Removal of Dabigatran by Hemodialysis

Don N. Chang, MD; William E. Dager, PharmD, BCPS; Andrew I. Chin, MD

Disclosures

Am J Kidney Dis. 2013;61(3):487-489. 

In This Article

Abstract and Introduction

Abstract

Dabigatran is a newly available oral direct thrombin inhibitor approved for anticoagulation therapy to prevent strokes in patients with nonvalvular atrial fibrillation. Unlike warfarin, dabigatran's observed therapeutic window and minimal drug-to-drug interaction suggest that invasive laboratory testing and dose adjustment is not necessary. In circumstances of excessive anticoagulation, such as overdoses, decreased kidney function, or instances of significant bleeding, reversing dabigatran's effects may be necessary. Unlike warfarin, no rapid-acting antidote to reverse the effects of dabigatran is known. However, hemodialysis has been suggested as a method of removing dabigatran and thereby reducing its anticoagulant effect. We describe a case in which hemodialysis was used in an attempt to remove dabigatran in a patient with excessive anticoagulation from dabigatran and severe intracranial hemorrhage. Serial dabigatran levels suggested that hemodialysis removed the drug. However, given the large volume of distribution of dabigatran in the terminal phase of elimination, a rebound in drug level was noted. We suggest that a longer duration of therapy or more continuous modality of hemodialysis may be needed in conjunction with the initial hemodialysis treatment of dabigatran coagulopathy.

Introduction

Until recently, the primary agents for long-term use in preventing thromboembolic events in patents with atrial fibrillation (AF) have been vitamin K antagonists such as warfarin.[1,2] However, using warfarin in the treatment of AF has a number of notable limitations. In particular, it has both a narrow therapeutic index and a high potential for significant food and drug interactions and it requires invasive laboratory monitoring with subsequent dose adjustment.[2,3] Dabigatran is as novel oral synthetic direct thrombin inhibitor that has been tested in patients with AF at increased risk of stroke.4 Compared to warfarin, dabigatran at 150 mg orally twice daily proved superior for the primary composite outcome of stroke or systemic embolism.[4] Dabigatran is eliminated primarily by the kidney without significant metabolism. The reliable pharmacokinetic profile and few drug-to-drug interactions along with no requirements for routine invasive monitoring are advantages of its use.[2,5,6]

Based on observations in the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial, dabigatran was approved by the US Food and Drug Administration in 2010 for use in reducing the risk of stroke and systemic embolism in patients with nonvalvular AF.[4] However, although administering vitamin K, fresh frozen plasma, or prothrombin complex concentrates can reverse warfarin's anticoagulant effects in the event of life-threatening bleeding, currently there is no clear information about methods to rapidly reverse the anticoagulation effects of dabigatran. Based on limited published analysis in nonbleeding individuals or animal models, potential options include providing recombinant activated factor VIIa, prothrombin complex concentrates, or hemodialysis. Of these, hemodialysis currently appears to be the best option in managing a life-threatening bleeding event in the presence of dabigatran.[2,6–8]

We present a case of an elderly man receiving dabigatran who presented with severe intracranial hemorrhage and was started on hemodialysis therapy in an attempt to rapidly decrease plasma dabigatran levels.

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