Rethinking the coagulation cascade.

The concept of coagulation as a "cascade" of proteolytic reactions was a conceptual breakthrough in understanding how the coagulation process acts as a biologic amplifier. The model that it evolved into, with "extrinsic" and "intrinsic" pathways meeting in a common pathway, delineates the interactions between the coagulation proteins and provides a framework for interpreting the common screening coagulation tests. The coagulation "cascade" has significant limitations as a model of how hemostasis occurs in vivo, however. This article describes how the modern view of hemostasis has evolved to emphasize the role of cells in controlling and directing the coagulation reactions. It also highlights how host factors that are not part of the coagulation process per se can influence the effectiveness of coagulation.