Abstract：
The precise measurement of very low levels of factor IX activity (FIX:C < 1 IU/dL) is essential for understanding clinical severity and risk of inhibitor development in patients with severe hemophilia B (Pw-SHB). However, such measurement sensitivity has not yet been achieved. We aimed to establish a measurement method using clot waveform analysis (CWA). Residual FIX:C by adding anti-FIX monoclonal antibody, FIX:C by adding recombinant (r)FIX to the commercial Pw-SHB plasmas, and FIX:C in our Pw-SHB were determined by CS-2000i™/CS-2400™, followed by analysis of CWA parameters. The presence of anti-FIX antibody in the commercial Pw-SHB plasmas significantly decreased coagulation potential compared to its absence. The addition of rFIX to these innate plasma samples produced significant changes in three parameters upon adding FIX:C at 0.1-1 IU/dL, supporting the presence of trace FIX:C in Pw-SHB. Therefore, appropriate FIX-depleted plasma containing minimum residual FIX:C was chosen from reference curves of FIX:C (0.01-1 IU/dL). Among patients with untreated Pw-SHB, two had FIX:C 0.6-0.7 IU/dL and two had lower than detectable levels using FIX-depleted plasma. One of the latter had detectable trough levels post-rFIX administration. In conclusion, CWA enabled measurement of very low levels of FIX:C using appropriate FIX-deficient plasma.
摘要：
精确测量极低水平的因子IX活性（FIX：C<1IU/dL）对于了解严重血友病B（Pw-SHB）患者的临床严重程度和抑制剂发展风险至关重要。然而,这种测量灵敏度尚未实现。我们旨在建立一种使用凝块波形分析（CWA）的测量方法。剩余的FIX：C通过添加抗FIX单克隆抗体，FIX：通过将重组（r）FIX添加到商业Pw-SHB等离子体中，和FIX：我们的Pw-SHB中的C由CS-2000i™/CS-2400™确定，其次是CWA参数分析。与不存在抗FIX抗体相比,在商业Pw-SHB血浆中存在抗FIX抗体显著降低凝血潜能。在这些先天血浆样品中添加rFIX后，在三个参数中产生了显着变化：在0.1-1IU/dL下添加FIX：C，支持Pw-SHB中存在traceFIX:C。因此,从FIX:C(0.01-1IU/dL)的参考曲线中选择含有最小残留FIX:C的适当FIX耗尽血浆.在未经治疗的Pw-SHB患者中，两个患者的FIX:C0.6-0.7IU/dL,两个患者的FIX耗尽血浆检测水平低于可检测水平.后者之一在rFIX施用后具有可检测的波谷水平。总之,CWA能够使用适当的FIX缺陷血浆测量非常低的FIX:C水平。
