Hemophilia (Royal Disease). KJFKLSDJKL. Royal Family Pedigree. Review 1. All coagulation pathways lead to activation of prothrombin and formation of fibrin clot! The activity = enzyme action Enzyme action depends on amount of protein present and the structure of protein.
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Royal Family Pedigree
Graphic accessed http://www.ganfyd.org/images/3/32/CoagulationAndFibrolyticPathways.png, 2009.
Information and graphic accessed http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=glossary&rendertype=box&id=further_illus-226, 2009.
Graphic accessed URL http://www.daviddarling.info/images/hemophilia_inheritance_1.gif, 2008.
A & B
genes for both FVIII and FIX are located on the long arm of chromosome X
The gene for FVIII (F8C) is unusually large
FVIII contains 2332 amino acids
Approximately 40% of cases of severe FVIII deficiency arise from a large inversion that disrupts the FVIII gene. Deletions, insertions, and point mutations account for the remaining 50-60% of hemophilia A defects
The FIX gene (F9) is small
FIX contains 415 amino acids
Point mutations and deletions in the FIX gene are the most common causes of hemophilia B
gene for factor XI is on the distal arm of chromosome 4
Mutations described so far are associated with mainly failed or reduced production of the active protein, and only a few are related to the production of a dysfunctional molecule.
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Graphic accessed http://kuwaitmd.hsc.edu.kw/main/files/images/Coagulation_cascade.png, 2009.
Graphic accessed URL http://library.thinkquest.org/05aug/00112/Images/knee.jpg, 2008.
Graphic accessed URL http://labtestsonline.org/understanding/analytes/coag_cascade/Coag%20Testing%20Cascade.pdf, 2008.
Factor VIII concentrate
DDAVP – increase vWF
Aminocaproic acid – anti-fibrinolytic
FVIII 1 U/kg increases FVIII plasma levels by 2%. The reaction half-time is 8-12 hours.
Treatment regimen examples
Factor concentrate until 50% level achieved
Also consider aminocaproic acid 1-2 days
Factor VII concentrate until 80% level achieved
Graphic accessed URL http://coursewareobjects.elsevier.com/objects/elr/Rodak3e/IC/jpg/Chapter41/041005.jpg, 2008.
PLT count – NL
PT - NL
PTT - prolonged
Factor XI - severe disease less than 1%; moderate disease 1-5%; mild disease greater than 5%.
Recombinant factor IX - level should be corrected to 100% of normal for potentially serious hemorrhage
Goal to keep trough level > 50% activity
Coagulation factor IX concentrates - used to correct the patient's native deficiency
Goals: 1) achieve a normal hematologic response to hemorrhage; 2) prevent hemorrhage
Factor IX complex concentrates (II, X, VII)
Circumvent inhibitor issue
Coagulation Factor VIIa (Recombinant) - activate coagulation factor X to factor Xa as well as coagulation factor IX to IXa
Epsilon aminocaproic acid (Amicar)
Matthew Prasad, MB, BS, DCH - Director, Hemostasis and Hematology Program, Professor of Pediatrics, University of New Mexico.