Lusher J M, Hillman-Wiseman C, Hurst D
Children's Hospital of Michigan, Detroit 48201, USA.
Haemophilia. 1998 Jul;4(4):641-5. doi: 10.1046/j.1365-2516.1998.440641.x.
In view of reports of FVIII assay discrepancies in post-infusion plasma samples depending on methods used, we compared FVIII results run by each of four different methods following infusion of rFVIII (Kogenate). Nine persons with haemophilia A were infused with each of two lots of product. Plasma samples were obtained at baseline, and at 10 min, 30 min, 1, 2, 4, 8, 12, 14, 30 and 48 h post-infusion for measurement of FVIII. FVIII assay methods were chromogenic, and one-stage APTT using three different types of activators: micronized, silica, ellagic acid, and kaolin. The same reference plasma standard was used throughout. Results demonstrated a consistent difference in FVIII values, with chromogenic assays being considerably higher than those run by one-stage assays. The discrepancy was greatest when kaolin was the activator. These results point out the problems in attempting to determine the "correct" FVIII level in patient plasma samples following infusion of high purity FVIII preparations. Potential "pitfalls" include the standard used for defining product potency, the methods, reagents, instrumentation and standards used in assaying plasma samples and, in some instances, the characteristics of the product itself. This situation has considerable cost implications, potential impact on patient care, and makes it difficult to compare results between laboratories.
鉴于有报告称，输注后血浆样本中FVIII检测结果会因所使用的方法不同而存在差异，我们比较了9名甲型血友病患者在输注重组FVIII（科跃奇）后，采用四种不同方法检测的FVIII结果。给这9名患者分别输注了两批产品。在基线时以及输注后10分钟、30分钟、1小时、2小时、4小时、8小时、12小时、14小时、30小时和48小时采集血浆样本，以检测FVIII。FVIII检测方法为发色底物法，以及使用三种不同激活剂（微粉化硅胶、鞣花酸和高岭土）的一步法APTT。整个过程使用相同的参考血浆标准品。结果显示，FVIII值存在一致的差异，发色底物法检测的结果显著高于一步法检测的结果。当以高岭土作为激活剂时，差异最大。这些结果指出了在试图确定高纯度FVIII制剂输注后患者血浆样本中“正确”FVIII水平时存在的问题。潜在的“陷阱”包括用于定义产品效力的标准、检测血浆样本时所使用的方法、试剂、仪器和标准品，以及在某些情况下产品本身的特性。这种情况会产生相当大的成本影响，对患者护理可能产生影响，并且使得不同实验室之间难以比较结果。
