Coagulation pathways

Factor VII. This is a vitamin K-dependent serine protease that functions in the extrinsic coagulation pathway and catalyzes the activation of Factors IX and X. Factor VII is present constitutively in the surface membrane of pericytes and fibroblasts in the adventitia of blood vessels, vascular endothehum, and monocytes. It is a single-chain glycoprotein of approximately 50,000 daltons. 

Hemostasis is the process that stops bleeding in a blood vessel. Normal hemostasis involves a complex process of extrinsic and intrinsic factors. Figure 44-1 shows the coagulation pathway and factors involved. The copulation cascade is so named because as each factor is activated it acts as a catalyst that enhances the next reaction, with the net result being a large collection of fibrin that forms a plug in the vessel. Fibrin is the insoluble protein that is essential to clot formation. 

We shall first describe the coagulation pathway leading to the formation of fibrin. Then we shall briefly describe some aspects of the involvement of platelets and blood vessel walls in the overall process. This separation of clotting factors and platelets is artificial, since both play intimate and often mutually interdependent roles in hemostasis and thrombosis, but it facifitates description of the overall processes involved. 

In chimpanzees, administration of Fab fragments of a monoclonal anti-F-VII antibody preceding an endotoxin bolus injection effectively blocked the activation of the coagulation pathway (B25). Administration of monoclonal anti-lL-6 under the same experimental conditions attenuated the activation of coagulation, while the fibrinolytic system remained unaltered. However, administration of monoclonal anti-TNF enhanced the tendency to microvascular thrombosis (P17,18). Monoclonal anti-TF antibodies administered to baboons as a pretreatment attenuated coagulopathy after induction of E. coli sepsis in these animals (T4). Primates pretreated with anti-C5a antibodies before infusion of E. coli developed less hypotension and had better survival rates than untreated animals, who developed ARDS and septic shock with a mortality rate of 75% (S35, Z6). No favorable treatment results have been published yet with one of these treatment modalities given to humans. 

Fig. S. Schematic representation of coagulation pathway as currently understood. TF, tissue factor PPL, platelet phospholipid.

McGee M. P., Li L. C. Functional difference between intrinsic and extrinsic coagulation pathways. Kinetics of factor X activation on human monocytes and alveolar macrophages. J Biol Chem 1991 266,8079-85. 

Figure 12.1 Schematic diagram of the initial steps of the extrinsic blood coagulation pathway. See text for details (TF tissue factor)...

Figure 12.2 The steps unique to the intrinsic coagulation pathway. Factor Xlla can also convert prekal-likrein to kallikrein by proteolysis, but this is omitted for the sake of clarity. Full details are given in the main text. The final steps of the coagulation cascade, which are shared by both extrinsic and intrinsic pathways, are outlined in Figure 12.3...

Refer to the next page for the complete coagulation pathway. 

Hanumanthaiah, R., Day, K., and Jagadeeswaran, P. (2002). Comprehensive analysis of blood coagulation pathways in teleostei Evolution of coagulation factor genes and identification of zebrafish factor VHi. Blood Cells 29, 57-68. 

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