The contact activation system: biochemistry and interactions of these surface-mediated defense reactions

Abstract

This review is intended to be a critical state-of-the-art overview of the activation and inhibition of the proteins (factor XII, prekallikrein, high molecular weight kininogen, and factor XI) of the contact phase of coagulation. Specifically, this review will reconsider the concept of the reciprocal activation of the proteases of the contact phase of coagulation, factor XII, and prekallikrein, in light of much recent evidence indicating that factor XII, itself, autoactivates when associated with negatively charged surfaces. In addition, the mechanisms for amplification of activation of the proteins of the contact phase of coagulation will be discussed from the pivotal role of high molecular weight kininogen, or one of its altered forms, serving as a cofactor to order the activation of the zymogens it is associated with. The role and relative importance of each of the naturally occurring plasma protease inhibitors (C1-inhibitor, alpha-2-macroglobulin, alpha-1-antitrypsin, antithrombin III, and alpha-1-antiplasmin) will be assessed as they relate to the dampening of contact phase activation. Finally, the contact phase of coagulation activation will be discussed not only as a plasma proteolytic mechanism, but also as it interacts with platelets.