Leukocyte interaction with protein cascades in blood coagulation

Coagulation preserves the homeostasis of internal body fluids against life-threatening blood losses. Although generally viewed as a regulated enzymatic cascade, this mechanism depends on the participation of vascular cells. Leukocytes, in particular, have evolved a formidable machinery to initiate and amplify blood clotting reactions through the recognition of cell surface receptors, proteolytic enzymes, and cofactor and regulatory molecules. The consequences of thrombin generation on the leukocyte surface are not exclusively restricted to the hemostatic balance. Rather, thrombin and other coagulation proteases influence a panoply of cellular functions, ranging from activation pathways and adherence phenomena, to DNA synthesis and cell proliferation of normal and malignant phenotypes. For this multivalency of cellular responses, the process of blood coagulation is now perceived as a broad cell signaling mechanism that participates in all pathophysiological aspects of host inflammatory responses.