Department of Clinical Chemistry, Sestre milosrdnice University Hospital Center, Zagreb, Croatia.
Department of Cardiovascular Diseases, Sestre milosrdnice University Hospital Center, Zagreb, Croatia.
Biochem Med (Zagreb). 2020 Feb 15;30(1):010702. doi: 10.11613/BM.2020.010702. Epub 2019 Dec 15.
Clinical application of rivaroxaban and apixaban does not require therapeutic monitoring. Commercial anti-activated factor X (anti-FXa) inhibition methods for all anti-FXa drugs are based on the same principle, so there are attempts to evaluate potential clinical application of heparin-calibrated anti-FXa assay as an alternative method for direct FXa inhibitors. We aimed to evaluate relationship between anti-FXa methods calibrated with low molecular weight heparin (LMWH) and with drug specific calibrators, and to determine whether commercial LMWH anti-FXa assay can be used to exclude the presence of clinically relevant concentrations of rivaroxaban and apixaban.
Low molecular weight heparin calibrated reagent (Siemens Healthineers, Marburg, Germany) was used for anti-FXa activity measurement. Innovance heparin (Siemens Healthineers, Marburg, Germany) calibrated with rivaroxaban and apixaban calibrators (Hyphen BioMed, Neuville-sur-Oise, France) was used for quantitative determination of FXa inhibitors.
Analysis showed good agreement between LMWH calibrated and rivaroxaban calibrated activity (κ = 0.76) and very good agreement with apixaban calibrated anti-Xa activity (κ = 0.82), respectively. Low molecular weight heparin anti-FXa activity cut-off values of 0.05 IU/mL and 0.1 IU/mL are suitable for excluding the presence of clinically relevant concentrations (< 30 ng/mL) of rivaroxaban and apixaban, respectively. Concentrations above 300 ng/mL exceeded upper measurement range for LMWH anti-FXa assay and cannot be determined by this method.
Low molecular weight heparin anti-FXa assay can be used in emergency clinical conditions for ruling out the presence of clinically relevant concentrations of rivaroxaban and apixaban. However, use of LMWH anti-FXa assay is not appropriate for their quantitative determination as an interchangeable method.
利伐沙班和阿哌沙班的临床应用不需要治疗监测。所有抗 FXa 药物的商业抗活化因子 X（抗-FXa）抑制方法均基于相同的原理，因此有人尝试评估肝素校准的抗-FXa 测定法作为直接 FXa 抑制剂的替代方法的潜在临床应用。我们旨在评估用低分子肝素（LMWH）校准的抗-FXa 方法与用药物特异性校准剂校准的抗-FXa 方法之间的关系，并确定商业 LMWH 抗-FXa 测定法是否可用于排除利伐沙班和阿哌沙班的临床相关浓度。
使用低分子肝素校准试剂（德国马堡西门子健康公司）测量抗-FXa 活性。使用用利伐沙班和阿哌沙班校准剂（法国诺伊维尔-sur-Oise Hyphen BioMed 公司）校准的 Innovance 肝素（德国马堡西门子健康公司）进行 FXa 抑制剂的定量测定。
分析显示，LMWH 校准和利伐沙班校准的活性之间具有良好的一致性（κ=0.76），与阿哌沙班校准的抗-Xa 活性之间具有非常好的一致性（κ=0.82）。LMWH 抗-FXa 活性 0.05 IU/mL 和 0.1 IU/mL 的截断值分别适合排除利伐沙班和阿哌沙班的临床相关浓度（＜30ng/mL）的存在。浓度高于 300ng/mL 超出 LMWH 抗-FXa 测定法的上限测量范围，无法用该方法测定。
LMWH 抗-FXa 测定法可用于排除临床相关浓度的利伐沙班和阿哌沙班的紧急临床情况。但是，作为可互换方法，不适合用于其定量测定。
