The present invention provides a safe DTI-antidote able to antagonize the anticoagulant functions of various DTI, such as dabigatran, hirudin, bivalirudin and argatroban. The exosite structures of thrombin are blocked by complex formation between thrombin and a recently developed aptamer (Müller et al. 2007). As this aptamer does not block the active center of thrombin, the aptamer caged thrombin (Apta-thrombin) retains full reactivity towards DTI but looses its procoagulant functions. This is an important prerequisite to avoid unwanted thrombotic site effects of the DTI antidote. The ability of apta-thrombin to antagonize the anticoagulant functions of various DTI has been demonstrated in plasma-based studies and in a mouse-model. A prothrombotic response was not induced by apta-thrombin as measured by molecular activation markers. This feature renders apta-thrombin a safe DTI antidote.
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