Reversal of these agents is usually not required due to their relatively short half-lives. This, in addition to the need to monitor activated partial thromboplastin time (aPTT) (especially with UFH), the risk of heparin-induced thrombocytopenia (HIT), risk of major bleeding episodes, and increased risk of osteoporosis and vertebral fractures, form the major limitations associated with heparin and LMWH therapy. Heparins are only bioavailable through parenteral administration, thus excluding the option of easy self-administration. As a result of this, heparins are considered indirect anticoagulants. UFH and LMWH bind and activate antithrombin, which acts to inhibit factor IIa (thrombin) and factor Xa, inhibiting further progression of the clotting cascade. Unfractionated heparin (UFH) and low-molecular weight heparin (LMWH) are often used in acute thrombosis because of their rapid onset of action and effectiveness. They are poised to replace traditional anticoagulants including warfarin.Īnticoagulants are important drugs used as the primary intervention for the prevention and treatment of thrombosis ( Table 1). Conclusions: A new generation of anticoagulants, the DOACs, and their reversal agents, are gaining prominence in clinical practice, having demonstrated superior efficacy and safety profiles. Additionally, ciraparantag, a potential “universal” reversal agent, is currently under clinical development. Two reversal agents have been approved within the last five years: idarucizumab for the reversal of dabigatran, and andexanet alfa for the reversal of rivaroxaban and apixaban. These DOACs all have a rapid onset of action and each has a predictable therapeutic response requiring no monitoring, unlike the older anticoagulants, such as warfarin. Results: The DOACs include the direct thrombin inhibitor-dabigatran, and the factor Xa inhibitors-rivaroxaban, apixaban, edoxaban, and betrixaban. Methods: Published literature was searched, and information extracted to provide an update on DOACS and their reversal agents. Like the older generation anticoagulants, DOACs require specific reversal agents in cases of life-threatening bleeding or the need for high-risk surgery. Background: Over the last ten years, a new class of drugs, known as the direct-acting oral anticoagulants (DOACs), have emerged at the forefront of anticoagulation therapy.
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