- Email: [email protected]
Hemorrhagic Complications of Dental Extractions in 181 Patients Undergoing Double Antiplatelet Therapy
Accepted Manuscript Hemorrhagic complications of dental extractions in 181 patients undergoing double antiplatelet therapy Olga Olmos-Carrasco, MD, FP Victoria Pastor-Ramos, MD, PhD, DDS Rafael Espinilla-Blanco, MD, DMD Ana Ortiz-Zárate, MD, DMD Irene García-Ávila, DMD, PhD Elías Rodríguez-Alonso, MD, DMD Rosario Herrero-Sanjuán, MD, DMD María-Magdalena Ruiz-García, DMD Paloma Gallego-Beuter, MD, DMD MaríaPaz Sánchez-Salgado, MD, DMD Ana-Isabel Terán-Agustín, MD, DMD Milagros Fernández-Behar, MD, DMD Inmaculada Peña-Sainz, MD, FP PII:
S0278-2391(14)01318-4
DOI:
10.1016/j.joms.2014.08.011
Reference:
YJOMS 56459
To appear in:
Journal of Oral and Maxillofacial Surgery
Received Date: 4 June 2014 Revised Date:
5 August 2014
Accepted Date: 5 August 2014
Please cite this article as: Olmos-Carrasco O, Pastor-Ramos V, Espinilla-Blanco R, Ortiz-Zárate A, García-Ávila I, Rodríguez-Alonso E, Herrero-Sanjuán R, Ruiz-García M-M, Gallego-Beuter P, SánchezSalgado M-P, Terán-Agustín A-I, Fernández-Behar M, Peña-Sainz I, Hemorrhagic complications of dental extractions in 181 patients undergoing double antiplatelet therapy, Journal of Oral and Maxillofacial Surgery (2014), doi: 10.1016/j.joms.2014.08.011. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Hemorrhagic complications of dental extractions in 181 patients undergoing double antiplatelet therapy.
Olga Olmos-Carrasco, MD, FP,a Victoria Pastor-Ramos, MD, PhD, DDS,b Rafael
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Espinilla-Blanco, MD, DMD,c Ana Ortiz-Zárate, MD, DMD,d Irene García-Ávila,
DMD, PhD,e Elías Rodríguez-Alonso, MD, DMD,f Rosario Herrero-Sanjuán, MD,
DMD,g María-Magdalena Ruiz-García, DMD,h Paloma Gallego-Beuter, MD, DMD,i
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María-Paz Sánchez-Salgado, MD, DMD,j Ana-Isabel Terán-Agustín, MD, DMD,k
a
Health center Jazmín. Servicio Madrileño de Salud. C/ Jazmín 33. 28033 Madrid.
Email: [email protected] b
Oral and dental care unit Alpes. Servicio Madrileño de Salud. Email:
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[email protected] c
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Milagros Fernández-Behar, MD, DMD,l Inmaculada Peña-Sainz, MD, FP m
Oral and dental care unit San Fermín. Servicio Madrileño de Salud. Email:
[email protected]
Oral and dental care unit Benita de Ávila. Servicio Madrileño de Salud. Email:
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d
[email protected] e
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Oral and dental care unit Silvano II. Servicio Madrileño de Salud. Assistant Professor.
University Dentistry Clinic. “Alfonso X El Sabio” University of Madrid. Email: [email protected] f
Oral and dental care unit Dr. Cirajas I. Servicio Madrileño de Salud. Associated
Professor. Department of Stomatology. Faculty of Health Sciences. “Rey Juan Carlos” University of Madrid. Email: [email protected]
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Oral and dental care unit Luis Vives. Servicio Madrileño de Salud. Email:
[email protected] h
Oral and dental care unit Daroca. Servicio Madrileño de Salud. Email:
[email protected] Oral and dental care unit Silvano I. Servicio Madrileño de Salud. Email:
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i
[email protected] j
Oral and dental care unit Jazmín. Servicio Madrileño de Salud. Email:
Oral and dental care unit Alameda. Servicio Madrileño de Salud. Email:
[email protected] l
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k
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[email protected]
Oral and dental care unit Canal de Panamá. Servicio Madrileño de Salud. Email:
[email protected] m
Health center Jazmín. Servicio Madrileño de Salud. Email:
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[email protected]
Corresponding author: Olga Olmos-Carrasco.
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Address: C/ Belice 52. 28027 Madrid. Spain Tel: 0034 687 595 530 – 0034 91 3204438
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Fax: 0034 91 3833216
Email: [email protected]
Disclosure of potential conflicts of interest: None. No financial support. No relationship with industry.
ACCEPTED MANUSCRIPT Is double antiplatelet therapy a handicap for dental extractions? Olga Olmos-Carrasco, MD, FP,a Victoria Pastor-Ramos, MD, PhD, DDS,b Rafael Espinilla-Blanco, MD, DMD,c Ana Ortiz-Zárate, MD, DMD,d Irene García-Ávila, DMD, PhD,e Elías Rodríguez-Alonso, MD, DMD,f Rosario Herrero-Sanjuán, MD,
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DMD,g María-Magdalena Ruiz-García, DMD,h Paloma Gallego-Beuter, MD, DMD,i María-Paz Sánchez-Salgado, MD, DMD,j Ana-Isabel Terán-Agustín, MD, DMD,k
Health center Jazmín. Servicio Madrileño de Salud. C/ Jazmín 33. 28033 Madrid.
Email: [email protected] b
Oral and dental care unit Alpes. Servicio Madrileño de Salud. Email:
[email protected] c
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a
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Milagros Fernández-Behar, MD, DMD,l Inmaculada Peña-Sainz, MD, FP m
Oral and dental care unit San Fermín. Servicio Madrileño de Salud. Email:
d
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[email protected]
Oral and dental care unit Benita de Ávila. Servicio Madrileño de Salud. Email:
[email protected] e
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Oral and dental care unit Silvano II. Servicio Madrileño de Salud. Assistant Professor.
University Dentistry Clinic. “Alfonso X El Sabio” University of Madrid. Email:
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[email protected] f
Oral and dental care unit Dr. Cirajas I. Servicio Madrileño de Salud. Associated
Professor. Department of Stomatology. Faculty of Health Sciences. “Rey Juan Carlos” University of Madrid. Email: [email protected] g
Oral and dental care unit Luis Vives. Servicio Madrileño de Salud. Email:
[email protected]
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Oral and dental care unit Daroca. Servicio Madrileño de Salud. Email:
[email protected] i
Oral and dental care unit Silvano I. Servicio Madrileño de Salud. Email:
[email protected] Oral and dental care unit Jazmín. Servicio Madrileño de Salud. Email:
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j
[email protected] k
Oral and dental care unit Alameda. Servicio Madrileño de Salud. Email:
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[email protected] l
[email protected] m
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Oral and dental care unit Canal de Panamá. Servicio Madrileño de Salud. Email:
Health center Jazmín. Servicio Madrileño de Salud. Email:
[email protected]
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Corresponding author: Olga Olmos-Carrasco. Address: C/ Belice 52. 28027 Madrid. Spain Tel: 0034 687 595 530 – 0034 91 3204438
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Fax: 0034 91 3833216
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Email: [email protected]
Disclosure of potential conflicts of interest: None. No financial support. No relationship with industry.
Word count: Abstract: 297. Manucrispt: 2761 Number of references: 32. Number of tables: 2
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Abstract Purpose There is limited information on hemorrhagic complications during invasive dental procedures in patients treated with double antiplatelet therapy. The objective of this
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study is to assess the frequency of hemorragic complications of patients taking dual antiplatelet medication undergoing dental extractions. Methods
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An observational, multicentric, prospective, cohort study was performed in 11 Oral and
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Dental Care units in Primary Care. The study sample was derived from the population of patients >18 years old 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.
