Prothrombin blood coagulation

Administration of zafirlukast and aspirin increases plasma levels of zafirlukast, When zafirlukast is administered with warfarin, there is an increased effect of the anti coagulant. Administration of zafirlukast and theophylline or erythromycin may result in a decreased level of zafirlukast. Administration of montelukast with other drugs has not revealed any adverse responses. Administration of montelukast with aspirin and NSAIDs is avoided in patients with known aspirin sensitivity. Administration of zileuton with propranolol increases the activity or the propranolol with theophylline increases serum theophylline levels and with warfarin may increase prothrombin time (PT). A prothrombin blood test should be done regularly in the event dosages of warfarin need to be decreased. 

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. 

By preparing planar lipid monolayers or bilayers on hydrophobically derivatized or native hydrophilic glass, respectively, the adsorption equilibrium constants of a blood coagulation cascade protein, prothrombin, have been examined by TIRF on a surface that more closely models actual cell surfaces and is amenable to alterations of surface charge. It was found that membranes of phosphatidylcholine (PC) that contain some phosphatidyl-serine (PS) bind prothrombin more strongly than pure PC membranes/83... 

This enzyme catalyzes the vitamin K-dependent post-translational carboxylation of specific glutamic acid residues in prothrombin and other blood coagulation proteins to form 4-glutamylcarboxylate side chains. 

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. 

Vitamin K activity is associated with several quinones, including phylloquinone (vitamin Kj), menadione (vitamin K3), and a variety of menaquinones (vitamin K2). These quinones promote the synthesis of proteins that are involved in the coagulation of blood. These proteins include prothrombin, factor VII (proconvertin), factor IX (plasma thromboplastin), and factor X (Stuart factor). A detailed discussion of blood coagulation is found in Chapter 22. The vitamin K quinones are obtained from three major sources. Vitamin K is present in vari-... 

Mechanism of Action A blood modifier that interferes with blood coagulation by blocking conversion of prothrombin to thrombin and fibrinogen to fibrin Therapeutic Effect Prevents further extension of existing thrombi or new clot formation. Has no effect on existing clots. 

The enzymes that participate in blood clotting also are activated by partial proteolysis, which again serves to keep them in check until they are needed. The blood coagulation system involves a cascade of at least seven serine proteases, each of which activates the subsequent enzyme in the series (fig. 9.2). Because each molecule of activated enzyme can, in turn, activate many molecules of the next enzyme, initiation of the process by factors that are exposed in damaged tissue leads explosively to the conversion of prothrombin to thrombin, the final serine protease in the series. Thrombin then cuts another protein, fibrin, into peptides that stick together to form a clot. 

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. 

Blood coagulation Rabbit Oral Coagulation time, clot retraction, prothrombin time... 

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. 

In blood coagulation in the mammal, a key final reaction is Prothrombin —> Thrombin... 

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. 

Compounds with vitamin K activity (Table 6.2) are required in our diets for y-carboxyglutamate biosynthesis (Table 4.1). This amino acid is produced from certain protein glutamyl residues by carboxylation. Proteins that contain y-carboxyglutamate are blood prothrombin and coagulation factors VII, IX, and X (see Chapter 7). Other proteins of this type are osteocalcin from bone and several kidney and muscle calcium-binding proteins. 

I7(x-Methyl-17 -hydroxy-estra-4,9,l l-trien-3-one (Methyltrienolone, N-99). In the course of a steroid total synthesis [293] this compound (Methyltrienolone, N-99) was prepared it was reported [55] to possess 6000% of the androgenic (ventral prostate index), 7500% of the androgenic (seminal vesicles index), and 12,000% of the anabolic (levator ani index) activity of methyltestosterone. Later the anabolic activity was reported [74] to be 30,000% of that of methyltestosterone. As measured by multiple parameters methyltrienolone turned out to be the most hepatotoxic steroid, causing biochemical symptoms of intrahepatic cholestasis [75]. It was also reported [74] to reduce the excretion of 17-ketosteroids and 17-hydroxycorticosteroids and to cause enhancement of the blood coagulation factors V, VII, and X. It also increases the prothrombin content of the plasma [74]. 

---