Hemorrhagic diatheses–adapted from Vezeau [15] and Goswami et al. [16].
\r\n\tIn the maintenance and conservation of our planet's biodiversity, knowledge of current biogeographical patterns, speciation or invasion processes, flora, fauna, natural history, and ecology have outstanding importance. Many areas of biodiversity are still completely undiscovered nowadays. The ecological impacts of global climate change, urbanization, overpopulation, environmental pollution, deforestation, land cover and land-use changes also have a significant impact on biodiversity, flora, and fauna, through biogeographical patterns.
\r\n\tThe management tools, methods and processes (as applied ecological aspects) of Protected Areas and National Parks are a very important part of conservation policy. I am sure that this book will be very useful for everybody who would like to get some insight into the recent problems of biodiversity research, ecology and conservation biology also from practical or theoretical viewpoints.
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.
\nThe 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.
\nThis 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.
\nThe 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].
\nHemorrhage in dental surgery can be categorized as:
Primary hemorrhage: bleeding occurs during surgery
Reactionary hemorrhage: bleeding occurs 2–3 hours after surgery
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.
\n\nThe 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].
\nOne 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].
\nThe 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.
\nBleeding 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.
\nThe 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.
\nTypes 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].
\nConsidered 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].
\nGelatin 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.
\nThe 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.
\nCollagen 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].
\nHelistat® 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].
\nSimple 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].
\nThe 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].
\nOxidized 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].
\nActCel® 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].
\nGelita-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].
\nPolysaccharide 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].
\nArista™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.
\nHemostatic 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.
\nActive hemostatic agents are biologically active, as they play a direct role in the coagulation cascade, inducing the formation of a fibrin clot [26, 27].
\nThrombin 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.
\nFibrin 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].
\nTisseel® 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.
\nAnother 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].
\nCrosseal™ 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.
\nThere 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].
\nSurgiflo® 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].
\nFloseal® 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].
\nBecause 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].
\nAlthough 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.
\nTopical 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].
\nIn 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.
\nThe 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.
\n\n
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].
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].
\nThe 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].
\nDental interventions that do not require anticoagulation therapy interruption*–adapted from Kaplovitch and Dounaevskaia [25].
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].
\nThe 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].
\nNational 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].
\nLately, 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].
\nAvailable 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.
\nExtended 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].
\nUndoubtedly, 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].
\nRegarding 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].
\nCommon anticoagulants and potential interactions with dental medications–adapted from Kaplovitch and Dounaevskaia [25].
Most studies evaluating the occurrence of peri- and postoperative bleeding show anticoagulation therapy can be maintained when adequate local hemostatic maneuvers are used.
\nAs 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.
\nBased 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.
The authors are grateful to Kisa Iqbal BSc Hons, DDS Candidate c/o 2020, New York University College of Dentistry, for editing this article.
\nThe authors declare no conflict of interest.
