Thursday, February 27, 2014
Figure 1. Factor XIIa pathways. The intrinsic pathway of coagulation and the kallikrein-kinin
system are both activated downstream of factor XII (FXII).
(I) In the
intrinsic pathway, activated FXII (FXIIa) initiates an activation cascade of
serine protease enzymes, including factor XIa (FXIa), factor IXa (FIXa), factor Xa (FXa) and thrombin (factor IIa; F2). Thrombin cleaves fibrinogen to form soluble fibrin, which aggregates or
polymerizes to form a clot or thrombus.
(II) In the
kallikrein-kinin system, FXIIa cleaves high-molecular weight (HMW) kininogen to form bradykinin. Bradykinin is degraded, and the
degradation products activate bradykinin B2 receptor (BDKRB2; B2R), leading to edema.
A number of
companies are developing inhibitors of the components of these two systems (see
"Targeting the intrinsic pathway of coagulation and the
kallikrein-kinin system). Reports in Science
Translational Medicine and Blood provide evidence that FXII and
FXIIa can be targeted to prevent clot formation without risk of bleeding.1,2