For more than 50 years, heparin(s) and warfarin have been the most important anticoagulant agents, and
clinicians are accustomed to their specific antidotes (protamine sulfate and vitamin K/plasma [or factor concentrates], respectively).
Recently, there has been an explosion of novel anticoagulant development: ideally, these newer agents should
have advantages over traditional anticoagulants, such as fewer side effects, a more predictable pharmacokinetic profile
(and potentially no need for monitoring), minimal drug-drug interactions, and so forth. But, unlike the older agents, the
newer anticoagulants do not have specific antidotes. There is increasing focus on the use of nonspecific procoagulants,
such as non-activated and activated prothrombin complex concentrates (PCCs) and recombinant factor VIIa (rFVIIa), to
manage major bleeding or need for emergency invasive procedures. This paper reviews several of the novel anticoagulants
and presents the available evidence for their “reversal”. Based on extrapolation from animal models, clinical anecdote,
and an understanding of their mechanism of action, we recommend treating major bleeding complications of DTIs,
as follows (in descending order of preference): activated PCCs; rFVIIa; and (non-activated) PCCs. For management of
fondaparinux-associated bleeding, rFVIIa has some rationale (for which we provide an illustrative case). The increasing
use of novel anticoagulants will require physicians to have an understanding of rational approaches to “reverse” their anticoagulant
effects when true antidotes do not exist.