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Michael W. Parra, Lloyd Zucker, Eric S. Johnson, Diane Gullett, Cristina Avila, Zachary A. Wichner, and Candace R. Kokaram

T he direct thrombin inhibitor dabigatran has recently been approved in the US as an alternative to warfarin for risk reduction in stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Several studies assessing the risk of major bleeding complications have shown dabigatran to have a reduced amount of risk compared with other anticoagulants. 12 , 14 , 18 , 21 However, the lack of guidelines, protocols, and an established specific antidote to reverse the anticoagulation effect of dabigatran potentially increases morbidity and

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Sarah T. Garber, Walavan Sivakumar, and Richard H. Schmidt

frequent monitoring, multiple interactions with food and other medications, and its increased risk of hemorrhage. 1 Newer agents have aimed at more direct coagulation factor inhibition. Large, randomized, multicenter noninferiority trials have shown that direct thrombin inhibitors, such as dabigatran, have lower rates of stroke and systemic embolism than warfarin with decreased rates of major hemorrhage. 1 , 3 In the event of traumatic hemorrhage in patients receiving dabigatran, however, there are currently no effective reversal agents. Familiarity with this new

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Ahmed J. Awad, Brian P. Walcott, Christopher J. Stapleton, Vijay Yanamadala, Brian V. Nahed, and Jean-Valery Coumans

direct thrombin antagonists such as dabigatran and factor Xa inhibitors such as rivaroxaban, apixaban, and edoxaban. 1 , 25 Since there are few clinical studies about Xa inhibitors because of the very recent approval by the US Food and Drug Administration, the focus of this review will be on dabigatran etexilate. Dabigatran etexilate (trade name Pradaxa; referred to in this article as dabigatran) is a novel anticoagulant approved by the FDA in 2010 for the prevention of ischemic stroke and systemic embolism in patients with nonvalvular atrial fibrillation. 32 When

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Robert F. James, Viktoras Palys, Jason R. Lomboy, J. Richard Lamm Jr., and Scott D. Simon

require blood-level monitoring. 12 , 54 , 75 These medications include dabigatran (a direct thrombin inhibitor), and rivaroxaban and apixaban, direct inhibitors of factor Xa. 12 Many cardiologists and neurologists have been increasingly prescribing these medications over the last few years. However, this enthusiasm has been tempered by the lack of an antidote and fear of being unable to safely manage patients taking these new medications who experience anticoagulant-related ICH. The silver lining to these uncertainties is that the incidence of major hemorrhage in

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Pasquale Scotti, Chantal Séguin, Benjamin W. Y. Lo, Elaine de Guise, Jean-Marc Troquet, and Judith Marcoux

with regard to which medications are more dangerous. 12 , 13 , 15 , 18 , 30 , 31 , 33 , 35 , 43 Other studies have been unable to confirm a significant relationship between AT use and elevated rates of ICH and/or mortality. 6 , 9 , 21 Direct oral anticoagulants (DOACs), including dabigatran, rivaroxaban, and apixaban, are increasingly replacing warfarin as ACs of choice, as they do not require monthly monitoring and have shorter half-lives, lower risks of fatal bleeding, and fewer drug and food interactions. 1 DOAC use is associated with decreased mortality

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Ruth S. Kuo, Wililiam D. Freeman, and Rabih G. Tawk

T o T he E ditor : We read with great interest the case report by Garber et al. 3 (Garber ST, Sivakumar W, Schmidt RH: Neurosurgical complications of direct thrombin inhibitors— catastrophic hemorrhage after mild traumatic brain injury in a patient receiving dabigatran. Case report. J Neurosurg 116: 1093–1096, May 2012) emphasizing the predicament physicians face when managing patients with dabigatran-related intracranial hemorrhage. It was unfortunate that the authors' patient's condition rapidly deteriorated, despite administration of recombinant

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Rebecca Gryka and Douglas C. Anderson Jr.

T o T he E ditor : We have lost loved ones and patients due to intracranial hemorrhage secondary to warfarin anticoagulation, and we know the pain of this tragedy. One case was eerily similar to the case report by Garber et al. 3 (Garber ST, Sivakumar W, Schmidt RH: Neurosurgical complications of direct thrombin inhibitors—catastrophic hemorrhage after mild traumatic brain injury in a patient receiving dabigatran. Case report. J Neurosurg 116: 1093–1096, May 2012). Our first experience with a fatal warfarin-induced hemorrhage was in a patient

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Peter Le Roux, Charles V. Pollack Jr., Melissa Milan, and Alisa Schaefer

treatment rises. 6 In 2004, there were 31 million outpatient prescriptions for warfarin in the United States, a 45% increase over a 6-year period. 6 The approval of the targeted oral anticoagulant (OAC) therapies dabigatran etexilate, rivaroxaban, and apixaban portends both a wider use of oral anticoagulation and a growing clinical concern about best practices in AAICH management. 11 Both thrombotic events due to discontinuing anticoagulation therapy and bleeding complications due to not reversing anticoagulation increase morbidity and mortality in AAICH patients

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Sunil Manjila, Tony Masri, Tanzila Shams, Shakeel A. Chowdhry, Cathy Sila, and Warren R. Selman

Prevention of Vascular Events (ACTIVE A) study reported a reduction in stroke risk with aspirin plus clopidogrel at 2.4% compared with 3.3% with aspirin alone in patients refusing or thought to be too high risk for anticoagulation therapy. 1 However, major bleeding was significantly greater (2% vs 1.3%) and similar to the bleeding risk with warfarin in other studies. 1 Other anticoagulants are emerging as an alternative to warfarin therapy. Dabigatran, a direct thrombin inhibitor, was the first to receive FDA approval in September 2010. The Randomized Evaluation of Long

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David W. Newell

, one by James et al. and the other by Awad et al., detail the use of anticoagulants, antiplatelet agents, and newer agents including Dabigatran and the need for reversal of the effects of these agents in the management of intracerebral hemorrhage. The common use of some of the newer agents for anticoagulation therapy and antiplatelet therapy and their different durations of action, as well as different strategies of reversal of these agents, has required new protocols to be put in place. Close cooperation with blood banks can help effect the reversal of these agents