Department of Anaesthesiology, Ludwig-Maximilian-University of Munich, Munich, Germany.
Department of Transfusion Medicine, Cell Therapeutics and Haemostaseology, Ludwig Maximilian-University of Munich, Munich, Germany.
Haemophilia. 2021 Mar;27(2):e214-e220. doi: 10.1111/hae.14264. Epub 2021 Feb 1.
A dedicated emicizumab assay based on the modified one-stage factor VIII (FVIII) assay (mOSA) is mainly available in haemophilia treatment centres (HTC). A method to estimate emicizumab plasma levels based on a widely available assay would be desirable, especially for emergency situations.
A method for emicizumab plasma level approximation (ELA) using a routine FVIII activity measurement with standard one-stage assay (sOSA) was developed and evaluated.
Within this pilot study, 59 samples from patients with severe haemophilia A with (n = 8) and without (n = 8) inhibitors under emicizumab treatment were analysed using sOSA following a manual 1:8 sample pre-test dilution with saline. The sOSA was determined in two different laboratories, using two different analyser platforms each.
The results demonstrated an excellent correlation of approximated emicizumab plasma levels (ELA) with the emicizumab plasma concentration determined with mOSA (r > .9; p < .05). The ELA showed a sensitivity of 93.3% and a specificity of 89.6% to predict a pre-defined cut-off-value of ≤30 µg/ml for the discrimination between subtherapeutic and therapeutic emicizumab plasma levels.
Approximation of emicizumab levels by standard one-stage FVIII assay discriminates between subtherapeutic and therapeutic emicizumab levels and might facilitate clinical decision-making in emergency situations, such as bleeding, trauma or urgent surgery in case that dedicated emicizumab assays are not available.
一种基于改良的一期因子 VIII（FVIII）测定法（mOSA）的专用依库珠单抗测定法主要在血友病治疗中心（HTC）中使用。特别在紧急情况下，需要有一种基于广泛可用的测定法来估计依库珠单抗血浆水平的方法。
开发并评估了一种使用常规 FVIII 活性测定法（sOSA）估算依库珠单抗血浆水平的方法（ELA）。
在这项初步研究中，使用 sOSA 对 59 份接受依库珠单抗治疗的严重血友病 A 患者的样本（有抑制剂组 n=8，无抑制剂组 n=8）进行分析，这些样本在进行 sOSA 之前先用盐水进行了 1:8 的手动预测试稀释。sOSA 在两个不同的实验室中使用两个不同的分析平台进行测定。
结果表明，估算的依库珠单抗血浆水平（ELA）与使用 mOSA 测定的依库珠单抗血浆浓度之间具有极好的相关性（r>.9；p<.05）。ELA 预测 ≤30μg/ml 作为区分亚治疗和治疗性依库珠单抗血浆水平的预定截止值时，其敏感性为 93.3%，特异性为 89.6%。
标准的一期 FVIII 测定法估算依库珠单抗水平可区分亚治疗和治疗性依库珠单抗水平，并在紧急情况下（如出血、创伤或紧急手术）可能有助于临床决策，例如在没有专用依库珠单抗测定法的情况下。
