage is limited to 0.04 mg
between hemorrhage severity at 10 days and the as- per session.28-30
sessed factors. Suturing was not included in our dental extraction
protocol.
We included patients taking oral anticoagulants
Discussion
and NSAIDs and patients with excessive alcohol
The purpose of this study was to address the consumption, liver pathology, or renal failure;
following question: Among patients with double anti- such patients are excluded from studies by other
platelet therapy, can dental extractions be carried authors because of their increased bleeding
out safely? Our hypothesis was that dental extractions risk.4,10,15,16 We do not advise the use of NSAIDs
had a low frequency of hemorrhagic complications. in patients with cardiovascular disease and
The specific aims were to estimate the frequency of antiplatelet therapy, but ibuprofen use in our
hemorrhagic complications in dental extractions of country is widespread, and often, self-medication
patients undergoing double platelet antiaggregant is used in the presence of acute pain.
therapy and to identify factors associated with an
increased risk of intraoperative hemorrhage. There also were several circumstances that may
The percentage of patients having intraoperative have decreased the duration of the bleeding:
hemorrhage lasting more than 30 minutes was only
8.3%. The presence of inflammation and the presence The compression with gauze impregnated with
of 3-root extractions increase the probability of hemor- tranexamic acid used as the hemostatic technique
rhage. Our results confirm the hypothesis that most likely explains the fact that all cases were
Table 1. DESCRIPTIVE ANALYSIS OF INTRAOPERATIVE HEMORRHAGE
Intraoperative Hemorrhage, n
Variable Data <30 Minutes >30 Minutes P Value
Age .49
<65 yr 65 (35.9) 58 7
$65 yr 116 (64.1) 107 9
Gender .86
Male 139 (76.8) 127 12
Female 42 (23.2) 38 4
Combination of antiaggregant drugs .48
ASA and clopidogrel 176 (97.2) 160 16
ASA and prasugrel 5 (2.8) 5 0
Anticoagulant drug .70
Acenocoumarol 16 (8.8) 15 1
None 165 (91.2) 150 15
Intake of NSAIDs .59
Yes 16 (8.8) 14 2
No 165 (91.2) 151 14
Presence of inflammation <.001*
Yes 36 (19.9) 29 7
No 145 (80.1) 136 9
Type of extraction performed .95
Routine exodontia 169 (93.4) 154 15
Complex exodontia 12 (6.6) 11 1
No. of anesthetic cartridges .025*
1 80 (44.2) 77 3
2 89 (49.2) 76 13
3 12 (6.6) 12 0
Anesthetic technique .31
Nerve block 36 (19.9) 35 1
Infiltration 131 (72.4) 118 13
Both techniques 14 (7.7) 12 2
No. of extracted teeth .56
1 148 (81.8) 136 12
2 30 (16.6) 26 4
3 3 (1.7) 3 0
No. of extracted roots .089*
1 74 (40.9) 72 2
2 61 (33.7) 53 8
3 43 (23.8) 37 6
4 3 (1.7) 3 0
Liver pathology .44
Yes 6 (3.3) 6 0
No 175 (96.7) 159 16
Kidney failure .95
Yes 12 (6.6) 11 1
No 169 (93.4) 154 15
Excessive alcohol consumption .041*
Yes 12 (6.6) 9 3
No 169 (93.4%) 156 13
Poorly controlled arterial hypertension .66
Yes 2 (1.1%) 2 0
No 179 (98.9%) 163 16
Long-term steroid treatment .66
Yes 2 (1.1%) 2 0
No 179 (98.9%) 163 16
Table 1. Cont’d
Intraoperative Hemorrhage, n
Variable Data <30 Minutes >30 Minutes P Value
Years of working experience .072*

<15 yr 2 professionals 20 5
15-24 yr 6 professionals 122 8
$25 yr 3 professionals 23 3
Note: Data are presented as number (percent) unless otherwise indicated.

