Hubbard A R, Bevan S A, Weller L J
Division of Haematology, National Institute for Biological Standards and Control, Potters Bar, Hertfordshire, UK.
Br J Haematol. 2001 May;113(2):533-6. doi: 10.1046/j.1365-2141.2001.02761.x.
Large potency discrepancies between the chromogenic and one-stage clotting methods have been reported for patients' plasma samples following the infusion of recombinant factor VIII (rFVIII) concentrates. We have investigated the potency estimation of two different full-length rFVIII concentrates using both assay methods relative to both plasma and concentrate standards. Potencies by the chromogenic method were significantly higher (53% and 45%) than potencies by the one-stage clotting method when a plasma standard was used. In contrast, there was no significant potency difference between methods when a concentrate standard was used. Time-course studies into thrombin and activated factor X (FXa) generation, in modified clotting and chromogenic methods, respectively, revealed that the two rFVIII concentrates behaved very similarly to the concentrate standard, whereas the plasma standard showed slightly more rapid thrombin generation and markedly slower FXa generation. The different behaviour of rFVIII and plasma FVIII in the chromogenic method is proposed as the main cause of the methods-based potency discrepancy. The results support the use of a concentrate standard to measure rFVIII in post-infusion plasma.
据报道，在输注重组凝血因子VIII（rFVIII）浓缩物后，患者血浆样本的发色底物法和一步凝血法之间存在较大的效价差异。我们使用这两种检测方法，相对于血浆标准品和浓缩物标准品，研究了两种不同全长rFVIII浓缩物的效价估计。当使用血浆标准品时，发色底物法测定的效价比一步凝血法显著更高（分别为53%和45%）。相比之下，当使用浓缩物标准品时，两种方法之间的效价没有显著差异。分别在改良凝血法和发色底物法中对凝血酶和活化因子X（FXa）生成的时间进程研究表明，两种rFVIII浓缩物的行为与浓缩物标准品非常相似，而血浆标准品显示凝血酶生成略快，FXa生成明显较慢。rFVIII和血浆FVIII在发色底物法中的不同行为被认为是基于方法的效价差异的主要原因。结果支持使用浓缩物标准品来测量输注后血浆中的rFVIII。