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He has both an MS and Ph.D. in Biomedical Engineering. He was previously a research scientist at the University of California Los Angeles (UCLA) and visiting professor and researcher at the University of North Dakota. He is currently working in artificial intelligence and its applications in medical signal processing. In addition, he is using digital signal processing in medical imaging and speech processing. Dr. Asadpour has developed brain-computer interfacing algorithms and has published books, book chapters, and several journal and conference papers in this field and other areas of intelligent signal processing. He has also designed medical devices, including a laser Doppler monitoring system.",institutionString:"Kaiser Permanente Southern California",institution:null},{id:"169608",title:"Prof.",name:"Marian",middleName:null,surname:"Găiceanu",slug:"marian-gaiceanu",fullName:"Marian Găiceanu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/169608/images/system/169608.png",biography:"Prof. Dr. Marian Gaiceanu graduated from the Naval and Electrical Engineering Faculty, Dunarea de Jos University of Galati, Romania, in 1997. He received a Ph.D. (Magna Cum Laude) in Electrical Engineering in 2002. Since 2017, Dr. Gaiceanu has been a Ph.D. supervisor for students in Electrical Engineering. He has been employed at Dunarea de Jos University of Galati since 1996, where he is currently a professor. Dr. Gaiceanu is a member of the National Council for Attesting Titles, Diplomas and Certificates, an expert of the Executive Agency for Higher Education, Research Funding, and a member of the Senate of the Dunarea de Jos University of Galati. He has been the head of the Integrated Energy Conversion Systems and Advanced Control of Complex Processes Research Center, Romania, since 2016. He has conducted several projects in power converter systems for electrical drives, power quality, PEM and SOFC fuel cell power converters for utilities, electric vehicles, and marine applications with the Department of Regulation and Control, SIEI S.pA. (2002–2004) and the Polytechnic University of Turin, Italy (2002–2004, 2006–2007). He is a member of the Institute of Electrical and Electronics Engineers (IEEE) and cofounder-member of the IEEE Power Electronics Romanian Chapter. He is a guest editor at Energies and an academic book editor for IntechOpen. He is also a member of the editorial boards of the Journal of Electrical Engineering, Electronics, Control and Computer Science and Sustainability. Dr. Gaiceanu has been General Chairman of the IEEE International Symposium on Electrical and Electronics Engineering in the last six editions.",institutionString:'"Dunarea de Jos" University of Galati',institution:{name:'"Dunarea de Jos" University of Galati',country:{name:"Romania"}}},{id:"4519",title:"Prof.",name:"Jaydip",middleName:null,surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4519/images/system/4519.jpeg",biography:"Jaydip Sen is associated with Praxis Business School, Kolkata, India, as a professor in the Department of Data Science. His research areas include security and privacy issues in computing and communication, intrusion detection systems, machine learning, deep learning, and artificial intelligence in the financial domain. He has more than 200 publications in reputed international journals, refereed conference proceedings, and 20 book chapters in books published by internationally renowned publishing houses, such as Springer, CRC press, IGI Global, etc. Currently, he is serving on the editorial board of the prestigious journal Frontiers in Communications and Networks and in the technical program committees of a number of high-ranked international conferences organized by the IEEE, USA, and the ACM, USA. He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:null},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). He leads the working group of experts representing Brazil in the Global Partnership on Artificial Intelligence (GPAI), on the theme \"AI and the Pandemic Response\".",institutionString:"Manufacturing and Technology Integrated Campus – SENAI CIMATEC",institution:null},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:"Polytechnic University of Timişoara",institution:{name:"Polytechnic University of Timişoara",country:{name:"Romania"}}},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:null},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"414880",title:"Dr.",name:"Maryam",middleName:null,surname:"Vatankhah",slug:"maryam-vatankhah",fullName:"Maryam Vatankhah",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Borough of Manhattan Community College",country:{name:"United States of America"}}},{id:"414879",title:"Prof.",name:"Mohammad-Reza",middleName:null,surname:"Akbarzadeh-Totonchi",slug:"mohammad-reza-akbarzadeh-totonchi",fullName:"Mohammad-Reza Akbarzadeh-Totonchi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ferdowsi University of Mashhad",country:{name:"Iran"}}},{id:"414878",title:"Prof.",name:"Reza",middleName:null,surname:"Fazel-Rezai",slug:"reza-fazel-rezai",fullName:"Reza Fazel-Rezai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"American Public University System",country:{name:"United States of America"}}},{id:"302698",title:"Dr.",name:"Yao",middleName:null,surname:"Shan",slug:"yao-shan",fullName:"Yao Shan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Dalian University of Technology",country:{name:"China"}}},{id:"125911",title:"Prof.",name:"Jia-Ching",middleName:null,surname:"Wang",slug:"jia-ching-wang",fullName:"Jia-Ching Wang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Central University",country:{name:"Taiwan"}}},{id:"357085",title:"Mr.",name:"P. 