CC
A 63-year-old male is referred to your office by a general dentist in your community for full-mouth extractions, alveoplasty, and mandibular tori removal before maxillary and mandibular complete denture fabrication.
HPI
The patient has poor oral health, generalized decay, and generalized stage III periodontal disease. He also has moderately sized mandibular tori that will impede the seating of the future prosthesis and will require removal at the time of extractions. The patient has had inconsistent dental care throughout the course of his life and has mainly sought dental care on an emergency basis only. He has had multiple maxillary and mandibular teeth extracted in the past because of pain and local infection. The patient is unhappy with his current smile and oral health and desires complete denture fabrication.
PMHX/PDHX/medications/allergies/SH/FH
The patient’s past medical history is significant for nonvalvular atrial fibrillation, type II diabetes mellitus, hyperlipidemia, and hypertension. He also has a history of deep vein thrombosis (DVT) in the right lower extremity at age 52 years. The patient’s surgical history is remarkable for an appendectomy at age 25 years and an abdominal hernia repair at age 34 years. His current medications include Eliquis (apixaban, a factor Xa inhibitor), metformin (a biguanide), atorvastatin (an HMG-CoA reductase inhibitor), and hydrochlorothiazide (a diuretic). He reports no known drug allergies. He has a 40-pack-year history of smoking and does not report any alcohol or recreational drug use.
Examination
General. The patient is an obese male in no acute distress and is awake, alert, and oriented to person, place, and time.
Vital signs. Blood pressure is 134/88, pulse is 78 bpm, respirations are 14 breaths per minute, and temperature is 36.7°C.
HEENT. Normocephalic, atraumatic. Extraocular movements are intact. Gross visual acuity is intact. Gross hearing is intact. Nose is midline. Throat and oropharynx are clear and hemostatic.
Intraoral. The patient has multiple missing teeth, periodontally compromised remaining dentition, gross carious decay on remaining dentition, multiple retained root tips, large bilateral mandibular tori, and prominent maxillary canine eminences.
Neurologic. Cranial nerves II to XII are grossly intact bilaterally.
Integumentary. Well-healed abdominal surgery scars. Notable contusions on the extremities secondary to anticoagulation therapy.
Labs
The patient’s complete blood count (CBC) results are as follows:
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White blood cell count: 8500 white blood cells per microliter
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Hemoglobin: 15.4 g/dL
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Hematocrit: 45.2%
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Platelets: 225,000 platelets per microliter
Coagulation study results are:
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Prothrombin time (PT): 17 seconds
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Activated partial thromboplastin time (aPTT): 75 seconds
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Partial thromboplastin time: 135 seconds
Spectrometry and high-pressure liquid chromatography is the standard approach for assessment of direct-acting oral anticoagulant (DOAC) plasma concentration, but this is often impractical in the general laboratory setting in regard to cost and time. As such, clinicians are often advised to evaluate the PT, aPTT, and thrombin time (TT) preoperatively. PT is a basic test of coagulation that is responsive to factors II, V, VII, and X and fibrinogen. aPTT is a basic test of coagulation that is responsive to all coagulation factors except factors VII and XIII. The TT is a basic test of coagulation that is responsive to fibrinogen and to the inhibitors of fibrin formation. PT, aPTT, and TT can all be prolonged by any DOAC. DOACs directly affect thrombin and factor Xa and consequently impact the ability of fibrinogen to convert to fibrin and form a clot. It should be noted, however, that all three aforementioned studies may be prolonged secondary to defects of coagulation other than the DOAC taken by the patient. Although not routinely used in the clinical perioperative setting, other specific tests used to assess plasma DOAC concentrations include dilute thrombin time, anti–factor IIa assay, Ecarin tests, and anti–factor Xa assay.
Imaging
Panorex imaging demonstrates multiple teeth with periapical radiolucencies suggestive of gross carious decay, multiple retained root tips, and generalized horizontal bone loss in maxillary and mandibular arches.
Assessment
63-year-old-male with a past medical history significant for nonvalvular atrial fibrillation, type II diabetes mellitus, hyperlipidemia, hypertension, and a history of DVT who requires full-mouth extractions and preprosthetic surgery. His atrial fibrillation is managed with a DOAC, Eliquis (apixaban, a factor Xa inhibitor).
