In vitro factor VIII recovery during the delivery of ultrapure factor VIII concentrate by continuous infusion

Factor VIII (FVIII) replacement by continuous infusion has been advocated as a cost-effective method for maintaining stable plasma levels of FVIII in the hemophilia A patients during surgery or life-threatening hemorrhage. Continuous delivery of monoclonal or recombinant FVIII concentrates to our pediatric patients using a traditional delivery system (dilution in normal saline of 2-10 U/ml infused at a rate of 20 ml/hr) has frequently yielded higher than expected factor usage to achieve desired levels and unexpected variability in plasma levels under presumed steady-state conditions. To determine if diminished in vitro FVIII recovery was responsible for these observations, a study of four ultrapure concentrates during 8 hr of in vitro continuous delivery was performed using four delivery systems. When reconstituted concentrate was added to normal saline in polyvinylchloride bags at a concentration of 10 U/ml (method IA), monoclonal products showed a stable recovery of 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 IB) did not improve recoveries. When reconstituted concentrate was delivered undiluted (method IIA), the early drop in recombinant recovery was eliminated; stable recovery of 78-117% of time 0 level was achieved with all products. In using method IA, a large discrepancy was seen between the actual time 0 recoveries and those expected based on vial assays, most 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% of expected.