Coagulation Factor IX concentrate: method of preparation and assessment of
potential in vivo thrombogenicity in animal models
D Menache, HE Behre, CL Orthner, H Nunez, HD Anderson, DC Triantaphyllopoulos and DP Kosow
Thrombosis and/or disseminated intravascular coagulation (DIC) are
complications specifically associated with the use of factor IX complex in
some patients. Assuming that these complications might result from zymogen
overload, we have produced, using diethylaminoethyl (DEAE)- Sephadex
(Pharmacia, Piscataway, NJ) and sulfated dextran chromatography, a factor
IX concentrate (coagulation factor IX) that is essentially free of
prothrombin, factor VII, and factor X. Factor IX specific activity is at
least 5 U/mg protein, a 250-fold purification compared to plasma. Amounts
of factors II, VII, and X are less than 5 units each per 100 units of
factor IX. The concentrate is essentially free of activated clotting
factors and contains no added heparin. In the rabbit stasis model, a dose
of 200 factor IX U/kg was less thrombogenic than 100 factor IX U/kg of the
DEAE-Sephadex eluate from which the concentrate was derived. Infusion of
200 factor IX U/kg did not induce DIC in the nonstasis rabbit model,
whereas 100 factor IX U/kg of the DEAE-Sephadex eluate resulted in DIC in
this model. Several factor IX lots were found to have shortened
nonactivated partial thromboplastin times (PTTs), but were nonthrombogenic
in both animal models. These data indicate that coagulation factor IX
concentrate is less thrombogenic than factor IX complex.
Volume 64,
Issue 6,
pp. 1220-1227,
12/01/1984
Copyright © 1984 by The American Society of Hematology
