Open access peer-reviewed chapter - ONLINE FIRST

Bleeding in Dental Surgery

Written By

Natália de Campos, Flávia Furlaneto and Yvonne De Paiva Buischi

Submitted: May 28th, 2019 Reviewed: October 1st, 2019 Published: November 6th, 2019

DOI: 10.5772/intechopen.89992

IntechOpen
Contemporary Applications of Biologic Hemostatic Agents across Surgical Specialties - Volu... Edited by Michael S. Firstenberg

From the Edited Volume

Contemporary Applications of Biologic Hemostatic Agents across Surgical Specialties - Volume 2 [Working Title]

Michael S. Firstenberg and Dr. Stanislaw P. Stawicki

Chapter metrics overview

1,530 Chapter Downloads

View Full Metrics

Abstract

Excessive bleeding complicates surgery and may result in a higher risk of morbidity in dentistry. Although multiple evidence-based clinical guidelines regard dental interventions as minor procedures, with low risk of bleeding, patients on anticoagulation therapy are at elevated risk of bleeding complications, during and following dental surgeries. In many instances, discontinuation or altering of anticoagulation can be avoided through the use of local hemostatic agents during or after the procedure (or both), while patients are therapeutically continued on their prescribed anticoagulant doses. In addition, patients with diagnosis of hereditary bleeding disorders, such as von Willebrand disease and hemophilia, and individuals without any history of bleeding complications can present the need for the use of topical hemostatic agents. In this chapter, we discuss the mechanisms of action, practical applications, effectiveness, and potential negative effects of biosurgical topical hemostatic agents, such as gelatin sponges, collagen, oxidized regenerated cellulose (ORC) and oxidized cellulose, fibrin sealants, flowables, adhesives, and topical thrombin in dental surgery.

Keywords

  • bleeding
  • antiplatelet
  • hemostasis
  • biosurgical agents
  • topical agents
  • dental surgery

1. Introduction

All surgical procedures, including dental surgery, present risk of complications, which may include pain, nerve injury, swelling, infections, and hemorrhage. Dental surgery is defined as any dental intervention including an incision in the oral mucosa or gingiva, including anything from a simple dental extraction to alveoloplasties [1]. Bleeding control is an important step during dental surgery procedures [2] because excessive bleeding complicates surgery and increases the risk of morbidity. To avoid such complications when long-lasting bleeding occurs, despite the proper use of traditional techniques for hemorrhage control, a broad range of hemostatic agents are available, as adjunctive measures to enhance hemostasis in the course of dental surgeries [3]. Despite the expressive rise in the amount and types of topical hemostats in the past decade, high-level evidence regarding the management of these agents during bleeding in dental surgery is still lacking.

The periprocedual management of patients receiving therapeutic anticoagulation represents a challenge for dental practitioners, as the risk of bleeding must be counterbalanced against the risk of systemic or local thromboembolic phenomena. Recommendations for dental interventions in individuals receiving anticoagulation therapy remain quite unclear, in spite of practice guidelines from both dental [4] and medical [5] fields.

This chapter aims to discuss the effective ways of managing bleeding complications in dental surgery, mainly in high-risk patients. The role of biosurgical materials to prevent or solve these complications, during and after dental surgery procedures, will also be addressed, as well as their modes of action, practical applications, adverse effects, and effectiveness.

Advertisement

2. Normal hemostasis

The physiological mechanism that prevents and hinders bleeding at the area of an injury while preserving regular blood flow everywhere else in the circulation is called hemostasis [6]. The hemostasis process has two major components. Primary hemostasis initiates promptly after vascular injury, and it can be divided into four consecutive and superposed stages: (A) vasoconstriction, (B) platelet adhesion, (C) platelet activation, and (D) platelet aggregation [7, 8, 9, 10]. Primary hemostasis results in the formation of a platelet plug [10]. Secondary hemostasis comprises a sequence of serine protease zymogens and their cofactors, which interact successively on phospholipid surfaces (damaged endothelial cells or platelets), leading to the development of covalently cross-linked fibrin [10, 11, 12]. This cross-linked fibrin mesh is then incorporated into and around the platelet plug. It strengthens and stabilizes the blood clot. These two processes are intertwined and occur at the same time [6]. These systems are regulated by multiple anticoagulant mechanisms, which are responsible for maintaining blood fluidity in the absence of injury, generating a clot that is consistent with the trauma. Hemostasis and the avoidance of bleeding or thrombosis are directly related to the adequate balance between procoagulant and anticoagulant systems [6].

Advertisement

3. Bleeding diathesis in dental surgery: acquired, autoimmune, or genetic

Hemorrhage in dental surgery can be categorized as:

  1. Primary hemorrhage: bleeding occurs during surgery

  2. Reactionary hemorrhage: bleeding occurs 2–3 hours after surgery

  3. Secondary hemorrhage: bleeding occurs until 14 days after surgery, probably due to an infection

Hemorrhage can also be categorized according to the area injured: vascular, bone, and soft tissue [13, 14]. Bleeding diathesis is an unusual susceptibility to bleeding and may be genetic, autoimmune, or acquired (Table 1) [15, 17]. Selected bleeding disorders will be covered in this chapter.

Table 1.

Hemorrhagic diatheses–adapted from Vezeau [15] and Goswami et al. [16].

3.1 von Willebrand disease and hemophilia

The most prevalent hereditary bleeding disorders are von Willebrand disease and hemophilia, affecting 1% of the population and 20,000 people in the USA, respectively [18, 19, 20, 21, 22]. Dental patients presenting inherited bleeding present a significantly higher risk of perioperative bleeding. The frequency and severity of bleeding are related to disease-related factors, such as the severity of the hemophilia. Factors related to the patient include the level of periodontal disease, vasculopathy or platelet dysfunction, and procedure-related factors (teeth extracted—type and the number—or the size of the wound area) [23].

3.2 Immune thrombocytopenia

One example of autoimmune bleeding diathesis is the immune thrombocytopenic purpura (ITP), an idiopathic thrombocytopenic purpura condition, characterized by isolated thrombocytopenia without a clinically apparent cause [24].

3.3 Common hemostasis-altering medications

The most common acquired bleeding diathesis is the one related to hemostasis-altering medications. Anticoagulant agents are among the most prescribed medications in the USA [25]. For decades, anticoagulants have been prescribed to prevent arterial and venous thromboembolism [1]. Prolonged bleeding and bruising are some of the adverse events related with these medications [4]. The most frequently used drugs are therapeutic platelet inhibitors, vitamin K antagonists, or direct oral anticoagulants. Patients susceptible to hemorrhage may present severe bleeding resulting from dental surgery procedures. The use of biosurgical hemostatic agents to decrease or control bleeding may be beneficial for patients at risk for bleeding diathesis.

Advertisement

4. Biosurgical topical hemostatic agents in dental surgery

Bleeding complications can occur either in healthy or systemically compromised patients. Some patients tend to bleed excessively during or after dental surgery, due to different factors, such as anticoagulant therapy, inherited bleeding disorders, uncontrolled hypertension, extreme trauma to soft tissues, and non-compliance to postoperative recommendations. In these cases, the use of an effective hemostatic agent enhances hemostasis, providing a wide spectrum of benefits, such as superior management of the anticoagulated patient, shorter operation time, as well as smaller wound exposure and shorter recovery time.

