Clotting system

Prothrombin and several other proteins of the blood clotting system (Factors VII, IX and X, and proteins C and S) each contain between four and six y-carboxygluta-mate residues which chelate calcium ions and so permit the binding of the blood clotting proteins to membranes. In vitamin K deficiency or in the presence of warfarin, an abnormal precursor of prothrombin (preprothrombin) containing little or no y-carboxyglutamate, and incapable of chelating calcium, is released into the circulation. 

Inherited deficiencies of the clotting system that result in bleeding are found in humans. The most common is deficiency of factor VIII, causing hemophilia A, an X chromosome-hnked disease that has played a major role in the history of the royal families of Europe. Hemophilia B is due to a deficiency of factor IX its clinical Feamres are almost identical to those of hemophilia A, but the conditions can be separated on the basis of specific assays that distinguish between the two factors. 

Celia G, Scattolo N, Luzzato G, Stevanato E, Vio C, Girolami A. Effects on platelets and on the clotting system of four glycosaminoglycans extracted from hog mucosa and one extracted from aortic intima of the calf, J Med 1986 17 331-346. 

The aim of the present review is to systematize and analyze the results of investigations concerning the synthesis and properties of HCP on the basis of literature data and own results. The probable mechanism of the effect of polymer-bound heparin on the blood clotting system will be discussed. A survey of the most promising pathways for further development of the chemistry of HCP involving the development of methods of their synthesis as well as the increase of the activity of immobilized heparin itself will be given. 

The fact that thromboresistance of HCP is dependent on the method of immobilization of heparin, together with a rather low activity of covalently immobilized heparin, makes the idea of long-term enhancement of thromboresistance of polymers on their heparinization doubtful 54,70,71J. Naturally, the answer can be given only after a detailed analysis of the interaction of HCP with blood and its components and clarification of the mechanism of the effect of the immobilized heparin on the blood clotting system and relying on the results of in vivo tests of these materials are necessary. 

Similar changes of the basic parameters of the blood clotting system were reported in actually all of the works dealing with the interaction of HCP with blood and its components. HCPS adsorb to the largest extent thrombin 32,96,lls-119( fibrinogen 65> 94>, factors IX, X, Xa, XI23-94.99,120,and antithrombin m 64,9-q the last onebeing the only protease adsorbed from plasma. The adsorbed thrombin retains its activity and... 

To clarify the mechanism of enhanced thromboresistance of such polymers, the state of the blood clotting system before and after the contact with the polymer was examined I36) (Table 19). Obviously, the changes of the blood clotting system parameters are of the same type as those accompanying the interaction of blood with HCP (see Table 16) but essentially exceeding the latter. Consequently, the heparin-protease-... 

The more profound and extensive effect of immobilized heparin on the blood clotting system observed in the presence of immobilized trypsin is due to the tryptic lysis of the protein constituents of the complexes of immobilized heparin with the most thrombogenic plasma proteins (thrombin and fibrinogen) (Fig. 11). 

The second answer with respect to the earlier acquisition of risk data must come from the laboratory. Not from animal studies, which in this field are of very restricted value, but from biochemical and particularly hematological work. When during the 1990s various groups began to examine in detail the effects of the third-generation contraceptives on processes related to the clotting system, they identified a series of properties that could very well explain an increased incidence of thrombosis. 

The serine proteases are divided into at least two genetic families the mammalian serine proteases, such as trypsin, chymotrypsin, elastase, the enzymes of the blood clotting system, and many other proteases with specific roles in control of systems and the bacterial proteases called subtilisins (first to be isolated from Bacillus amyloliquefaciens), which are genetically unrelated to the mammalian enzymes but independently evolved the same mechanism (evolutionary convergence). 

Sugar-amine interactions in the blood clotting system and their effects on haemostasis. Proc. Vth Int. Congr. Thromb. Haemostasis 1975, Paris Int. Soc. Thromb. Haemostasis through ref. 72. 

Mester, L. Kraska, B. Crisba, J. Mester, M. "Sugar-amine Interactions in the Blood Clotting System and Their Effects on Haemostasis", Proc. 5th Intern. Congr. Thrombosis Haemostasis, Paris, 1975. 

Hie serine protease thrombin takes a central position in the clotting system. It splits off fibrinopeptides A and B from the amino terminal ends of the a- and -chains of fibrinogen. The resulting fibrin monomer then undergoes polymerization to forma fibrin dot. Via activation of the clotting factors V and VIII, further thrombin is Generated from wothramhin. and via activation of blood dale lets and... 

Perhaps the reader can see why the blood-clotting system is called a cascade—a system where one component activates another component, which activates a third component, and so on. Since things are beginning to get complicated, it will help a lot to keep track of the discussion with Figure 4-3. 

Slogging through a description of the blood-clotting system makes a fellow yearn for the simplicity of a cartoon Rube Goldberg machine. 

There are other ways to stop blood flow from wounds, but those ways are not step-by-step precursors to the clotting cascade. For example, the body can constrict blood vessels near a cut to help stanch blood flow. Also, blood cells called platelets stick to the area around a cut, helping to plug small wounds. But those systems cannot be transformed gradually into the blood-clotting system any more than a glue trap can be transformed into a mechanical mousetrap. 

One could imagine a blood-clotting system that was somewhat simpler than the real one—where, say, Stuart factor, after activation by... 

Schulze HJ, Wendel HP, Kleinhans M, Oehmichen S, Heller W, Elert O. Effects of the propofol combination anesthesia on the intrinsic blood-clotting system. Immunopharmacology 1999 43(2-3) 141 -A. 

The standard assay measures the time taken for the formation of a fihrin clot in citrated plasma after the addition of calcium ions and thromhoplastin to activate the extrinsic clotting system - the prothrombin time. The normal prothrombin time is 11 to 13 seconds greater than 25 seconds is associated with severe bleeding. 

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