Molecular Classification
Enzyme, Serine protease, Coagulation factor
Other Names
Activated Hageman factor, Hageman factor, Beta-factor XIIA
Disease Roles
ThrombosisInflammation

Coagulation Factor XIIa Overview

Coagulation factor XIIa (FXIIa), also known as activated Hageman factor, is a serine protease enzyme that plays a central role in the initiation of the intrinsic pathway of blood coagulation and links coagulation with inflammation. It is generated from its zymogen precursor, coagulation factor XII (FXII), upon activation by contact with negatively charged surfaces. FXIIa initiates the intrinsic pathway of blood coagulation by activating factor XI to XIa and converting prekallikrein to kallikrein. Inhibiting FXIIa can reduce thrombosis risk without increasing bleeding tendency.

Mechanism of Action

Inhibition of FXIIa prevents activation of the intrinsic coagulation pathway and reduces thrombin generation without significantly affecting hemostasis, thus reducing thrombosis risk.

Biological Functions

Initiates intrinsic coagulation cascade
Activates factor XI
Activates prekallikrein/kallikrein system
Releases bradykinin
Thrombin generation
Inflammation

Disease Associations

Thrombosis
Inflammation

Safety Considerations

  • Potential for off-target effects on other serine proteases
  • Need for careful dose titration to avoid bleeding complications, although the bleeding risk is expected to be low compared to other anticoagulants.
  • Long-term effects of FXIIa inhibition are not fully understood.