Targeting factor XI as a compromise between thrombosis and bleeding

Area of Science:

• * Pharmacology and Therapeutics
• * Hematology
• * Drug Development

Background:

• * Thromboembolic diseases are a major cause of death, with current anticoagulants like heparins, vitamin K antagonists, and direct oral anticoagulants (DOACs) carrying significant bleeding risks.
• * Existing anticoagulants require frequent monitoring and dose adjustments, and can cause serious side effects such as osteoporosis and heparin-induced thrombocytopenia.
• * There is a need for safer and more effective anticoagulant therapies that minimize bleeding complications while preventing thromboembolic events.

Purpose of the Study:

• * To discuss the characteristics of Factor XI (FXI) inhibitors as a novel class of anticoagulants.
• * To summarize preclinical and clinical data on the efficacy and safety of FXI inhibitors.
• * To outline future perspectives for FXI inhibition in managing venous thrombosis.

Main Methods:

• * Review of existing literature on FXI inhibitors, including small molecules, monoclonal antibodies, and antisense oligonucleotides.
• * Analysis of preclinical and clinical study data regarding the effectiveness and safety profiles of FXI inhibitors.
• * Discussion of therapeutic strategies and future directions for FXI inhibition in anticoagulation.

Main Results:

• * FXI inhibitors, including oral small molecules (milvexian, asundexian), monoclonal antibodies (abelacimab, osocimab, xisomab), and FXI-antisense oligonucleotides (FXI-ASO), represent a new generation of anticoagulants.
• * Available data suggest that FXI inhibitors effectively reduce thromboembolic events.
• * FXI inhibitors are associated with a lower incidence of major bleeding compared to current standard anticoagulants.

Conclusions:

• * FXI inhibitors demonstrate a favorable balance between preventing thromboembolic events and reducing bleeding risk.
• * These agents hold potential as a preferred anticoagulant class, particularly for patients with a high risk of bleeding.
• * FXI inhibitors mark a significant advancement in anticoagulant therapy, aiming to improve patient outcomes by optimizing the risk-benefit profile.