The ideal topical hemostatic agent should be biocompatible, affordable, and effective [14, 26, 27]. In recent years, the number of different topical hemostatic agents has increased significantly (Table 2). Knowledge and familiarity with the wide range of topical hemostatic agents available are essential for dental practitioners, including their effectiveness, mode of action, and adverse effects. A well-informed professional will be able to opt for the most effective and practical agent for each situation. In relation to the use of local hemostatic in dental procedures, available scientific data is not homogenous. Most publications use one or more local hemostatic agents to compensate for the anticoagulant effect and prevent postoperative bleeding [29]. The most common local biosurgical hemostatic agents used in dentistry and approved by the Food and Drug Administration (FDA) are listed in Table 2.

Table 2.

Types and trade name of some biosurgical agents–adapted from Pereira et al. [28].

Local biosurgical hemostatic agents can be classified into (A) passive or mechanical, (B) active, and (C) flowables [30].

4.1 Passive or mechanical agents

Considered as the most effective agents for small amounts of bleeding, passive or mechanical agents provide platelet activation and aggregation. This results in a matrix formation in the bleeding area that works as a barrier to stop bleeding, by activating the extrinsic clotting pathway and providing a surface that will allow coagulation to occur faster [30]. As these agents are biologically inactive, they rely on the individual’s own fibrin production to attain hemostasis. Passive hemostats are only indicated for individuals with an unscathed coagulation cascade [27]. They are generally applied as frontline agents, since they are readily available, do not require special storage or handling, and are relatively affordable [14, 27, 31].

4.1.1 Gelatin (Gelfoam®, Surgifoam®, Gelfilm®, Gelita-Spon®, Geli Putty®)

Gelatin is a hydrocolloid derived from acid partial hydrolysis of purified animal collagen. It is presented as a gelatin sponge, powder (mixed to form a paste), or film. Gelatin can be placed dry or after moistening it with saline [14, 28, 32, 33]. Gelatin-based products adapt effortlessly to wounds making it appropriate for application into irregular surfaces [27]. Although their mode of action is not completely understood, gelatin-based products likely act more physically than chemically in the coagulation cascade [28, 34]. Affordability, ease of use and good hemostatic activity make topical hemostats with gelatin matrix a popular tool for reducing the morbidity caused by hemorrhage [27, 28] after dental extractions and periodontal surgeries.

The most popular absorbable gelatin sponge in dentistry is Gelfoam®. It is a hemostatic compressed sponge obtained from purified porcine skin gelatin. Gelfoam® is capable of absorbing many times its weight of whole blood [35]. Generally, when applied in soft tissues, its complete absorption occurs within 4–6 weeks.

4.1.2 Collagen (Helistat®, Instat®, Helitene®)

Collagen absorbable products are nontoxic and non-pyrogenic. They are sourced from either bovine dermal collagen or bovine tendon. Collagen hemostats provide a matrix for clot formation and consolidation. These products also improve clotting factor release and platelet aggregation and degranulation, thereby breaking up clot formation. Their presentation in sheets and flours allows for easy adaptation and adhesion to irregular surfaces. Although they are commercialized at a higher price than gelatin-based hemostats, hemostasis can usually be accomplished relatively quicker (1–5 min). Collagen absorbable products are easily removed, reducing the risks of rebleeding and the need for various applications. They are absorbed in 8–10 weeks if remained in place. Adverse effects linked to bovine collagen products might include swelling and allergic reaction [30].

Helistat® is a collagen-based product originated from purified and freeze-dried bovine flexor tendon and is available as a spongelike structure [14, 27]. Helistat® can hold many times its own weight of fluid, as it is highly absorbent. Collagen induces platelet agglomeration when in contact with blood. In order to achieve hemostasis, Helistat® must be kept at the site (approximately 2–5 minutes). Subsequently, it can be removed, replaced, or left in place. It is easily manipulated, and it must be handled dry, and any excess must be removed. Complete reabsorption occurs within 14–56 days [14, 27, 36]. Helistat® may foster bacterial growth, acting as a nidus for abscess formation [14, 27, 37]; therefore, it should not be placed in wounds with any kind of contamination or infection. Possible adverse reactions of Helistat® or similar products are allergic reaction, foreign body reaction, and adhesion formation [27, 38].

4.1.3 Cellulose-based products

4.1.3.1 Oxidized regenerated cellulose (Surgicel®, Oxycel®, Surgicel Nu-Knit®, Surgicel Original®, Surgicel Fibrillar®, Interceed®, Gelita-Cel®)

Simple oxidized cellulose was first introduced in the early 1940s in the USA. In the 1960s, a new topical hemostatic-oxidized regenerated cellulose (ORC) was launched as a meshwork made from treated and sterilized cellulose—Surgicel®. ORC products are originated from vegetal-based alpha cellulose, available in absorbable knitted fabrics (low or high density), and prepared as sterile fabric meshworks. They are ready-to-use products that may be kept at room temperature and absorb 7–10 times its own weight [27, 30]. ORC cause contact activation and platelet activation, and, when absorbed, a gelatinous mass is created, assisting in the establishment of the clot formation [30]. Thrombin is ineffective with these agents due to low-pH factors. ORC are utilized in the management of capillary, venous, and small arterial bleeding, and they require dry application, without addition of saline or thrombin [27, 39] and are absorbed within 4–8 weeks, depending on the volume applied, the tissue bed, and the magnitude of blood saturation [27, 40, 41, 42]. To prevent delayed healing, excessive volumes should be removed [27]. ORC should not be used in osseous defects as it may intervene with bone regeneration [14, 27, 31]. Adverse effects also include reactions related to the acidic nature of ORC. This characteristic may induce necrosis and inflammation of the surrounding tissue and makes thrombin inefficient with these agents. When left in the wound, they may lead to fluid encapsulation and foreign body reaction [14, 27].

The most common commercial products in this category are Surgicel®, Oxycel®, and Surgicel Nu-Knit®. Surgicel® and Surgicel Nu-Knit® come in knit, solid fiber form, whereas Oxycel® comes in knit, hollow fiber form; however, they function basically in a similar manner [30].

4.1.3.2 Oxidized cellulose (ActCel®, Gelita-Cel®)

Oxidized cellulose (OC) agents are produced from sterilized and treated cellulose, presented as a meshwork. In the presence of blood, they present a three- to fourfold increase in volume and are converted into gel. OC dissolve completely in 1–2 weeks into biodegradable end products glucose and water, and they do not interfere with wound healing [14, 27].

ActCel® binds to calcium ions, resulting in more calcium available for the coagulation cascade [14, 27, 37]. Biochemically, it intensifies the coagulation process by increasing platelet aggregation and physically by 3D clot stabilization. ActCel® is especially indicated in third molar extractions, to avoid the occurrence of dry sockets, and in orthognathic and periodontal surgeries [27]. ActCel® is hypoallergenic, as it does not contain collagen, thrombin, or chemical additives. It also has important bacteriostatic properties [27, 43], which are particularity relevant in infected wounds [27].

