Gran Charlotte, Frisk Tony, Homström Margareta, Magnusson Maria, Ranta Susanna, Sjöström Anna, Lambert Marjan Shafaati, Soutari Nida Mahmoud Hourani, Antovic Jovan P, Chaireti Roza
Department of Molecular Medicine and Surgery, Coagulation Research, Karolinska Institutet, Stockholm, Sweden.
Clinical Chemistry, Medical Diagnostics, Karolinska University Hospital, Stockholm, Sweden.
Clin Appl Thromb Hemost. 2025 Jan-Dec;31:10760296251378458. doi: 10.1177/10760296251378458. Epub 2025 Sep 26.
BackgroundEmicizumab has emerged as a promising therapy for hemophilia A (HA), employing a bypassing mechanism to restore hemostasis. However, since the traditional factor assays cannot be used for measuring the effect of emicizumab, treatment monitoring is difficult.ObjectivesTo assess the impact of emicizumab on global hemostatic potential (OHP), as well as on chromogenic and modified one-stage (mOSA) FVIII assays calibrated for emicizumab in patient samples.MethodsPeripheral blood samples from patients with HA on emicizumab were utilized for a validation (n = 28) and a clinical cohort (n = 9). Emicizumab concentration was measured by chromogenic FVIII and mOSA (Actin FS, Actin FSL, and PTT-LA), while overall haemostatic potential (OHP) was used to assess global hemostasis.ResultsSignificantly lower emicizumab concentrations were observed using chromogenic FVIII assay compared to mOSA ( < .005, < .005, and < .005 for mOSA Actin FSL, mOSA Actin FS, and mOSA PTT-LA respectively) in the validation cohort. In the clinical cohort, emicizumab concentrations were significantly lower with chromogenic FVIII assay compared to mOSA Actin FS ( < .005) and mOSA PTT-LA ( = .009), but not mOSA Actin FSL. In the clinical cohort, no correlation was seen between OHP and emicizumab.ConclusionAccurate measurement of emicizumab concentration may have the potential to understand assay variability, which is important for informed clinical decision-making in HA patients. Our findings underscore the need for introducing new methods for measuring emicizumab concentration and suggest chromogenic-based methodologies as a viable option for mitigating assay interference.
背景
艾美赛珠单抗已成为治疗A型血友病（HA）的一种有前景的疗法，它采用旁路机制来恢复止血功能。然而，由于传统的凝血因子检测方法无法用于测量艾美赛珠单抗的疗效，治疗监测存在困难。
目的
评估艾美赛珠单抗对患者样本中整体止血潜能（OHP）以及针对艾美赛珠单抗校准的发色底物法和改良一步法（mOSA）FVIII检测的影响。
方法
将接受艾美赛珠单抗治疗的HA患者的外周血样本用于验证（n = 28）和临床队列研究（n = 9）。通过发色底物法FVIII和mOSA（Actin FS、Actin FSL和PTT - LA）测量艾美赛珠单抗浓度，同时使用整体止血潜能（OHP）评估整体止血情况。
结果
在验证队列中，与mOSA相比，发色底物法FVIII检测观察到的艾美赛珠单抗浓度显著更低（mOSA Actin FSL、mOSA Actin FS和mOSA PTT - LA的P值分别<0.005、<0.005和<0.005）。在临床队列中，与mOSA Actin FS（P<0.005）和mOSA PTT - LA（P = 0.009）相比，发色底物法FVIII检测的艾美赛珠单抗浓度显著更低，但与mOSA Actin FSL相比无差异。在临床队列中，未观察到OHP与艾美赛珠单抗之间存在相关性。
结论
准确测量艾美赛珠单抗浓度可能有助于了解检测变异性，这对于HA患者的明智临床决策很重要。我们的研究结果强调需要引入测量艾美赛珠单抗浓度的新方法，并建议基于发色底物法的方法作为减轻检测干扰的可行选择。
