Factor IX, recombinant

Blood coagulation factors antihemophilic factor (recombinant) eptacog alfa (activated) factor IX contentrate (human) factor IX (recombinant) moroctocog alfa... 

Dosage form BeneFix is formulated as a sterile nonpyrogenic, lyophilized preparation, intended for injection after reconstitution with sterile water for injection. It is available in single-use vials containing the labeled amount of factor IX activity, expressed in international units (lU). Each vial contains nominally 250,500, or 1000 lU of Coagulation Factor IX (Recombinant). 

Clinical pharmacology Activated factor IX in combination with activated factor VIII activates factor X. This results ultimately in the conversion of prothrombin to thrombin. Thrombin then converts fibrinogen to fibrin, and a clot can be formed. Factor IX is the specific clotting factor deficient in patients with hemophilia B and in patients with acquired factor IX deficiencies. The administration of Coagulation Factor IX (Recombinant) increases plasma levels of factor IX and can temporarily correct the coagulation defect in these patients. 

Coagulation Factor IX (recombinant) is a glycoprotein with an approximate molecular mass of 55,000 Da consisting of 415 amino acids in a single chain. 

Factor IX Replacement Hemophilia B therapy may include recombinant (produced via transfection of mammalian cells with the human factor IX gene) or plasma-derived (concentrate from pooled plasma) factor IX (see Table 64-2). Guidelines for choosing the factor-concentrate formulation for hemophilia B are similar to the guidelines for hemophilia A. However, older-generation factor IX concentrates containing other vitamin K-dependent proteins (e.g., factors II, VII, and IX), called prothrombin complex concentrates (PCCs), have been associated with thrombogenic side effects. Consequently, these products are not first-line treatment for hemophilia B.11... 

Because it is a small protein, the factor IX molecule passes into the intravascular and the extravascular spaces. Therefore, the volume of distribution of recombinant factor IX is twice that of factor VIII. Consequently, 1 unit of factor IX administered per kilogram of body weight yields a 1% rise in the plasma factor IX level (0.01 unit/mL, or 1 IU/dL). Thus 1750 units of factor IX provides an incremental increase of 50% of normal (0.5 unit/mL, or 50 IU/dL), that is, 1750 units/70 kg x 0.01 unit/mL (1 IU/dL).12 Additionally, the recovery rate with recombinant factor IX is 20% lower than that with the plasma-derived products. Therefore, initial and subsequent maintenance doses should be adjusted accordingly. 

Factor IX = (desired concentration - current level) X wt (kg) -multiply this value by 1.2 when using recombinant factor IX... 

Mononine—average of 250, 500, or 1000 factor IX units/vial Recombinant... 

Individuals who display a deficiency of factor IX develop haemophilia B, also known as Christmas disease. Although its clinical consequences are very similar to that of a deficiency of factor VIII, its general incidence in the population is far lower. Persons suffering from haemophilia B are treated by i.v. administration of a concentrate of factor IX. This was traditionally obtained by fractionation of human blood. Recombinant factor IX is now also produced in genetically engineered CHO cells (Table 12.2 and Box 12.1). 

Factor IX may also be purified by immuno-alfinity chromatography, using immobilized anti-IX murine monoclonals. Purification to homogeneity is particularly important in the case of recombinant products. At least one monoclonal antibody has been raised that specifically binds only to factor IX, which contains pre-bound Ca + (i.e. the Ca +-dependent conformation of factor IX). Immobilization of this antibody allowed the development of an immuno-alfinity system in which factor IX binds to the column in the presence of a Ca -containing bufier. Subsequent elution is promoted simply by inclusion of a chelating agent (e.g. EDTA) in the elution buffer. 

Clinical trials have demonstrated excellent efficacy with recombinant human factor VIII concentrates available as Recombinate and Kogenate. These recombinant factor VIII products are purified from the cell culture of plasmids, not viral DNA-transfected hamster cells and therefore do not express viral sequences. The addition of human serum albumin for stabilization, constitutes the sole possible source for human viral contamination. More recently recombinant factor IX has been genetically engineered by insertion of the human factor IX gene into a Chinese hamster ovary cell line. It has been proved to be safe and effective in the treatment of patients with hemophilia B. 

F. Place in therapy Micromedex notes that the major use of factor IX is in the therapy of hemophilia B, but it may also be useful in patients with clotting disorders secondary to hepatic dysfunction and other conditions. Recombinant factor IX BeneFix), however, is used specifically for the prevention and control of bleeding in patients with hemophilia B. 

Coagulation factor IX (human recombinant), produced in CHO cells... 

IX Hemophilia Christmas disease 30-50% 100% for major bleeding or trauma 24 hours Recombinant factor IX products Plasma-derived high purity concentrates... 

BeneFIX (Nonacog alfa) Wyeth [CHO-expressed glycoprotein-recombinant human coagulation factor IX]... 

J. F. Zhou, E.F. Vanin, and A.W. Nienhuis. 2001. Factors influencing in vivo transduction by recombinant adeno-associated viral vectors expressing the human factor IX cDNA. Blood 97 1258-1265. 

Herzog, R. W., Hagstrom, J. N., Rung, S. H., Tai, S. J., Wilson, J. M., Fisher, K. J. and High, K. A. (1997). Stable gene transfer and expression of human blood coagulation factor IX after intramuscular injection of recombinant adeno-associated virus. Proc. Natl. Acad. Sci. USA 94, 5804-5809. 

White GC, Beebe A, Nielsen B, Recombinant factor IX, Thromb Haemost 1997 77 261-265. 

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