Factor XI: hemostasis, thrombosis, and antithrombosis.

Area of Science:

• Hematology
• Biochemistry
• Molecular Biology

Background:

• Coagulation factor XI (FXI) is a serine protease zymogen crucial for hemostasis.
• Distinct activation pathways of FXI (FXIIa-mediated vs. tissue factor/thrombin-mediated) have different roles in thrombosis and hemostasis.
• Understanding FXI's structure-function relationship is enhanced by studying genetic deficiencies.

Purpose of the Study:

• To review recent advancements in FXI molecular physiology and pathogenesis of FXI deficiency.
• To discuss the development and evidence for FXI-targeting antithrombotics.
• To highlight the potential of FXI inhibition as a novel antithrombotic approach.

Main Methods:

• Review of recent literature on FXI structure, function, and activation pathways.
• Analysis of studies on FXI deficiency and its genetic basis.
• Examination of preclinical and clinical data on FXI inhibitors.

Main Results:

• FXI activation pathways differentially contribute to thrombosis and hemostasis.
• FXI possesses both procoagulant and antifibrinolytic activities.
• FXI deficiency in humans and animal models supports its role in thrombosis.
• FXI inhibitors demonstrate promising antithrombotic effects.

Conclusions:

• FXI is a critical regulator of hemostasis and thrombosis.
• Targeting FXI represents a novel antithrombotic strategy with a favorable benefit-risk ratio.
• Further development of FXI inhibitors is warranted for managing thrombotic disorders.