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In vitro factor VIII recovery during the delivery of ultra‐pure factor VIII concentrate by continuous infusion
Author(s) -
DiMichele Donna M.,
Lasak Martin E.,
Miller Connie H.
Publication year - 1996
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/(sici)1096-8652(199602)51:2<99::aid-ajh1>3.0.co;2-1
Subject(s) - vial , recombinant dna , saline , medicine , in vitro , continuous infusion , delivery system , chromatography , chemistry , pharmacology , anesthesia , biochemistry , gene
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 patient 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. © 1996 Wiley‐Liss, Inc.