title: A systematic update on the state of novel anticoagulants and a primer on reversal and bridging.
abstract: BACKGROUND
  Current prevention and treatment of venous thromboembolism (VTE) includes familiar agents that have been in use for many years, including unfractionated heparin, low-molecular-weight heparin (LMWH), and vitamin K antagonists (VKAs). A number of novel oral anticoagulants are currently developed or are in stages of development to either replace VKAs in concert with initial heparin or LMWH, or to replace both heparin/LMWH and VKAs totally as monotherapy. These agents hold the promise of not requiring monitoring, being safer in terms of bleeding risk than current agents, and being of equal or improved efficacy compared with established anticoagulants.
  
  
  METHODS
  In the following report, we systematically review the oral agents currently approved or closest to approval for both VTE and atrial fibrillation treatment, focusing on the treatment of VTE: dabigatran, rivaroxaban, and apixaban.
  
  
  RESULTS
  Findings of clinical use and comparisons to standard care of these agents are summarized in depth, by succinctly reviewing all major randomized controlled trials. Mechanistic and functional differences are reviewed, as Dabigatran targets activated factor II (factor IIa), while rivaroxaban and apixaban target activated factor X (factor Xa). We also discuss the inability at the present time to reliably reverse the anticoagulant effects of these agents, provide a suggested strategy for reversal, and finally discuss an approach to bridging these agents when other procedures are required while currently taking one of these three agents.
  
  
  CONCLUSIONS
  These agents, while still with many unanswered questions, demonstrate great promise in the prevention and treatment of VTE.
authors.affiliation: Department of Surgery, Section of Vascular Surgery, University of Michigan, Ann Arbor, Mich. Electronic address: jordankn@umich.edu.
authors.forename: Jordan
authors.initials: J
authors.lastname: Knepper
authors.affiliation: Department of Surgery, Section of Vascular Surgery, University of Michigan, Ann Arbor, Mich.
authors.forename: Danielle
authors.initials: D
authors.lastname: Horne
authors.affiliation: Department of Surgery, Section of Vascular Surgery, University of Michigan, Ann Arbor, Mich.
authors.forename: Andrea
authors.initials: A
authors.lastname: Obi
authors.affiliation: Department of Surgery, Section of Vascular Surgery, University of Michigan, Ann Arbor, Mich.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Wakefield