Coagulation cascade factors

Factor V. High in sialic acid content. Factor V is a large asymmetric single-chain glycoprotein that becomes an active participant in the coagulation cascade when it is converted to its active form by a-thrombin. Approximately 25% of human Factor V is found in the whole blood associated with platelets. Factor V is an essential cofactor along with Factor Xa plus phosphohpid plus Ca " in the conversion of prothrombin to thrombin. 

During activation of the coagulation cascade, coagulation factors form multimolecular (often trimolecular)... 

Binding calcium ions (Ca2+) is a prerequisite for the activation of seven clotting factors in the coagulation cascade that are dependent on vitamin K. The term cascade indicates, that the factois involved depend from... 

Figure 51-1. The pathways of blood coagulation. The intrinsic and extrinsic pathways are indicated. The events depicted below factor Xa are designated the final common pathway, culminating in the formation of cross-linked fibrin. New observations (dotted arrow) include the finding that complexes of tissue factor and factor Vila activate not only factor X (in the classic extrinsic pathway) but also factor IX in the intrinsic pathway, in addition, thrombin and factor Xa feedback-activate at the two sites indicated (dashed arrows). (PK, prekallikrein HK, HMW kininogen PL, phospholipids.) (Reproduced, with permission, from Roberts HR, Lozier JN New perspectives on the coagulation cascade. Hosp Pract [Off Ed] 1992Jan 27 97.)...

Activated platelets, besides forming a platelet aggregate, are required, via newly expressed anionic phospholipids on the membrane surface, for acceleration of the activation of factors X and II in the coagulation cascade (Figure 51—1). 

FIGURE 7-4. Coagulation cascade. AT, antithrombin HCII, heparin cofactor II TFPI, tissue factor pathway inhibitor. (Reproduced from Haines ST, Zeolla M, Witt DM. Venous thromboembolism. In ... 

The pathophysiology of hemophilia is based on the factor VIII or IX deficiency resulting in inadequate thrombin generation and an impaired intrinsic-pathway coagulation cascade (see... 

PCCs contain the vitamin K-dependent factors II, VII, IX, and X. These agents represent another attempt to bypass the factor at which the antibody is directed (see Fig. 64-2). However, PCCs carry the risk of serious thrombotic complications. Porcine factor VIII is most useful when the inhibitor titer is less than 50 BU (see Fig. 64-2 for dose and frequency). Owing to its similarity to human factor VIII, porcine factor VIII participates in the coagulation cascade. However, most inhibitors have very weak neutralizing activity against it. Porcine factor VIII is a third-line agent (only after factor Vila and a PCC have failed) owing to a 15% incidence of cross-reactivity.15... 

Thromboplastin A substance that triggers the coagulation cascade. Tissue factor is a naturally-occurring thromboplastin and is used in the prothrombin time test. 

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... 

The concept that different structural domains on the heparin chains are principally involved for optimal activity in the foregoing interactions could not be perceived in early work on structure-activity correlations, because the activity of heparin has been most frequently evaluated only with whole-blood-clotting tests (such as the U.S.P. assay). Development of assays for specific clotting-factors (especially Factor Xa and thrombin) has permitted a better insight into the mechanism of action of heparin at different levels of the coagulation cascade. 

There are various inhibitors within the coagulation system that counterregulate activation of the coagulation cascade. Among them, antithrombin III (AT-III) and protein C (PC) are the most important (SI). AT-III binds in the presence of heparin the activated factors F-IXa, F-Xa, and F-IIa (thrombin). PC is activated by a complex formed between thrombin and thrombomodulin, a surface protein of endothelial cells. Once activated, PC in the presence of protein S (PS) specifically degrades activated factors F-Va and F-VIIIa. PC decreases in the course of sepsis in relation to the severity of the condition (L15). Experimental studies have... 

Broze G. J., Jr. The role of tissue factor pathway inhibitor in a revised coagulation cascade. Semin Hematol 1992 29, 159-69. 

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...

Direct administration of factor Xa, thus bypassing the non-functional step in the coagulation cascade (Figures 12.2 and 12.3). 

Some 5-25 per cent of individuals suffering from haemophilia A develop anti-factor VIII antibodies, and 3-6 per cent of haemophilia B sufferers develop anti-factor IX antibodies. This complicates treatment of these conditions and, as mentioned previously, one approach to their treatment is direct administration of factor Vila. The therapeutic rationale is that factor Vila could directly activate the final common steps of the coagulation cascade, independently of either factor VIII or IX (Figure 12.1). Factor Vila forms a complex with tissue factor that, in the presence of phospholipids and Ca2+, activates factor X. 

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. 

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