With prothrombin formation

Albumin formation is generally stated to take place solely in the liver. The available evidence, reviewed by Madden and Whipple (219), favors this view, but is not compelling, does not exclude other possibilities, and leaves unexplained a number of discrepancies which are noted in certain disease states, for example, the marked hypoalbuminemia observed in some instances of the nephrotic syndrome associated with relatively little albuminuria, and in so-called idiopathic hypoproteinemia. In both these conditions, the serum albumin may reach extremely low levels yet there is no impairment of hepatic function that can be demonstrated by available methods (which does not, to be sure, exclude the possibility of a specific hepatic defect such as occurs in connection with prothrombin formation and other hepatic functions). 

Inhibitor formation has been observed in only a few patients with factor XI deficiency. Like patients with hemophilia A and B, these patients may be treated with prothrombin complex concentrates or recombinant factor Vila (2). 

As seen in Figure 2, the ac polarogram resulting from the interaction of the monolayer with prothrombin shows that an electroactive group contributes to the capacitance curve a pseudocapacitance peak, at around - 0.7 V, which is ascribed to the oxy-reduction of the disulfide bridges at pH 7.8. Since the formation of cysteine requires hydrogen ions, the half-wave potential and thus also the pseudocapacitance peak is shifted with decreasing pH to more positive polarization. Since two contributions, one from the protein and the other from the phospholipid monolayer, are involved in the capacitance values, it was of importance to study particularly the behavior of the protein in direct contact with the electrode, in order to be able to interpret better the data obtained when prothrombin interacts with phospholipid monolayers. 

The main way of determining vitamin K status, and monitoring the efficacy of anticoagulant therapy, is by measuring the time required for the formation of a fibrin clot in citrated blood plasma after the addition of calcium ions and thromboplastin — the prothrombin time. A more sensitive index is provided by direct measurement of preprothrombin in plasma, most commonly by immunoassay using antisera against preprothrombin that do not react with prothrombin. 

Antihemophilic factor [9001-28-9] (AHF) is a protein found in normal plasma that is necessary for clot formation. It is needed for transformation of prothrombin to thrombin. Administration of AHF by injection or infusion can temporarily correct the coagulation defect present in patients with hemophilia. Antihemophilic factor VIII (Alpha Therapeutic) has been approved by the FDA as replacement therapy in patients with hemophilia B to prevent bleeding episodes, and also during surgery to correct defective hemostasis (178). 

The last of the fat-soluble vitamins to be identified was vitamin K, found by Dam to be an anti-hemorrhagic factor for young chicks, distinct from vitamin C. Its structure was determined by Dam in collaboration with Karrer. Interest in the vitamin was intensified when it was discovered (Link, 1941) that dicoumarol, present in spoiled sweet clover, was the agent producing hypothrombinemia (giving prolonged blood-clotting time) in cattle. Since vitamin K is structurally similar to dicoumarol, the vitamin was presumptively implicated in thrombin formation. This has been fully substantiated by recent work on the role of vitamin K in the synthesis of prothrombin in the liver. 

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. 

When used in therapeutic doses, dimercaprol is associated with a high incidence of adverse effects, including hypertension, tachycardia, nausea, vomiting, lacrimation, salivation, fever (particularly in children), and pain at the injection site. Its use has also been associated with thrombocytopenia and increased prothrombin time—factors that may limit intramuscular injection because of the risk of hematoma formation at the injection site. Despite its protective effects in acutely intoxicated animals, dimercaprol may redistribute arsenic and mercury to the central nervous system, and it is not advocated for treatment of chronic poisoning. Water-soluble analogs of dimercaprol—unithiol and succimer—have higher therapeutic indices and have replaced dimercaprol in many settings. 

Warfarin (Fig. 10-22c) is a synthetic compound that inhibits the formation of active prothrombin. It is particularly poisonous to rats, causing death by internal bleeding. Ironically, this potent rodenticide is also an invaluable anticoagulant drug for treating humans at risk for excessive blood clotting, such as surgical patients and those with coronary thrombosis. ... 

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