Five purified concentrates--Nanotiv (Kabi Pharmacia), Immunine (Immuno),
Factor IX VHP (Biotransfusion), Alphanine (Alpha Therapeutic Corporation), and
Mononine (Armour
Pharmaceutical Company)--were characterized biochemically and their in vivo pharmacokinetic and thrombogenic properties evaluated. The results were compared with those for two
prothrombin complex concentrates (PCCs):
Preconativ (Kabi Pharmacia) and Prothromplex TIM4 (Immuno). The measured values for
factor IX coagulant activity (FIX:C) generally agreed with the manufacturers' labeled values. The purified concentrates were virtually devoid of other
vitamin K-dependent
coagulation factors, the inhibitor
proteins C and S, and either
fibrinogen,
fibronectin, or
immunoglobulins. Indicators of
thrombin generation (i.e.,
prothrombin fragments F1 + 2 and
thrombin-antithrombin complex) were present in varying amounts in all preparations. The level of specific activity in the purified concentrates exceeded that in the PCCs by
a factor of 50- to 100-fold. Pharmacokinetic variables were studied in severe
hemophilia B patients: Nanotiv was compared with
Preconativ; Immunine was compared with Prothromplex TIM4 in crossover studies; and
Mononine was tested in a single-
drug study. No differences were apparent between Nanotiv,
Preconativ, and
Mononine, but recovery rates were lower, clearance rates higher, and FIX:C half-life shorter for Immunine and Prothromplex TIM4, although the disparate results might have been attributable to methodologic differences. Purified
factor IX concentrates were used successfully as cover for surgery and in immune tolerance induction without observable adverse effects.