Biochemistry of Hemophilia
Tuesday, June 5, 2012
8:43 AM
Multiple mutations such as frameshift mutations, missense mutations, nonsense mutations, gene inversions, large deletions and splicing errors have been linked to the cause of hemophilia.
Blood Clotting Cascade:
When there is tissue damage, enzymes get activated.
Those enzymes (commonly known as factors) cleave other enzymes, and those enzymes cleave other enzymes.
A cascade starts, sort of like a domino-effect and eventually they work together to make a blood clot.
However, in the case of Hemophilia, either Factor VIII or IX is missing. Think of it this way, if one domino is missing, it is harder to make the next one fall and to continue the cascade to make the best clot possible.
For hemophilia A, it is a complex of a large inert carrier protein and a noncovalently bound small fragment which contains the procoagulant active site. The factor VIII complex, with a molecular weight in excess of 1 million, has 2 components:
(1) factor VIII (molecular weight of 293,000 ) called factor VIII C, when measured by procoagulant activity and factor VIII Ag, when measured immunologically
(2) factor VIII R (the von Willebrand factor or vWF) has a molecular weight of 220,000. Polymerization leads to the high molecular weight of the factor VIII complex (Levin, 1979). Factor VIII is encoded by the factor VIII gene on Xq28.
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About Inhibitors
Treatment products called factor clotting concentrate are used for hemophiliacs which improves blood clotting and is used to stop or prevent a bleeding episode. Inhibitors develop when the body’s immune system stops accepting the factor (factor VIII for hemophilia A and factor IX for hemophilia B) as a normal part of blood. The body thinks the factor is a foreign substance and tries to destroy it using inhibitors. The inhibitors stop the factor from working. This makes it more difficult to stop a bleeding episode. People with hemophilia who develop an inhibitor do not respond as well to treatment. Inhibitors most often appear during the first year of treatment but they can appear at any time. This disallow the treatment to work thus the symptoms of hemophilia will not alleviate. This causes inconvenience and pain to the hemophiliacs.
Links:
http://themedicalbiochemistrypage.org/hemophilia-a.php
http://answers.yahoo.com/question/index?qid=20080503180614AADLHEY (response by Amian G)
http://en.wikipedia.org/wiki/Coagulation
http://www.daviddarling.info/images/blood_clot_formation.jpg
http://www.cdc.gov/ncbddd/hemophilia/inhibitors.html
http://www.google.com.sg/url?sa=t&rct=j&q=&esrc=s&frm=1&source=web&cd=6&ved=0CGQQFjAF&url=http%3A%2F%2Fvgn.uvm.edu%2Foutreach%2Fdata%2FBio-UVM-fall-2006%2FHemophilia%2520%2520A.ppt&ei=s8IGUO3xD9DirAehyvnKBg&usg=AFQjCNGGhyUjuqOpFjp2TppKwvJ2_2RHiw&sig2=Gf8-uTnvm2apBH5Z0B7PVA
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Inhibitors
Although there are many various ways to allow hemophiliacs to cope with the illness now, complications can still occur. Almost one third of hemophiliacs will develop an antibody,also known as an inhibitor, to the products that is used to treat or prevent bleeding episodes. Developing an inhibitor is one of the most serious and costly complications of hemophilia.About Inhibitors
Treatment products called factor clotting concentrate are used for hemophiliacs which improves blood clotting and is used to stop or prevent a bleeding episode. Inhibitors develop when the body’s immune system stops accepting the factor (factor VIII for hemophilia A and factor IX for hemophilia B) as a normal part of blood. The body thinks the factor is a foreign substance and tries to destroy it using inhibitors. The inhibitors stop the factor from working. This makes it more difficult to stop a bleeding episode. People with hemophilia who develop an inhibitor do not respond as well to treatment. Inhibitors most often appear during the first year of treatment but they can appear at any time. This disallow the treatment to work thus the symptoms of hemophilia will not alleviate. This causes inconvenience and pain to the hemophiliacs.
Links:
http://themedicalbiochemistrypage.org/hemophilia-a.php
http://answers.yahoo.com/question/index?qid=20080503180614AADLHEY (response by Amian G)
http://en.wikipedia.org/wiki/Coagulation
http://www.daviddarling.info/images/blood_clot_formation.jpg
http://www.cdc.gov/ncbddd/hemophilia/inhibitors.html
http://www.google.com.sg/url?sa=t&rct=j&q=&esrc=s&frm=1&source=web&cd=6&ved=0CGQQFjAF&url=http%3A%2F%2Fvgn.uvm.edu%2Foutreach%2Fdata%2FBio-UVM-fall-2006%2FHemophilia%2520%2520A.ppt&ei=s8IGUO3xD9DirAehyvnKBg&usg=AFQjCNGGhyUjuqOpFjp2TppKwvJ2_2RHiw&sig2=Gf8-uTnvm2apBH5Z0B7PVA
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