HealthJune 17, 2015

Perioperative management of patients taking dabigatran (Pradaxa): published experiences

By: Richard L. Wynn

Dabigatran (Pradaxa) is a member of a group of new oral anticoagulants which include rivoraxaban (Xarelto), apixaban (Eliquis) and edoxaban (Savaysa). At the present time, there are no evidence-based guidelines for dental periprocedural protocols for these new oral anticoagulants.

A recent medical report and five reports in dental literature describing clinicians’ experiences and observations provide some insight in managing dental patients taking dabigatran.

Published experiences managing patients taking dabigatran

Reports are emerging describing the handling of dabigatran-medicated patients undergoing surgery. The strategy for the perioperative management of patients on dabigatran involves the relative acceptance of bleeding versus thrombotic risks in the decision-making process. Based on medical reports, in dental patients using the drug who are undergoing procedures involving low bleeding risk, discontinuation of dabigatran is not recommended. For patients undergoing multiple extractions or other procedures likely to have a high bleeding risk, temporary cessation of the dabigatran 24 hours before the procedure has been recommended. However, cessation of dabigatran prior to surgery should only be made in consultation with the patient’s physician.

Medical report from University of Colorado Anschutz Medical Campus, Aurora

Anderson, M, et al. “When patients on target-specific oral anticoagulants need surgery.” Cleve Clinic J Med 2014; 81:629-39.

This report states that many physicians lack the experience with the perioperative management of patients on dabigatran. More than 2.5 million patients in the U.S. are on anticoagulant therapy, such as warfarin or the new oral anticoagulants for various cardiovascular conditions, and each year, 10% of those undergo surgery that requires temporary interruption of anticoagulation.

Unlike warfarin, which works through the inhibition of those coagulation factors that are vitamin-K dependent, dabigatran works by directly inhibiting thrombin (factor IIa), thereby blocking the generation of fibrin. It is approved for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. It is formulated as a prodrug, dabigatran etexilate, and available as a capsule, which when swallowed, releases the drug in the stomach to be absorbed across the gastric mucosa and rapidly converted to its active form. Plasma concentrations peak within 2 hours of ingestion. Nearly 85% of the drug is eliminated in the urine. It has a half-life of 12-17 hours in patients with normal renal function. Its half-life increases to 28 hours in patients whose creatinine clearance is less than 30 ml/min. Dosing is based on creatinine clearance values. For values greater than 30 ml/min (normal renal function), dosing is 150 mg twice daily. For values of 15-30 ml/min (renal impairment), dosing is 75 mg twice daily; less than 15 ml/min, and dabigatran is avoided.

The authors’ suggested strategy for the perioperative management of patients on dabigatran involves the relative acceptance of bleeding versus thrombotic risks in the decision-making process. In procedures that pose very low bleeding risks such as cataract surgery, dermatologic procedures or minor dental extractions, discontinuation of dabigtran is not recommended. In those medical procedures considered to be high bleeding risk, discontinuation 1 to 2 days prior to surgery is appropriate. For example, the authors state that in medical surgery involving highly vascular organs, such as the liver and spleen, zero or minimal residual anticoagulation effects is acceptable.

The clinician is reminded that the INR test is relatively insensitive to the activity of dabigatran and may not be elevated in patients having the drug in their system. At recommended therapeutic doses, dabigatran prolongs the activated partial thromboplastin time (aPTT). With an oral dose of 150 mg twice daily, the mean peak aPTT is approximately twice that of control values. Twelve hours after the last dose, the median aPTT is 1.5 x control.

Dental reports

The following reports, published in the dental literature, are generally based on those guidelines from the medical literature, such as that described above.

From the University of Kentucky, Lexington

Romond, KK; Miller, CS; Henry, RG. “Dental management considerations for a patient taking dabigatran etexilate: a case report.” Oral Surg Oral Med Oral Pathol Oral Radiol 2013; 116:e191-e195.

This early report on the management of a dabigatran-medicated dental patient was published in 2013. The authors stated at that time that information on management of bleeding during dental surgery in patients taking dabigatran was sparse. This report is of a single case in which dabigatran was temporarily discontinued prior to elective oral surgery. The authors used general guidelines previously reported in the medical literature.

The patient was a 67-year-old man with a positive history of atrial fibrillation, coronary artery disease, intermittent angina, hypertension, type 2 diabetes, and normal renal function. He was taking dabigatran 150 mg, twice daily. He underwent eight surgical extractions, alveoloplasty and tuberosity reduction. Per guidelines in the medical literature similar to the aforementioned, the patient’s dabigatran was withheld the night before surgery and resumed the day after surgery. Prolonged bleeding was not observed in the postoperative period, healing occurred within normal time frame, and no adverse outcomes were reported secondary to cessation of dabigatran. The authors stated that because of the short half-life, dabigatran can be temporarily discontinued 24 hours prior to elective oral surgery with consent of the physician and restarted the following day resulting in minimal complications.

