Coagulation, Sheffield Haemophilia and Thrombosis Centre, Sheffield, UK.
Haematology, SA Pathology, Adelaide, SA, Australia.
Haemophilia. 2018 Jul;24(4):578-583. doi: 10.1111/hae.13520. Epub 2018 May 29.
The laboratory diagnosis and monitoring of factors VIII and IX have been primarily by one-stage clotting assay (OSA) for many years. Chromogenic assays (CSA) have been available only in specialist laboratories and not for routine use. Significant differences, of more than 1.5-fold in results between the 2 assay methods, have been described in Europe and Australia in approximately one-third of patients with mild haemophilia A. In certain discrepant groups with restricted F8 gene mutations, the OSA results are more than 1.5-fold higher than CSA and risk a missed or misleading diagnostic result. More recently, an assay discrepancy in haemophilia B has been reported. With the introduction of extended half-life (EHL) FVIII and FIX products, it is likely most coagulation laboratories will need to evaluate at least one CSA and gain experience with this technique. The validation of CSA involves a careful appraisal of calibration curve linearity, limit of detection, precision, reference range, quality control material, sample analysis, method comparison and cost. This review will discuss the current status of FVIII and FIX CSA for the diagnosis of haemophilia A and B and describe approaches to implement CSA into the laboratory repertoire.
多年来，因子 VIII 和 IX 的实验室诊断和监测主要采用一期凝血测定法（OSA）。显色测定法（CSA）仅在专门的实验室中可用，不适用于常规使用。在欧洲和澳大利亚，约有三分之一的轻度血友病 A 患者的两种检测方法之间的结果存在 1.5 倍以上的显著差异。在某些具有受限 F8 基因突变的不一致群体中，OSA 结果比 CSA 高 1.5 倍以上，可能导致漏诊或误导性诊断结果。最近，据报道乙型血友病也存在检测差异。随着长效（EHL）FVIII 和 FIX 产品的推出，很可能大多数凝血实验室将需要至少评估一种 CSA 并获得该技术的经验。CSA 的验证涉及对校准曲线线性、检测限、精密度、参考范围、质控材料、样本分析、方法比较和成本的仔细评估。这篇综述将讨论目前用于诊断血友病 A 和 B 的因子 VIII 和 FIX CSA 的现状，并描述将 CSA 纳入实验室常规的方法。
