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KJ Smith
Department of Pathology, University of New Mexico School of Medicine,
Albuquerque 87131.
Thrombosis and transmission of viral diseases are the principal adverse
effects of current replacement therapy for factor IX deficiency when using
heat-treated concentrates of vitamin K-dependent coagulation factors. More
highly purified factor IX preparations could decrease the risk of disease
transmission, reduce patient exposure to allogeneic proteins, and reduce
the risk of thrombosis. In this study, two immunoaffinity-purified factor
IX preparations from commercial vitamin K-dependent coagulation factor
concentrates had specific activities of 134 and 155 U/mg. Crude
concentrates and purified factor IX preparations were tested for
thrombogenicity in rabbits. One of two crude concentrates tested in the
stasis-thrombosis assay caused large thrombi at doses of 50 U/kg. Purified
factor IX from this concentrate was not thrombogenic at 106 to 234 U/kg. A
heparin-treated concentrate that was not active in the stasis model at 100
U/kg caused significant (P less than .05) delayed consumption of rabbit
fibrinogen, platelets, antithrombin III antigen, and factor VIII activity
at the same dose. Factor IX prepared from this concentrate caused no
consumption of coagulation factors at 214 to 243 U/kg despite the presence
of trace amounts of activated factor IX. These results indicate that more
highly purified preparations could reduce the risk of thrombosis in
replacement therapy for hemophilia B. Also, at least for the preparations
tested, factor IX and factor IXa were not the thrombogenic components of
the crude concentrates.
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