Anticoagulant therapy is used for a wide variety of clinical indications, including post-operative thromboprophylaxis, prevention of stroke and arterial thromboembolism in atrial fibrillation, treatment of venous thromboembolic disease, and maintaining patency of extracorporeal circuits and vascular access devices. With unfractionated heparin (UFH) and the vitamin K-antagonist warfarin, dosing regimens have been published and laboratory tests are available for monitoring the depth of anticoagulation. Dabigatran, which was recently approved by the FDA for patients with atrial fibrillation, and other antithrombotic agents in development target specific coagulation factors to provide their anticoagulant effect. Currently, it is unclear whether these new therapies will be similarly efficacious and safe In all clinical settings, particularly in certain clinical settings and specific patient populations. For example, fondaparinux, which is an antithrombin dependent selective inhibitor of factor Xa, is effective in the prevention and treatment of VTE, but it has been shown to incompletely block thrombotic complications associated with catheter guide wires. While laboratory strategies are not necessary for routine monitoring of these new therapies in most clinical situations, we currentiy have essentially no testing capability for an assessment of antithrombotic activity, or hemostatic impact, of any of these compounds. With the expanding number of anticoagulant alternatives, and the extreme range of therapeutic uses, there exists a critical need for diagnostic tools to effectively assess patients being treated with these new therapies.
|Soule, Erin E; Bompiani, Kristin M; Woodruff, Rebecca S et al. (2016) Targeting Two Coagulation Cascade Proteases with a Bivalent Aptamer Yields a Potent and Antidote-Controllable Anticoagulant. Nucleic Acid Ther 26:1-9|
|Woodruff, Rebecca S; Sullenger, Bruce A (2015) Modulation of the Coagulation Cascade Using Aptamers. Arterioscler Thromb Vasc Biol 35:2083-91|
|Bompiani, Kristin M; Lohrmann, Jens L; Pitoc, George A et al. (2014) Probing the coagulation pathway with aptamers identifies combinations that synergistically inhibit blood clot formation. Chem Biol 21:935-44|