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The predictor variables were: type of extraction performed, number of extracted teeth, number of extracted roots, presence of inflammation.
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The primary outcome variable was intraoperative hemorrhage and the secondary were hemorrhage at 24 hours and 10 days.
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First, a univariate analysis that considered all studied variables was performed. All variables with p < 0.25 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 >30 minutes in 15 patients (8.3%) and >60 minutes in only one patient, whose hemorrhage was controlled by local
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ACCEPTED MANUSCRIPT measures. The presence of inflammation and three-root extractions increased the probability of hemorrhage persisting for >30 minutes by factors of 10 and 7.3, respectively. Conclusions
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In patients treated with dual antipletelet therapy, dental extractions cause 8.3% of hemorrhagic complications >30 minutes in duration that are resolved using local
hemostatic measures. The results of the present study support the safety of dental
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extraction without withdrawal double antiplatelet therapy.
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Key words: dual antiplatelet therapy, dental surgery, tooth extraction.
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Statement of Clinical Relevance This study has the size needed to draw conclusion applicable to the general population in this situation. It has been conducted within primary care by 11 different dentists. Our results confirm the hypothesis that most dental extractions can be carried out safely
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without stopping dual antiplatelet therapy.
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Introduction Double antiplatelet therapy should not be prematurely stopped after an acute coronary syndrome or a stent implant because of the risk of heart attack and death.1 Numerous studies have assessed the frequency and severity of hemorrhagic complications of dental
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interventions in patients undergoing anticoagulant treatment, antiplatelet monotherapy, and anticoagulant-antiplatelet combination therapy.2–13 However, information on these complications in patients with double antiplatelet therapy is scarce. Few studies include
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patients with double antiaggregant therapy, and some have methodological deficiencies with regard to their small sample size and the bias inherent to retrospective data
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collection.5,14–16
Despite this paucity of information, the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Physicians, American College of Surgeons, American Dental Association,
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National Health Service, and numerous authors recommend either maintaining double antiplatelet therapy in dental interventions and applying the necessary local hemostatic measures in order to control the hemorrhage or delaying the intervention until the dual
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therapy can be withdrawn without risk.1,17–26
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The purpose of the present study was to address the following question: among patients with double antiplatelet therapy, can dental extractions be carried out safely? We hypothesized that dental extractions have a low frequency of hemorrhagic complications that are resolved using local hemostatic measures. The specific aims of this study were estimate the frequency of hemorrhagic complications in dental extractions of patients undergoing double antiplatelet therapy and to identify factors associated with an increased risk for intraoperative hemorrhage.
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Methods Study design To address the research purpose, we designed and implemented an observational,
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multicentric, prospective, cohort study.
This project was approved by the Ethics and Clinical Research Board of “Hospital Ramón y Cajal” and by the Central Research Committee of Primary Care of the
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Community of Madrid. The study was performed in accordance with the Declaration of
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Helsinki. Written informed consent was obtained from all patients prior to enrollment in the study. Study sample
The scope of the study included 11 Oral and Dental Care units of Primary Care of the Community of Madrid that serve a population of 561,603 people >14 years old. Of
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these, 2170 people (0.39 %) were undergoing double antiplatelet therapy at the beginning of the study. The study sample was derived from the population of patients
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who were undergoing double antiplatelet therapy and presented to the Oral and Dental Care units needing of dental extraction between October 1, 2011 and December 31,
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2013. Double antiplatelet therapy is the combination of 100 mg per day of acetylsalicylic acid and a second antiplatelet agent (clopidogrel, ticlopidine, prasugrel or ticagrelor).
To be included in the study sample, patients must be over 18 years, be treated at least the last 7 days and consent to participate in the study. Patients were excluded as study subjects if they were <18 years old, had stopped the single or double antiplatelet treatment for more than 48 hours before extraction, or refused study enrollment.
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ACCEPTED MANUSCRIPT Study variables The primary outcome variable was intraoperative hemorrhage. The secondary outcome variables were hemorrhage at 24 hours and hemorrhage at 10 days. Intraoperative hemorrhage was defined as hemorrhage occurring either during the
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intervention or the subsequent time the patient spent under observation at the
consultation. The severity of the hemorrhage was classified as a function of its duration and the measures needed to control it as follows: light hemorrhage if hemostasis was
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achieved in <30 minutes using the protocol described above; moderate if the bleeding continued for >30 minutes but less than 60; intense if bleeding continued for >60
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minutes; and severe when it required general measures and referral to a hospital. The hemorrhage at 24 hours and hemorrhage at 10 days were classified as absent, light, moderate, intense, or severe.
We defined as predictor variables the following: type of extraction performed, number
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of extracted teeth, number of extracted roots, presence of inflammation. Both simple and complex exodontias were performed. The extraction of the tooth from its socket without damaging it was considered a simple exodontia, and the procedures in
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which an osteotomy, odontosection, or elevation of mucoperiosteal flap was necessary were considered complex.
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Inflammation was considered to exist if signs or symptons of periodontitis or purulent discharge, swelling, or erythema of soft tissues are present close to the tooth. Other patient variables collected included: age, sex, anesthetic technique (infiltration/ nerve block/ both techniques), number of anesthetic cartridges, association of antiaggregant drugs (acetylsalicylic acid + clopidogrel, ticlopidine, prasugrel or ticagrelor)., anticoagulant drugs (yes/no), and intake of NSAIDs. Information collected from their family doctor clinical file included data regarding excessive alcohol
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ACCEPTED MANUSCRIPT consumption (yes/no), hepatopathology (yes/no), kidney failure (yes/no), poorly controlled arterial hypertension (yes/no), coagulopathies (yes/no), chemotherapy (yes/no), and chronic steroid treatment (yes/no). Patients were considered to have undergone NSAIDs treatment if they had taken the
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dosage indicated in the drug technical file during the 24 hours previous to the intervention.
Each health professional's total work experience was recorded as well.
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Intervention
The extractions were performed by the 11 dentists of the Oral and Dental Care units,
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who followed their usual dental extraction procedures in patients undergoing treatments that interfere with hemostasis. In all cases, 3% mepivacaine without a vasoconstrictor was the anesthetic used.
The hemostatic technique employed was 30 minutes of compression with gauze
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impregnated with a 500 mg ampoule of tranexamic acid. If the hemorrhage continued beyond 30 minutes, the gauze compression with tranexamic acid was repeated for an additional 30 minutes. The aim of the application of tranexamic acid is locally stabilize
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the clot formed, once hemostasis phase has ended. Tranexamic acid forms a reversible complex that displaces plasminogen from fibrin resulting in inhibition of fibrinolysis; it
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also inhibits the proteolytic activity of plasmin. This technique is part of our usual protocol to prevent postoperative bleeding in patients undergoing anticoagulant and antiplatelet therapy requiring dental extractions .27 Following the procedure, the patient received written instructions on recommended home care that included mouth washing with a 500 mg ampoule of tranexamic acid for 2 minutes, starting at 2 hours after the intervention, with repeated washings every 6 hours during the initial 48 hours after the extraction. In the case of a hemorrhagic
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ACCEPTED MANUSCRIPT episode, the patient was instructed to record its duration in order to communicate it at the following consultation. The patient was scheduled for a clinical consultation at 24 hours and 10 days after the intervention, or a phone inquiry was made to determine if any hemorrhagic complications had occurred.
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Data collection, management, and analyses
A specific protocol was designed to collect data and included in the electronic clinical record. All data handling and analysis were performed by the first author and were
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analyzed using the statistical software SPSS® version 18 for Microsoft Windows (SPSS Inc., Chicago, IL)..
