Recombinant Factor

Hunseler C, Kribs A, Eifmger F et al (2006) Recombinant factor seven in acute life-threatening bleeding in neonates report of three cases and review of the literature. JPerinatol 26 706-713... 

Recombinant factor Vila may be considered as an alternative to prothrombin complex concentrate... 

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

Intracerebral Hemorrhage Trial compared three different doses and placebo. Doses were 40,80, or 160 mcg/kg or placebo given as an IV infusion over 1 to 2 minutes within 4 hours after the onset of symptoms. Hematoma growth was decreased at 24 hours, mortality was decreased at 90 days, and overall functioning was increased at 90 days. Further studies are ongoing to evaluate the role of recombinant factor Vila in ICH treatment.41... 

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... 

Production of recombinant factor VIII (Table 12.2) has ended dependence on blood as the only source of this product, and eliminated the possibility of transmitting blood-borne diseases specifically derived from infected blood. In the past, over 60 per cent of haemophiliacs were likely to be accidentally infected via contaminated products at some stage of their life. 

Several companies have expressed the cDNA coding for human factor VIII C in a variety of eukaryotic production systems (human VIII C contains 25 potential glycosylation sites). CHO cells and BHK cell lines have been most commonly used, in addition to other cell lines, such as various mouse carcinoma cell lines. The recombinant factor VIII product generally contains only VIII C (i.e. is devoid of vWF). However, both clinical and preclinical studies have shown that administration of this product to patients suffering from haemophilia A is equally as effective as administering blood-derived factor VIII complex. The recombinant VIII C product appears to bind plasma... 

Owing to the frequency of product administration, the purification procedure for recombinant factor VIII C must be particularly stringent. Unlike the situation pertaining when the product is purified from human blood, any contaminant present in the final product will be non-human and, hence, immunogenic. Sources of such contaminants would include ... 

Recombinant factor VIII is gaining an increasing market share of the factor VIII market. Researchers are also attempting to develop modified forms of VIII C (by site-directed mutagenesis) that display additional desirable characteristics. Particularly attractive in this regard would be the development of a product exhibiting an extended circulatory half-life. This could reduce... 

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). 

Klausen, N. K., and Kornfelt, T. (1995). Analysis of the glycoforms of human recombinant factor Vila by capillary electrophoresis and high-performance liquid chromatography.. Chromatogr. A 718, 195-202. 

Natural source may carry risk of infection. Recombinant Factor VIII used to treat hemophilia A has helped reduce the incidence of HIV infection in hemophiliacs. Recombinant HbsAg is now used to immunize against hepatitis B, eliminating the risk of introducing a viral infection during vaccination. 

Van Komen, S., Petukhova, G., Sigurdsson, S., Stratton, S., and Sung, P. (2000) Superhelicity-driven homologous DNA pairing by yeast recombination factors Rad51 and Rad54. Mol. Cell 6, 563-572. 

Palsson, E., Smeds, A.L., Petersson, A., and Larsson, P.-O., Faster isolation of recombinant factor VIII SQ, with a superporous agarose matrix, J. Chromatogr. A, 840, 39-50, 1999. 

Monroe, D. M., Hoffman, M., Allen, G. A., and Roberts, H. R., The factor Vll latelet interplay Effectiveness of recombinant factor Vila in the treatment of bleeding in severe thrombocytopathia. 

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. 

E Role in therapy Antihemophilic factor is indicated for the treatment of bleeding episodes or perioperative treatment in patients with hemophilia A. Prophylactic use has also been advocated for the prevention and/or reduction of bleeding episodes. The largest issue in treatment with antihemophilic factor is the choice of formulations because of the relative risk of viral transmission. Recombinant factor VIII has the lowest risk of transmission of blood-borne viruses, but its use may be limited due to cost and availability. 

Antihemophilic factor, human recombinant factor VIII produced in BHK cells... 

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