Abstract
The plasma kallikrein/kinin system that consists of the proteins factor XII, prekallikrein, and high molecular weight kininogen was first recognized as a surface-activated coagulation system arising when blood or plasma interacts with artificial surfaces. Although surface-activated contact activation occurs in vivo when various negatively charged surfaces become exposed, including a developing platelet thrombus, a physiologic, non-injury mechanism for activation, regulation, and function of this system has been elusive. Recent investigations have shown that there is a physiologic pathway for assembly and activation of this system independent of factor XII. Gene deficient mice of the bradykinin B2 receptor and factor XII have been recognized to have reduced risk for arterial thrombosis. This plasma proteolytic system influences arterial thrombosis independent of influencing hemostasis. Thus, the plasma kallikrein/kinin system has two mechanisms for its activation: one that is dependent and another independent of factor XII. Better understanding of this system may lead to insight into mechanisms for arterial thrombosis, independent of hemostasis.