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Previous research has found a high rate of bleeding complications that seem far higher to those produced in our area.5,14,15 Therefore, the sample size calculation was based on our previous experience, and a value of approximately 8% was estimated for hemorrhagic complications >30 minutes in duration. The necessary sample size was 164
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patients (α error = 5%, β error = 20%, precision = 4%).
Data are presented as the mean ± standard deviation for quantitative variables, and percentages and frequency distribution for qualitative variables. Age was evaluated as a
years old.
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categorical variable by splitting the patients into two groups: <65 years old and >65
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First, a univariate analysis that considered all studied variables was performed. All variables with p < 0.25 in the univariate analysis were included in a multivariate analysis. Possible interactions were considered and added to the initial model. The results of the logistic regression analysis are presented as the OR using a 95% CI.
Results One hundred and eighty-one patients with a mean age of 66.98 ± 12.8 years were included in the study. Most were male, 139 (76.8 %). A total of 217 teeth were
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ACCEPTED MANUSCRIPT extracted, with an average of 1.2 ± 0.4 teeth per patient. The most common antiplatelet combination was acetylsalicylic acid, 100 mg per day, and clopidogrel, 75 mg per day (97.2%). Only 5 patients were treated with 100 mg per day of acetylsalicylic acid and 10 mg of prasugrel.
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Intraoperative hemorrhage
During the course of extraction, 165 patients (91.2%) experienced light hemorrhage, defined as hemorrhage lasting <30 minutes. In 15 instances (8.3%), the hemorrhage
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continued for over 30 minutes, and one patient had a hemorrhagic episode exceeding 60 minutes. Hence, intraoperative hemorrhage was classified according to its duration as
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<30 minutes or >30 minutes. Table 1 shows the results of the descriptive analysis. The single patient with hemorrhage persisting >60 minutes had a vertical fracture of the extracted tooth, which was a mandibular molar; in this case, granulation tissue had replaced the bone and vestibular table, and it was necessary to perform a extensive
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curettage.
The logistic regression model included the following variables: years of working experience, number of anesthetic cartridges, number of extracted roots, presence of
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inflammation, and excessive alcohol consumption. The final model results are shown in Table 2. Only the presence of inflammation and three-root extractions were found to be
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risk factors for intraoperative hemorrhage. Neither working experience time nor excessive alcohol consumption were related to the severity of the hemorrhage. Hemorrhage at 24 hours One hundred and sixty-two patients (89.5%) reported an absence of bleeding, 15 patients (8.3%) suffered from light hemorrhage, and 4 patients (2.2%) recounted a bleeding episode >30 minutes in duration that was self-controlled using the
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ACCEPTED MANUSCRIPT recommended local hemostatic measures. No relevant statistical association was found between hemorrhage severity at 24 hours and the studied factors. Hemorrhage at 10 days One hundred and seventy-four patients (96.1%) reported an absence of bleeding, and 7
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patients (3.9%) suffered from light hemorrhage that was controlled with local
hemostatic measures. No significant statistical association was found between
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hemorrhage severity at 10 days and the assessed factors.
Discussion
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The purpose of this study was to address the following question: among patients with double antiplatelet therapy, can dental extractions be carried out safely?. Our hypothesis was that dental extractions had a low frequency of hemorrhagic complications. The specific aims were estimate the frequency of hemorrhagic complications in dental
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extractions of patients undergoing double platelet antiaggregant therapy and to identify factors associated with an increased risk for intraoperative hemorrhage. The percentage of patients experiencing intraoperative hemorrhage >30 minutes in
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duration was only 8.3%. The presence of inflammation and three-root extractions increase the probability of hemorrhage. Our results confirm the hypothesis that most
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dental extractions can be carried out safely without stopping dual antiplatelet therapy. There is no standard definition for hemorrhage severity after dental extractions. In the existing literature, the method used to measure the severity of hemorrhagic complications is frequently not described, and there is substantial heterogeneity in the definitions of those that do describe it, 3–5,9–16,27 which complicates the comparison of studies.26 The classification used in this study was based on the duration of the hemorrhage, which appears to be appropriate because of its ease of use and adaptation
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ACCEPTED MANUSCRIPT to our usual protocol. In a study by Lillis et al.,15 66.7% of 33 patients undergoing double antiplatelet therapy experienced hemorrhage lasting >30 minutes. In a study by Cañigral et al.,5 4 of the 9 patients (44.4%) under dual therapy had moderate hemorrhage that was defined as >10
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minutes long and stopped by using local hemostatic measures in less than 60 minutes in all cases. A study from University of Korea, by Park et al.16, with all dental extractions performed in hospital by the same dentist, included 100 patients with double and triple
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antiplatelet therapy, and only 2 cases of excessive hemorrhage (4, and 5 hours long)
hemorrhages of shorter duration.
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were present; however, the authors did not discuss the number of patients with
In our study, there were several circumstances that may have increased the duration of the bleeding:
- Contrary to the procedure of other authors,4,9–11,15,16,18,23,25 we used anesthesia without
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a vasoconstrictor to avoid adverse reactions in patients suffering from coronary disease, whose adrenaline dosage is limited to 0.04 mg per session.28–30 - Suturing is not included in our dental extractions protocol.
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- We included patients on oral anticoagulants and NSAIDs, with excessive alcohol consumption, liver pathology, or renal failure, which are excluded from studies by other
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authors because of their increased bleeding risk.4,10,15,16 We don´t advise the use of NSAIDs in patients with cardiovascular disease and antiplatelet therapy, but ibuprofen use in our country is widespread and often self-medication is used in the presence of acute pain. And there were also several circumstances that may have decreased the duration of the bleeding:
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ACCEPTED MANUSCRIPT - The compression with gauze impregnated with tranexamic acid used as the hemostatic technique likely explains the fact that all were controlled by local measures without further need of suture, as other authors have recommended.10,11,15,16,18 - The low percentage of complex exodontias (6.6%) in our study compared to other
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studies by Cañigral et al.5 (38.4%) and Napeñas et al.14 (51.7%). However, neither our study nor the one by Cañigral et al.5 found an association between the hemorrhage severity and the type of extraction.
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- The mean number of extracted teeth (1.2 ± 0.4) in our study, which was lower than that in other studies.14–16 However, we found no association between the number of
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extracted teeth and hemorrhagic complications, which differs from other authors.6 Our mean patient age was higher than that of other studies where double antiplatelet therapy was used,5,14–16 and, in contrast to a study by Cañigral et al.,5 it showed no influence on hemorrhage severity, although statistical significance was not reached in
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the former.
Only one of the 16 patients who were undergoing combined oral anticoagulant-double antiplatelet therapy suffered from hemorrhage >30 minutes in duration and, similarly to
found.
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other studies,10,11 no significant statistical association with a more severe bleeding was
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The presence of inflammation increased the risk of hemorrhage persisting >30 minutes by a factor of 10. In a study by Lillis et al.,15 all patients undergoing double therapy and suffering from periodontitis experienced prolonged bleeding. In other studies by Morimoto et al.,10,Carter et al 27 and a review of the literature by Rodríguez-Cabrera et al31, a greater frequency of postoperative hemorrhage was also found in patients undergoing antiplatelet and/or anticoagulant therapy with acute inflammation.
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ACCEPTED MANUSCRIPT Three-root extractions also increased the risk of moderate hemorrhage by a factor of 7. In a retrospective study by Svensson et al.,32 in 124 patients on warfarin, all patients with a postoperative bleeding (5/124) had received a surgical extraction in the posterior part of the maxilla. Four-root extractions were performed in only three patients, who all
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experienced light bleeding; therefore, we were unable to conclude whether it may be considered as a risk factor.
