Blood factor VIII recombinant

Antihemophilic factor USP [USP] Blood-coagulation factor VIII, complex [CAS] Factor VIII, recombinant [SY]... 

Blood factor VIII (FVIII) is a glycoprotein with 2351 amino acids and 330 kDa. Its deficiency causes hemophilia A. The first products based on recombinant factor VIII to reach the market were Recombinate and Kogenate, expressed in CHO and BHK cells, respectively. Over the last decade, other rFVIII products were approved, with modifications to the molecule (e.g. deletion of the B-domain), in the formulation or in the production processes. 

Bray GL, Gomperts ED, Courier S, Gmppo R, Gorden EM, Manco-Johnson M, Shapiro A, Scheibel E, White G, 3rd, Lee M. A multicenter study of recombinant factor VIII (Recombinate) safety, efficacy and inhibitor risk in previously untreated patients with hemophiha A. The Recombinate Study Group. Blood 1994 83(9) 2428-35. 

Recombinant Antihemophilic Factor VIII 424 Recombinant blood factor 9 Recombinant factor VIII (rFVII) 420,459 Recombinant HB 1422 Recombinant hematopoietic growth factor 15 Recombinant hepatitis B surface antigen (rHBsAg) 3... 

Persons expressing 5 per cent or above of the normal complex levels experience less severe clinical symptoms. Treatment normally entails administration of factor VIII complex purified from donated blood. More recently, recombinant forms of the product have also become available. Therapeutic regimens can require product administration on a weekly basis, for life. About 1 in 10 000 males are born with a defect in the factor VIII complex and there are approximately 25 000 haemophiliacs currently resident in the USA. 

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 ... 

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). 

Along with the production of insulin, many other medical uses have been achieved for recombinant DNA. This includes the production of erythropoetin, a hormone used to stimulate production of red blood cells in anemic people tissue plasminogen activator, an enzyme that dissolves blood clots in heart attack victims and antihemophilic human factor VIII, used to prevent and control bleeding for hemophiliacs. These three important genetically engineered proteins were all cloned in hamster cell cultures. 

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. 

Cryoprecipitate may also be used for patients with factor VIII deficiency and von Willebrand disease if desmopressin is not indicated and a pathogen-inactivated, recombinant, or plasma-derived product is not available. The concentration of factor VIII and von Willebrand factor in cryoprecipitate is not as great as that found in the concentrated plasma fractions. Moreover, cryoprecipitate is not treated in any manner to decrease the risk of viral exposure. For infusion, the frozen cryoprecipitate unit is thawed and dissolved in a small volume of sterile citrate-saline solution and pooled with other units. Rh-negative women with potential for childbearing should receive only Rh-negative cryoprecipitate because of possible contamination of the product with Rh-positive blood cells. 

Factor VIII promotes clotting it is deficient in hemophiliacs treatment with factor VIII produced by recombinant DNA technology eliminates infection risks associated with blood transfusions. 

Giles AR,Tinlin S, Hoogendoorn H, Fournel MA, Ng P, Pancham N. In vivo characterization of recombinant factor VIII in a canine model of hemophilia a (factor VIII deficiency). Blood 1988 72 335-9. 

Genetically, determined clotting diseases include classical haemophilia, which is due to lack of factor VIII, and there is another form of haemophilia due to deficiency of factor IX (Christmas factor). These are treated by giving fresh donor blood or plasma, preparations of factor VIII or factor IX, or increasingly as one of the recombinant versions which are becoming available. 

Azzi A, De Santis R, Morfini M, Zakrzewska K, Musso R, Santagostino E, et al. TT virus contaminates first-generation recombinant factor VIII concentrates. Blood 2001 98 2571-73. 

Studies of pharmacokinetic parameters of recombinant factor VIII infused into baboons revealed that its half-life in blood circulation is similar to that of plasma-derived factor VIII, suggesting that the oligosaccharide structural differences between them do not affect the fate of factor VIII in vivo [43]. 

Biopharmaceuticals include recombinant cytokines (interferons, IL-2, GM-CSF), blocking antibodies (such as the anti-TNF-a drug infliximab), and vaccines, as well as products not directly related to the immune system, such as blood clotting factors and hormones (Factor VIII, erythropoietin, heparin), enzymes, and hormones (Crommelin et al., 2003). 

Recombinant DNA techniques have enabled the cloning of Factor VIII, which is missing from most patients with the inherited bleeding disorder hemophilia. Factor VIII is essential for proper blood clotting, and untreated hemophilia patients suffer from severe uncontrolled bleeding. Recombinant Factor VIII is used to restore clotting activity to the blood of hemophiliacs. 

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