For more than 60 years,
heparin and
coumarin have been mainstays of anticoagulation
therapy. They are widely available, inexpensive, effective, and have specific antidotes but are regarded as problematic because of their need for careful monitoring. In addition,
coumarin has a delayed onset of action, interacts with many medications, has a narrow therapeutic window, and is paradoxically prothrombotic in certain settings (ie, can precipitate "
coumarin necrosis").
Heparin may require monitoring of its
therapeutic effect and can also cause
thrombosis (
heparin-induced
thrombocytopenia/
thrombosis syndrome). These limitations have led to the development of new
anticoagulants with the potential to replace current agents. These newer agents fall into 2 classes, based on whether they are
antithrombin dependent (
low-molecular-weight heparin,
fondaparinux) or
antithrombin independent (direct inhibitors of
factor Xa and
thrombin [
factor IIa]). This paper addresses newer
anticoagulants, reviewing their efficacy and limitations, and focuses on the risk of major
bleeding that may complicate their use. In contrast to
heparin and
coumarin, none of these newer agents has a specific
antidote that completely reverses its
anticoagulant effect. Available data on the efficacy and safety of current and experimental agents for
anticoagulant reversal are reviewed, and a plan for management of
anticoagulant-induced
bleeding is presented.