Blood clot coagulation cascade pathway

Simultaneously, activation of the extrinsic coagulation cascade occurs as a result of exposure of blood to the thrombogenic lipid core and endothelium, which are rich in tissue factor. This pathway ultimately leads to the formation of a fibrin clot composed of fibrin strands, cross-linked platelets, and trapped red blood cells. 

Interactions between serine proteases are common, and substrates of serine proteases are usually other serine proteases that are activated from an inactive precursor [66]. The involvement of serine proteases in cascade pathways is well documented. One important example is the blood coagulation cascade. Blood clots are formed by a series of zymogen activations. In this enzymatic cascade, the activated form of one factor catalyzes the activation of the next factor. Very small amounts of the initial factors are sufficient to trigger the cascade because of the catalytic nature of the process. These numerous steps yield a large amplification, thus ensuring a rapid and amplified response to trauma. A similar mechanism is involved in the dissolution of blood clots. A third important example of the coordinated action of serine proteases is the intestinal digestive enzymes. The apoptosis pathway is another important example of coordinated action of other types of proteases. 

Activation of the blood coagulation cascade is triggered by the reaction of plasma proteins with the subendothelium at the same time that platelets are adhering to the subendothelial layer. Historically, two different pathways were discovered, one dependent on external stimuli (such as blunt trauma, which initiates the extrinsic pathway) and one using internal stimuli (the intrinsic pathway). As our understanding of blood clotting has expanded, it has become obvious that these distinctions are no longer correct, because there is overlap between the pathways, but the terms have persisted in the description of the pathways. 

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. 

Fig.7 Blood compatibility of PEU surfaces modified by MPEO-derived SMAs. A Simplified cascade model for material-induced blood coagulation highlighting three clotting pathways plasma fibrin formation, platelet aggregation, and hemolysis-inflammation, respectively characterized by B-C...

Blood coagulation occurs as a "cascade" of proteolytic factors are activated. Each factor is proteolyzed into an active protease. The newly-formed protease in turn proteolyzes the next factor into an active protease. The cascade produces fibrin, which forms an insoluble network that entangles blood cells and platelets. The clotting cascade can be activated by factors that reside only in the bloodstream (intrinsic pathway) or by tissue factors that are not present in blood (extrinsic pathway). 

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