Treatment
Given the patient’s history of nonvalvular atrial fibrillation and prior DVT, a discussion with the patient’s primary care provider and cardiologist is warranted in regard to the perioperative management of Eliquis. We must determine whether the risks of holding the DOAC preoperatively outweigh the benefits of decreased intraoperative hemorrhage and postoperative bleeding. Based on the risk stratification, two scenarios should be discussed: (1) the patient’s physician provides clearance to hold the DOAC preoperatively or (2) the risks of thromboembolism or recurrent DVT are too high to hold the DOAC perioperatively.
Per the American Heart Association (AHA), the length of time to stop DOAC use varies based on the bleeding risk of the procedure. For minor bleeding risk procedures, the patient can stop 12 to 24 hours before the procedure and restart 6 hours after intervention. The time to stop the DOAC increases up to 96 hours before the procedure for low bleeding risk procedures. Generally, dental procedures, cutaneous procedures (i.e., skin biopsy), and other procedures less than 1 hour in length are considered low-risk bleeding procedures. Procedures with high bleeding risk include otorhinolaryngologic surgery, invasive procedures at deep lesions, and other procedures longer than 1 hour in length. The determination of bleeding risk must also take into account the patient’s medical comorbidities. As such, risk stratification can be best determined with the patient’s physician to guide timing of perioperative DOAC discontinuation. In our vignette, if the patient is to hold their normal DOAC dose for 72 hours preoperatively, then the aforementioned dentoalveolar treatment should be completed in one appointment as long as the patient can tolerate the length of the procedure and there are manageable expected levels of intraoperative bleeding. For our patient, treatment was completed under general anesthesia. The remaining dentition was extracted in an atraumatic fashion with conservative mucoperiosteal flaps. Local hemostatic measures were used to aid in hemostasis, with the authors’ preference being placement of Gelfoam saturated with thrombin directly in the extraction sockets. The surgical sites were then primarily closed using 3-0 chromic gut suture in a running locking fashion to aid with hemostasis. Per AHA guidelines, we can then recommend the patient to restart their DOAC 6 hours after surgery.
In the equally likely situation that the risk stratification deems it unacceptable to hold the patient’s DOAC, a discussion is held with the patient to explain the reasoning for staging the procedure as to minimize intraoperative and postoperative hemorrhage. Based on current American Dental Association recommendations cited from the European Heart Rhythm Association, it is not necessary to hold a DOAC for extraction of up to three teeth. A limited number of studies have recommended performing dentoalveolar surgery at least 4 hours after the patient’s last DOAC dose in an attempt to complete the procedure during the DOAC’s blood concentration trough. As such, in our patient, we would recommend they continue to take their normal medications ahead of their surgery. Based on their medication schedule, the patient would be scheduled to have surgery 4 hours after his morning DOAC dose. The teeth will be atraumatically extracted with associated alveoplasty with special attention to minimize the extent of the mucoperiosteal flap. Sites will be packed with Gelfoam saturated in thrombin and primarily closed with 3-0 chromic gut sutures in a running locking fashion to further promote hemostasis. The patient would continue to follow up until his staged treatment was completed in a safe manner that ultimately reduced the risks of perioperative hemorrhage.
Complications
Intraoperative and postoperative hemorrhage are risks for any patient undergoing an oral and maxillofacial procedure; however, patients on anticoagulative therapy should be identified before surgery, and special care and attention should be taken in an attempt to reduce and control bleeding. Whether treating a patient in the office setting under local anesthesia with or without intravenous sedation or in the operating room under general anesthesia, preoperative identification of patients who are at increased risk for perioperative bleeding should prompt the surgeon and staff to have materials and instruments ready and available to aid in hemostasis and hemorrhage control. Reasons for perioperative bleeding can broadly be divided into two categories: bleeding from local factors or bleeding secondary to systemic factors. Local factors include bleeding that occurs as a result of performing the procedure itself and include hemorrhage secondary to soft tissue and bone manipulation, inflammation, or the presence of infection at the operative site. Bleeding from systemic factors is attributed to the use of anticoagulant medications or presence of systemic coagulopathy.
Generally, patients who do not have systemic coagulopathy and who experience increased levels of intraoperative bleeding can be adequately treated with local hemostatic measures. This list of patients usually includes those taking anticoagulant medications. There are myriad products available that aid in providing hemostasis in oral and maxillofacial procedures; however, the first-line treatment to control local hemorrhage is direct pressure with gauze. If direct pressure is inadequate or the surgeon would like to use additional materials to ensure postoperative hemostasis, many products exist, including, but not limited to, electrocautery, local anesthetic with a vasoconstrictor, absorbable gelatin sponge (Gelfoam), bone wax, oxidized cellulose (Surgicel), and silver nitrate. Gauze can also be impregnated with thrombin or tranexamic acid, and firm pressure can be applied directly to the site of hemorrhage. After local hemostasis is achieved and indicated materials have been used for hemorrhage control, closure of the operative site with appropriate sutures also aids in continued hemostasis after surgery.
