Blood coagulation prothrombin activator formation

It is believed that heparin acts by neutralizing a number of active blood coagulation factors, thus disrupting the transformation of prothrombin into thrombin. Heparin is used to prevent thrombo-formation in myocardial infarctions, thrombosis, and embolism, for maintaining liquid conditions in the blood in artificial blood drcnlation and hemodialysis. Synonyms of this drug are arteven, hepalen, leparan, Uquemin, panheprin, vetren, and many others. 

An important step in the blood coagulation pathway is the formation of the prothrombinase complex. The latter is a mixture of factor V, factor Xa, Ca2+, and phospholipid. In this case, a phospholipid mixture with a net negative charge will allow the prothrombinase complex to form. This active enzyme is important in cleaving prothrombin to yield thrombin. The most active phospholipid mixture for in vitro studies has proven to be phosphatidylserine-phosphatidylcholine. Subsequently the hypothesis has developed that phosphatidylserine is key to the formation of prothrombinase. 

Quinones and, in particular, naphthoquinone derivatives are industrially valuable products for further processing and for direct use due to their pronounced bioactivity [la,b], 2-Methyl-1,4-naphthoquinone, vitamin K3 ( menadione ), is the basis of the vitamin K group (coagulation vitamins). The skeleton of 2-methyl-1,4-naphthoquinone is common to all fat-soluble K vitamins. Derivatives of vitamin K promote the formation of prothrombin and other blood coagulation factors. They are used on an industrial scale as supplement in animal feed, but are also employed in the treatment of Melaena neonatorum in newborn babies. Trimethyl-p-benzoquinone is a key compound for the synthesis of vitamin E, active as antioxidant agent. As an example, the current method of the production of trimethyl-p-benzoquinone on an industrial scale is p-sulfo-nation of 2,3,6-trimethylphenol followed by stoichiometric oxidation using Mn02 [Ic]. 

Phytonadione is a blood modifier/vitamin K. It promotes hepatic synthesis of active prothrombin (factor II), proconvertin (factor VII), plasma thromboplastin component (factor IX) and Stuart factor (factor X). It is indicated in the management of coagulation disorders due to faulty formation of factors II, Vn, IX, and X due to vitamin K deficiency or interference with vitamin K activity. Oral/parenteral used for treatment of anticoagulant-induced prothrombin deficiency treatment of hypoprothrombinemia secondary to salicylates or antibacterial therapy, or secondary to obstructive jaundice and biliary fistulas, provided bile salts are also given. Parenteral used for treatment of hypoprothrombinemia secondary to conditions limiting absorption or synthesis of vitamin K prophylaxis and therapy of hemorrhagic disease of the newborn. 

When blood is lost or clotting is initiated in some other way, a complex cascade of biochemical reactions is set in motion, which ends in the formation of a network or clot of insoluble protein threads enmeshing the blood cells. These threads are produced by the polymerisation of the molecules of fibrinogen (a soluble protein present in the plasma) into threads of insoluble fibrin. The penultimate step in the chain of reactions requires the presence of an enzyme, thrombin, which is produced from its precursor prothrombin, already present in the plasma. This is initiated by factor lit (tissue thromboplastin), and subsequently involves various factors including activated factor Vn, DC, X, XI and XII, and is inhibited by antithrombin in. Platelets are also involved in the coagulation process. Fibrinolysis is the mechanism of dissolution of fibrin clots, which can be promoted with thrombolytics. For further information on platelet aggregation and clot dissolution, see Antiplatelet drugs and thrombolytics , (p.697). 

Vitamin K is essential for the formation of prothrombin in the liver. A deficiency reduces the amount of prothrombin in the blood, thus reducing the coagulation power and increasing the tendency to Weed. Many different compounds, all related to 2-methyl-l, 4r-naphthoquinone, possess some degree of vitamin K activity. There is no indication yet of the way vitamin K takes part in prothrombin formation (Dam, 1953). 

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