Blood coagulation cascade triggering

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. 

The demonstration of the hematological and cardiovascular relevance of such basic bioelectrochemical studies is necessary and the former has to some extent been exemplified in this and the earlier subsections. In the cardiovascular system, especially when metallic implants are used, it is likely that such types of electrochemical reactions are triggered and provide an alternate pathway for the blood coagulation cascade. This aspect will be dealt with in Section 4.1. 

The adsorption of proteins is the first interaction which occurs when a foreign surface comes in contact with blood. The processes which then lead to hemostasis are attachment of cellular elements to the surface, platelet adhesion and release, and triggering of the blood coagulation cascade. Investigations of interactions of proteins at the interface, which are the primary steps in blood clotting and determine whether it will occur, are hence of fundamental importance. 

The fluidity of blood is a result of the inhibition of a complex series of enzymic reactions in the coagulation cascade (see Fig. 10). When triggered either intrinsically (by contact with foreign surfaces ), or extrinsically (by tissue factors from damaged cells), inactive proenzymes (factors XII, XI, IX, and X) are transformed into activated pro-teinases (XHa, XIa, IXa, and Xa, respectively). Each proteinase catalyzes the activation of the following proenzyme in the sequence, up to formation of thrombin (Factor Ha), another proteinase that catalyzes partial... 

Figure 6. Triggering of kinin formation, blood coagulation, and fibrinolysis through specific proteolytic activation of the Hageman Factor (Factor XII). In the cascades, the factor on the left side of the reaction (zymogen) is converted to an active enzyme by proteolysis. PL = phospholipids.

Thrombus versus embolus A clot that adheres to a vessel wall is called a thrombus, whereas an intravascular clot that floats within the blood is termed an embolus. Thus, a detached thrombus becomes an embolus. Both thrombi and emboli are dangerous, because they may occlude blood vessels and deprive tissues of oxygen and nutrients. Arterial thrombosis most often involves medium-sized vessels rendered thrombogenic by surface lesions of endothelial cells caused by atherosclerosis. In contrast, venous thrombosis is triggered by blood stasis or inappropriate activation of the coagulation cascade, often as a result of a defect in the normal defense hemostatic mechanisms. 

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