Similar to reports from other authors, no relevant clinical complications were found
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during the patients' assessments at 24 hours and 10 days following the extractions.14–16 Limitations and strengths
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We believe these results are generalizable because this study was conducted in oral and dental care consultations within primary care by 11 different dentists, without excluding patients suffering from pathologies that might increase hemorrhagic complications. All the interventions performed were dental extractions, which are the only dental
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procedures for adults covered by the Spanish National Health System; therefore, our results cannot be extrapolated to other types of interventions. Our mean number of extracted teeth is low, that may have decreased the duration of the bleeding, however,
complications.
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we found no association between the number of extractions and hemorrhagic
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Antiplatelet combinations other than acetylsalicylic acid and clopidogrel were not assessed, since this is the most common association in our population (97.2% of our patients).
The assessment of other possible pathologies of patients was done by the dentists at the consultation by reviewing their family doctor clinical file exclusively, and excessive alcohol consumption or the degree of kidney failure was not quantified in the cases where it existed. Neither these patients nor the ones with hepatopathology, chronic
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ACCEPTED MANUSCRIPT steroid treatment, or poorly controlled arterial hypertension experienced more hemorrhagic complications, but the number of these cases was very small, and differences might have gone undetected. Conclusions
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Dental extractions in patients on double oral antiplatelet therapy cause a 8.3% of hemorrhagic complications exceeding 30 minutes, which are resolved by local
hemostatic measures. The presence of inflammation and three-root extractions increase
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the probability of hemorrhage. Our results confirm the hypothesis that most dental extractions can be carried out safely without stopping dual antiplatelet therapy.
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Additional research is needed to assess the frequency of hemorrhagic complications during invasive dental procedures in patients treated with antiplatelet combinations other than acetylsalicylic acid and clopidogrel, and during interventions other than
Acknowledgments
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dental extractions.
We thank Dr. Ricardo Rodríguez and Dra. María José Torijano for their assistance in
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the preparation of the manuscript, and the patients for participating in the study.
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13. Barrero MV, Knezevic M, Tapia M, Llorente AV, Carlos J, Valverde O, Garc F,
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Pžrez OL, Dom S, Manuel J, Cremades D, Reyes JC, Canaria G.: Cirugía oral en pacientes en tratamiento con anticoagulantes orales . Pauta de actuación. Med Oral7:63–70, 2002.
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14. Napeñas J, Hong C.: The frequency of bleeding complications after invasive dental treatment in patients receiving single and dual antiplatelet therapy. J Am Dent
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Assoc140:690–5, 2009. Available at: http://europepmc.org/abstract/MED/19491165.
15. Lillis T, Ziakas A, Koskinas K.: Safety of dental extractions during uninterrupted single or dual antiplatelet treatment. Am J Cardiol108:964–7, 2011. Available at:
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http://www.sciencedirect.com/science/article/pii/S0002914911019151.
16. Park M-W, Her S-H, Kwon JB, Lee JB, Choi M-S, Cho JS, Kim D-B, Chung W-S, Seung K-B, Kim K-Y.: Safety of dental extractions in coronary drug-eluting stenting
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17. Grines CL, Bonow RO, Casey DE, Gardner TJ, Lockhart PB, Moliterno DJ, O’Gara P, Whitlow P.: Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions,. J Am Coll Cardiol49:734–9, 2007. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17291948.
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ACCEPTED MANUSCRIPT 18. Pototski M, Amenábar J.: Dental management of patients receiving anticoagulation or antiplatelet treatment. J Oral Sci49:253–8, 2007. Available at: http://jlc.jst.go.jp/JST.JSTAGE/josnusd/49.253?from=Google.
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19. Brennan M, Wynn R, Miller C.: Aspirin and bleeding in dentistry: an update and recommendations. Oral Surg Oral Med Oral Pathol Oral Radiol Endod104:316–23, 2007. Available at:
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B, Martí G, Cascant P, Martín-Yuste V, Brugaletta S, Sabaté M, Alfonso F, Capote ML, La Torre JM De, Ruíz-Lera M, Sanmiguel D, Cárdenas M, Pujol B, Baz J a, Iñiguez A, Trillo R, González-Béjar O, Casanova J, Sánchez-Gila J, García-Dorado D.: Background, incidence, and predictors of antiplatelet therapy discontinuation during the
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21. Douketis JD, Berger PB, Dunn AS, Jaffer AK, Spyropoulos AC, Becker RC, Ansell J.: The perioperative management of antithrombotic therapy: American College of
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Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest133:299S–339S, 2008. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18574269.
22. Ferrari E, Benhamou M, Cerboni P, Marcel B.: Coronary syndromes following aspirin withdrawal: a special risk for late stent thrombosis. J Am Coll Cardiol45:456–9, 2005. Available at: http://www.ncbi.nlm.nih.gov/pubmed/15680728.
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ACCEPTED MANUSCRIPT 23. Chee F, How C.: Doctor, my dentist wants your opinion. Singapore Med J54:11–3; quiz p.14, 2013. Available at: http://europepmc.org/abstract/med/23338910.
24. Wahl M.: Dental surgery and antiplatelet agents: bleed or die. Am J Med, 2014.
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25. Randall C.: Surgical management of the Primary Care dental patient on antipltelet medication. Available at: http://www.ukmi.nhs.uk/activities/specialistServices/. Access
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May 19, 2011.
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26. Napeñas JJ, Hong CHL, Brennan T, Furney SL, Fox PC, Lockhart PB, Brennan MT.: Review of postoperative bleeding risk in dental patients on antiplatelet therapy. Oral Surg Oral Med Oral Pathol Oral Radiol3:262, 2013. Available at: http://www.ncbi.nlm.nih.gov/pubmed/25062587.
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27. Carter G, Goss a.: Tranexamic acid mouthwash — A prospective randomized study of a 2-day regimen vs 5-day regimen to prevent postoperative bleeding in anticoagulated patients requiring dental extractions. Int J Oral Maxillofac Surg32:504–
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28. Davis B.: What dose of epinephrine contained in local anesthesia can be safely administered to a patient with underlying cardiac disease during a dental procedure. J Can Dent Assoc76:76:a36, 2010. Available at: http://scholar.google.com/scholar?hl=en&btnG=Search&q=intitle:What+dose+of+epine phrine+contained+in+local+anesthesia+can+be+safely+administered+to+a+patient+wit h+underlying+cardiac+disease+during+a+dental+procedure?#2.
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ACCEPTED MANUSCRIPT 29. Su N, Liu Y, Yang X, Shi Z, Huang Y.: Efficacy and safety of mepivacaine compared with lidocaine in local anaesthesia in dentistry: a meta-analysis of randomised controlled trials. Int Dent J64:96–107, 2014. Available at:
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http://www.ncbi.nlm.nih.gov/pubmed/24428507.
30. Serrera Figallo M a, Velázquez Cayón RT, Torres Lagares D, Corcuera Flores JR, Machuca Portillo G.: Use of anesthetics associated to vasoconstrictors for dentistry in
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patients with cardiopathies. Review of the literature published in the last decade. J Clin Exp Dent4:e107–11, 2012. Available at:
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http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3908793&tool=pmcentrez& rendertype=abstract.
31. Rodriguez-Cabrera M, Barona-Dorado C, Leco-Berrocal I, Gomez-Moreno G, Martinez-Gonzalez J.: Extractions without eliminating anticoagulant treatment: A
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literature review. Med Oral Patol Oral y Cir Bucal16:e800–e804, 2011. Available at: http://www.medicinaoral.com/pubmed/medoralv16_i6_p800.pdf.
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32. Svensson R, Hallmer F, Englesson CS, Svensson PJ, Becktor JP.: Treatment with local hemostatic agents and primary closure after tooth extraction in warfarin treated
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patients. Swed Dent J37:71–7, 2013. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23957141.
