Escolar G, Diaz-Ricart M, Arellano-Rodrigo E
Servicio de Anatomia Patológica, Hematopatología, Hospital Clínic, IDIBAPS, Universitat de Barcelona, Barcelona, Spain.
Servicio de Hemostasia, ICHMO, Hospital Clínic de Barcelona, Barcelona, Spain.
Drugs Today (Barc). 2017 May;53(5):271-282. doi: 10.1358/dot.2017.53.5.2630780.
Activated coagulation factor X (FXa) is a common target for classic and newer anticoagulants. Parenteral anticoagulants with an indirect inhibitory action on FXa (low-molecular-weight heparins) have a well-established clinical efficacy in the prophylaxis and therapy of thromboembolic conditions. More recently developed direct oral anticoagulants (DOACs) have emerged as a new class of antithrombotic drugs. Rivaroxaban, apixaban and edoxaban are direct inhibitors of FXa approved for the management of venous thromboembolism and stroke prevention in atrial fibrillation. Although these DOACs are associated with fewer hemorrhagic side effects than classic vitamin K antagonists, bleeding is still a main complication. FXa antagonists had no specific agents that could reverse their antihemostatic effects. Andexanet alfa is a modified, recombinant human FXa molecule with an enhanced ability to bind to both direct and indirect FXa inhibitors, but unable to contribute to blood coagulation mechanisms. Andexanet alfa is designed to reverse the anticoagulant effects of FXa inhibitors. This review will address the preclinical pharmacology and the main aspects of the clinical development of andexanet alfa for the reversal of anticoagulant therapies with an inhibitory action on FXa. It will also summarize additional completed or ongoing studies on andexanet alfa available to the scientific community until present.
活化凝血因子X（FXa）是传统抗凝剂和新型抗凝剂的常见靶点。对FXa具有间接抑制作用的肠外抗凝剂（低分子量肝素）在血栓栓塞性疾病的预防和治疗中具有公认的临床疗效。最近开发的直接口服抗凝剂（DOACs）已成为一类新型抗血栓药物。利伐沙班、阿哌沙班和依度沙班是已获批准用于治疗静脉血栓栓塞和预防房颤中风的FXa直接抑制剂。尽管这些DOACs与传统维生素K拮抗剂相比出血副作用较少，但出血仍是主要并发症。FXa拮抗剂没有能够逆转其抗止血作用的特异性药物。andexanet alfa是一种经过修饰的重组人FXa分子，与直接和间接FXa抑制剂结合的能力增强，但不能参与血液凝固机制。andexanet alfa旨在逆转FXa抑制剂的抗凝作用。本综述将阐述andexanet alfa在逆转对FXa有抑制作用的抗凝治疗方面的临床前药理学及临床开发的主要方面。它还将总结截至目前科学界可获得的关于andexanet alfa的其他已完成或正在进行的研究。
