Interruption of dabigatran therapy at times of surgery, colonoscopy and other procedures

Dabigatran is an oral anticoagulant - a synthetic thrombin inhibitor – that is approved in the United States for the prevention of stroke and systemic arterial thromboembolism in patients with non-valvular atrial fibrillation.

The approved dose of dabigatran (Pradaxa, Boehringer Ingelheim) is 150 mg twice daily for patients with a glomerular filtration rate of more than 30 mL/min, and 75 mg twice daily for patients with a GFR of 15 mL/min to 30 mL/min.

It has been investigated for treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), but it is not FDA approved for that indication. However, based on published data, it sometimes is used off-label in patients with DVT and PE.

The hematologist-oncologist may be called upon for assistance with anticoagulation management in the patient on dabigatran who needs interruption of therapy for a medical procedure, such as colonoscopy or esophagogastroduodenoscopy (EGD), a minor or major surgical procedure, or dental work.

Stephan Moll

The point before a procedure that a patient should take the last dose of dabigatran depends on several factors, including what type of procedure is planned and how much bleeding is expected with it, whether the patient is at high or low risk for thrombosis while off anticoagulants for some period of time, and the patient’s renal function.

About 80% of dabigatran is excreted unchanged via the kidney. The remainder is excreted via the bile.

The half-life of dabigatran primarily is determined by renal function (see Table).

In most patients with normal renal function, dabigatran’s anticoagulant effect is mostly gone within 1 to 2 days after the last dose has been taken, as the drug is excreted by the kidney relatively quickly. Typically, after three half-lives, most of the drug (87.5%) is gone.

Most surgeries with a normal, standard risk of bleeding can be done safely when the majority of anticoagulant effect is gone. For people with normal renal function, this is about 24 hours after the last dose has been taken (Table). However, in patients with impaired renal function, dabigatran must be discontinued earlier because of its prolonged half-life (ie, stopped 2 or more days before surgery).

Beth Waldron

Also, if surgeries with a high risk of bleeding are planned, one will want all the drug out of the system and, depending on the patient’s renal function, the last dose of dabigatran should be taken 2 or more days before the surgery.

Dental procedures

Many dental procedures can be done on full-dose anticoagulation. Detailed recommendations as to which dental procedures can be done on full dose anticoagulation with warfarin — such as teeth cleaning, root canal, or one or two teeth extractions — and for which the anticoagulant level needs to be reduced have been published.

A similar approach can likely be taken in patients on dabigatran. However, it also is easy to tell the patient not to take his or her evening dose of dabigatran on the day before the procedure, not to take the morning dose on the day of the dental procedure, and to restart in the evening of the day of the procedure. However, individualized recommendations must be given.

Colonoscopies and EGDs

Colonoscopies and EGDs typically can be done safely on full-dose anticoagulants. However, as biopsies and polypectomies may have to be performed, many gastroenterologists prefer to see the patient off anticoagulation.

As discussed, the renal function must be taken into consideration as to when to have the patient take the last dose of dabigatran (Table gives guidance).

The patient with normal renal function may not want to take dabigatran 1 day before surgery, nor in the morning of the day of the procedure (ie, the last dose of dabigatran would have to be taken more than 36 hours before the colonoscopy or EGD).

Surgery

When to take the last dose before minor or major surgery depends on the degree of expected peri-surgical bleeding. The Table gives guidance.

Dabigatran is rapidly effective after oral intake, reaching its maximum anticoagulant effect within 2 to 3 hours of intake.

Therefore, for patients with significant risk for bleeding after a procedure or after surgery, the re-initiation of dabigatran may have to be delayed by a few days. However, individualized decisions need to be made, depending on a patient’s risk for bleeding and thrombosis.

Stephan Moll, MD, is an associate professor in the Department of Medicine and Division of Hematology-Oncology at the University of North Carolina School of Medicine in Chapel Hill, N.C. Beth Waldron, MA, is the program director of the UNC Blood Clot Outreach Program and Clot Connect project in the Hemophilia and Thrombosis Center at the University of North Carolina at Chapel Hill. The above text is modified from literature from Clot Connect, an initiative of the University of North Carolina Hemophilia and Thrombosis Center that connects patients and health care professionals to clinical-practical information and support resources related to venous thromboembolism, thrombophilia and anticoagulation. Disclosure: Dr. Moll has been a consultant for OrthoMcNeil and Bayer. Ms. Waldron reports no relevant financial disclosures.

For more information:

• Clotconnect.wordpress.com/2010/11/12/dental-work-on-warfarin. Accessed Nov. 1, 2011.
• Clotconnectmd.wordpress.com/2011/04/14/pradaxa-interruption-for-colonoscopies-dental-procedures-surgery-etc. Accessed Nov. 1, 2011.
• Herman WW. J Am Dent Assoc. 1997;128:327-335.
• Schulman S. N Engl J Med. 200910;361:2342-2352.
• Van Ryn J. Thromb Haemost. 2010;103:1116-1127.