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Table 1. Descriptive analysis of intraoperative hemorrhage Intraoperative hemorrhage Variable
Number (%)
P-value >30 minutes
<65 years old: 65 (35.9)
58
7
>65 years old: 116 (64.1)
107
Male: 139 (76.8)
127
a
Sex Female: 42 (23.2)
16
5
0
Acenocumarol: 16 (8.8)
15
1
No: 165 (91.2)
150
15
Yes: 16 (8.8)
14
2
No: 165 (91.2)
151
14
Yes: 36 (19.9)
29
7
No: 145 (80.1)
136
9
Routine exodontia: 169 (93.4)
154
15
Complex exodontia: 12 (6.6)
11
1
1: 80 (44.2)
77
3
2: 89 (49.2)
76
13
3: 12 (6.6)
12
0
Nerve block: 36 (19.9)
35
1
Infiltration: 131 (72.4)
118
13
a
ASA + prasugrel: 5 (2.8)
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Anticoagulant drugs
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antiaggregant drugs
b
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Presence of inflammation
performed
0.86
160
ASA + clopidogrel: 176 (97.2)
Type of extraction
12 4
a
0.49
9
38
Association of
Intake of NSAIDs
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Age
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<30 minutes
0.48
0.70
0.59
0.000
0.95
Number of anesthetic
0.025
cartridges
Anesthetic technique
0.31
23
ACCEPTED MANUSCRIPT 12
2
1: 148 (81.8)
136
12
2: 30 (16.6)
26
4
3: 3 (1.7)
3
0
1: 74 (40.9)
72
2
2: 61 (33.7)
53
3: 43 (23.8)
37
4: 3 (1.7)
3
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Number of extracted roots
Yes: 6 (3.3)
0
159
16
11
1
154
15
9
3
156
13
2
0
163
16
2
0
163
16
<15 years: 2 professionals
20
5
15-24 years: 6 professionals
122
8
>25 years: 3 professionals
23
3
Kidney failure No: 169 (93.4) Yes: 12 (6.6)
consumption
No: 169 (93.4%)
Poorly controlled arterial
Yes: 2 (1.1%)
hypertension
No: 179 (98.9%)
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Excessive alcohol
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Yes: 12 (6.6)
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Yes: 2 (1.1%)
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No: 179 (98.9%)
0.089
6
0
No: 175 (96.7)
Chronic steroid treatment
8
6
Liver pathology
0.56
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Number of extracted teeth
Both techniques: 14 (7.7)
0.44
0.95
0.041
0.66
0.66
Years of working experience a
ASA: acetylsalicylic acid
b
NSAIDs: non-steroidal anti-inflammatory drugs
0.072
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Variable
Beta
Presence of inflammation
2.310
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Table 2. Multivariate analysis of intraoperative hemorrhagea
Odds Ratio (IC 95%) P-value 10.07 (2.38-42.54)
0.17
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Number of extracted roots
0.002
1.543
4.68 (0.87- 25.17)
0.07
Three-root extractions
2.006
7.34 (1.28-43.31)
0.03
Four-root extractions
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Two-root extractions
-18.992
Number of anesthetic cartridges
1.141
3 cartridges
-18.259
a
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2 cartridges
3.13 (0.79-12.35)
0.99 0.27 0.10 0.99
Hosmer-Lemeshow statistical test for goodness of fit: p = 0.99.
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-2 log likelihood = 80.97; Cox and Snell R2 = 0.14.
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S0278-2391(14)01318-4
DOI:
10.1016/j.joms.2014.08.011
Reference:
YJOMS 56459
To appear in:
Journal of Oral and Maxillofacial Surgery
Received Date: 4 June 2014 Revised Date:
5 August 2014
Accepted Date: 5 August 2014
Please cite this article as: Olmos-Carrasco O, Pastor-Ramos V, Espinilla-Blanco R, Ortiz-Zárate A, García-Ávila I, Rodríguez-Alonso E, Herrero-Sanjuán R, Ruiz-García M-M, Gallego-Beuter P, SánchezSalgado M-P, Terán-Agustín A-I, Fernández-Behar M, Peña-Sainz I, Hemorrhagic complications of dental extractions in 181 patients undergoing double antiplatelet therapy, Journal of Oral and Maxillofacial Surgery (2014), doi: 10.1016/j.joms.2014.08.011. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Hemorrhagic complications of dental extractions in 181 patients undergoing double antiplatelet therapy.
Olga Olmos-Carrasco, MD, FP,a Victoria Pastor-Ramos, MD, PhD, DDS,b Rafael
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Espinilla-Blanco, MD, DMD,c Ana Ortiz-Zárate, MD, DMD,d Irene García-Ávila,
DMD, PhD,e Elías Rodríguez-Alonso, MD, DMD,f Rosario Herrero-Sanjuán, MD,
DMD,g María-Magdalena Ruiz-García, DMD,h Paloma Gallego-Beuter, MD, DMD,i
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María-Paz Sánchez-Salgado, MD, DMD,j Ana-Isabel Terán-Agustín, MD, DMD,k
a
Health center Jazmín. Servicio Madrileño de Salud. C/ Jazmín 33. 28033 Madrid.
Email: [email protected] b
Oral and dental care unit Alpes. Servicio Madrileño de Salud. Email:
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[email protected] c
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Milagros Fernández-Behar, MD, DMD,l Inmaculada Peña-Sainz, MD, FP m
Oral and dental care unit San Fermín. Servicio Madrileño de Salud. Email:
[email protected]
Oral and dental care unit Benita de Ávila. Servicio Madrileño de Salud. Email:
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d
[email protected] e
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Oral and dental care unit Silvano II. Servicio Madrileño de Salud. Assistant Professor.
University Dentistry Clinic. “Alfonso X El Sabio” University of Madrid. Email: [email protected] f
Oral and dental care unit Dr. Cirajas I. Servicio Madrileño de Salud. Associated
Professor. Department of Stomatology. Faculty of Health Sciences. “Rey Juan Carlos” University of Madrid. Email: [email protected]
ACCEPTED MANUSCRIPT g
Oral and dental care unit Luis Vives. Servicio Madrileño de Salud. Email:
[email protected] h
Oral and dental care unit Daroca. Servicio Madrileño de Salud. Email:
[email protected] Oral and dental care unit Silvano I. Servicio Madrileño de Salud. Email:
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i
[email protected] j
Oral and dental care unit Jazmín. Servicio Madrileño de Salud. Email:
Oral and dental care unit Alameda. Servicio Madrileño de Salud. Email:
[email protected] l
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k
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[email protected]
Oral and dental care unit Canal de Panamá. Servicio Madrileño de Salud. Email:
[email protected] m
Health center Jazmín. Servicio Madrileño de Salud. Email:
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[email protected]
Corresponding author: Olga Olmos-Carrasco.
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Address: C/ Belice 52. 28027 Madrid. Spain Tel: 0034 687 595 530 – 0034 91 3204438
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Fax: 0034 91 3833216
Email: [email protected]
Disclosure of potential conflicts of interest: None. No financial support. No relationship with industry.
ACCEPTED MANUSCRIPT Is double antiplatelet therapy a handicap for dental extractions? Olga Olmos-Carrasco, MD, FP,a Victoria Pastor-Ramos, MD, PhD, DDS,b Rafael Espinilla-Blanco, MD, DMD,c Ana Ortiz-Zárate, MD, DMD,d Irene García-Ávila, DMD, PhD,e Elías Rodríguez-Alonso, MD, DMD,f Rosario Herrero-Sanjuán, MD,
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DMD,g María-Magdalena Ruiz-García, DMD,h Paloma Gallego-Beuter, MD, DMD,i María-Paz Sánchez-Salgado, MD, DMD,j Ana-Isabel Terán-Agustín, MD, DMD,k
Health center Jazmín. Servicio Madrileño de Salud. C/ Jazmín 33. 28033 Madrid.
