How Best to Reverse Anticoagulation With Dabigatran?
Consultations & Comments
Reader Reaction and Timely Answers From Experts
I offer the following hypothetical scenario: A patient who is taking dabigatran is referred to the hospital for emergent surgery. The surgeon wants to know whether he can operate. Is there any readily available laboratory test that can assess the bleeding status of the patient and provide results that are immediate and exact, not an approximation?
Further, just as vitamin K can be given to correct anticoagulation in patients who take warfarin, what antidote could be given in an emergency situation to a patient who is taking dabigatran?
Robert P. Blereau, MD
Morgan City, La
You ask a most important and pertinent question regarding dabigatran reversibility in emergent situations, which would include not only emergency surgery but also serious bleeding in patients who use the drug. Although we lack peer-reviewed, full-length, patient data–based publications to guide us in such situations, our knowledge of dabigatran pharmacology and anecdotal experience can be reviewed to provide guidance.1
Dabigatran is an oral, small molecule, direct thrombin inhibitor that has been shown to be equivalent or even slightly superior to warfarin in the prevention of embolism in patients with atrial fibrillation.2 Dabigatran has a half-life of approximately 12 hours in patients with normal (greater than 50 mL/min) creatinine clearance, 18 hours when the creatinine clearance is 30 to 50 mL/min, and 27 hours when the creatinine clearance is less than 30 mL/min. I thus avoid its use for now in patients who do not have normal renal function.3
There is, quite simply, no true antidote (eg, such as vitamin K for warfarin) for dabigatran. Therefore, the first maneuver is simply time, if and when available. Since the half-life is 12 hours, each 12 hours from dosing will halve the concentration and anticoagulant effect to allow surgery. If that degree of delay is not possible or kidney function has worsened, aggressive efforts to maintain good renal output and even hemodialysis to hasten metabolism have been used, as has activated charcoal to prevent absorption in cases of recent dabigatran ingestion.1 As previously mentioned, such experience is anecdotal and derived from pharmacological data and will require corroboration as dabigatran use increases.
A variety of nonspecific therapies, including fresh frozen plasma and activated factor VIIa also appear in abstract and case report literature4,5 and are likely worth a try in desperate cases, although the use of factor VIIa in a patient with atrial fibrillation who is at risk for thrombosis/embolism is problematic. Currently, therefore, available literature suggests that because of the reasonably short half-life of dabigatran, discontinuation usually should be sufficient. In overdose situations (eg, in a patient with renal insufficiency), the nonspecific therapies mentioned above should be considered.
Regarding laboratory testing for dabigatran effect, thrombin time is sensitive as an indicator to its presence and somewhat to its degree of effect. This test is available in most hospital coagulation laboratories and has an acceptable turnaround time. The partial thromboplastin time is also useful as a qualitative test (ie, to determine whether dabigatran is having an anticoagulant effect in the patient). The prothrombin time is less sensitive and useful for dabigatran.4
Ronald N. Rubin, MD
Professor of Medicine
Temple University School of Medicine
Chief of Clinical Hematology
Temple University Hospital, Philadelphia
1. Moll S. Ask the hematologist. The Hematologist. 2011;March:4.
2. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139-1151.
3. Beasley BN, Unger EF, Temple R. Anticoagulant options—why the FDA approved a higher but not a lower dose of dabigatran. N Engl J Med. 2011;364:1788-1790.
4. van Ryn J, Stangier J, Haertter S, et al. Dabigatran etexilate—a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity.Thromb Haemost. 2010;103:1116-1127.
5. van Ryn J, Ruehl D, Priepke H, et al. Reversibility of the anticoagulant effect of high doses of the direct thrombin inhibitor dabigatran by recombinant factor VIIa or activated prothrombin complex concentrate. (Abstract 0370). Haematologica. 2008;93(suppl 1):148.