The Intrinsic Coagulation/Kinin-Forming Cascade: Assembly in Plasma and Cell Surfaces in Inflammation

Publisher Summary This chapter discusses the intrinsic coagulation/kinin-forming cascade. The plasma kinin-forming system consists of three essential plasma proteins that interact upon binding to certain negatively charged surfaces or macromolecular complexes. These are coagulation factor XII (Hageman factor or HF), prekallikrein, and high-molecular-weight kininogen (HK). The rate of factor XII conversion to factor XIIa is dependent on each protein of the kinin-forming pathway, and thus all the proteins are coagulation factors. This intrinsic coagulation/kinin-forming cascade is in equilibrium in plasma even in the absence of any exogenous surface—that is, there is a finite rate at which activation occurs continuously, but plasma inhibitors hold the system in check. The addition of a macromolecular surface augments the activation rate such that the significant generation of bradykinin occurs; then a combination of kininases and protease inhibitors re-establish the equilibrium. Certain blood cells and vascular wall endothelial cells are capable of binding the proteins of the kinin-forming cascade. Thus, activation may preferentially occur along the cell surface and some of the binding proteins may actually function as endogenous activators.