Bowyer Annette E, Lowe Anna E, Tiefenbacher Stefan
Department of Coagulation, Sheffield Haemophilia and Thrombosis Centre, Sheffield, UK.
UK National External Quality Assurance Scheme (NEQAS) for Blood Coagulation, Sheffield, UK.
Haemophilia. 2021 Feb;27 Suppl 3:142-147. doi: 10.1111/hae.13976. Epub 2020 May 29.
The treatment options for the haemostatic disorders, haemophilia A and haemophilia B, have progressed rapidly over the last decade. The introduction of extended half-life recombinant factor VIII (FVIII) and factor IX (FIX) concentrates to replace these missing clotting factors highlighted discordance between one-stage activated partial thromboplastin time (APTT)-based clotting factor assays and chromogenic factor assays with some products. This raised awareness of the importance of investigation of potential reagent or assay differences by pharmaceutical companies. In 2017, the FVIII mimetic, emicizumab, was approved as a prophylactic treatment for haemophilia A patients with anti-FVIII inhibitors. The mechanism of action of emicizumab causes interference with some commonly used haemostasis tests including the APTT and its associated one-stage APTT-based clotting assays. Chromogenic assays may also be affected but this is dependent on the particular constituents of the reagents. Chromogenic assays containing human factor IXa (FIXa) and factor X (FX) are sensitive to the presence of emicizumab but those containing bovine FIXa and FX are unaffected. Many haemostasis laboratories have been required to evaluate new assays to enable accurate monitoring of emicizumab in patient plasma. A number of gene therapy approaches have been trialled in both haemophilia A and haemophilia B but there are scant data published on the measurement of FVIII and FIX in these patients and whether there are discrepancies between reagents or assay methodologies.
在过去十年中，血友病A和血友病B这两种止血障碍疾病的治疗选择取得了迅速进展。延长半衰期的重组凝血因子VIII（FVIII）和凝血因子IX（FIX）浓缩物的引入，用于替代这些缺失的凝血因子，凸显了基于一步活化部分凝血活酶时间（APTT）的凝血因子检测与某些产品的发色底物法凝血因子检测之间的不一致。这提高了制药公司对研究潜在试剂或检测差异重要性的认识。2017年，FVIII模拟物emicizumab被批准用于治疗患有抗FVIII抑制剂的血友病A患者。emicizumab的作用机制会干扰一些常用的止血检测，包括APTT及其相关的基于一步APTT的凝血检测。发色底物法检测也可能受到影响，但这取决于试剂的特定成分。含有人类凝血因子IXa（FIXa）和凝血因子X（FX）的发色底物法检测对emicizumab的存在敏感，但含有牛FIXa和FX的检测不受影响。许多止血实验室需要评估新的检测方法，以便准确监测患者血浆中的emicizumab。在血友病A和血友病B中都已经试验了多种基因治疗方法，但关于这些患者中FVIII和FIX的测量以及试剂或检测方法之间是否存在差异的公开数据很少。
