Factor VII

Extrinsic Pathway. Coagulation is initiated when tissue extracts with Hpid—protein properties are released from the membranes of endothehal cells following injury or insult. These substances, collectively designated tissue thromboplastin, complex with circulating Factor VII and in the presence of calcium ions subsequentiy activate Factor X (Fig. 1). In vitro evidence suggests that Factor X can be activated less rapidly through the interaction of kaUikrein [9001-01-8] with Factor VII. 

Factor VII. This is a vitamin K-dependent serine protease that functions in the extrinsic coagulation pathway and catalyzes the activation of Factors IX and X. Factor VII is present constitutively in the surface membrane of pericytes and fibroblasts in the adventitia of blood vessels, vascular endothehum, and monocytes. It is a single-chain glycoprotein of approximately 50,000 daltons. 

Deficiency of Factor VII is relatively rare and inherited as an autosomal recessive disorder. Deficiency of Factor VII has been reported to be associated with bond abnormal bleeding and thrombotic tendencies. Deep vein thrombosis and pulmonary emboli have been reported in affected individuals. There is a very high frequency of Factor VII deficiency in people with the Dubin-Johnson syndrome, which is a congenital disorder of Hver function. 

Factor IX. This factor is dependent on the presence of vitamin K for its activity as a biologicaUy functional procoagulant glycoprotein. Factor IX is converted to its active form by XIa in the classic scheme of the intrinsic pathway. However, it can also be activated via interaction with Factor Xa or the complex Factor III plus Factor VII in the presence of calcium. 

Table 4 contains products available for Factor VII, Factor VIIFC (hemophilia A), Factor IX, and von Willebrand protein deficiency. Table 5 fists miscellaneous hemostatics and thein proposed mechanisms of action. 

Prothrombin and several other proteins of the blood clotting system (Factors VII, IX and X, and proteins C and S) each contain between four and six y-carboxygluta-mate residues which chelate calcium ions and so permit the binding of the blood clotting proteins to membranes. In vitamin K deficiency or in the presence of warfarin, an abnormal precursor of prothrombin (preprothrombin) containing little or no y-carboxyglutamate, and incapable of chelating calcium, is released into the circulation. 

Strancar, A., Barut, M., Podgomik, A., Koselj, P, Schwinn, H., Raspor, P, and Josic, D., Application of compact porous tubes from preparative isolation of clotting factor VII from human plasma, /. Chromatogr. A, 760, 117, 1997. 

Weak anticoagulant when excessively dosed (decreases factor VII levels). May have an antiplatelet effect... 

Recombinant factor Vila has been shown to have a benefit in the treatment of ICH. The Recombinant Activated Factor VII... 

Research also continues into the use of recombinant activated factor VII (rFVIIa) as an adjunctive agent to treat uncontrolled hemorrhage. Initial experiences with rFVIIa show that it can decrease transfusions, though large studies have not been performed.41 Ultimately, pharmacoeconomic... 

Hematologic von Willebrand disease Idiopathic thrombocytopenic purpura Factor VII defect causing impaired platelet adhesion and increased bleeding time Decrease in circulating platelets—can be acute or chronic... 

Ensure that the factor VII level is greater than or equal to 50% for 1 week prior to major surgery, 1 to 3 days prior to minor surgery, and just prior to a dental extraction. 

VII Mucosal tract, joint and normal aPTT Prolonged PT Specific factor VII assay... 

Clotting factor Plasma proteins found in the blood that are essential to the formation of blood clots clotting factors circulate in inactive forms, but are activated by their predecessor in the clotting cascade or a thrombogenic substance. Each clotting factor is designated by a Roman numeral (e.g., factor VII) and by the letter a when activated (e.g., factor Vila). 

The activity of factor Vila is enhanced astronomically (10 millionfold) upon binding to tissue factor. The VII or VHa-tissue factor complex activates factors IX and X and autoactivates factor VII. Although the activity of the tissue factor-factor VII complex is expressed without the presence of the negatively charged phosphatidylserine, the activity can be enhanced by its presence (9). 

A specific immunoassay for measuring two-chain factor VIIa levels in plasma has been developed to identify activation of factor VII in patients with acute coronary syndromes suchs as myocardial infarction and unstable angina (12). Because regulation of factor VIIa is believed to be mediated by tissue factor pathway inhibitor (TFPI), its measurement is also useful in assessing thombotic and cardio-vasular disorders. Because TFPI is released by heparin, its measurement is also useful in assessing the efficacy of heparin and endothelial cell function (93). 

The storage temperature of a specimen influences the results of coagulation tests. Generally, when plasma is stored in contact with cells and maintained at4°C for up to 7 hours, the PT is not artifactually shortened (103). However, beyond 7 hours factor VII is activated, thereby shortening the PT (104). At room temperature (25°C), provided the specimen container is well stoppered, the PT has been shown to be stable for up to 48 hours (104). Even freezing plasma at — 20°C and at - 70°C did not activate factor VII. Both PT and APTT results were shown to be stable in plasma frozen at —20°C for 10 days and at -70°C for 21 days (104). 

The extrinsic mechanism of blood coagulation begins when a blood vessel is ruptured and the surrounding tissues are damaged. The traumatized tissue releases a complex of substances referred to as tissue thromboplastin. The tissue thromboplastin further complexes with factor VII and Ca++ ions to activate factor X directly. 

Proplex T (Factor IX Complex)—used for factor VIII inhibitors, and factor VII or IX deficiency... 

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