Coagulation factor XII contributes to hemostasis when activated by soil in wounds

Area of Science:

• * Hemostasis and Thrombosis
• * Mammalian Physiology
• * Environmental Microbiology

Background:

• * Bleeding is a significant cause of death and illness in animals, driving the evolution of the coagulation system.
• * Coagulation factor XII (FXII) activates on non-biologic surfaces in vitro, but its in vivo role in hemostasis is unclear.
• * Individuals lacking FXII do not exhibit increased bleeding from clean wounds.

Purpose of the Study:

• * To investigate the hypothesis that soil, a common environmental silicate, activates FXII and coagulation in vivo.
• * To determine if FXII plays a role in hemostasis in soil-contaminated wounds.

Main Methods:

• * Comparison of blood loss in wild-type (WT) and FXII-knockout (FXII-/-) mice after soil or tissue factor application to transected tails.
• * In vitro analysis of FXII and coagulation system activation using plasma from various species.
• * Characterization of soil properties using mass spectrometry and dynamic light scattering.

Main Results:

• * Soil significantly reduced blood loss in WT mice but not in FXII-/- mice.
• * Soil accelerated blood clotting in human and mouse plasma in an FXII-dependent manner.
• * Soil procoagulant activity correlated with silicon concentration, suggesting a mechanism for FXII activation.

Conclusions:

• * Coagulation factor XII augments hemostasis in soil-contaminated wounds of terrestrial mammals.
• * The findings provide a potential explanation for FXII's seemingly minor role in clean wound hemostasis.