Email: [email protected] b
Oral and dental care unit Alpes. Servicio Madrileño de Salud. Email:
[email protected] c
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a
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Milagros Fernández-Behar, MD, DMD,l Inmaculada Peña-Sainz, MD, FP m
Oral and dental care unit San Fermín. Servicio Madrileño de Salud. Email:
d
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[email protected]
Oral and dental care unit Benita de Ávila. Servicio Madrileño de Salud. Email:
[email protected] e
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Oral and dental care unit Silvano II. Servicio Madrileño de Salud. Assistant Professor.
University Dentistry Clinic. “Alfonso X El Sabio” University of Madrid. Email:
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[email protected] f
Oral and dental care unit Dr. Cirajas I. Servicio Madrileño de Salud. Associated
Professor. Department of Stomatology. Faculty of Health Sciences. “Rey Juan Carlos” University of Madrid. Email: [email protected] g
Oral and dental care unit Luis Vives. Servicio Madrileño de Salud. Email:
[email protected]
1
ACCEPTED MANUSCRIPT h
Oral and dental care unit Daroca. Servicio Madrileño de Salud. Email:
[email protected] i
Oral and dental care unit Silvano I. Servicio Madrileño de Salud. Email:
[email protected] Oral and dental care unit Jazmín. Servicio Madrileño de Salud. Email:
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j
[email protected] k
Oral and dental care unit Alameda. Servicio Madrileño de Salud. Email:
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[email protected] l
[email protected] m
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Oral and dental care unit Canal de Panamá. Servicio Madrileño de Salud. Email:
Health center Jazmín. Servicio Madrileño de Salud. Email:
[email protected]
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Corresponding author: Olga Olmos-Carrasco. Address: C/ Belice 52. 28027 Madrid. Spain Tel: 0034 687 595 530 – 0034 91 3204438
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Fax: 0034 91 3833216
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Email: [email protected]
Disclosure of potential conflicts of interest: None. No financial support. No relationship with industry.
Word count: Abstract: 297. Manucrispt: 2761 Number of references: 32. Number of tables: 2
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Abstract Purpose There is limited information on hemorrhagic complications during invasive dental procedures in patients treated with double antiplatelet therapy. The objective of this
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study is to assess the frequency of hemorragic complications of patients taking dual antiplatelet medication undergoing dental extractions. Methods
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An observational, multicentric, prospective, cohort study was performed in 11 Oral and
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Dental Care units in Primary Care. The study sample was derived from the population of patients >18 years old 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.
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The predictor variables were: type of extraction performed, number of extracted teeth, number of extracted roots, presence of inflammation.
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The primary outcome variable was intraoperative hemorrhage and the secondary were hemorrhage at 24 hours and 10 days.
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First, a univariate analysis that considered all studied variables was performed. All variables with p < 0.25 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 >30 minutes in 15 patients (8.3%) and >60 minutes in only one patient, whose hemorrhage was controlled by local
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ACCEPTED MANUSCRIPT measures. The presence of inflammation and three-root extractions increased the probability of hemorrhage persisting for >30 minutes by factors of 10 and 7.3, respectively. Conclusions
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In patients treated with dual antipletelet therapy, dental extractions cause 8.3% of hemorrhagic complications >30 minutes in duration that are resolved using local
hemostatic measures. The results of the present study support the safety of dental
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extraction without withdrawal double antiplatelet therapy.
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Key words: dual antiplatelet therapy, dental surgery, tooth extraction.
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Statement of Clinical Relevance This study has the size needed to draw conclusion applicable to the general population in this situation. It has been conducted within primary care by 11 different dentists. Our results confirm the hypothesis that most dental extractions can be carried out safely
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without stopping dual antiplatelet therapy.
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Introduction Double antiplatelet therapy should not be prematurely stopped after an acute coronary syndrome or a stent implant because of the risk of heart attack and death.1 Numerous studies have assessed the frequency and severity of hemorrhagic complications of dental
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interventions in patients undergoing anticoagulant treatment, antiplatelet monotherapy, and anticoagulant-antiplatelet combination therapy.2–13 However, information on these complications in patients with double antiplatelet therapy is scarce. Few studies include
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patients with double antiaggregant therapy, and some have methodological deficiencies with regard to their small sample size and the bias inherent to retrospective data
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collection.5,14–16
Despite this paucity of information, the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Physicians, American College of Surgeons, American Dental Association,
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National Health Service, and numerous authors recommend either maintaining double antiplatelet therapy in dental interventions and applying the necessary local hemostatic measures in order to control the hemorrhage or delaying the intervention until the dual
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therapy can be withdrawn without risk.1,17–26
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The purpose of the present study was to address the following question: among patients with double antiplatelet therapy, can dental extractions be carried out safely? We hypothesized that dental extractions have a low frequency of hemorrhagic complications that are resolved using local hemostatic measures. The specific aims of this study were estimate the frequency of hemorrhagic complications in dental extractions of patients undergoing double antiplatelet therapy and to identify factors associated with an increased risk for intraoperative hemorrhage.
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Methods Study design To address the research purpose, we designed and implemented an observational,
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multicentric, prospective, cohort study.
This project was approved by the Ethics and Clinical Research Board of “Hospital Ramón y Cajal” and by the Central Research Committee of Primary Care of the
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Community of Madrid. The study was performed in accordance with the Declaration of
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Helsinki. Written informed consent was obtained from all patients prior to enrollment in the study. Study sample
The scope of the study included 11 Oral and Dental Care units of Primary Care of the Community of Madrid that serve a population of 561,603 people >14 years old. Of
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these, 2170 people (0.39 %) were undergoing double antiplatelet therapy at the beginning of the study. The study sample was derived from the population of patients
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who were undergoing double antiplatelet therapy and presented to the Oral and Dental Care units needing of dental extraction between October 1, 2011 and December 31,
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2013. Double antiplatelet therapy is the combination of 100 mg per day of acetylsalicylic acid and a second antiplatelet agent (clopidogrel, ticlopidine, prasugrel or ticagrelor).
To be included in the study sample, patients must be over 18 years, be treated at least the last 7 days and consent to participate in the study. Patients were excluded as study subjects if they were <18 years old, had stopped the single or double antiplatelet treatment for more than 48 hours before extraction, or refused study enrollment.
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ACCEPTED MANUSCRIPT Study variables The primary outcome variable was intraoperative hemorrhage. The secondary outcome variables were hemorrhage at 24 hours and hemorrhage at 10 days. Intraoperative hemorrhage was defined as hemorrhage occurring either during the
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intervention or the subsequent time the patient spent under observation at the
consultation. The severity of the hemorrhage was classified as a function of its duration and the measures needed to control it as follows: light hemorrhage if hemostasis was
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achieved in <30 minutes using the protocol described above; moderate if the bleeding continued for >30 minutes but less than 60; intense if bleeding continued for >60
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minutes; and severe when it required general measures and referral to a hospital. The hemorrhage at 24 hours and hemorrhage at 10 days were classified as absent, light, moderate, intense, or severe.
We defined as predictor variables the following: type of extraction performed, number
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of extracted teeth, number of extracted roots, presence of inflammation. Both simple and complex exodontias were performed. The extraction of the tooth from its socket without damaging it was considered a simple exodontia, and the procedures in
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which an osteotomy, odontosection, or elevation of mucoperiosteal flap was necessary were considered complex.
