Factor IX replacement

Factor IX Replacement Hemophilia B therapy may include recombinant (produced via transfection of mammalian cells with the human factor IX gene) or plasma-derived (concentrate from pooled plasma) factor IX (see Table 64-2). Guidelines for choosing the factor-concentrate formulation for hemophilia B are similar to the guidelines for hemophilia A. However, older-generation factor IX concentrates containing other vitamin K-dependent proteins (e.g., factors II, VII, and IX), called prothrombin complex concentrates (PCCs), have been associated with thrombogenic side effects. Consequently, these products are not first-line treatment for hemophilia B.11... 

Factor IX replacement dose = desired increase X wt (kg) -Factor VII replacement dose = desired increase in factor VII level Xwt (kg) X 0.5 High purity (> 160 factor IX units/mg protein)... 

An uncomplicated hemorrhage into a joint should be treated with sufficient factor VIII or factor IX replacement to maintain a level of at least 30-50% of the normal concentration for 24 hours. Soft... 

Brinkhouse KM, Sigman JL, Read MS, Stewart PE, McCarthy KP, Timony GA et al. Recombinant human Factor IX Replacement therapy, prophylaxis, and pharmacokinetics in canine hemophilia B. Blood 1996 88 2603-10. 

Thorland EC, Drost JB, Lusher JM, Warrier I, Shapiro A, Koerper MA, Dimichele D, Westman J, Key NS, Sommer SS. Anaphylactic response to factor IX replacement therapy in haemophilia B patients complete gene deletions confer the highest risk. Haemophiha 1999 5(2) 101-5. 

TABLE 64-3. Guidelines for Replacement Dosing with Factor VIII and Factor IX... 

Management is the same as that outlined above but replacement is with fresh frozen plasma or freeze-dried factor IX concentrate. A wide range of commercial equivalents can be used but are costly. 

Lowe G, Upton M, Rumley A, et al. Different effects of oral and trans-dermal hormone replacement regimens on factor IX, APC-resistance, t-PA, PAI and C-reactive protein A cross-sectional population survey. Thromb Haemost 2001 86 550-556. 

Because the half-life of factor IX is approximately 24 hours, dosing can be less frequentthan with factor VIII. Table 100-5 provides general guidelines for dosing factor IX, based on the site and severity of the bleeding episode. As with factor VIII replacement therapy, individual pharmacokinetics may vary, and monitoring the patient s factor IX levels helps optimize therapy. 

In many cases the most important aspect of structural studies is that knowledge of the structure of a protein leads to improved understanding of its function. For instance, if a protein has to be administered for lifetime or longterm replacement therapy (e.g., insulin, growth hormone, factor IX), it is important to know all about its structure-function-stability relationships. A longer turnover time or a higher specific activity, for example, allows for a smaller dose to be administered, which has medicinal and financial benefits. 

Factor VIII and IX inhibitors are antibodies that develop in 20% and 12% of hemophilia A and hemophilia B patients, respectively, in response to replacement therapy. These antibodies bind to and neutralize the activity of infused factor concentrates. Although the inhibitors do not increase hemorrhage frequency, their existence challenges the treatment of bleeding episodes. Titers of inhibitors are measured and... 

Fresh frozen plasma contains the components of the coagulation system and is indicated for the replacement of deficient coagulation factors II, V, VII, X, XI, and XIII. Factor VIII and IX deficiencies are treated with specific factor concentrates. Fresh frozen plasma is also used for the rapid reversal of warfarin anticoagulation and in the treatment of disseminated intravascular coagulation. Thrombotic thrombocytopenic purpura is treated by means of therapeutic plasma exchange with fresh frozen plasma as the replacement fluid. Cryo-precipitate, which contains factor VIII, von Willebrand s factor, and fibrinogen, is indicated for the treatment of von Willebrand s disease that does not respond to desmopressin acetate, and for fibrinogen replacement (see Chap. 100). 

---