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An Update on the "Novel" and Direct Oral Anticoagulants, and Long-Term Anticoagulant Therapy. The mainstay of treatment of venous thromboembolism (VTE) is anticoagulation. Direct oral anticoagulants (DOAC) have revolutionized anticoagulation management, although their efficacy and safety in specialized populations such as antiphospholipid syndrome, advanced renal disease, cancer thrombosis, and geriatric patients remain uncertain. Concerns about bleeding risks of DOACs persist despite reassuring data in the literature and the development of specific antidotes. In this article, the authors present an overview of the basic pharmacology of DOACs and discuss their use in acute VTE, secondary VTE prevention, and specialized VTE patient populations and discuss therapeutic monitoring and reversal in the event of major bleeding.