Gelita-Cel® is a relatively quick acting, oxidized resorbable cellulose hemostatic gauze of natural origin. It presents a decreased risk for encapsulation, as it resorbs as fast as 96 hours [14, 27, 37].

4.1.4 Polysaccharide hemospheres (Arista™AH)

Polysaccharide hemospheres are a fairly new class of topical biosurgical hemostatic agents, produced from vegetable starch, and they contain no animal or human elements. They are commercially presented in powder form. Polysaccharide hemospheres increase barrier formation by creating a hydrophilic effect, dehydrating the blood, and concentrating its solid components [14, 27]. Due to their 3D scaffold, they are devised to enhance clot formation and organization, even in the absence of intrinsic coagulation activity [14, 44, 45]. Polysaccharide hemospheres should be used with caution in diabetic patients, as they consist of sugars [27].

Arista™AH is the only FDA-approved product in the polysaccharide hemosphere category. It is used in dental surgery as an adjunctive hemostatic agent, when conventional mechanical procedures, such as pressure and ligature, are not effective or practical.

4.1.5 Adhesives (BioGlue®)

Hemostatic adhesives are often used as adjuncts to standard hemostatic procedures to control bleeding from surgical areas [30]. One of the most well-known products in this category is BioGlue®. It consists of a solution of 10% glutaraldehyde and 45% bovine albumin solution purified by precipitation, heat, and chromatography radiation [28, 46]. BioGlue® has been extensively used for its sealants and hemostatic characteristics. The risk of leaking through the suture tracks is the main disadvantage of BiolGue® [27]. In the search for newly created adhesives with the chemical features and the safe reabsorptive profile required to benefit dental surgery patients, several clinical trials are currently in process.

4.2 Active agents

Active hemostatic agents are biologically active, as they play a direct role in the coagulation cascade, inducing the formation of a fibrin clot [26, 27].

4.2.1 Topical thrombin (Thrombin-JMI®, Evithrom®, Recothrom®)

Thrombin is key to hemostasis, as well as to the inflammatory and cell signaling processes. It is the base of the fibrin clot, fostering the transformation of fibrinogen to fibrin [28]. Topical thrombin hemostats are originated from either bovine or human plasma, and they can also be produced through recombinant DNA techniques [14, 27]. In the past, the only thrombin hemostat available was composed of bovine plasma (Thrombin-JMI). Although it has proven to be efficient in terminating bleeding, bovine thrombin induces an important immune response [28, 47]. Individuals on hemodialysis, with increased levels of antibodies against topical bovine thrombin, had higher incidence of vascular access thrombosis, severe coagulopathy, and bleeding after exposure to bovine thrombin [28, 48]. As an attempt to avoid these hazardous effects, thrombin derived from human plasma (Evithrom®) and recombinant human thrombin (Recothrom®) were developed. In 2010, Browman et al. [49] demonstrated, in a comparative study between recombinant human thrombin and bovine thrombin, that human recombinant thrombin showed the same efficacy in surgical hemostasis, a comparable safety profile, and a remarkably lower immune response than bovine thrombin. Thrombin may be applied topically, as a solution combined with gelatin sponges mixed with a gelatin matrix, as a dry powder, or as a spray [14, 27]. It is commonly used in conjunction with Gelfoam® to stop moderate to severe bleeding.

4.2.2 Fibrin sealants (Tisseel®, Evicel®, Crosseal™)

Fibrin sealant or fibrin glue originates from bovine and/or human blood components and simulates the last phases of the coagulation cascade, generating a fibrin clot [30]. These agents control local, as well as diffuse, bleeding from the surgical area. Nevertheless, they are ineffective in controlling intense bleeding. Its use in dentistry includes tooth extraction sites, bone grafting, and periodontal surgery [14].

Tisseel® was the first fibrin sealant approved by the FDA. It has in its composition human thrombin and fibrinogen, intermixed with aprotinin and CaCl2. Because aprotinin is a bovine protein, it is a potential allergen. Multiple exposures may cause allergic reactions, as well as anaphylactic reaction approaching lethality [30, 50]. As for its ideal application, a dry operating field is required; Tisseel® is particularly effective when applied prior to bleeding. In this situation, fibrinogen may polymerize before blood pressure increases local microcirculation flow. When used after the onset of bleeding, one should apply local pressure over the wound to allow polymerization [28, 51]. Tisseel® is available in a pre-filled syringe, allowing for effective application using the EasySpray and DuploSpray MIS systems.

Another option for fibrin sealants, Evicel®, originates from pooled human plasma. It is available as two separate vials of fibrinogen and human thrombin. Prior to use, the two deep frozen solutions must be thawed and mixed after defrosting and heating up (20–30°C) [30].

Crosseal™ is a virally inactivated, second-generation surgical sealant. It is produced from concentrated human clottable proteins, namely, biological active component (BAC), which contains the active component fibrinogen, and human α-thrombin (1000 IU/ml) [52]. This fibrin sealant is applied using an application device which drips/sprays Crosseal™ onto the bleeding site.

4.3 Flowables (Surgiflo®, Floseal®)

There are two main categories of flowable biosurgicals: products containing porcine gelatin, which can be combined with thrombins (bovine, human-pooled plasma thrombin, or rhThrombin), and bovine collagen-based agents, packed with human-pooled plasma thrombin. The flowable agents are deemed the most effective of all the local hemostatic agents [30, 53].

Surgiflo® is an absorbable, sterile, hemostatic porcine gelatin matrix, combined with Thrombin-JMI, a topical bovine-derived thrombin. It should be placed directly to the bleeding areas to activate the hemostatic process [30]. A compression period is required for polymerization of the sealant components [28].

Floseal® consists of a bovine gelatin matrix, plasma-extracted human thrombin, and CaCl2. Its gelatin granules expand (10–20%), as it comes in contact with blood, producing a seal when the product is applied to a bleeding area [27, 30]. The thrombin fraction of the product triggers the regular pathway of the coagulation cascade, converting fibrinogen to a fibrin polymer and creating a clot around the firm matrix [27], which is reabsorbed within the expected period of standard wound healing (6–8 weeks) [14, 27, 33, 42, 54]. A distinctive feature of Floseal® is the need for the presence of blood for activation [30, 55]. Neither compression, nor a dry surgical field is required for its application [28].

Because of this biosurgical flowability, they can easily adapt to irregular wounds. Flowables have been utilized as frontline topical hemostats in major dental surgeries, in patients where conventional procedures are ineffective. They can be utilized as an adjunct to hemostasis in practically all dental surgical interventions. Flowables are effective on both hard and soft tissues [27, 30]. They have a risk of transmitting infectious agents and are contraindicated in patients who are allergic to materials of bovine origin [27].

Advertisement

5. Effectiveness of different biosurgical hemostatic agents in dentistry

Although traditional methods, such as ligature and manual pressure, can promote hemostasis, they are not an effective approach of bleeding control in less accessible sites and complex injuries. Furthermore, bleeding control is especially challenging in patients presenting acquired or congenital coagulation disorders.

