External Quality Control for Assays and Tests (ECAT) Foundation, Voorschoten, The Netherlands.
Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands.
Clin Chem Lab Med. 2020 Oct 25;58(11):1921-1930. doi: 10.1515/cclm-2020-0130.
Objectives Chromogenic anti-activated factor X (FXa) assays are currently the "gold standard" for monitoring indirect anticoagulants. However, anti-FXa has been shown to vary according to the choice of reagents. In the present study, the performance of anti-FXa measurement was evaluated in order to gain more insight into the clinical applications. Furthermore, the longitudinal coefficient of variation (CV) was studied to investigate whether there is improvement over time. Methods Laboratory tests results were evaluated for samples spiked with unfractionated heparin (UFH), low-molecular-weight-heparin (LMWH), fondaparinux and danaparoid sodium. External quality assessment (EQA) data from multiple years were used from more than 100 laboratories. Results Comparison of the results for all methods showed significant differences in measured values between the frequently used methods (ANOVA: p < 0.001). The largest differences were observed for LMWH and UFH measurements. These differences may be caused by differences in method composition, such as the addition of dextran sulphate. Substantial interlaboratory variation in anti-FXa monitoring was observed for all parameters, particularly at low concentrations. Our results showed that below 0.35 IU/mL, the CVs for UFH and LMWH increase dramatically and results below this limit should be used with caution. Conclusions Our study demonstrates that the choice of the anti-FXa method is particularly important for UFH and LMWH measurement. The variation in measurements may have an effect on clinical implications, such as therapeutic ranges. Furthermore, the longitudinal EQA data demonstrated a constant performance and, in at least 50% of the cases, improvement in the CV% of the anti-Xa results over time.
目的 显色法抗活化因子 X（FXa）测定目前是监测间接抗凝剂的“金标准”。然而，抗 FXa 已被证明会因试剂选择的不同而有所差异。在本研究中，评估了抗 FXa 测量的性能，以便更深入地了解其临床应用。此外，还研究了纵向变异系数（CV），以探讨是否随时间有所改善。
方法 对添加未分级肝素（UFH）、低分子肝素（LMWH）、磺达肝素钠和达那肝素钠的样本进行实验室检测结果评估。使用来自 100 多个实验室的多年外部质量评估（EQA）数据。
结果 对所有方法的结果进行比较显示，常用方法的测量值之间存在显著差异（ANOVA：p<0.001）。LMWH 和 UFH 测量的差异最大。这些差异可能是由于方法组成的差异，如添加硫酸葡聚糖引起的。所有参数的抗 FXa 监测都存在明显的实验室间差异，尤其是在低浓度时。我们的结果表明，在 0.35 IU/mL 以下，UFH 和 LMWH 的 CV 急剧增加，低于该限值的结果应谨慎使用。
结论 本研究表明，抗 FXa 方法的选择对 UFH 和 LMWH 的测量尤为重要。测量的差异可能会对临床意义产生影响，例如治疗范围。此外，纵向 EQA 数据表明，至少在 50%的情况下，抗 Xa 结果的 CV%随时间不断改善。
