Toxicity of factor IX concentrates in mice.
Mice to which Factor IX concentrates are administered intraperitoneally at high doses (approximately 1000 u/kg) die between 4 and 18 hours thereafter. Histologic examination reveals hemorrhage in the lung and liver. Death is prevented by reduction of the concentrate with dithiothreitol but not by treatment of the preparation with enzyme inhibitors (diisopropyperosphorofluoridate, soybean trypsin inhibitor, heparin). Prothrombin, devoid of Factors VII, IX and X, also is lethal to mice. Activation of the Factor IX concentrate by insolubilized Russel's Viper Venom (NAPTT 1/5000 less than 20'') resulted in decreased mortality when compared to controls (4/30 vs. 11/20). These experiments indicate that some of the adverse effects of Factor IX concentrates may result from high levels of zymogens rather than the presence of small amounts of active enzymes. Intensive animal testing might be indicated for routine quality control of Factor IX concentrates.
D000818:Animals; D005164:Factor IX / Q000032:analysis / Q000633:toxicity*; D005167:Factor VII / Q000032:analysis; D005170:Factor X / Q000032:analysis; D006470:Hemorrhage; D006801:Humans; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D051379:Mice; D011516:Prothrombin / Q000032:analysis
D005167:Factor VII; D011516:Prothrombin; D005164:Factor IX; D005170:Factor X