Cellular Mechanisms for the Activation of Blood Coagulation

This chapter describes the biology of the cellular activators of the extrinsic coagulation pathway. These procoagulants do not act in isolation. Upon stimulation of both Mos and endothelial cells, there is a concomitant upregulation of the antifibrinolytic system by decreased or unchanged plasminogen activator synthesis and increased production of inhibitors of plasminogen activator. Downregulation of procoagulant expression may occur via inhibitors, cytokines, and other agents which regulate gene transcription and translation, by availability of phospholipids and other cofactors, and by the physiochemical presentation of these factors within the cell membrane. Investigation in this complex area is likely to have important clinical relevance, particularly in the development of more specific and potent inhibitors, and should be extended to include the possible interactions of Tissue factor/factor VIIa/Mac-l/factor X on adhesive substrates and on the extracellular matrix (ECM). The sequestration of coagulation factors to the ECM may have additional functions in inflammation. Under these circumstances, their effects on cell migration and activation may be of major significance.