DiMichele D M, Lasak M E, Miller C H
Children's Memorial Hospital, Northwestern University Medical School, Chicago, USA.
Am J Hematol. 1996 Feb;51(2):99-103. doi: 10.1002/(SICI)1096-8652(199602)51:2<99::AID-AJH1>3.0.CO;2-1.
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.
连续输注凝血因子VIII（FVIII）已被提倡作为一种具有成本效益的方法，用于在手术或危及生命的出血期间维持血友病A患者FVIII的稳定血浆水平。使用传统输送系统（在生理盐水中稀释至2 - 10 U/ml，以20 ml/hr的速率输注）向我们的儿科患者连续输送单克隆或重组FVIII浓缩物，常常会出现为达到期望水平而使用的因子高于预期，以及在假定的稳态条件下血浆水平出现意外波动的情况。为了确定体外FVIII回收率降低是否是这些观察结果的原因，使用四种输送系统对四种超纯浓缩物进行了8小时的体外连续输送研究。当将复溶后的浓缩物以10 U/ml的浓度加入聚氯乙烯袋中的生理盐水中时（方法IA），单克隆产品显示回收率稳定在初始水平的84 - 109%。重组产品回收率在2小时前降至初始水平的57 - 76%，然后在2小时时重新接近初始水平。向袋中添加10 mg/ml人白蛋白（方法IB）并未提高回收率。当未稀释地输送复溶后的浓缩物时（方法IIA），重组产品回收率的早期下降被消除；所有产品均实现了初始水平78 - 117%的稳定回收率。在使用方法IA时，实际初始回收率与基于瓶内检测预期的回收率之间存在很大差异，重组产品最为显著（为预期的49 - 57%）。方法IIA的回收率为75 - 90%；向复溶但未稀释的浓缩物中添加20 mg/ml白蛋白（方法IIB）可使回收率最大化，达到预期的85 - 98%。
