Clotting factors, vitamin dependent

Vitamin cycle—metabolic interconversions of vitamin associated with the synthesis of vitamin -dependent clotting factors. Vitamin K1 or K2 is activated by reduction to the hydroquinone form (KH2). Stepwise oxidation to vitamin epoxide ( ) is coupled... 

Vitamin K cycle—metabolic interconversions of vitamin K associated with the synthesis of vitamin K-dependent clotting factors. Vitamin K1 or K2 is activated by reduction to the hydroquinone form (KH2). Stepwise oxidation to vitamin K epoxide (KO) is coupled to prothrombin carboxylation by the enzyme carboxylase. The reactivation of vitamin K epoxide is the warfarin-sensitive step (warfarin). The R on the vitamin K molecule represents a 20-carbon phytyl side chain in vitamin Ki and a 30- to 65-carbon polyprenyl side chain in vitamin K2. 

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... 

All anticoagulants interfere with the clotting mechanism of the blood. Warfarin and anisindione interfere with the manufacturing of vitamin K-dependent clotting factors... 

The most commonly used oral anticoagulant drug in the U.S. is warfarin. It acts by altering vitamin K so that it is unavailable to participate in synthesis of vitamin K-dependent coagulation factors in the liver (coagulation factors II, VII, IX, and X). Because of the presence of preformed clotting factors in the blood, the full antithrombotic effect of warfarin therapy may require 36 to 72 h. 

The answer is a. (Hardman, pp 1086—1089.) Intolerance of alcohol (disulfiram-like reaction) has been noted only with certain cephalosporins. Cephalosporins with the methylthiotetrazole side chain have been associated with a disulfi ram-like reaction because the methyl thiotetrazole group has a configuration similar to disulfi ram, which blocks the metabolism of alcohol at the acetaldehyde step. Accumulation of acetaldehyde is associated with the symptoms. The methyl thiotetrazole side chain also results in hypopro thrombi nemia by interfering with the synthesis of vitamin K-dependent clotting factors. 

Vitamin K-dependent clotting factor, including factor VII, is affected early. 

Compounds showing vitamin K activity are substituted naphthoquinones. The parent compound, 2-methyl-1,4-naphthoquinone, does show some biological activity as do other similar but synthetic compounds. The production of the complete naturally active forms is thought to depend upon the addition of an isoprene chain at position 3 on the aromatic ring. Differences in this side chain produce the various K vitamins (Figure 12.10). A most important physiological role of vitamin K is in the synthesis of the blood clotting factors, II (prothrombin), VII, IX and X. 

Oral anticoagulants. Structurally related to vitamin K, 4-hydroxycouma-rins act as false vitamin K and prevent regeneration of reduced (active) vitamin I< from vitamin K epoxide, hence the synthesis of vitamin K-dependent clotting factors. 

In normal individuals phytonadione and the menaquinones have no activity while in vitamin K deficiency the vitamin promotes the hepatic biosynthesis of factor II (prothrombin), factor VII, factor IX and factor X. Vitamin K functions as an essential cofactor for the enzymatic activation of precursors of these vitamin K dependent clotting factors. The quinone structure of the active form of vitamin K, i.e. reduced vitamin K or hydroquinone. 

L B. Warfarin does not produce an anticoagulant effect in vitro. It inhibits coagulation of blood only in vivo, because the effect depends upon warfarin s effect in the liver on the production of clotting factors. Warfarin does not require conversion into an active drug. It inhibits the post-ribosomal carboxy-lation of glutamic acid residues in the vitamin K-dependent clotting factors. Therefore, heparin rather than warfarin is used when blood is collected from donors and stored. 

Another concern in infants of mothers with epilepsy is a serious hemorrhagic disorder that is associated with a high (25-35%) mortality. This probably results from the finding that many AEDs can act as competitive inhibitors of vitamin K-dependent clotting factors. The competitive inhibition can be overcome by the administration of oral vitamin K supplements to the mother during the last week or 10 days of pregnancy. 

As the plasma levels of T4 and T3 fall after the administration of antithyroid drugs, the catabolism of vitamin K-dependent clotting factors decreases, thus reducing... 

Mechanism of Action A coumarin derivative that interferes with hepatic synthesis of vitamin K-dependent clotting factors, resulting in depletion of coagulation factors II, VII, IX, and X. Therapeutic Effect Prevents further extension of formed existing clot prevents new clot formation or secondary thromboembolic complications. Pharmacokinetics ... 

They act by interfering with synthesis of vitamin K dependent clotting factors in liver. They act as competitive antagonists of vitamin K and reduce plasma levels of clotting factors in a dose dependent manner. They act by interfering with regeneration of active form of vitamin K. Factor VII levels are reduced first followed by factor IX, X and II. 

FIGURE 25-2 Role of vitamin K in the synthesis of vitamin K-dependent clotting factors (II, VII, IX and X). Vitamin K catalyzes the reaction necessary for completion of clotting factor synthesis, but it is oxidized in the process to vitamin K epoxide. Regeneration of vitamin K occurs via vitamin K epoxide reductase. Oral anticoagulants such as warfarin (Coumadin) block the regeneration of the vitamin K, thus halting the further synthesis of the vitamin K-dependent factors. 

Deficiencies in vitamin K and the related synthesis of the vitamin K-dependent clotting factors are treated by administering exogenous vitamin K.20 Various commercial forms of this vitamin are available for oral or parenteral (intramuscular or subcutaneous) administration. Specifically, individuals with a poor diet, intestinal disease, or impaired intestinal absorption may require vitamin K to maintain proper hemostasis. 

Vitamin E has received much publicity as one of several antioxidants that may be useful in treating a variety of disorders, including cardiovascular disease. Vitamin E may inhibit the oxidation of reduced vitamin K. Vitamin K oxidation is necessary for carboxylation of vitamin-K-dependent clotting factors, which must occur for these clotting factors to be fully functional. Increased prothrombin times, induced by combined vitamin E and warfarin therapy, may be managed by discontinuing vitamin E and, if necessary, by administering vitamin K. 

Hemorrhagic complications are generally believed to result from decreased synthesis of clotting factors like fibrinogen, vitamin K-dependent factors, and inde-... 

Heparin acts by binding to anti thrombin III, which serves as a major inhibitor of serine protease clotting enzymes. Abruptly ending heparin treatment can be hazardous because of reduced levels of antithrombin III. Coumarins, typified by warfarin, are structurally similar to vitamin K, which plays an important role in blood coagulation. By interfering with the function of vitamin K, vitamin K-dependent proteins such as clotting factors VII, IX, X and prothrombin are reduced. 

The increased susceptibility to bleeding observed in patients with liver failure (raised INR) results from depressed fibrinogen levels and the reduced synthesis of clotting factors by the cirrhotic liver. In addition, the absorption of fat-soluble vitamin K is impaired in cholestasis and subsequently the synthesis of vitamin K-dependent clotting factors is reduced. 

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