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凝血因子XI及XIa抑制:抗凝治疗的新方法。

Factor XI and XIa inhibition: a new approach to anticoagulant therapy.

作者信息

Sammut Mark Anthony, Elamin Nadir, Storey Robert F

机构信息

Specialist Registrar in Cardiology and Clinical Research Fellow.

Specialist Registrar in Cardiology.

出版信息

Br J Cardiol. 2024 May 14;31(2):018. doi: 10.5837/bjc.2024.018. eCollection 2024.

Abstract

Factor (F) XI or XIa inhibition has Fattracted interest due to the protection from thrombotic events and minimal bleeding tendency observed in FXI-deficient individuals. The prospect of uncoupling the management of thrombosis from the bleeding risk inadvertently associated with current therapy inspired the development of agents directed towards this step in the coagulation process. This review describes the physiological rationale behind FXI/FXIa inhibition and the pharmacological properties of existing FXI/FXIa inhibitors. It also explores the potential clinical use of these agents in various thromboembolic pathologies, predominantly through the phase II clinical trials conducted so far comparing them to current anticoagulant therapy or placebo.

摘要

由于在缺乏因子(F)XI的个体中观察到对血栓形成事件的保护作用以及最小的出血倾向,XI因子或XIa因子抑制已引起关注。将血栓形成的管理与当前治疗无意中关联的出血风险相分离的前景,激发了针对凝血过程这一步骤的药物开发。本综述描述了XI因子/XIa因子抑制背后的生理原理以及现有XI因子/XIa因子抑制剂的药理学特性。它还探讨了这些药物在各种血栓栓塞性疾病中的潜在临床应用,主要是通过迄今为止进行的将它们与当前抗凝治疗或安慰剂进行比较的II期临床试验。

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本文引用的文献

1
Factor XI Inhibitors in Early Clinical Trials: A Meta-analysis.
Thromb Haemost. 2023 Jun;123(6):576-584. doi: 10.1055/a-2043-0346. Epub 2023 Feb 25.
5
Factor XI Inhibitors for Prevention and Treatment of Venous Thromboembolism: A Review on the Rationale and Update on Current Evidence.
Front Cardiovasc Med. 2022 May 12;9:903029. doi: 10.3389/fcvm.2022.903029. eCollection 2022.
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Effects of Itraconazole and Diltiazem on the Pharmacokinetics and Pharmacodynamics of Milvexian, A Factor XIa Inhibitor.
Cardiol Ther. 2022 Sep;11(3):407-419. doi: 10.1007/s40119-022-00266-6. Epub 2022 May 31.
8
Single-Dose Pharmacokinetics of Milvexian in Participants with Mild or Moderate Hepatic Impairment Compared with Healthy Participants.
Clin Pharmacokinet. 2022 Jun;61(6):857-867. doi: 10.1007/s40262-022-01110-9. Epub 2022 Mar 9.
9
Phase 2 Study of the Factor XI Antisense Inhibitor IONIS-FXI in Patients With ESRD.
Kidney Int Rep. 2021 Nov 24;7(2):200-209. doi: 10.1016/j.ekir.2021.11.011. eCollection 2022 Feb.

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