Abbreviations: ASA, acetylsalicylic acid; NSAIDs, nonsteroidal anti-inflammatory drugs.
* Variables with P < .25 in univariate analysis.
Olmos-Carrasco et al. Hemorrhagic Complications of Dental Extractions. J Oral Maxillofac Surg 2015.
controlled by local hemostatic measures without used.5,14-16 In contrast to the study by Ca~ nigral and
further need for suture, as other authors have rec- Silvestre,5 it showed no influence on hemorrhage
ommended.10,11,15,16,18 severity, although statistical significance was not
There was a low percentage of complex exodon- reached in the former study.
tias (6.6%) in our study compared with studies Only 1 of the 16 patients who underwent combined
by Ca~ nigral and Silvestre5 (38.4%) and Nape~ nas oral anticoagulant–double antiplatelet therapy had
and Hong14 (51.7%). However, neither our study hemorrhage lasting more than 30 minutes, and simi-
nor the study by Ca~ nigral and Silvestre found an larly to other studies,10,11 no significant statistical
association between the hemorrhage severity association with more severe bleeding was found.
and the type of extraction. The presence of inflammation increased the risk of
The mean number of extracted teeth (1.2 0.4) hemorrhage persisting more than 30 minutes by a fac-
in our study was lower than that in other tor of 10. In the study by Lillis et al,15 all patients who
studies.14-16 However, we found no association had periodontitis and underwent double therapy had
between the number of extracted teeth and prolonged bleeding. In studies by Morimoto et al10
hemorrhagic complications, which differs from and Carter and Goss,27 as well as a review of the liter-
other authors.6 ature by Rodrıguez-Cabrera et al,31 a greater frequency
of postoperative hemorrhage also was found in pa-
Our mean patient age was higher than that in other tients undergoing antiplatelet or anticoagulant ther-
studies in which double antiplatelet therapy was apy (or both) with acute inflammation.
Three-root extractions also increased the risk of
Table 2. MULTIVARIATE ANALYSIS OF moderate hemorrhage, by a factor of 7. In a retrospec-
INTRAOPERATIVE HEMORRHAGE* tive study by Svensson et al,32 among 124 patients tak-
ing warfarin, all patients with postoperative bleeding
Variable b OR (95% CI) P Value
(5 of 124 patients) had undergone a surgical extraction
Presence of 2.310y 10.07 (2.38-42.54)y .002y
in the posterior part of the maxilla. In our study 4-root
inflammation extractions were performed in only 3 patients, who all
No. of extracted .17 had light bleeding; therefore we were unable to
roots conclude whether this may be considered as a
2 1.543 4.68 (0.87-25.17) .07 risk factor.
3 2.006y 7.34 (1.28-43.31)y .03y Similar to reports from other authors, no relevant
4 18.992 .99 clinical complications were found during the patients’
No. of anesthetic .27 assessments at 24 hours and 10 days after the extrac-
cartridges tions.14-16
2 1.141 3.13 (0.79-12.35) .10
3 18.259 .99
Abbreviations: CI, confidence interval; OR, odds ratio. LIMITATIONS AND STRENGTHS
* The Hosmer-Lemeshow statistical test for goodness of fit
We believe that our results are generalizable
yielded P = .99. The 2 log likelihood value equaled 80.97,
and the Cox and Snell R2 value equaled 0.14. because this study was conducted in oral and dental
y Statistically significant. care consultations within primary care by 11 different
Olmos-Carrasco et al. Hemorrhagic Complications of Dental dentists, without excluding patients who had pathol-
Extractions. J Oral Maxillofac Surg 2015. ogies that might increase hemorrhagic complications.
All the interventions performed were dental extrac- 4. Brennan MT, Valerin MA, Noll JL, et al: Aspirin use and post-
operative bleeding from dental extractions. J Dent Res 87:740,
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Acknowledgments
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assistance in the preparation of the manuscript, as well as the agement of antithrombotic therapy: American College of Chest
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Cirugía - 01 - Hemorragia Complicaciones Exodoncia

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DENTOALVEOLAR SURGERY

Hemorrhagic Complications of Dental

HEMORRHAGE AT 10 DAYS Contrary to the procedure of other

Table 1. DESCRIPTIVE ANALYSIS OF INTRAOPERATIVE HEMORRHAGE

Variable Data <30 Minutes >30 Minutes P Value

Variable Data <30 Minutes >30 Minutes P Value

Years of working experience .072*

Note: Data are presented as number (percent) unless otherwise indicated.

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