Bleeding risk and the management of bleeding complications in patients undergoing anticoagulant therapy: focus on new anticoagulant agents
Bleeding risk and the management of bleeding complications in patients undergoing anticoagulant therapy: focus on new anticoagulant agents
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DOI：
10.1182/blood-2007-10-120543
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发表时间：
2008-05-15
期刊：
影响因子：
20.3
通讯作者：
Warkentin, Theodore E.
中科院分区：
文献类型：
--
作者：
Crowther, Mark A.;Warkentin, Theodore E.
60多年来，肝素和香豆素一直是抗凝治疗的主要药物。它们广泛可用，价格低廉，有效，并具有特定的解毒剂，但被认为是有问题的，因为它们需要仔细监测。此外，香豆素具有延迟起效，与许多药物相互作用，具有狭窄的治疗窗口，并且在某些情况下具有矛盾的促血栓形成作用（即，可以促进“香豆素坏死”）。肝素可能需要监测其治疗效果，也可能导致血栓形成（肝素诱导的血小板减少症/血栓形成综合征）。这些局限性导致了新抗凝剂的开发，有可能取代目前的药物。这些新的药物分为2类，根据它们是否是抗凝血酶依赖性（低分子量肝素，磺达肝素）或抗凝血酶非依赖性（因子Xa和凝血酶[因子IIa]的直接抑制剂）。本文讨论了新的抗凝剂，审查其疗效和局限性，并重点关注可能使其使用复杂化的大出血风险。与肝素和香豆素相反，这些新药物都没有完全逆转其抗凝作用的特异性解毒剂。现有的数据的有效性和安全性，目前和实验性药物抗凝逆转进行审查，并提出了一个计划，抗凝剂诱导出血的管理。
For more than 60 years, heparin and coumarin have been mainstays of anticoagulation therapy. They are widely available, inexpensive, effective, and have specific antidotes but are regarded as problematic because of their need for careful monitoring. In addition, coumarin has a delayed onset of action, interacts with many medications, has a narrow therapeutic window, and is paradoxically prothrombotic in certain settings (ie, can precipitate "coumarin necrosis"). Heparin may require monitoring of its therapeutic effect and can also cause thrombosis (heparin-induced thrombocytopenia/thrombosis syndrome). These limitations have led to the development of new anticoagulants with the potential to replace current agents. These newer agents fall into 2 classes, based on whether they are antithrombin dependent (low-molecular-weight heparin, fondaparinux) or antithrombin independent (direct inhibitors of factor Xa and thrombin [factor IIa]). This paper addresses newer anticoagulants, reviewing their efficacy and limitations, and focuses on the risk of major bleeding that may complicate their use. In contrast to heparin and coumarin, none of these newer agents has a specific antidote that completely reverses its anticoagulant effect. Available data on the efficacy and safety of current and experimental agents for anticoagulant reversal are reviewed, and a plan for management of anticoagulant-induced bleeding is presented.