IN-VITRO FACTOR-VIII RECOVERY DURING THE DELIVERY OF ULTRA-PURE FACTOR-VIII CONCENTRATE BY CONTINUOUS-INFUSION

Factor VIII (FVIII) replacement by continuous infusion has been advoca ted as a cost-effective method for maintaining stable plasma levels of FVIII in the hemophilia A patient during surgery or life-threatening hemorrhage. Continuous delivery of monoclonal or recombinant FVIII con centrates to our pediatric patients using a traditional delivery syste m (dilution in normal saline of 2-10 U/ml infused at a rate of 20 ml/h r) has frequently yielded higher than expected factor usage to achieve desired levels and unexpected variability in plasma levels under pres umed steady-state conditions. To determine if diminished in vitro FVII I recovery was responsible for these observations, a study of four ult rapure concentrates during 8 hr of in vitro continuous delivery was pe rformed using four delivery systems, When reconstituted concentrate wa s added to normal saline in polyvinylchloride bags at a concentration of 10 U/ml (method IA), monoclonal products showed a stable recovery o f 84-109% of time 0 levels, Recombinant product recovery dropped to 57 -76% of time 0 levels before reapproximating the time 0 level at 2 hr. The addition of 10 mg/ml human albumin to the bags (method is) did no t improve recoveries. When reconstituted concentrate was delivered und iluted (method IIA), the early drop in recombinant recovery was elimin ated; stable recovery of 78-117% of time 0 level was achieved with all products. In using method IA, a large discrepancy was seen between th e actual time 0 recoveries and those expected based on vial assays, mo st striking for recombinant products (49-57% of expected). Method IIA allowed 75-90% recovery; addition of 20 mg/ml albumin of reconstituted but undiluted concentrate (method IIB) maximized recovery at 85-98% o f expected. (C) 1996 Wiley-Liss, Inc.