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Inflammation was considered to exist if signs or symptons of periodontitis or purulent discharge, swelling, or erythema of soft tissues are present close to the tooth. Other patient variables collected included: age, sex, anesthetic technique (infiltration/ nerve block/ both techniques), number of anesthetic cartridges, association of antiaggregant drugs (acetylsalicylic acid + clopidogrel, ticlopidine, prasugrel or ticagrelor)., anticoagulant drugs (yes/no), and intake of NSAIDs. Information collected from their family doctor clinical file included data regarding excessive alcohol
8
ACCEPTED MANUSCRIPT consumption (yes/no), hepatopathology (yes/no), kidney failure (yes/no), poorly controlled arterial hypertension (yes/no), coagulopathies (yes/no), chemotherapy (yes/no), and chronic steroid treatment (yes/no). Patients were considered to have undergone NSAIDs treatment if they had taken the
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dosage indicated in the drug technical file during the 24 hours previous to the intervention.
Each health professional's total work experience was recorded as well.
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Intervention
The extractions were performed by the 11 dentists of the Oral and Dental Care units,
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who followed their usual dental extraction procedures in patients undergoing treatments that interfere with hemostasis. In all cases, 3% mepivacaine without a vasoconstrictor was the anesthetic used.
The hemostatic technique employed was 30 minutes of compression with gauze
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impregnated with a 500 mg ampoule of tranexamic acid. If the hemorrhage continued beyond 30 minutes, the gauze compression with tranexamic acid was repeated for an additional 30 minutes. The aim of the application of tranexamic acid is locally stabilize
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the clot formed, once hemostasis phase has ended. Tranexamic acid forms a reversible complex that displaces plasminogen from fibrin resulting in inhibition of fibrinolysis; it
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also inhibits the proteolytic activity of plasmin. This technique is part of our usual protocol to prevent postoperative bleeding in patients undergoing anticoagulant and antiplatelet therapy requiring dental extractions .27 Following the procedure, the patient received written instructions on recommended home care that included mouth washing with a 500 mg ampoule of tranexamic acid for 2 minutes, starting at 2 hours after the intervention, with repeated washings every 6 hours during the initial 48 hours after the extraction. In the case of a hemorrhagic
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ACCEPTED MANUSCRIPT episode, the patient was instructed to record its duration in order to communicate it at the following consultation. The patient was scheduled for a clinical consultation at 24 hours and 10 days after the intervention, or a phone inquiry was made to determine if any hemorrhagic complications had occurred.
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Data collection, management, and analyses
A specific protocol was designed to collect data and included in the electronic clinical record. All data handling and analysis were performed by the first author and were
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analyzed using the statistical software SPSS® version 18 for Microsoft Windows (SPSS Inc., Chicago, IL)..
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Previous research has found a high rate of bleeding complications that seem far higher to those produced in our area.5,14,15 Therefore, the sample size calculation was based on our previous experience, and a value of approximately 8% was estimated for hemorrhagic complications >30 minutes in duration. The necessary sample size was 164
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patients (α error = 5%, β error = 20%, precision = 4%).
Data are presented as the mean ± standard deviation for quantitative variables, and percentages and frequency distribution for qualitative variables. Age was evaluated as a
years old.
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categorical variable by splitting the patients into two groups: <65 years old and >65
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First, a univariate analysis that considered all studied variables was performed. All variables with p < 0.25 in the univariate analysis were included in a multivariate analysis. Possible interactions were considered and added to the initial model. The results of the logistic regression analysis are presented as the OR using a 95% CI.
Results One hundred and eighty-one patients with a mean age of 66.98 ± 12.8 years were included in the study. Most were male, 139 (76.8 %). A total of 217 teeth were
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ACCEPTED MANUSCRIPT extracted, with an average of 1.2 ± 0.4 teeth per patient. The most common antiplatelet combination was acetylsalicylic acid, 100 mg per day, and clopidogrel, 75 mg per day (97.2%). Only 5 patients were treated with 100 mg per day of acetylsalicylic acid and 10 mg of prasugrel.
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Intraoperative hemorrhage
During the course of extraction, 165 patients (91.2%) experienced light hemorrhage, defined as hemorrhage lasting <30 minutes. In 15 instances (8.3%), the hemorrhage
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continued for over 30 minutes, and one patient had a hemorrhagic episode exceeding 60 minutes. Hence, intraoperative hemorrhage was classified according to its duration as
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<30 minutes or >30 minutes. Table 1 shows the results of the descriptive analysis. The single patient with hemorrhage persisting >60 minutes had a vertical fracture of the extracted tooth, which was a mandibular molar; in this case, granulation tissue had replaced the bone and vestibular table, and it was necessary to perform a extensive
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curettage.
The logistic regression model included the following variables: years of working experience, number of anesthetic cartridges, number of extracted roots, presence of
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inflammation, and excessive alcohol consumption. The final model results are shown in Table 2. Only the presence of inflammation and three-root extractions were found to be
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risk factors for intraoperative hemorrhage. Neither working experience time nor excessive alcohol consumption were related to the severity of the hemorrhage. Hemorrhage at 24 hours One hundred and sixty-two patients (89.5%) reported an absence of bleeding, 15 patients (8.3%) suffered from light hemorrhage, and 4 patients (2.2%) recounted a bleeding episode >30 minutes in duration that was self-controlled using the
11
ACCEPTED MANUSCRIPT recommended local hemostatic measures. No relevant statistical association was found between hemorrhage severity at 24 hours and the studied factors. Hemorrhage at 10 days One hundred and seventy-four patients (96.1%) reported an absence of bleeding, and 7
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patients (3.9%) suffered from light hemorrhage that was controlled with local
hemostatic measures. No significant statistical association was found between
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hemorrhage severity at 10 days and the assessed factors.
Discussion
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The purpose of this study was to address the following question: among patients with double antiplatelet therapy, can dental extractions be carried out safely?. Our hypothesis was that dental extractions had a low frequency of hemorrhagic complications. The specific aims were estimate the frequency of hemorrhagic complications in dental
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extractions of patients undergoing double platelet antiaggregant therapy and to identify factors associated with an increased risk for intraoperative hemorrhage. The percentage of patients experiencing intraoperative hemorrhage >30 minutes in
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duration was only 8.3%. The presence of inflammation and three-root extractions increase the probability of hemorrhage. Our results confirm the hypothesis that most
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dental extractions can be carried out safely without stopping dual antiplatelet therapy. There is no standard definition for hemorrhage severity after dental extractions. In the existing literature, the method used to measure the severity of hemorrhagic complications is frequently not described, and there is substantial heterogeneity in the definitions of those that do describe it, 3–5,9–16,27 which complicates the comparison of studies.26 The classification used in this study was based on the duration of the hemorrhage, which appears to be appropriate because of its ease of use and adaptation
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ACCEPTED MANUSCRIPT to our usual protocol. In a study by Lillis et al.,15 66.7% of 33 patients undergoing double antiplatelet therapy experienced hemorrhage lasting >30 minutes. In a study by Cañigral et al.,5 4 of the 9 patients (44.4%) under dual therapy had moderate hemorrhage that was defined as >10
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minutes long and stopped by using local hemostatic measures in less than 60 minutes in all cases. A study from University of Korea, by Park et al.16, with all dental extractions performed in hospital by the same dentist, included 100 patients with double and triple
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antiplatelet therapy, and only 2 cases of excessive hemorrhage (4, and 5 hours long)
hemorrhages of shorter duration.
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were present; however, the authors did not discuss the number of patients with
In our study, there were several circumstances that may have increased the duration of the bleeding:
- Contrary to the procedure of other authors,4,9–11,15,16,18,23,25 we used anesthesia without
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a vasoconstrictor to avoid adverse reactions in patients suffering from coronary disease, whose adrenaline dosage is limited to 0.04 mg per session.28–30 - Suturing is not included in our dental extractions protocol.
