Reversal of target-specific oral anticoagulants
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Reversal of target-specific oral anticoagulants Scott Kaatz • Mark Crowther
Published online: 9 May 2013 Ó Springer Science+Business Media New York 2013
Abstract The target-specific oral anticoagulants represent the first new oral anti-thrombotic therapy in over 50 years and have the potential to make therapy easier and hence more accessible to many patients. Like any new therapy, the potential benefits must be weighed against the potential challenges and one of the most concerning aspects of the new target-specific oral anticoagulants is the lack of a proven method to reverse their effect. Unlike the vitamin K antagonist, i.e. warfarin, there is no specific antidote for these medications. This paper will review the limited data on the use of non-specific therapies to reverse anticoagulation for the new agents. We hope to prepare clinicians who are faced with a patient who has serious bleeding or needs emergent surgery while taking dabigatran, rivaroxaban or apixaban. Keywords Reversal Target specific oral anticoagulants Apixaban Dabigatran Rivaroxaban
S. Kaatz (&) Hospital Medicine, Hurley Medical Center, One Hurley Plaza, Flint, MI 48503, USA e-mail: [email protected] M. Crowther Hamilton Regional Laboratory Medicine Program, Hamilton Health Sciences, Hamilton, ON, Canada
Introduction Unlike warfarin or other vitamin K antagonists which take several days to produce an anticoagulant effect by reducing the concentration of functional clotting factors II, VII, IX and X, the target-specific oral anticoagulants (TSOAs) directly and immediately inhibit a single clotting factor. These agents have a more rapid onset and offset of action and they do not require the levels of circulating coagulation factors to decline or to re-accumulate over days (as is seen with warfarin) after therapy has been started or stopped. The rapid offset of action gives the option of simply stopping therapy for minor bleeding complications or for non-emergent surgery. When a patient presents with severe bleeding or needs emergent surgery, however, there may be a need to quickly reverse the anticoagulant effect. For patients treated with warfarin fresh frozen plasma (FFP), non-activated and activated prothrombin complex concentrates (PCC) and activated recombinant factor VII (rVIIa) have been used to restore coagulation. Since the novel agents directly inhibit either factor IIa (dabigatran) or Xa (rivaroxaban and apixaban), simple supplementation of coagulation factors may not effectively reverse their anticoagulant effect. This review will discuss the laboratory, animal and scarce human data on reversal of dabigatran, rivaroxaban and apixaban.
Background Target-specific oral anticoagulants
M. Crowther St Joseph’s Healthcare, Hamilton, ON, Canada M. Crowther McMaster University, Hamilton, ON, Canada
Dabigatran, a direct thrombin (IIa) inhibitor was the first TSOAs to be licensed and approved in the United States for stroke prevention in patients with atrial fibrillation. It
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reaches peak effect in 1–3 h and has a half-
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