Blood Coagulation Processes

Heparin and the closely related molecule heparan sulfate act as cofactors in AT III inhibition process by affording a 1000-fold increase in the rate at which AT III inhibits coagulation enzymes (9). In the absence of heparin, AT III is a relatively ineffective inhibitor of factor Xa and thrombin (kgssoc [factor Xa] = 2.6 x 10  

The role of individual saccharide residues of the heparin pentasaccharide in the allosteric activation of AT III has also been determined by studying the effect of truncating the pentasaccharide residue, at either its reducing or its nonreducing end. These studies established that the three saccharide residues on the nonreducing end of the pentasaccharide sequence are capable of fully activating AT III. While the reducing end residues are not essential for the activation, they stabilize the activated conformation (13). 

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Several substances that contribute to the blood coagulation process are formed in the liver. These include fibrinogen, prothrombin, and several of the blood clotting factors (II, VII, IX, and X). Deficiency in any of these substances leads to impaired blood coagulation. 

Interactions of heparinoids with the most diverse proteins such as enzymes and enzyme inhibitors, cytokines, and adhesion molecules have been described. To date, many more than a hundred heparin binding proteins are known. A number of heparin binding proteins are members of the serpin family of serine protease inhibitors. The best described example is antithrombin [4]. Antithrombin III (AT III) is able to inhibit various serine proteases involved in the blood coagulation process by formation of stable, equimolar complexes. Binding of heparin to AT III accelerates the kinetics of this complex formation by several orders of magnitude. This has been the basis for the successful clinical use of heparin as an anticoagulant for nearly sixty years. 

The key role played by the thrombin in the blood coagulation process has led to its extensive study and mainly to the understanding of its complex formation from its zymogen, prothrombin. 

In addition to its role in the blood-coagulation process, heparin shows other types of biological activity, such as its action in clearing fat globules from the blood stream (alimentary lipemia) and its use in the treatment of frost-bite. For an extensive account of the development and use of heparin in medical and surgical practice, the reader is referred to Jorpes book. ... 

Figure 4-13 A pentasaccharide segment of heparin which binds with high affinity to the serum protein antithrombin causing it to inhibit most of the serine protease enzymes participating in the blood coagulation process (see Chapter 12). See Lindahl et al. ...

The use of thrombin, an enzyme that serves several roles in the blood-coagulating process, is a useful adjunct to tryptic hydrolysis. Its action is more specific and it cleaves only a limited number of arginyl bonds as a rule. Some arginyl bonds are only slowly hydrolysed by thrombin so that enzymic digests of protein can be quite complex in composition because degradation of substrate is incomplete. 

Among seven isoforms of 3-OST, only 3-OST-1 has been knocked out in mice. The study was originally aimed to determine the effect of the level of anticoagulant HS on the blood coagulation process, provided that... 

The coumarin anticoagulants are employed in therapy to depress blood coagulation and to prevent thrombosis in diseases of the coronary artery and in other conditions [419]. These compounds act only in vivo by blocking the synthesis of four proteins in the prothrombin complex (factors II = prothrombin, VII = proconvertin, IX = plasma thromboplastin component, and X = Stuart-Prower factor) necessary for the normal blood coagulation process. These proteins are... 

Tests performed. We studied three types of properties of our polymer films their hemocompatibility, their influence on.the blood coagulation process and their eventual toxicity. 

The influence of the polymer films on the blood coagulation process was studied by thromboelastography. 

In order to determine the effect of the polymers on the blood coagulation process we used the thromboelastography that allow a full and easy preliminary study of the different phases of the coagulation. 

Lei KF, Chen K-H, Tsui P-H, Tsang N-M. Real-time electrical impedimetric monitoring of blood coagulation process under temperature and hematocrit variations conducted in a microfluidic chip. PLoS One 2013 8 e76243. 

At this time, there is no evidence that vitamin K has any functions in humans or animals other than in the blood coagulation process, although vitamin K-dependent proteins have been identified in the bone, kidney, and liver. 

A modifier-specifier role for proteins, wherein a new biologic function or enhanced activity is achieved, may well be more common than is presently appreciated. For example, factors V and VIII in the blood coagulation process appear to act in this way (Davie et al., 1979), as do specific protein initiation factors which participate in protein synthesis (Weissbach and Ochoa, 1976). 

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