Emergency Management of Bleeding Associated With Old and New Oral Anticoagulants

Abstract

As major prescribers of oral anticoagulants, cardiologists must be familiar with strategies to manage bleeding, the principal complication associated with all anticoagulants, and to reverse anticoagulant effects in acute‐care settings. The purpose of this manuscript is to review currently available information regarding dabigatran and rivaroxaban, the 2 novel oral anticoagulants approved to date in the United States. Further, we suggest reasonable interventions for the clinician faced with a patient who suffers a major bleeding event while receiving one of these agents. Data sources were peer‐reviewed publications, US Food and Drug Administration documents in the public domain, and approved US prescribing information for dabigatran (Pradaxa) and rivaroxaban (Xarelto). Strategies for management of bleeding and reversal of anticoagulant effects from warfarin include vitamin K, fresh frozen plasma, and prothrombin complex concentrates. For rivaroxaban and dabigatran, appropriate therapies include support and observation, which are likely to be effective for the majority of patients because of the short half‐lives of these agents. In severe life‐threatening hemorrhage, clotting‐factor substitutes may be appropriate in certain situations. Validated protocols specific to each agent remain to be developed. Clin. Cardiol. 2012 doi: 10.1002/clc.22037Editorial support for this paper was provided by Janssen Scientific Affairs, LLC. W.F.P. has received research grants (>$10 000) from Abbott, Alere, Baxter, Brahms, Novartis, and The Medicines Company. He has been a consultant (<$10 000) for Abbott, Alere, Eli Lilly, and The Medicines Company; served on the speaker's bureau (<$10 000) for Abbott and Alere; and has ownership interest (<$10 000) in Comprehensive Research Associates LLC, Vital Sensors, and Emergencies in Medicine LLC. M.M.G and R.M.M. are full‐time employees of Janssen Scientific Affairs, LLC. The authors have no other funding, financial relationships, or conflicts of interest to disclose.

Overview of direct oral anticoagulant therapy reversal

“…These patients can generally be managed by withholding the anticoagulant, observing the patient, and providing supportive care. 15 Blood products and fluids should be used if clinically direct oral anticoagulant therapy indicated, and local measures for controlling the bleeding should be implemented. The anticoagulation effect will dissipate over time, depending on the agent and renal function of the patient, with clearance times being similar to the timing of interruption of therapy before major surgery (Table 3).…”

“…[1][2][3][4][5] Due to their short half-lives (Table 2), [6][7][8][9][10][11][12][13] the anticoagulant effect of DOACs diminish within one to two days after administration of the most recent dose in patients with normal renal function, but could be extended in patients with diminished renal function, particularly when dabigatran is used. 14,15 Although DOACs appear to decrease the risk of intracranial hemorrhage (ICH) in patients with direct oral anticoagulant therapy NVAF when compared with warfarin, they are still associated with a risk of bleeding complications. [16][17][18][19][20] Thus, the anticoagulant effect of DOACs must be reversed in patients experiencing spontaneous or traumatic bleeding and in patients undergoing emergency surgery or other urgent invasive procedures.…”

Management of antiplatelet and anticoagulant therapy for endoscopic procedures: Introduction to novel oral anticoagulants

“…Its half-life is 5 to 9 hours in younger patients and 11 to 13 hours in the elderly (15). It is partially excreted through urine and the rest is metabolized by the liver, which is why it is contraindicated in patients with advanced liver disease and severe renal insufficiency (26). It is administered in a single daily dose.…”

Oral Direct Anticoagulants in Thrombosis Management in Anti-Phospholipid Syndrome: Unanswered Questions

“…factor VIII inhibitor bypass activity (FEIBA), or recombinant factor VIIa (rVIIa) as well as antifibrinolytic therapy (tranexamic acid) can be used . Renal replacement therapy should be considered for dabigatran which is dialyzable [42][43][44][45][46].…”