Topical biosurgical hemostatic agents comprise a wide range of products aiming at minimizing the risk of bleeding. In recent years, several clinical trials have analyzed the effectiveness, advantages, and limitations of biosurgicals, as well as performed comparisons among the different types of biosurgicals and other non-biologic agents. Despite the beneficial effect of these local hemostatic agents in preventing bleeding in dental surgery, available data comparing their effectiveness and efficiency is still scarce and inconclusive. Methodological heterogeneities, such as the lack of a standard therapy and comparable treatment regimens, are noticeable among studies, as well as the reduced number of randomized controlled trials [2, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70].

In summary, local hemostatic agents are very distinct products with diverse indications. Presently, there is no definite evidence-based approach to guide the dental practitioner when selecting a local hemostatic agent. They must be aware of the characteristics of each single hemostatic agent, to elect the most suitable product for every particular clinical situation. In addition, current available data shows that no topical agent can be regarded as superior or more effective than the others [2]. Further experimental research and controlled clinical trials are warranted to define the most cost-effective biosurgical hemostatic agents in dentistry.

Advertisement

6. Preoperative assessment and risk of bleeding

The dental practitioner should assess the bleeding risk of the patient, as well as the bleeding risk of the surgical intervention, preoperatively. After assessing both bleeding risks, the professional can then conceive an intraoperative and postoperative plan. The international normalized ratio (INR) must be evaluated in patients reporting an elevated risk of bleeding. While a standard parameter of coagulation has an INR of 1 [71], the therapeutic range runs from 2.0 to 3.5. In this case, it is recommended to use local hemostatic measures independently or in combination with conventional methods. These agents can be used before, during, and after dental surgeries.

6.1 Preoperative assessment

  • Comprehensive medical history, including all medications in the patient’s regimen, to identify potential bleeding issues prior to the surgery [26].

  • In order to decrease surgical bleeding, patients receiving anticoagulant therapy may need to break up exodontia into multiple appointments [26, 72].

  • Laboratory values such as platelet count, INR, and prothrombin time are of critical value in medically compromised patients [26].

  • Demographic risk factors (female sex and older age) [73].

  • Supplemental patient-related risk determinants: diabetes mellitus, hypertension, obesity, hemostatic disorders, renal impairment, and other major organ system failures [73, 74, 75].

  • Timing of the appointment: early morning visits allowing patients to return to the dental office in case of postsurgical hemorrhage [26].

6.2 Identifying patients at risk of bleeding

Patients at a higher bleeding risk are those reporting family history of bleeding and previous bleeding problems after dental surgery or trauma and individuals using medications, such as aspirin, anticoagulants, and/or long-term antibiotics. Any illnesses associated with bleeding problems, such as leukemia, congenital heart disease, liver disease, or hemophilia, present a higher risk of bleeding. The dental professional needs to be aware and prepared for any intercurrence, during or after a surgical procedure. Individuals presenting advanced periodontal disease are also considered as having a higher risk of perioperative bleeding. In such cases, the surgical plan should include a preoperative phase, consisting of scaling and root planning and a proper chlorhexidine gluconate mouth rinse regimen, 2 weeks before an elective procedure [26].

The risk of bleeding of a dental intervention may be ranked as high, moderate, and low [25, 76, 77, 78]. In most patients, antithrombotic therapy is not interrupted before dental interventions with low bleeding risk, due to the disastrous complications of thrombosis (Table 3) [25, 76, 77, 78]. Moderate and high bleeding potential interventions might need the temporary discontinuation of the antithrombotic therapy [25, 76, 77, 78].

Table 3.

Dental interventions that do not require anticoagulation therapy interruption*–adapted from Kaplovitch and Dounaevskaia [25].

Advertisement

7. Bleeding in dental surgery: clinical implications

Dental surgical interventions are considered by most recommendations, as minor procedures presenting self-limited blood loss and low bleeding risk. Bleeding, in most cases, can be managed with local hemostatic agents [79, 80].

7.1 Should anticoagulants, antiplatelets, or direct oral anticoagulants be discontinued for minor dental surgeries?

The dental care of individuals receiving therapeutic anticoagulation becomes critical when invasive procedures are needed. At this time, the clinician must decide either to maintain the anticoagulation therapy and risk bleeding complications or withdraw the anticoagulation medication and risk developing systemic thrombosis [1]. After decades of controversial data, there is currently a nearly unanimous consensus that anticoagulation therapy, for most dental surgeries, should not be discontinued. The higher risk of bleeding complications is compensated by the elevated risk of developing thromboembolic complications [1, 81, 82, 83, 84].

National dental and medical group statements and multiple evidence-based clinical guidelines have considered the issue independently and support the maintenance, for most dental patients, of anticoagulation therapy (American Dental Association; American Academy of Dental Sleep Medicine; American Heart Association; American College of Cardiology; American Academy of Neurology; American Society of Anesthesiologists; Society for Neuroscience in Anesthesiology and Critical Care; American College of Chest Physicians (ACCP)) [1]. In a 2012 statement [76], the ACCP recommended continuing anticoagulation therapy with warfarin, with the additional utilization of a local hemostatic. The ACCP advised a 2–3-day anticoagulation therapy suspension, in order to lower the INR levels to a range of 1.6 and 1.9 [76, 85].

Lately, the dental care of patients receiving anticoagulant treatment has been the focus of expressive scientific interest, in both dental and medical fields. A recent literature review showed that only 31 (0.6%) of more than 5400 patients receiving over 11,300 dental surgical interventions while continuing to take vitamin K antagonist anticoagulants (warfarin in most cases) demanded more than local maneuvers for hemostasis. No cases of fatal hemorrhage were reported. In over 2600 individuals whose anticoagulation was discontinued for dental interventions, 22 thromboembolic complications (0.8% of medication withheld), including 6 fatal events (0.2% of medication withheld), were observed [83]. Similar results have been shown in a literature review of dental surgery and antiplatelet medications. Of more than 1200 patients receiving over 2300 dental surgical procedures while continuing their antiplatelet medications (aspirin in most cases), only 2 (0.2%) needed more than local measures for hemostasis. Conversely, in over 320 individuals undergoing 370 antiplatelet interruptions for dental procedures, 17 (5.3%) suffered thromboembolic complications [86].

Available data shows that the majority of dental interventions can be safely conducted in patients receiving anticoagulation treatment, when considering older medications [4]. However, there are fewer studies reporting the provision of dental care in individuals using newer direct oral anticoagulants. The clinical implications of these newer anticoagulant and antiplatelet therapies have only been recently investigated [80, 87]. The protocol followed by the dental practitioner when managing these patients varies significantly and shows inconsistencies reflecting the lack of large-scale studies and evidence-based clinical guidelines [80, 88, 89]. The risk of postoperative bleeding after invasive periodontal treatment in individuals using different anticoagulation therapies was assessed, retrospectively, in 456 individuals receiving an antiplatelet and/or anticoagulant therapy [90]. Data was collected after 484 invasive periodontal interventions, with 99.6% of patients continuing their medications during the procedures. Postoperative bleeding was reported only following three interventions (0.35%), and it was controlled with local hemostatic maneuvers. Although the authors did not specify which type of local hemostatic procedure was used, this retrospective study showed a very low risk of bleeding in patients receiving an invasive periodontal intervention while using an anticoagulant or antiplatelet medication [90]. These results support the recommendation that such medications do not need to be discontinued in anticipation to invasive periodontal interventions.

