Immunoaffinity purification of factor IX from commercial concentrates and infusion studies in animals.

Abstract

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.

• Authors: K J Smith
• Journal: Blood (Blood) Vol. 72 Issue 4 Pg. 1269-77 (Oct 1988) ISSN: 0006-4971 [Print] United States
• PMID: 3262386 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Factor IX
• Serine Endopeptidases
• Factor IXa

Topics

• Animals
• Blood Coagulation Tests
• Chromatography, Affinity
• Factor IX (administration & dosage, isolation & purification, pharmacokinetics)
• Factor IXa
• Half-Life
• Hemostasis (drug effects)
• Infusions, Intravenous
• Rabbits
• Serine Endopeptidases (metabolism)
• Thrombophlebitis (etiology)