Abstract
Introduction
Dabigatran (Pradaxa™), an orally active direct thrombin inhibitor, was approved by the United States Food and Drug Administration for the prevention of stroke in patients with atrial fibrillation in October 2010. Life-threatening consequences from dabigatran therapy include hemorrhage and bleeding complications, but they typically occur after renal impairment. We describe the first case report of intentional, acute overdose with dabigatran.
Case Report
A 57-year-old woman with a medical history of depression and atrial fibrillation presented to the emergency department after ingesting 11.25 g of dabigatran in a suicide attempt. Despite an ecchymosis indicative of prior trauma, there was no evidence of acute bleeding. After receiving gastric lavage and activated charcoal therapy in the emergency department, she was admitted to the ICU. On presentation, dabigatran blood levels measured 970 ng/mL and thrombin clot times measured above the testable limits (>120 s) until 52 h post-arrival. The remainder of her clinical course was uncomplicated, and the patient was transferred to an inpatient psychiatric unit for depression follow-up.
Discussion
This case shows the clinical course of a patient with an acute, massive dabigatran overdose with no significant clinical consequences. Currently, there is no ideal method to monitor anticoagulation levels; there is no pharmacologic reversal method, and hemodialysis is an undesirable treatment option.
References
US-FDA. (2010) FDA approves Pradaxa to prevent stroke in people with atrial fibrillation. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm230241.htm. Accessed 17 July 2012
US-FDA. (2011) FDA drug safety communication: safety review of post-market reports of serious bleeding events with the anticoagulant Pradaxa (dabigatran etexilate mesylate). http://www.fda.gov/drugs/drugsafety/ucm282724.htm. Accessed 5 May 2012
Garber ST, Sivakumar W, Schmidt RH (2012) Neurosurgical complications of direct thrombin inhibitors—catastrophic hemorrhage after mild traumatic brain injury in a patient receiving dabigatran. J Neurosurg 116(5):1093–1096
Cano EL, Miyares MA (2012) Clinical challenges in a patient with dabigatran-induced fatal hemorrhage. Am J Geriatr Pharmacother 10(2):160–163
Barton CA et al (2012) Hemopericardium in a patient treated with dabigatran etexilate. Pharmacotherapy 32(5):e103–e107
Bene J et al (2012) Rectal bleeding and hemostatic disorders induced by dabigatran etexilate in two elderly patients. Ann Pharmacother 46(6):e14
Fellows SE et al (2012) Hemorrhagic gastritis with dabigatran in a patient with renal insufficiency. J Emerg Med. doi:10.1016/j.jemermed.2012.02.042
Wychowski MK, Kouides PA (2012) Dabigatran-induced gastrointestinal bleeding in an elderly patient with moderate renal impairment. Ann Pharmacother 46(4):e10
Warkentin TE et al (2012) Recombinant factor VIIa (rFVIIa) and hemodialysis to manage massive dabigatran-associated postcardiac surgery bleeding. Blood 119(9):2172–2174
van Ryn J, Baruch L, Clemens A (2012) Interpretation of point-of-care INR results in patients treated with dabigatran. Am J Med 125(4):417–420
Miyares MA, Davis K (2012) Newer oral anticoagulants: a review of laboratory monitoring options and reversal agents in the hemorrhagic patient. Am J Health Syst Pharm 69(17):1473–1484
Avecilla ST et al (2012) Plasma-diluted thrombin time to measure dabigatran concentrations during dabigatran etexilate therapy. Am J Clin Pathol 137(4):572–574
US-FDA. (2012) FDA advisory committee briefing document—dabigatran etexilate (DE). http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/cardiovascularandrenaldrugsadvisorycommittee/ucm226009.pdf. Accessed 20 May 2012
Bauer KA (2012) Reversal of antithrombotic agents. Am J Hematol 87(Suppl 1):S119–S26
Douxfils J et al (2012) Impact of dabigatran on a large panel of routine or specific coagulation assays. Laboratory recommendations for monitoring of dabigatran etexilate. Thromb Haemost 107(5):985–997
Van Ryn J, Sieger P, Kink-Eiband M, Gansser D, Clemens A. (2009) Adsorption of dabigatran etexilate in water or dabigatran in pooled human plasma by activated charcoal in vitro. In: 51st ASH Annual Meeting and Exposition, Ernest N. Morial Convention Center, New Orleans, 5-8 Dec 2009. https://ash.confex.com/ash/2009/webprogram/Paper21383.html. Accessed 15 May 2012
Vale JA, Kulig K (2004) Position paper: gastric lavage. J Toxicol Clin Toxicol 42(7):933–943
Kaatz S et al (2012) Guidance on the emergent reversal of oral thrombin and factor Xa inhibitors. Am J Hematol 87(Suppl 1):S141–S145
Zhou W et al (2011) Hemostatic therapy in experimental intracerebral hemorrhage associated with the direct thrombin inhibitor dabigatran. Stroke 42(12):3594–3599
Stangier J et al (2010) Influence of renal impairment on the pharmacokinetics and pharmacodynamics of oral dabigatran etexilate: an open-label, parallel-group, single-centre study. Clin Pharmacokinet 49(4):259–268
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Woo, J.S., Kapadia, N., Phanco, S.E. et al. Positive Outcome After Intentional Overdose of Dabigatran. J. Med. Toxicol. 9, 192–195 (2013). https://doi.org/10.1007/s13181-012-0276-5
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DOI: https://doi.org/10.1007/s13181-012-0276-5