Potential antidotes for reversal of old and new oral anticoagulants

The prescription of new oral anticoagulants is on the rise. As opposed to vitamin K antagonists and heparins the new agents have single targets in the coagulation cascade, more predictable pharmacokinetics and they lack validated and available antidotes. In general, the new agents have similar or lower bleeding risk than vitamin K antagonists, especially risk of intracranial bleeding. Risk factors for bleeding are typically the same for old and new anticoagulants. Old age, renal dysfunction and concomitant antiplatelet agents seem to be recurring risk factors. Adequate supportive care and temporary removal of all antithrombotic agents constitute the basis for management of serious bleeding complications. With the exception of vitamin K (for vitamin K antagonists) and protamine (for heparin) the same array of prohemostatic agents--unactivated or activated prothrombin complex concentrate, and activated factor VIIa--have been tried for almost all anticocoagulants in different models, and for some agents also in patients, with varying success. Hemodialysis can reduce the level of dabigatran efficiently and activated charcoal may be used for very recent oral ingestion of lipophilic agents. In view of the shorter half life of the new agents compared to warfarin the need for reversal agents may be less critical. Nevertheless, highly specific reversal agents for the thrombin- and factor Xa-inhibitors are under development and might be available within two years.