Contact activation by the intrinsic pathway of blood plasma coagulation

It is well known that the biomaterial surfaces that comprise biomedical devices will initiate blood coagulation. This can occur through the adhesion and activation of platelets, but also through the activation of the proteins of the intrinsic coagulation cascade. Nominally, this involves activation of the zymogen FXII (Hageman Factor) which in turn activates FXI, prekallikrein and high-molecular-weight kininogen to form an activation complex. The end result of this sequence of zymogen/enzyme conversion steps is the production of thrombin, the conversion of fibrinogen to fibrin and the development of fibrin strands. In this chapter, we discuss the proteins of the intrinsic pathway, the traditional view of contact activation, and finally alternative ideas about the activation of this important pathway. Notably, we attempt to reconcile the inconsistencies between protein adsorption and function at biomaterial surfaces and the traditional views of contact activation.