Clotting factors recombinant

Hemophiliacs are treated with clotting factors when they have severe bleeding episodes, and are also treated to prevent bleeding if surgery or any other activity that might lead to bleeding is planned. Before recombinant technology, the fluid part of normal human... 

Better methods for preparing clotting factors from blood and the development of recombinant clotting factors provided the solutions. Methods of detecting, inactivating, and removing viruses were improved, and none of the hemophilia replacement products— conventional or recombinant—has transmitted either HIV or hepatitis since 1987. As an alternative, recombinant clotting factors 8 and 9, produced in animal cells, were approved in 1992 and 1997, without the risk associated with human blood products. 

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. 

Recombinant DNA technology was applied lu the problem the first time a lew decades ago. One group has been successful in inducing the bacterium Eschetirhiu mli to manufacture and secrete rat proinsulin. an immediate precursor of rat insulin that incorporates insulin itself. Research like this is an important step toward the objective of developing bacterium-based industrial systems that can replace animal and human tissues us the source of medically useful proteins, such as insulin, growth hormone, and clotting factor... 

Morrill, P. R., Gupta, G., Sproule, K., et al. (2002) Rational combinatorial chemistry-based selection, synthesis and evaluation of an affinity adsorbent for recombinant human clotting factor VII. J. Chromatogr. B 774, 1-15. 

Pipe SW. The promise and challenges of bioengineered recombinant clotting factors. J Thromb Haemost 2005 3(8) 1692-1701. 

Walsh (2003) defined biopharmaceuticals as therapeutic protein or nucleic acid preparations made by techniques involving recombinant deoxyribonucleic acid (DNA) technology. Therapeutic proteins include blood clotting factors and plasminogen activators, hemopoietic factors, hormones, interferons and interleukins, and monoclonal antibodies (LeVine, 2006). Over time, the term biopharmaceutical has broadened, and, in addition to proteins and nucleic acids, now includes bacteriophages, viral and bacterial vaccines, vectors for gene therapy, and cells for cell therapy (Primrose and Twyman, 2004). Attention here focuses on proteins, since the majority of approved biopharmaceuticals are proteins. 

Lusher JM. Recombinant clotting factor concentrates. Baillieres Clin Haematol... 

Pipe S. The promise and challenges of bioengineered recombinant clotting factors. 

Allergenic extracts Antitoxins, antivenoms, venoms Blood, blood components, plasma-derived products (e.g., albumin, immunoglobulins, clotting factors, fibrin sealants, proteinase inhibitors), recombinant and transgenic versions of plasma derivatives... 

Factor VII is the most sensitive of the vitamin K-dependent clotting factors. The mode of action is tissue factor-dependent activation of factors Xa and IXa on the surfaces of activated platelets (1). Factor Xa leads to thrombin generation and hemostasis, by converting fibrinogen to fibrin. This process is limited to the site of injury, since exposure of tissue factor from the subendothelial matrix has a role in the action of recombinant factor Vila, thereby reducing the risk of thromboembohc events (2). 

Thrombophlebitis at the infusion site is a common complication of continuous infusion of various clotting factor concentrates and has been noted after infusion of factor Vila (9,10). Thrombophlebitis occurred in one of eight hemophiliacs with inhibitors who received continuous infusion of recombinant factor Vila to allow elective surgery (11). In 25 hemophilia patients with inhibitors, who received recombinant factor Vila for surgical procedures or spontaneous bleeding, there was one case of thrombophlebitis in 35 continuous infusion courses (12). In most instances, thrombophlebitis can be prevented by parallel infusion of saline or heparin. 

Treatment options for patients with inhibitors are high dosages of clotting factor or recombinant factor Vila for both hemophilia A and B or, in the case of hemophiha A, porcine factor VlllrC or activated prothrombin complex (37). Regular administration of intermediate or low-dose factor Vin concentrates leads to the rapid disappearance of factor VIII inhibitors in some high responders (27) this is thought to be due to the development of immune tolerance. 

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