Extended inter- or postoperative bleeding following dental surgery is infrequent, seldom demanding anything more than the use of local hemostatic biosurgicals. The judgment of whether or not to interrupt anticoagulation treatment can be both intricate and dynamic, and it should be based on the indication for pharmacological therapy, as well as previous thromboembolic history. The discontinuation of anticoagulant therapy may be required in dental interventions with moderate and high bleeding risk [25, 76, 77, 78]. Currently, most clinicians dealing with anticoagulant management tend to personalize the periprocedural management of the bleeding potential, according to the individual risk of each procedure—low, moderate, or high—following the current clinical practice recommendations based on best evidence and maintaining the anticoagulant therapy. Thereby, the patient anticoagulant regimen should be continued in specific low-risk dental procedures, without consultation or fear of disproportionate bleeding demanding additional intervention (Table 3) [25].

7.2 Common anticoagulants and potential interactions with dental medications

Undoubtedly, anticoagulant agents are effective in preventing thromboembolism. Nevertheless, their potential for critical adverse effects cannot be ignored. The use of antithrombotic medications is the most frequent cause of an adverse drug event requiring individuals to seek out emergency care [25, 91]. The majority of drug interactions with anticoagulants lead to elevated risk of bleeding. The nature of the interactions cannot be predicted, as they are expressed through both pharmacodynamic mechanisms and pharmacokinetic properties [25].

Regarding patient safety, potential risk for interaction, as well as knowledge of appropriate prescribing and monitoring, is crucial. Equally decisive is selecting the appropriate anticoagulant agent and monitoring the potential for drug–drug interaction [10, 11, 12, 13, 14, 15, 17, 25]. Common anticoagulants and their interaction with the most common medications prescribed for dental patients are described in Table 4 [25, 92, 93, 94, 95, 96, 97, 98].

Table 4.

Common anticoagulants and potential interactions with dental medications–adapted from Kaplovitch and Dounaevskaia [25].

7.3 What is the difference in the risk of bleeding between patients ongoing anticoagulant therapy and patients not treated?

Most studies evaluating the occurrence of peri- and postoperative bleeding show anticoagulation therapy can be maintained when adequate local hemostatic maneuvers are used.

As an example, a controlled clinical trial compared the occurrence of bleeding following dental extractions in individuals receiving oral anticoagulants (experimental group) versus patients that had never received oral anticoagulant therapy (control group). Tooth extractions were performed, and a piece of oxidized cellulose was placed only into the sockets in the experimental group. The wound borders were sutured, and a gauze saturated with tranexamic for 30–60 minutes was applied with pressure in the wound. Both groups presented similar bleeding complications [99]. In a similar clinical trial [100], 161 tooth extractions were performed in patients undertaking warfarin. After tooth extraction, an oxidized cellulose gauze was placed in the socket, and the wound was sutured. Patients were assigned to four groups, according to their INR range (INR was 1.5–1.99 in group 1; 2.0–2.49 in group 2; 2.5–2.99 in group 3; and 3.0–3.7 in group 4). No significant differences were found in the postoperative bleeding among groups.

Advertisement

8. Conclusions

Based on the latest evidence and clinical practice recommendations on the perioperative management of dental patients receiving direct oral anticoagulants, on single or dual antiplatelet therapy or vitamin K antagonists, as well as on the current scientific knowledge on biosurgical hemostatic agents, the following conclusions can be made:

  • The majority of dental procedures can be securely executed without the withholding of anticoagulants, using only local hemostatic therapy. In fact, current recommendations and consensus support the continuation of antiplatelet or anticoagulant therapy. Discontinuing these drugs can increase the risk of thromboembolism, at the cost of minor bleeding, which can be restrained without difficulty. The appropriate use of local hemostatic measures, such as topical biosurgical hemostatic agents, should always be considered whenever indicated.

  • In order to safely treat a patient receiving anticoagulant therapy, familiarity with anticoagulants and with the potential for drug–drug interactions is required, in addition to knowledge about the topical hemostatic options available.

  • Topical biosurgical hemostatic agents are diverse agents with distinct indications. The dental practitioner must be aware of the properties of each single agent, in order to properly select the product needed in each different clinical condition.

  • Based on current available data, no topical hemostatic agent can be regarded as superior or more effective than the others. Further experimental research and controlled clinical trials are warranted to define the most cost-effective biosurgical hemostatic agents in dentistry.

  • A definite protocol for excessive bleeding is still required for dental surgery in patients with hemorrhagic diathesis. The most effective local hemostatic agent with lesser complications should be determined in future research, considering their availability and cost-effectiveness.

Advertisement

Acknowledgments

The authors are grateful to Kisa Iqbal BSc Hons, DDS Candidate c/o 2020, New York University College of Dentistry, for editing this article.

Advertisement

Conflict of interest

The authors declare no conflict of interest.