From the Capital Health & Dalhousie University QEII Health Science Center, Nova Scotia

Davis, C, et al. “Implications of dabigatran, a direct thrombin inhibitor, for oral surgery practice.” J Can Dent Assoc 2013; 79:d74

Studies involving dabigatran that were reviewed by the authors showed a risk of hemorrhage statistically similar to that of warfarin when the warfarin INR was between 2.0 and 3.0. For patients who are undergoing dental procedures or minor oral surgery procedures, such as simple or surgical extractions, it is assumed that the risk of a major bleeding event will be low, similar to that of a patient medicated with warfarin with INR between 2.0 and 3.0. Dabigatran need not be discontinued in these situations. For patients requiring multiple surgical extractions or significant oral surgical procedures, consideration should be given to discontinuing dabigatran prior to the procedure, with timing determined by renal function.

Also, with a relatively short half-life for dabigatran (12-17 hours), it is suggested that procedures be performed as late as possible after the most recent dose. In conjunction with the patient’s physician, a dental professional might also consider omitting one dose before the appointment for minor procedures with a suspected higher risk of bleeding.

From the Royal Adelaide Hospital, Australia

Breik, O, et al. “Protocol in managing oral surgical patients taking dabigatran.” Australian Dental Journal 2014; 59:296-301.

This review described dabigatran and reported on the authors’ experience of five cases. It provides clinical advice on how to manage patients on dabigatran who require dental treatment, particularly extractions.

When considering the management of patients taking dabigatran, one should always keep in mind that stopping dabigatran leads to an increased risk of stroke or venous thrombosis in those patients. Intraoral bleeding can often be managed and is rarely catastrophic, whereas stroke can be permanently debilitating.

Of the five case reports, the three involving single tooth extractions were managed without discontinuing the dabigatran, and there were no episodes of significant postoperative bleeding. Thus, the authors concluded that for simple procedures with a minor bleeding risk such as scaling, restoration with use of a matrix band, endodontic treatment, or single tooth extractions, dabigatran will likely not need to be stopped.

A fourth case involved the successful extraction of multiple teeth after ceasing dabigatran for 48 hours. According to the authors, ceasing the dabigatran for 24 hours would have been equally effective. The last case involved extraction of 18 teeth while taking dabigatran. Significant postoperative bleeding occurred requiring suturing under anesthesia and ceasing dabigatran.

Breik, et al, suggest several management scenarios:

  • Scenario #1: For simple procedures with a minor bleeding risk such as scaling, restoration with use of a matrix band, endodontic treatment, or single tooth extractions, it is not necessary to stop dabigatran in patients with normal renal function. For single uncomplicated tooth extractions, local hemostatic measures, such as mechanical pressures, suturing, and topical hemostatic agents such as Gelfoam or Surgicel should be adequate to control bleeding.
  • Scenario #2: For patients undergoing elective surgery involving multiple extractions or other procedures likely to have a high bleeding risk, patients should be assessed by their own physician before the procedure is undertaken. Cessation of dabigatran should only be made in consultation with the patient’s physician. For patients with normal renal function, the temporary cessation of the dabigatran 24 hours before the procedure is usually recommended. For patients with abnormal renal function, one should consider discontinuing for 48 hours or longer depending on degree of renal impairment. If dabigatran is ceased, it can be restarted when the risk of postoperative bleeding is minimal, usually 24-48 hours after surgery. When restarting the dabigatran, the anticoagulant effect reaches its optimum level within two hours after administration.

The authors summarize:

  • Dabigatran is a direct thrombin inhibitor that is likely to become more widely prescribed due to its ease of use
  • Due to its more predictable standard dose regimens, stopping and restarting the dabigratran is easier and causes less risk than warfarin
  • These decisions should still only be made in conjunction with the patient’s physician

From the University of Padova, Padua, Italy

Sivolella, S, et al. “Managing dentoalveolar surgical procedures in patients taking new oral anticoagulants.” Odontology, published online: 06 February 2015.

Sivolella, et al, concurred with published reports that single tooth extractions can be managed without suspending the patient’s dabigatran, and that no episodes of significant bleeding should be expected. These were patients with normal renal function and standard bleeding risks in whom local hemostatic measures were used. With multiple dental extractions, patients may require discontinuation of dabaigtran therapy at least 24 hours before elective surgery. This usually results in adequate hemostasis.

The authors agreed that dabigatran need not be suspended in dental patients due to undergo elective surgical procedures that carry a standard bleeding risk. It has been suggested that surgery be performed as late as possible after the last dose of the drug, and that appropriate hemostatic measures be used. In cases of surgery carrying a high bleeding risk, dabigatran should be discontinued for 2-3 half-lives before surgery (half-life in patient with normal renal function is 12-17 hours).

Richard L. Wynn
Professor of Pharmacology at the Baltimore College of Dental Surgery, Dental School, University of Maryland Baltimore
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