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Coag2

Overview of the complex coagulation process Image:http://flipper.diff.org/app../pathways/4972

BackgroundEdit

Hemostasis is how the body strives to maintain a constant equilibrium between thrombosis and hemorrhage to maintain vascular integrity in the blood vessel (4).  The process of coagulation (clot formation) occurs when there is damage to the blood vessel components.  This system is extremely complex and involves a multitude of coagulation proteins, platelets, activation factors, cofactors, and inhibitor proteins and ions to form the final clot. In a basic sense this system can be described as a cascade that involves activation of enzymes by previous enzymes and precursors in the biochemical pathway to reach the end result of clot formation.

Factor VIII BackgroundEdit

Factor VIII (8) is
A6170061-Factor VIII protein molecule-SPL

Factor VIII protein model Image source: http://www.sciencephoto.com/media/7149/view

an essential component to the coagulation process in humans. In the cascade it forms a complex with Factor IX and then acts as an activator for Factor X which leads to platelet aggregation associated with blood clot formation.

The F8 gene encodes this protein and is located on the X chromosome. Defects in this gene result in a deficiency or lack of Factor VIII and is known as the X-linked recessive blood coagulation disorder called Hemophilia A. Symptoms associated with this disorder are mainly centered around the inability to form clots, which results in excessive bleeding and bleeding into joints which causes swelling and pain (2).

Factor VIII RecombinantEdit

Factor VIII was first successfully  cloned in 1984 and was available on the pharmaceutical market by 1992 for treating Hemophilia A. It was considered a huge breakthrough since it was a safer alternative to human plasma derived Factor VIII, which involved combining thousands of plasma donors as the source and therefore increased the risk of blood diseases such as hepatitis and HIV (3). There are multiple Factor VIII drugs currently being used today such as Kogenate, Helixate FS, and Recombinate.

The protein is normally expressed in mammalian cell cultures such as Chinese hamster ovarian cells. In most of the available drugs the B domain of this protein is knocked out since it appears to have no effect on the protein's function in order to reduce cloning size of the cDNA from 8967 to 6288 base pairs (5). The purification process includes usages of a detergent along multiple forms of chromatology such as ion exchange chromatology and monoclonal antibody immunoaffinity chromatography.

ReferencesEdit

1. Gerbi, Alice. "Deficiency Of Factor V And Factor VIIICoagulation." Deficiency Of Factor V And Factor VIII RSS. N.p., 26 Nov. 2012.

2. Gernsten, Todd. "Hemophilia A: MedlinePlus Medical Encyclopedia." U.S National Library of Medicine. National Institutes of Health, 8 Sept. 2014.

3. "American Society of Hematology." Hemophilia: From Plasma to Recombinant Factors. American Society of Hematology, Dec. 2008.

4. Dr. Beth Bouchard, Biochemisty of Human Diseases Notes, Dept. of Biochemistry. Spring 2014

5.http://www.kiok.com/penn/biotechnology/che554-project.pdf