References

  1. 1. Wahl MJ. The mythology of anticoagulation therapy interruption for dental surgery. Journal of the American Dental Association (1939). 2018;149:e1-e10. DOI: 10.1016/j.adaj.2017.09.054
  2. 2. Akolkar AR, Kulkarni DG, Gangwani KD, Shetty L, Channe SP, Sarve PH. Bleeding control measures during dental and maxillofacial surgical procedures: A systematic review. Journal of Dental Research and Review. 2017;4:79-89. DOI: 10.4103/jdrr.jdrr_54_17
  3. 3. Chiara O, Cimbanassi S, Bellanova G, Chiarugi M, Mingoli A, Olivero G, et al. A systematic review on the use of topical hemostats in trauma and emergency surgery. BMC Surgery. 2018;18:68. DOI: 10.1186/s12893-018-0398-z
  4. 4. American Dental Association. Anticoagulant and Antiplatelet Medications and Dental Procedures. Available from:https://www.ada.org/en/member-center/dental-health-topics/anticoagulant-antiplatelet-medications-and-dental[Accessed: August 27, 2019]
  5. 5. Hirsh J, Fuster V, Ansell J, Halperin JL. American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. Circulation. 2003;107:1692-1711. DOI: 10.1161/01.CIR.0000063575.17904.4E
  6. 6. Gale AJ. Current understanding of hemostasis. Toxicologic Pathology. 2011;391:273-280. DOI: 10.1177/0192623310389474
  7. 7. Israels SJ, Kahr WH, Blanchette VS, Luban NL, Rivard GE, Rand ML. Platelet disorders in children: A diagnostic approach. Pediatric Blood & Cancer. 2011;56:975-983. DOI: 10.1002/pbc.22988
  8. 8. Israels SJ, Rand ML. What we have learned from inherited platelet disorders. Pediatric Blood & Cancer. 2013;60:S2-S7. DOI: 10.1002/pbc.24345
  9. 9. Revel-Vilk SR, Rand ML, Israles SJ. Primary and secondary hemostasis, regulators of coagulation, and fibrinolysis: Understanding the basics. In: Blanchette VS, Brandão LR, Breakey VR, Revel-Vilk S, editors. SickKids Handbook of Pediatric Thrombosis and Hemostasis. 2nd ed. Switzerland: Karger; 2017. pp. 8-16
  10. 10. Kumar R, Carcao M. Inherited abnormalities of coagulation. Hemophilia, von Willebrand disease, and beyond. Pediatric Clinics of North America. 2013;60:1419-1441. DOI: 10.1016/j.pcl.2013.09.002
  11. 11. Lippi G, Favaloro EJ, Franchini M, Guidi GC. Milestones and perspectives in coagulation and hemostasis. Seminars in Thrombosis and Hemostasis. 2009;35:9-22. DOI: 10.1055/s-0029-1214144
  12. 12. Goodnight SH, Hathaway WE. Mechanisms of hemostasis and thrombosis. In: Goodnight SH, Hathaway WE, editors. Disorders of Haemostasis and Thrombosis. 2nd ed. Lancester: McGraw-Hill Professional; 2001
  13. 13. Robinson P. Tooth Extraction: A Practical Guide (Chapter 5). Oxford: Elsevier; 2000
  14. 14. Mani A, Anarthe R, Kale P, Maniyar S, Anuraga S. Hemostatic agents in dentistry. Galore International Journal of Health Sciences & Research. 2018;3:40-46
  15. 15. Vezeau PJ. Topical hemostatic agents: What the dental and maxillofacial surgeon needs to know. Oral and Maxillofacial Surgery Clinics of North America. 2016;28:523-532. DOI: 10.1016/j.coms.2016.06.007
  16. 16. Goswami A, Bora A, Kundu GK, Ghosh S, Goswami A. Bleeding disorders in dental practice: A diagnostic overview. Journal of International Clinical Dental Research Organization. 2014;6:143-150
  17. 17. Triplett D. Coagulation and bleeding disorders: Review and update. Clinical Chemistry. 2000;46:1260-1269
  18. 18. Centers for Disease Control and Prevention. Von Willebrand Diseases (VWD). Available from:https://www.cdc.gov/ncbddd/vwd/data.html[Accessed: September 22, 2019]
  19. 19. Rodeghiero F, Castaman G, Dini E. Epidemiological investigation of the prevalence of von Willebrand’s disease. Blood. 1987;69:454-459
  20. 20. Werner EJ, Broxson EH, Tucker EL, Giroux DS, Shults J, Abshire TC. Prevalence of von Willebrand disease in children: A multiethnic study. The Journal of Pediatrics. 1993;1236:893-898
  21. 21. Centers for Disease Control and Prevention. Hemophilia. Available from:https://www.cdc.gov/ncbddd/hemophilia/data.html[Accessed: September 22, 2019]
  22. 22. Soucie JM, Evatt B, Jackson D. Occurrence of hemophilia in the United States. The hemophilia surveillance system project investigators. American Journal of Hematology. 1998;59:288-294
  23. 23. van Galen KP, Engelen ET, Mauser-Bunschoten EP, van Es RJ, Schutgens RE. Antifibrinolytic therapy for preventing dental bleeding in patients with haemophilia or Von Willebrand disease undergoing minor dental surgery or dental extractions. Cochrane Database of Systematic Reviews. 2019;23:CD011385. DOI: 10.1002/14651858.CD011385.pub3
  24. 24. Sugiura T, Yamamoto K, Murakami K, Horita S, Matsusue Y, Nakashima C, et al. Immune thrombocytopenic purpura detected with dental hemorrhage: A case report. Journal of Dentistry. 2018;19:159-163
  25. 25. Kaplovitch E, Dounaevskaia V. Treatment in the dental practice of the patient receiving anticoagulation therapy. Journal of the American Dental Association (1939). 2019;150:602-608. DOI: 10.1016/j.adaj.2019.02.011
  26. 26. Kamoh A, Swantek J. Hemostasis in Dental Surgery. Dental Clinics of North America. 2012;56:17-23. DOI: 10.1016/j.cden.2011.06.004
  27. 27. Kumar S. Local hemostatic agents in the management of bleeding in dental surgery. Asian Journal of Pharmaceutical and Clinical Research. 2016;9:35-41
  28. 28. Pereira BM, Bortoto JB, Fraga GP. Topical hemostatic agents in surgery: Review and prospects. Revista do Colégio Brasileiro de Cirurgiões. 2018;45:e1900. DOI: 10.1590/0100-6991e-20181900
  29. 29. Svensson R, Hallmer F, Englesson CS, Svensson PJ, Becktor JP. Treatment with local hemostatic agents and primary closure after tooth extraction in warfarin treated patients. Swedish Dental Journal. 2013;37:71-77
  30. 30. Vyas KS, Saha SP. Comparison of hemostatic agents used in vascular surgery. Expert Opinion on Biological Therapy. 2013;13:1663-1672. DOI: 10.1517/14712598.2013.848193
  31. 31. Brodbelt AR, Miles JB, Foy PM, Broome JC. Intraspinal oxidized cellulose (surgicel) causing delayed paraplegia after thoracotomy: A report of three cases. Annals of the Royal College of Surgeons of England. 2002;84:97-99
  32. 32. Szpalski M, Gunzburg R, Sztern B. An overview of blood-sparing techniques used in spine surgery during the perioperative period. European Spine Journal. 2004;13:S18-S27
  33. 33. Spotnitz WD, Burks S. Hemostats, sealants, and adhesives: Components of the surgical toolbox. Transfusion. 2008;48:1502-1516. DOI: 10.1111/j.1537-2995.2008.01703.x
  34. 34. Sabel M, Stummer W. The use of local agents: Surgicel and surgifoam. European Spine Journal. 2004;13:S97-S101
  35. 35. Council on Pharmacy and Chemistry. Absorbable gelatin sponge—New and nonofficial remedies. JAMA. 1947;135:921
  36. 36. Ogle OE. Perioperative hemorrhage. In: Dym H, Ogle OE, editors. Atlas of Minor Dental Surgery. Philadelphia: W.B. Saunders; 2000. pp. 62-63
