Blood-coagulation cascade

Schenone M, Furie B (2004) The blood coagulation cascade. Curr Opin Hematol 11 272-277... 

Induction of the blood coagulation cascade. This culminates in the conversion of a soluble serum protein, fibrinogen, into insoluble fibrin. Fibrin monomers then aggregate at the site of... 

Figure 12.3 Overview of the blood coagulation cascade, with emphasis upon the molecular detail of its terminal stages. Refer to text for specific detail...

By preparing planar lipid monolayers or bilayers on hydrophobically derivatized or native hydrophilic glass, respectively, the adsorption equilibrium constants of a blood coagulation cascade protein, prothrombin, have been examined by TIRF on a surface that more closely models actual cell surfaces and is amenable to alterations of surface charge. It was found that membranes of phosphatidylcholine (PC) that contain some phosphatidyl-serine (PS) bind prothrombin more strongly than pure PC membranes/83... 

Pharmacology The antithrombotic activity is the result of antithrombin III (ATIII)-mediated selective inhibition of Factor Xa. Neutralization of Factor Xa interrupts the blood coagulation cascade and thus inhibits thrombin formation and thrombus development. 

The endotoxin molecule activates a coagulation cascade quite similar in design to the mammalian blood coagulation cascade (Figure 3.38). Activation of the cascade also requires the... 

Mectianism of Action A factorXa inhibitor and pentasaccharide that selectively binds to antithrombin, and increases its affinity for factor Xa, thereby inhibiting factor Xa and stopping the blood coagulation cascade. Therapeutic Effect Indirectly prevents formation of thrombin and subsequently the fibrin clot. 

Koyama, T., Noguchi, K., Aniya, Y., and Sakanashi, M. (1998). Analysis for sites of anticoagulant action of plancinin, a new anticoagulant peptide isolated from the starfish Acantha-ster planci, in the blood coagulation cascade. Gen. Pharmacol. 31, 277-282. 

The blood coagulation cascade. Each of the curved red arrows represents a proteolytic reaction, in which a protein is cleaved at one or more specific sites. With the exception of fibrinogen, the substrate in each reaction is an inactive zymogen except for fibrin, each product is an active protease that proceeds to cleave another member in the series. Many of the steps also depend on interactions of the proteins with Ca2+ ions and phospholipids. The cascade starts when factor XII and prekallikrein come into contact with materials that are released or exposed in injured tissue. (The exact nature of these materials is still not fully clear.) When thrombin cleaves fibrinogen at several points, the trimmed protein (fibrin) polymerizes to form a clot. 

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. 

The blood coagulation cascade. Proteins whose names are... 

Know the components and the operation of the blood coagulation cascade. 

A series of proteins collectively called the complement participate in the immune response to the entry of foreign cellular or viral material into the organism. This group of proteins consists of about 20 entities, some of which are enzymes. Complement was first associated with the lysis of foreign red blood cells in the nineteenth century it also participates in the lysis of bacterial cells. The complement activation cascade, very similar to the blood coagulation cascade, involves the stepwise activation, via proteolysis, of various components of the complement system until a final protein complex, the membrane attack unit (also called the C5b-9 complex), is generated. It then punches holes in the membrane to which it is bound. 

Many pharmaceutical companies are actively working on the development of orally active inhibitors of the serine protease thrombin as one important enzyme in the blood coagulation cascade. In many cases, however, the systemic exposure to thrombin inhibitors... 

Factor VIII (F8) and Factor V (F5) are key regulatory elements of the blood coagulation cascade of sequential proteolytic activation of serine... 

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