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- We included patients on oral anticoagulants and NSAIDs, with excessive alcohol consumption, liver pathology, or renal failure, which are excluded from studies by other
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authors because of their increased bleeding risk.4,10,15,16 We don´t advise the use of NSAIDs in patients with cardiovascular disease and antiplatelet therapy, but ibuprofen use in our country is widespread and often self-medication is used in the presence of acute pain. And there were also several circumstances that may have decreased the duration of the bleeding:
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ACCEPTED MANUSCRIPT - The compression with gauze impregnated with tranexamic acid used as the hemostatic technique likely explains the fact that all were controlled by local measures without further need of suture, as other authors have recommended.10,11,15,16,18 - The low percentage of complex exodontias (6.6%) in our study compared to other
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studies by Cañigral et al.5 (38.4%) and Napeñas et al.14 (51.7%). However, neither our study nor the one by Cañigral et al.5 found an association between the hemorrhage severity and the type of extraction.
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- The mean number of extracted teeth (1.2 ± 0.4) in our study, which was lower than that in other studies.14–16 However, we found no association between the number of
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extracted teeth and hemorrhagic complications, which differs from other authors.6 Our mean patient age was higher than that of other studies where double antiplatelet therapy was used,5,14–16 and, in contrast to a study by Cañigral et al.,5 it showed no influence on hemorrhage severity, although statistical significance was not reached in
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the former.
Only one of the 16 patients who were undergoing combined oral anticoagulant-double antiplatelet therapy suffered from hemorrhage >30 minutes in duration and, similarly to
found.
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other studies,10,11 no significant statistical association with a more severe bleeding was
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The presence of inflammation increased the risk of hemorrhage persisting >30 minutes by a factor of 10. In a study by Lillis et al.,15 all patients undergoing double therapy and suffering from periodontitis experienced prolonged bleeding. In other studies by Morimoto et al.,10,Carter et al 27 and a review of the literature by Rodríguez-Cabrera et al31, a greater frequency of postoperative hemorrhage was also found in patients undergoing antiplatelet and/or anticoagulant therapy with acute inflammation.
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ACCEPTED MANUSCRIPT Three-root extractions also increased the risk of moderate hemorrhage by a factor of 7. In a retrospective study by Svensson et al.,32 in 124 patients on warfarin, all patients with a postoperative bleeding (5/124) had received a surgical extraction in the posterior part of the maxilla. Four-root extractions were performed in only three patients, who all
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experienced light bleeding; therefore, we were unable to conclude whether it may be considered as a risk factor.
Similar to reports from other authors, no relevant clinical complications were found
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during the patients' assessments at 24 hours and 10 days following the extractions.14–16 Limitations and strengths
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We believe these results are generalizable because this study was conducted in oral and dental care consultations within primary care by 11 different dentists, without excluding patients suffering from pathologies that might increase hemorrhagic complications. All the interventions performed were dental extractions, which are the only dental
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procedures for adults covered by the Spanish National Health System; therefore, our results cannot be extrapolated to other types of interventions. Our mean number of extracted teeth is low, that may have decreased the duration of the bleeding, however,
complications.
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we found no association between the number of extractions and hemorrhagic
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Antiplatelet combinations other than acetylsalicylic acid and clopidogrel were not assessed, since this is the most common association in our population (97.2% of our patients).
The assessment of other possible pathologies of patients was done by the dentists at the consultation by reviewing their family doctor clinical file exclusively, and excessive alcohol consumption or the degree of kidney failure was not quantified in the cases where it existed. Neither these patients nor the ones with hepatopathology, chronic
15
ACCEPTED MANUSCRIPT steroid treatment, or poorly controlled arterial hypertension experienced more hemorrhagic complications, but the number of these cases was very small, and differences might have gone undetected. Conclusions
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Dental extractions in patients on double oral antiplatelet therapy cause a 8.3% of hemorrhagic complications exceeding 30 minutes, which are resolved by local
hemostatic measures. The presence of inflammation and three-root extractions increase
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the probability of hemorrhage. Our results confirm the hypothesis that most dental extractions can be carried out safely without stopping dual antiplatelet therapy.
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Additional research is needed to assess the frequency of hemorrhagic complications during invasive dental procedures in patients treated with antiplatelet combinations other than acetylsalicylic acid and clopidogrel, and during interventions other than
Acknowledgments
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dental extractions.
We thank Dr. Ricardo Rodríguez and Dra. María José Torijano for their assistance in
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the preparation of the manuscript, and the patients for participating in the study.
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Table 1. Descriptive analysis of intraoperative hemorrhage Intraoperative hemorrhage Variable
Number (%)
P-value >30 minutes
<65 years old: 65 (35.9)
58
7
>65 years old: 116 (64.1)
107
Male: 139 (76.8)
127
a
Sex Female: 42 (23.2)
16
5
0
Acenocumarol: 16 (8.8)
15
1
No: 165 (91.2)
150
15
Yes: 16 (8.8)
14
2
No: 165 (91.2)
151
14
Yes: 36 (19.9)
29
7
No: 145 (80.1)
136
9
Routine exodontia: 169 (93.4)
154
15
Complex exodontia: 12 (6.6)
11
1
1: 80 (44.2)
77
3
2: 89 (49.2)
76
13
3: 12 (6.6)
12
0
Nerve block: 36 (19.9)
35
1
Infiltration: 131 (72.4)
118
13
a
ASA + prasugrel: 5 (2.8)
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Anticoagulant drugs
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antiaggregant drugs
b
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Presence of inflammation
performed
0.86
160
ASA + clopidogrel: 176 (97.2)
Type of extraction
12 4
a
0.49
9
38
Association of
Intake of NSAIDs
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Age
RI PT
<30 minutes
0.48
0.70
0.59
0.000
0.95
Number of anesthetic
0.025
cartridges
Anesthetic technique
0.31
23
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2
1: 148 (81.8)
136
12
2: 30 (16.6)
26
4
3: 3 (1.7)
3
0
1: 74 (40.9)
72
2
2: 61 (33.7)
53
3: 43 (23.8)
37
4: 3 (1.7)
3
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Number of extracted roots
Yes: 6 (3.3)
0
159
16
11
1
154
15
9
3
156
13
2
0
163
16
2
0
163
16
<15 years: 2 professionals
20
5
15-24 years: 6 professionals
122
8
>25 years: 3 professionals
23
3
Kidney failure No: 169 (93.4) Yes: 12 (6.6)
consumption
No: 169 (93.4%)
Poorly controlled arterial
Yes: 2 (1.1%)
hypertension
No: 179 (98.9%)
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Excessive alcohol
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Yes: 12 (6.6)
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Yes: 2 (1.1%)
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No: 179 (98.9%)
0.089
6
0
No: 175 (96.7)
Chronic steroid treatment
8
6
Liver pathology
0.56
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Number of extracted teeth
Both techniques: 14 (7.7)
0.44
0.95
0.041
0.66
0.66
Years of working experience a
ASA: acetylsalicylic acid
b
NSAIDs: non-steroidal anti-inflammatory drugs
0.072
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Variable
Beta
Presence of inflammation
2.310
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Table 2. Multivariate analysis of intraoperative hemorrhagea
Odds Ratio (IC 95%) P-value 10.07 (2.38-42.54)
0.17
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Number of extracted roots
0.002
1.543
4.68 (0.87- 25.17)
0.07
Three-root extractions
2.006
7.34 (1.28-43.31)
0.03
Four-root extractions
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Two-root extractions
-18.992
Number of anesthetic cartridges
1.141
3 cartridges
-18.259
a
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2 cartridges
3.13 (0.79-12.35)
0.99 0.27 0.10 0.99
Hosmer-Lemeshow statistical test for goodness of fit: p = 0.99.
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-2 log likelihood = 80.97; Cox and Snell R2 = 0.14.
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