Clotting inhibitors

Kim, D. C., Chae, H. J., and In, M. J. (2004). Existence of stable fibrin-clotting inhibitor in salt fermented anchovy sauce. J. Food Compost. Anal. 17,113-118. 

Nazare (4) prepared oxybenzamide derivatives, (IV) which were effective as factor Xa-specific blood clotting inhibitors with enhanced stability in plasma and liver. 

The coagulation proteins that are synthesized in the liver are listed in Table 47-1. These proteins interact to produce a fibrin clot. Inhibitors of the coagulation system, including antithrombin, protein C, and protein S, are also synthesized in the fiver. Some of the coagulation factors (II, VII, IX, and X) require vitamin K for posttranslational carboxylation within the hepatocyte. Protein C and S are also carboxylated by a vitamin K-dependent enzyme. Activated protein C in plasma inhibits coagulation by inactivating factors V and... 

GAGs are classified into several major types based on the nature of the repeating disaccharide unit heparan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, and hyaluronan. A hypersulfated form of heparan sulfate called heparin, produced mostly by mast cells, plays a key role In allergic reactions. It is also used medically as an anticlotting drug because of its ability to activate a natural clotting inhibitor called antlthrombln III. 

This scheme does not Include many of the clotting inhibitors. 

COX-2 synthesises PGI2 (prostacyclin) and the high incidence of myocardial infarctions with selective COX-2 inhibitors has been attributed to inhibition of COX-2 in vascular tissues. Prostacyclin, made by blood vessel walls, inhibits aggregation of platelets and maintains a balance with thromboxane. Thromboxane, which is released by platelets, promotes clotting. Prostacyclin is synthesised mostly by COX-1, but in humans selective COX-2 inhibition reduces its biosynthesis in vivo. This reduced synthesis may lead to an overactive thromboxane system and increased risk of thromboembolism. 

Dipyridamole is a PDE5/PDE6 selective inhibitor that is used widely in conjunction with aspirin to reduce clotting and prevent stroke. More recent studies with a fixed combination of these two drugs (Aggrenox) has been shown in the recent European Stroke Prevention Study 2 to be of greatly added benefit over aspirin alone for prevention of recurrent stroke. 

Use of clotting-factor concentrates to check for the development of inhibitors, especially in patients with severe disease and poor treatment responders... 

Activated partial thromboplastin time aPTT is performed by adding calcium phospholipids and kaolin to citrated blood and measures the time required for a fibrin clot to form. In this manner, aPTT measures the activity of intrinsic and common pathways. Prolongation of aPTT may be due to a deficiency or inhibitor for factors II, V, VIII, IX, X, XI, and XII. It also may be due to heparin, direct thrombin inhibitors, vitamin K deficiency, liver disease, or lupus anticoagulant. 

B30. De Boer, J. R, Creasey, A. A., Chang, A., Abbink, J. J., Roem, D., Eerenberg, A. J., Hack, C. E., and Taylor, F. B., Alpha-2 macroglobulin functions as an inhibitor of fibrinolytic, clotting and neutrophilic proteinases in sepsis Studies using a baboon model. Infect. Immun. 61,5035-5043 (1993). 

The fibrinolytic activity of scu-PA is more efficient than that of either LMW-UK or HMW-UK. Apparently, fibrin within a clot neutralizes an inhibitor in plasma that normally hinders binding of scu-PA to plasminogen, thereby facilitating binding of scu-PA to Glu-plasminogen and its resultant activation (37, 38). A cell surface receptor for scu-PA has been implicated in the activation of plasminogen and the internalization and degradation of u-PA complexed to inhibitors (39). 

A protease inhibitor to prevent formation of intravascular blood clots due to activity of thrombin. 

Weitz JI, Hudoba M, Messel D, Maraganore J, Hirsh J. (1990) Clot-bound thrombin is protected from inhibition by heparin-antithrombin 111 but is susceptible to inactivation by antithrombin Ill-independent inhibitors. J Clin Invest 86 385-391. 

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