  37. 37. Qin-Shang Z, Zhong Q. Application of S-99 Soluble Styptic Gauze to Wounds. Beijing, China: Beijing Xuan Wu Hospital, Departments of Pathology and Stomatology; 1982
  38. 38. ILSC. CollaPlug [Package Insert]. Plainsboro, NJ: Integra Life Sciences Corp.; 2001
  39. 39. Loescher AR, Robinson PP. The effect of surgical medicaments on peripheral nerve function. British Journal of Oral and Maxillofacial Surgery. 1998;36:327-332
  40. 40. McCarthy JR. Methods for assuring surgical hemostasis. In: Rothrock JC, Seifert PC, editors. Assisting in Surgery: Patient-Centered Care. Denver: CCI; 2009. pp. 137-194
  41. 41. Hoogerwerf BJ. Provide hemostasis. In: Phippen ML, Ulmer BC, Wells MP, editors. Competency for Safe Patient Care during Operative and Invasive Procedures. Denver: CCI; 2009. pp. 599-532
  42. 42. Schreiber MA, Neveleff DJ. Achieving hemostasis with topical hemostats: Making clinically and economically appropriate decisions in the surgical and trauma settings. AORN Journal. 2011;94:S1-S20
  43. 43. Nelson Laboratories. Data On File. Salt Lake City, Utah: Nelson Laboratories, Inc.; 2012
  44. 44. Spangler D, Rothenburger S, Nguyen K, Jampani H, Weiss S, Bhende S. In vitro antimicrobial activity of oxidized regenerated cellulose against antibiotic-resistant microorganisms. Surgical Infections. 2003;4:255-262
  45. 45. Ward BB, Smith MH. Dentoalveolar procedures for the anticoagulated patient: Literature recommendations versus current practice. Journal of Dental and Maxillofacial Surgery. 2007;65:1454-1460
  46. 46. Biggs G, Hafron J, Feliciano J, Hoenig DM. Treatment of splenic injury during laparoscopic nephrectomy with BioGlue, a surgical adhesive. Urology. 2005;66:882
  47. 47. Lawson JH, Lynn KA, Vanmatre RM, Domzalski T, Klemp KF, Ortel TL, et al. Antihuman factor V antibodies after use of relatively pure bovine thrombin. The Annals of Thoracic Surgery. 2005;79:1037-1038
  48. 48. Lo CY, Jones C, Glader B, Zehnder JL. Development of antibodies to human thrombin and factor V in a pediatric patient exposed to topical bovine thrombin. Pediatric Blood & Cancer. 2010;55:1195-1197
  49. 49. Bowman LJ, Anderson CD, Chapman WC. Topical recombinant human thrombin in surgical hemostasis. Seminars in Thrombosis and Hemostasis. 2010;36:477-484. DOI: 10.1055/s-0030-1255441
  50. 50. Cohen DM, Norberto J, Cartabuke R, Ryu G. Severe anaphylactic reaction after primary exposure to aprotinin. The Annals of Thoracic Surgery. 1999;67:837-838
  51. 51. Kraus TW, Mehrabi A, Schemmer P, Kashfi A, Berberat P, Buchler MW. Scientific evidence for application of topical hemostats, tissue glues, and sealants in hepatobiliary surgery. Journal of the American College of Surgeons. 2005;200:418-427
  52. 52. Schwartz M, Madariaga J, Hirose R, Shaver T, Sher L, Chari R, et al. Comparison of a new fibrin sealant with standard topical hemostatic agents. Archives of Surgery. 2004;139:1148-1154
  53. 53. Spotnitz WD. Hemostats, sealants, and adhesives: A practical guide for the surgeon. The American Surgeon. 2012;78:1305-1321
  54. 54. Spotnitz WD, Burks S. State-of-the-art review: Hemostats, sealants, and adhesives II: Update as well as how and when to use the components of the surgical toolbox. Clinical and Applied Thrombosis/Hemostasis. 2010;16:497-514. DOI: 10.1177/1076029610363589
  55. 55. Galanakis I, Vasdev N, Soomro N. A review of current hemostatic agents and tissue sealants used in laparoscopic partial nephrectomy. Revista de Urología. 2011;13:131-138
  56. 56. Wagenhäuser MU, Mulorz J, Ibing W, Simon F, Spin JM, Schelzig H, et al. Oxidized (non)-regenerated cellulose affects fundamental cellular processes of wound healing. Scientific Reports. 2016;6:32238. DOI: 10.1038/srep32238
  57. 57. Soares ECS, Costa FWG, Bezerra TP, Nogueira CB, de Barros Silva PG, Batista SH, et al. Postoperative hemostatic efficacy of gauze soaked in tranexamic acid, fibrin sponge, and dry gauze compression following dental extractions in anticoagulated patients with cardiovascular disease: A prospective, randomized study. Oral and Maxillofacial Surgery. 2015;19:209-216. DOI: 10.1007/s10006-014-0479-9
  58. 58. Bajkin BV, Selakovic SD, Mirkovic SM, Sarcev IN, Tadic AJ, Milekic BR. Comparison of efficacy of local hemostatic modalities in anticoagulated patients undergoing tooth extractions. Vojnosanitetski Pregled. 2014;71:1097-1101
  59. 59. Lewis KM, Spazierer D, Urban MD, Lin L, Redl H, Goppelt A. Comparison of regenerated and non-regenerated oxidized cellulose hemostatic agents. European Surgery. 2013;45:213-220
  60. 60. Manimegalai AG. A comparative study on the efficacy of a commercial fibrin adhesive (Tisseel) Vis-à-Vis silk suture on wound closure following periodontal surgical procedures. Journal of Indian Society of Periodontology. 2010;14:231-235. DOI: 10.4103/0972-124X.76925
  61. 61. Sacco R, Sacco M, Carpenedo M, Mannucci PM. Dental surgery in patients on dental anticoagulant therapy: A randomized comparison of different intensity targets. Journal of the Canadian Dental Association. 2007;104:18-21
  62. 62. Kim JC, Choi SS, Wang SJ, Kim SG. Minor complications after mandibular third molar surgery: Type, incidence, and possible prevention. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2006;102:4-11
  63. 63. 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. International Journal of Oral and Maxillofacial Surgery. 2003;32:504-507
  64. 64. Carter G, Goss A, Lloyd J, Tocchetti R. Tranexamic acid mouthwash versus autologous fibrin glue in patients taking warfarin undergoing dental extractions: A randomized prospective clinical study. Journal of Dental and Maxillofacial Surgery. 2003;61:1432-1435
  65. 65. Al-Belasy FA, Amer MZ. Hemostatic effect of n-butyl-2-cyanoacrylate (histoacryl) glue in warfarin-treated patients undergoing dental surgery. Journal of Oral and Maxillofacial Surgery. 2003;61:1405-1409
  66. 66. Blinder D, Manor Y, Martinowitz U, Taicher S. Dental extractions in patients maintained on oral anticoagulant therapy: Comparison of INR value with occurrence of postoperative bleeding. International Journal of Oral and Maxillofacial Surgery. 2001;30:518-521
  67. 67. Halfpenny W, Fraser JS, Adlam DM. Comparison of 2 hemostatic agents for the prevention of postextraction hemorrhage in patients on anticoagulants. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2001;92:257-259
  68. 68. Blinder D, Manor Y, Martinowitz U, Taicher S. Dental extractions in patients maintained on continued oral anticoagulant: Comparison of local hemostatic modalities. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 1999;88:137-140
  69. 69. Souto JC, Oliver A, Zuazu-Jausoro I, Vives A, Fontcuberta J. Oral surgery in anticoagulated patients without reducing the dose of oral anticoagulant: A prospective randomized study. Journal of Oral and Maxillofacial Surgery. 1996;54:27-32
