Thomas K B, Urbancik W, Turecek P L, Gritsch H, Schreiber J, Weber A, Schönhofer W, Strauss M, Linnau Y, Schoppmann A
Hyland Immuno Division, Baxter Healthcare, Vienna, Austria.
Haemophilia. 1999 Jan;5(1):17-25. doi: 10.1046/j.1365-2516.1999.00210.x.
A high purity factor VIII/von Willebrand Factor (FVIII/vWF) concentrate (IMMUNATE [STIM plus]) (n = 6 batches), and a high purity factor IX (FIX) concentrate (IMMUNINE [STIM plus]) (n = 7 batches), were assessed in vitro for their applicability to continuous infusion. Parameters pertinent to continuous infusion were investigated and included stability, sterility and, in the case of FIX, the generation of potentially thrombogenic components. Four stationary or transportable mini infusion pumps, equipped with polyethylene, polypropylene or polyvinylchloride plastic components were used. The concentrates were reconstituted without extra filling volume and perfused at 12.5 mL h-1 and 1 mL h-1; sampling was carried out at the start of the experiment and for up to 48 h. The FVIII procoagulant activity (FVIII:C) was assayed by amidolytic, 1-stage and 2-stage assays; vWF was examined for ristocetin cofactor activity, antigen and multimers. The FIX coagulation activity (FIX:C) was determined by a 1-stage coagulation assay; thrombogenicity potential was assessed in vivo (Wessler stasis model in rabbits) and in vitro (FIXa and nonactivated thromboplastin time). Reconstituted concentrate incubated under the same conditions served as a control. Both concentrates remained sterile throughout the testing period. The perfused and control samples remained stable, retaining over 95% of activity for FVIII:C and over 90% for FIX:C for up to 48 h. Intermittent decrease of FVIII:C or FIX:C was not observed, suggesting no adsorption of FVIII or FIX onto plastic surfaces during either short or long-term exposure. No thrombogenic components were detected in the high purity FIX concentrate. Thus, under the in vitro conditions used, FVIII/vWF and FIX were found to be suitable for administration by continuous infusion.
对一种高纯度的凝血因子VIII/血管性血友病因子（FVIII/vWF）浓缩物（免疫原[刺激加]）（n = 6批）和一种高纯度的凝血因子IX（FIX）浓缩物（免疫宁[刺激加]）（n = 7批）进行了体外连续输注适用性评估。研究了与连续输注相关的参数，包括稳定性、无菌性，对于FIX，还包括潜在致血栓形成成分的产生。使用了四台配备聚乙烯、聚丙烯或聚氯乙烯塑料部件的固定式或便携式微型输液泵。浓缩物复溶时无额外填充体积，并以12.5 mL/h和1 mL/h的速度灌注；在实验开始时及长达48小时内进行采样。通过酰胺水解法、1期和2期试验测定FVIII促凝血活性（FVIII:C）；检测vWF的瑞斯托霉素辅因子活性、抗原和多聚体。通过1期凝血试验测定FIX凝血活性（FIX:C）；在体内（兔的韦氏停滞模型）和体外（FIXa和非活化凝血活酶时间）评估致血栓形成潜力。在相同条件下孵育的复溶浓缩物用作对照。两种浓缩物在整个测试期间均保持无菌。灌注样品和对照样品保持稳定，FVIII:C活性在长达48小时内保持超过95%，FIX:C活性保持超过90%。未观察到FVIII:C或FIX:C的间歇性下降，表明在短期或长期暴露期间FVIII或FIX均未吸附到塑料表面。在高纯度FIX浓缩物中未检测到致血栓形成成分。因此，在所使用的体外条件下，发现FVIII/vWF和FIX适合通过连续输注给药。
