HealthMarch 28, 2016

The new anticoagulants: Bleeding risks in dental management

By: Richard L. Wynn

In a previous article, we examined emerging reports regarding dental management of patients taking the anticoagulant dabigatran (Pradaxa).

Now there is more information on dabigatran, as well as rivoraxaban (Xarelto), apixaban (Eliquis), and edoxaban (Savaysa).

Currently, there are no data to support clear, evidence-based recommendations for the management of patients on these new anticoagulants and undergoing dental surgery. The authors of a new review suggest that many dental procedures can be accommodated with either no discontinuation or only a short discontinuation of these new blood thinners. For procedures which generate extensive bleeding, if the risk of thromboembolism is low based on medical consult and renal function is normal, then discontinuation of any of these the anticoagulants 48-72 hours before the procedure is appropriate. For procedures which generate extensive bleeding, if the risk of thromboembolism is high based on medical consult, then it is suggested to time the surgery as late as possible after the last dose of anticoagulant or skip one daily dose the day before.

Keep in mind that there are no validated laboratory tests which would allow for anticipating the extent of bleeding during dental surgery.

Rochester study of anticoagulants

The authors of the review are from the University of Rochester Medical Center, including the Eastman Institute for Oral Health, and from the Wilmot Cancer Center in Rochester, NY. The review article, which has 50 references, can be accessed at:

Elad S, Marshall J, Meyerowitz C, Connolly G. “Novel anticoagulants: general overview and practical considerations for dental practitioners.” Oral Disease 2016; 22:23-32.

Their review provides some guidance on the perioperative management of dental surgical patients taking any of these new medications. It addresses some general information on how these drugs work, the medical conditions for which they are used, some monitoring information, bleeding risks, and the risk of thromboembolism associated with discontinuation of the new anticoagulants in patients undergoing dental surgery. Most importantly it provides suggestions as to which conditions warrant discontinuation prior to surgery and which conditions do not warrant discontinuation.

General information on how these drugs work

Dabigatran is known as a direct thrombin inhibitor. Rivaroxaban, apixaban and edoxaban are known as factor Xa inhibitors. These agents are taken orally and act directly on these factors within the coagulation pathways. According to the authors, the International Society of Thrombosis and Hemostasis suggests that the preferred nomenclature for these drugs to be “direct oral anticoagulants,” or DOACs. This is based on their direct targeting of thrombin and factor Xa.

Their half lives in plasma are:

  • Dabigatran = 12-17 hrs
  • Rivaroxaban =7-13 hrs
  • Apixaban = 8-13 hrs
  • Edoxaban = 10-14 hrs

The drugs undergo significant renal excretion:

  • Dabigatran = 80%
  • Rivaroxaban =67-85%
  • Apixaban = 30%
  • Edoxaban = 35%

Medical conditions for use

These new anticoagulants are used in conditions where chronic anticoagulation is indicated. Such conditions include the prevention of embolism and stroke in atrial fibrillation, prevention of thromboembolism in patients with mechanical heart valves, and treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). In addition, anticoagulation is indicated for the prevention of DVT in patients undergoing knee and hip replacement surgery.

Monitoring and reversal

The standard monitoring test for patients with warfarin in their system is prothrombin times, expressed as the International Normalized Ratio (INR). This predictable monitoring presents an advantage not offered by the new anticoagulants. At this time, there are no validated and reliable laboratory tests which would allow for anticipating the extent of bleeding during dental surgery.

Warfarin is easily reversed with vitamin K (Menadione). For dabigatan (Pradaxa), an antidote has been approved and is presently on the market as idarucizumab, brand name Praxbind. There are no known antidotes for reversal of rivaroxaban, apixaban or edoxaban. The study authors claim that new antidotes for the three are presently in the development and testing stages.

Risk of bleeding in patients on the DOACs

Bleeding risks were summarized using reports from medical settings. These reports were retrieved from PubMed and included all English papers through 2013 using the key words of the individual drug names, as well as the words “bleeding,” “direct oral anticoagulants,” and “novel anticoagulants.” The authors identified 18 randomized, controlled trials with mixed results in regard to the risk for bleeding.

When dabigatran was compared to warfarin, bleeding rates for dabigatran (usual dosing of 150 mg twice daily) were equivalent or lower. This suggests that the risk of both major and minor bleeding for patients medicated with dabigatran is similar to or lower than patients using warfarin.