  70. 70. Ramstrom G, Sindet-Pedersen S, Hall G, Blomback M, Alander U. Prevention of postsurgical bleeding in oral surgery using tranexamic acid without dose modification of oral anticoagulants. Journal of Oral and Maxillofacial Surgery. 1993;51:1211-1216
  71. 71. Hirsh J, Levine M. Confusion over the therapeutic range for monitoring oral anticoagulant therapy in North America. Thrombosis and Haemostasis. 1988;59:129-132. DOI: 10.1055/s-0038-1642740
  72. 72. Brennan MT, Wynn RL, Miller CS. Aspirin and bleeding in dentistry: An update and recommendations. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2007;104:316-323
  73. 73. Verma G. Dental extraction can be performed safely in patients on aspirin therapy: A timely reminder. ISRN Dentistry. 2014;463684:1-11. DOI: 10.1155/2014/463684
  74. 74. Collet JP, Montalescot G. Premature withdrawal and alternative therapies to dual oral antiplatelet therapy. European Heart Journal Supplements. 2006, 2006;8:G46-G52. DOI: 10.1093/eurheartj/sul055
  75. 75. Eikelboom JW, Hirsh J. Bleeding and management of bleeding. European Heart Journal Supplements. 2006;8:G38-G45. DOI: 10.1093/eurheartj/sul054
  76. 76. Douketis JD, Spyropoulos AC, Spencer FA, Mayr M, Jaffer AK, Eckman MH, et al. Perioperative management of antithrombotictherapy: Antithrombotic therapy and prevention of thrombosis, 9th eddAmerican College of Chest Physicians evidence based clinical practice guidelines. Chest. 2012;141:e326S-e350S. DOI: 10.1378/chest.11-2298
  77. 77. Spyropoulos AC, Al-Badri A, Sherwood MW, Douketis JD. Periprocedural management of patients receiving a vitamin K antagonist or a direct oral anticoagulant requiring an elective procedure or surgery. Journal of Thrombosis and Haemostasis. 2016;14:875-885. DOI: 10.1111/jth.13305
  78. 78. Thrombosis Canada. Warfarin: Peri-Operative Management. Available from:http://thrombosiscanada.ca/wpcontent/uploads/2017/06/14.-Warfarin-Peri-Operative-2017May24-Final-1.pdf[Accessed: August 01, 2018]
  79. 79. Scottish Dental Clinical Effectiveness Programme (SDCEP). Management of Dental Patients Taking Anticoagulants or Antiplatelet Drugs. Dental Clinical Guidance. Available from:http://www.sdcep.org.uk/wp-content/uploads/2015/09/SDCEP-Anticoagulants-Guidance.pdf[Accessed: August 01, 2019]
  80. 80. Dézsi CA, Dézsi BB, Dézsi AD. Management of dental patients receiving antiplatelet therapy or chronic dental anticoagulation: A review of the latest evidence. The European Journal of General Practice. 2017;23:196-201. DOI: 10.1080/13814788.2017.1350645
  81. 81. Wahl MJ. Dental surgery in anticoagulated patients. Archives of Internal Medicine. 1998;158:1610-1616
  82. 82. Little JW, Miller CS, Henry RG, McIntosh BA. Antithrombotic agents: Implications in dentistry. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2002;93:544-551
  83. 83. Wahl MJ, Pintos A, Kilham J, Lalla RV. Dental surgery in anticoagulated patients: Stop the interruption. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology. 2015;119:136-157. DOI: 10.1016/j.oooo.2014.10.011
  84. 84. Lusk KA, Snoga JL, Benitez RM, Sarbacker GB. Management of direct-acting oral anticoagulants surrounding dental procedures with low-to-moderate risk of bleeding. Journal of Pharmacy Practice. 2018;31:202-207. DOI: 10.1177/0897190017707126
  85. 85. Kunz R, Spyropoulos AC, Spencer FA, Mayr M, Jaffer AK, Eckman MH, et al. Response [letter]. Chest. 2013;144:1424-1426. DOI: 10.1378/chest.13-1728
  86. 86. Wahl MJ. Dental surgery and antiplatelet agents: Bleed or die. The American Journal of Medicine. 2014;127:260-267. DOI: 10.1016/j.amjmed.2013.11.013
  87. 87. Constantinides F, Rizzo R, Pascazio L, Maglione M. Managing patients taking novel oral anticoagulants (NOAs) in dentistry: A discussion paper on clinical implications. BMC Oral Health. 2016;16:5. DOI: 10.1186/s12903-016-0170-7
  88. 88. Johnston S. A study of the management of patients taking novel oral antiplatelet or direct oral anticoagulant medication undergoing dental surgery in a rural setting. Dentistry Journal. 2015;3:102-110. DOI: 10.3390/dj3040102
  89. 89. Sivolella S, De Biagi M, Brunello G, et al. Managing dentoalveolar surgical procedures in patients taking new oral anticoagulants. Odontology. 2015;103:258-263. DOI: 10.1007/s10266-015-0195-4
  90. 90. Rubino RT, Dawson DR 3rd, Kryscio RJ, Al-Sabbagh M, Miller CS. Postoperative bleeding associated with antiplatelet and anticoagulant drugs: A retrospective study. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology. 2019;128:243-249. DOI: 10.1016/j.oooo.2019.04.005
  91. 91. Shehab N, Lovegrove MC, Geller AI, Rose KO, Weidle NJ, Budnitz DS. US emergency department visits for outpatient adverse drug events, 2013-2014. Journal of the American Medical Association. 2016;316:2115-2125. DOI: 10.1001/jama.2016.16201
  92. 92. Baillargeon J, Holmes HM, Lin YL, Raji MA, Sharma G, Kuo YF. Concurrent use of warfarin and antibiotics and the risk of bleeding in older adults. The American Journal of Medicine. 2012;125:183-189. DOI: 10.1016/j.amjmed.2011.08.014
  93. 93. Rice PJ, Perry RJ, Afzal Z, Stockley IH. Antibacterial prescribing and warfarin: A review. British Dental Journal. 2003;194:411-415
  94. 94. Jaffer A, Bragg L. Practical tips for warfarin dosing and monitoring. Cleveland Clinic Journal of Medicine. 2003;70:361-371
  95. 95. Battistella M, Mamdami MM, Juurlink DN, Rabeneck L, Laupacis A. Risk of upper gastrointestinal hemorrhage in warfarin users treated with nonselective NSAIDs or COX-2 inhibitors. Archives of Internal Medicine. 2005;165:189-192
  96. 96. Shorr RI, Ray WA, Daugherty JR, Griffin MR. Concurrent use of nonsteroidal anti-inflammatory drugs and oral anticoagulants places elderly persons at high risk for hemorrhagic peptic ulcer disease. Archives of Internal Medicine. 1993;153:1665-1670
  97. 97. Burnett AE, Mahan CE, Vazquez SR, Oertel LB, Garcia DA, Ansell J. Guidance for the practical management of the direct oral anticoagulants (DOACs) in VTE treatment. Journal of Thrombosis and Thrombolysis. 2016;41:206-232. DOI: 10.1007/s11239-015-1310-7
  98. 98. Macie C, Forbes L, Foster GA, Douketis JD. Dosing practices and risk factors for bleeding in patients receiving enoxaparin for the treatment of an acute coronary syndrome. Chest. 2004;125:1616-1621
  99. 99. Zanon E, Martinelli F, Bacci C, Cordioli G, Girolami A. Safety of dental extraction among consecutive patients on oral anticoagulant treatment managed using a specific dental management protocol. Blood Coagulation and Fibrinolysis. 2003;14:27-30
  100. 100. Morimoto Y, Niwa H, Minematsu K. Hemostatic management of tooth extractions in patients on oral antithrombotic therapy. Journal of Oral and Maxillofacial Surgery. 2008;66:51-57

Written By

Natália de Campos, Flávia Furlaneto and Yvonne De Paiva Buischi

Submitted: May 28th, 2019 Reviewed: October 1st, 2019 Published: November 6th, 2019