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Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. She is an author of about 90 publications (According to Scopus: H-Index: 23; According to WOS: H-Index: 20) on peer-reviewed journals, a member of the “Società Italiana di Biochimica e Biologia Molecolare,“ and a Consultant Reviewer for International Journal of Molecular Science, Journal of Chromatography A, COPD, Plos ONE and Nutritional Neuroscience.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,series:{id:"11",title:"Biochemistry"}}},seriesLanding:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"June 29th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:4,numberOfPublishedChapters:318,numberOfPublishedBooks:32,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},subseries:[{id:"14",title:"Cell and Molecular Biology",keywords:"Omics (Transcriptomics; Proteomics; Metabolomics), Molecular Biology, Cell Biology, Signal Transduction and Regulation, Cell Growth and Differentiation, Apoptosis, Necroptosis, Ferroptosis, Autophagy, Cell Cycle, Macromolecules and Complexes, Gene Expression",scope:"The Cell and Molecular Biology topic within the IntechOpen Biochemistry Series aims to rapidly publish contributions on all aspects of cell and molecular biology, including aspects related to biochemical and genetic research (not only in humans but all living beings). We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics include, but are not limited to: Advanced techniques of cellular and molecular biology (Molecular methodologies, imaging techniques, and bioinformatics); Biological activities at the molecular level; Biological processes of cell functions, cell division, senescence, maintenance, and cell death; Biomolecules interactions; Cancer; Cell biology; Chemical biology; Computational biology; Cytochemistry; Developmental biology; Disease mechanisms and therapeutics; DNA, and RNA metabolism; Gene functions, genetics, and genomics; Genetics; Immunology; Medical microbiology; Molecular biology; Molecular genetics; Molecular processes of cell and organelle dynamics; Neuroscience; Protein biosynthesis, degradation, and functions; Regulation of molecular interactions in a cell; Signalling networks and system biology; Structural biology; Virology and microbiology.",annualVolume:11410,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},{id:"15",title:"Chemical Biology",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors",scope:"Chemical biology spans the fields of chemistry and biology involving the application of biological and chemical molecules and techniques. In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. This topic will closely deal with all emerging trends in this discipline.",annualVolume:11411,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null,editorialBoard:[{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",fullName:"Abdulsamed Kükürt",profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",institutionString:null,institution:{name:"Kafkas University",institutionURL:null,country:{name:"Turkey"}}},{id:"241413",title:"Dr.",name:"Azhar",middleName:null,surname:"Rasul",fullName:"Azhar Rasul",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRT1oQAG/Profile_Picture_1635251978933",institutionString:null,institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",fullName:"Sergey Sedykh",profilePictureURL:"https://mts.intechopen.com/storage/users/178316/images/system/178316.jfif",institutionString:null,institution:{name:"Novosibirsk State University",institutionURL:null,country:{name:"Russia"}}}]},{id:"17",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",annualVolume:11413,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",fullName:"Anca Pantea Stoian",profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"203824",title:"Dr.",name:"Attilio",middleName:null,surname:"Rigotti",fullName:"Attilio Rigotti",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"Pontifical Catholic University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"300470",title:"Dr.",name:"Yanfei (Jacob)",middleName:null,surname:"Qi",fullName:"Yanfei (Jacob) Qi",profilePictureURL:"https://mts.intechopen.com/storage/users/300470/images/system/300470.jpg",institutionString:null,institution:{name:"Centenary Institute of Cancer Medicine and Cell Biology",institutionURL:null,country:{name:"Australia"}}}]},{id:"18",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",annualVolume:11414,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life Sciences",institutionURL:null,country:{name:"Indonesia"}}},{id:"40928",title:"Dr.",name:"Cesar",middleName:null,surname:"Lopez-Camarillo",fullName:"Cesar Lopez-Camarillo",profilePictureURL:"https://mts.intechopen.com/storage/users/40928/images/3884_n.png",institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",institutionURL:null,country:{name:"Mexico"}}},{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",fullName:"Shymaa Enany",profilePictureURL:"https://mts.intechopen.com/storage/users/81926/images/system/81926.png",institutionString:"Suez Canal University",institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/137002",hash:"",query:{},params:{id:"137002"},fullPath:"/profiles/137002",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()