Factor XII (FXII) is a coagulation
protein that is essential for surface-activated blood coagulation tests but whose deficiency is not associated with
bleeding. For over forty years, investigators in hemostasis have not considered FXII important because its deficiency is not associated with
bleeding. It is because there is a dichotomy between abnormal laboratory assay findings due to FXII deficiency and clinical hemostasis that investigators sought explanations for physiologic hemostasis independent of FXII. FXII is a multidomain
protein that contains two
fibronectin binding consensual sequences, two
epidermal growth factor regions, a kringle region, a
proline-rich domain, and a catalytic domain that when proteolyzed turns into a plasma
serine protease. Recent investigations with FXII deleted mice that are protected from
thrombosis indicate that it contributes to the extent of developing
thrombus in the intravascular compartment. These findings suggest that it has a role in
thrombus formation without influencing hemostasis. Last, FXII has been newly appreciated to be a
growth factor that may influence tissue injury repair and angiogenesis. These combined studies suggest that FXII may become a pharmacologic target to reduce arterial
thrombosis risk and promote cell repair after injury, without influencing hemostasis.