Unfortunately, for patients with systemic coagulopathies, local measures can aid in hemostasis but are generally not sufficient alone to control perioperative bleeding. These patients require a thorough work-up, including pertinent laboratory tests (CBC, PT or INR, PTT), and a discussion with the patient’s hematologist preoperatively. Because of the significant risk of perioperative bleeding in these patients, they are most commonly treated in the operating room under general anesthesia and frequently require postoperative admission for observation. Depending on the cause of the coagulopathy, these patients often require perioperative treatment with certain factors, medications, or platelets. Patients with hemophilia A or B are deficient in factor VIII and IX, respectively, and generally require preoperative treatment with appropriate recombinant factor replacement before oral and maxillofacial surgery procedures. Postoperative use of systemic tranexamic acid or topical use in the form of a mouthwash can aid in reduction of postoperative bleeding. Patients with von Willebrand’s disease usually require pretreatment with desmopressin (DDAVP), factor VIII, tranexamic acid, or a combination of these options. Patients with platelet disorders, such as Glanzmann’s thrombasthenia, Bernard Soulier disease, and idiopathic thrombocytopenic purpura, should be medically optimized before surgery and may require platelet transfusions and steroids. Each patient and their specific circumstances should be evaluated on an individual basis, but it is generally optimal for platelet counts to be greater than 100,000 cells/mm 3 before surgery. As previously mentioned, patients with systemic coagulopathies frequently require postoperative admission for observation to ensure continued hemostasis after completion of the surgical procedure. Postoperative admission planning and preoperative optimization with appropriate medications are coordinated in conjunction with the patient’s hematology team.
Although rare in oral and maxillofacial surgery, a mention of the possibility of life-threatening bleeding and appropriate treatment must be discussed. For patients taking warfarin, two main options exist for reversal, vitamin K and fresh-frozen plasma (FFP). Although vitamin K is an option, the time required to achieve reversal with this medication limits its use in the setting of life-threatening hemorrhage when emergent reversal is needed. Vitamin K has been shown to require 10 to 12 hours for full reversal to occur. As a result, the choice for patients on warfarin experiencing life-threatening hemorrhage and in need of emergent reversal is FFP. Patients taking unfractionated heparin (UFH) and in need of emergent reversal because of hemorrhage should be given protamine sulfate. Until recently, no specific reversal agents were available for the direct factor Xa inhibitors (apixaban, rivaroxaban). The Food and Drug Administration (FDA) approved andexanet alfa in May of 2018 for reversal of apixaban and rivaroxaban in patients experiencing life-threatening hemorrhage or uncontrolled bleeding. The medication is given intravenously and is a recombinant human coagulation factor Xa. For those who are taking the direct thrombin inhibitor dabigatran, reversal is achieved with the monoclonal antibody idarucizumab. This drug binds dabigatran reversibly with high affinity and is useful for life-threatening hemorrhage. Because of their recent approval and expense, however, these reversal agents are not yet widely available in hospitals across the United States.
Discussion
Direct oral anticoagulants have grown increasingly popular since they were first approved by the FDA in 2010. They are arguably considered superior to anticoagulation with vitamin K antagonists (i.e., warfarin) or low-molecular-weight heparins (LMWHs) in reducing the risks of thromboembolic complications with similar or reduced bleeding risks. Moreover, the DOACs require fewer monitoring requirements, offer more immediate drug onset and offset, and have fewer drug and food interactions. As a result of these preferable qualities, the AHA notes that DOAC prescriptions have exceeded those for warfarin, with apixaban most commonly prescribed for patients with nonvalvular atrial fibrillation (as our patient in the vignette).
Surgeons should recognize that DOACs are categorized into two main classes based on their mechanism: direct thrombin inhibitors and factor Xa inhibitors ( Table 104.1 ). Consequently, being aware of the specific DOAC can prove useful in the event that a patient requires a reversal agent for life-threatening bleeding. Moreover, it is noteworthy that each DOAC has variations in half-life, which can theoretically impact perioperative bleeding risks based on when the patient took their last dose. For example, in patients whose DOACs cannot be stopped preoperatively, the surgeon should attempt to complete treatment at least 4 hours from the last dose to provide treatment during the drug concentration trough.