In one trial comparing rivaroxaban to conventional anticoagulants for the treatment of acute pulmonary embolism, the rate of major bleeding was significantly lower. Five additional trials, however, showed no significant difference. In another trial, minor bleeding in patients using rivaroxaban was not significantly different compared to standard anticoagulation therapy.

According to the authors, the risk of major or minor bleeding for patients using apixaban as compared to warfarin is unclear, but is probably higher than for patients using aspirin.

There were less major bleeding events with edoxaban than with warfarin and less minor bleeding when tested for prevention of stroke in patients with atrial fibrillation.

Discontinuation risks in patients undergoing dental surgery

Currently, random, placebo-controlled trials do not provide any clear conclusion regarding the risks associated with discontinuing the new anticoagulants in patient populations other than those post knee or hip replacement. The knee- or hip-replacement population is at risk of thrombosis for a relatively short period of time after orthopedic surgery. The likelihood that these patients will seek dental treatment during that short period of time while on the anticoagulants is low. Specifically for a patient following hip or knee replacement, the risk of a thromboembolic event decreases significantly four months post operation.

The authors provide a list from the American College of Chest Physicians of those factors increasing the risk of a thromboembolic event during discontinuation of the anticoagulants. These include recent DVT or PE (within three months), high-risk prosthetic heart valve, high-risk atrial fibrillation, atrial fibrillation with rheumatic heart disease, and a recent stroke from atrial fibrillation or heart valve (within six months).

The authors emphasized that the thromboembolic complications that could occur upon discontinuation in specific situations can be significant and include deep vein thrombosis, cerebral artery infarct, stent thrombosis, and pulmonary embolism.

So this begs the question — what are the present recommendations, if any, for the periprocedural management of patients on these new anticoagulants?

There are no standard monitoring tests to assess bleeding risk on these new anticoagulants, nor is there any reversal agent except for idarucizumab (Praxbind) indicated as a dabigatran reversal drug. Communication with the patient’s physician is important in the dental treatment planning. The patient’s medical history, medication list, and known allergies should be obtained.

Factors to consider prior to dental invasive procedure are:

  1. Type of procedure with the extent of expected bleeding
  2. Patient’s medical background to assess the risk of bleeding versus the risk of thromboembolisms
  3. Availability of local and systemic hemostatic measures

Type of procedure with the extent of expected bleeding

Dental procedures that could generate bleeding are extractions, incisional biopsy from a vascular or inflamed area, and periodontal grafting. The authors state that factors, such as the level of invasiveness, number of teeth involved, and the severity of local inflammation, should all be integrated into the general assessment of bleeding risk. If little risk of bleeding is expected, there should be no change in the anticoagulant protocol.

If the conditions predisposing for thromboembolism are identified, the risk of discontinuing the anticoagulant versus the benefit of doing the procedure is to then be considered. The authors presented three options:

  1. Continue regular dose administration
  2. Postpone the timing of the daily dose of the anticoagulant or timing the dental treatment as late as possible after the last dose of anticoagulant
  3. Temporarily interrupt medication for 1-2 days

Authors’ suggestions for discontinuing anticoagulants

For procedure which could generate extensive bleeding:

  • If risk of thromboembolism is LOW based on medical consult:
    • With normal renal function — discontinue for 24-48 hours before (for edoxaban, 24 hours before)
    • With impaired renal function — discontinue 48-72 hours before (for edoxaban, 2 days before)
  • If risk of thromboembolism is HIGH based on medical consult:
    • Time the surgery as late as possible after the last dose of anticoagulant
    • Or skip one daily dose day before

For procedure in which less bleeding is anticipated:

  • If risk of thromboembolism is LOW based on medical consult:
    • Time the surgery as late as possible after the last dose of anticoagulant
    • Or skip one daily dose day before
  • If risk of thromboembolism is HIGH based on medical consult:
    • Continue with no alterations in dosing or timing

NOTE: The authors believe that most dental surgical procedures can be accommodated with a minimal or short discontinuation of the anticoagulants. Local hemostatic measures to control bleeding should be applied as needed. If the anticoagulant was discontinued, ensure there is no late bleeding before resuming the anticoagulant post-surgically.

Until some clear evidence-based recommendations evolve, information on dental management of patients taking these new medications relies on expert opinion suggestions.


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