Department of Clinical Laboratory Science, Division of Health Sciences, Graduate School of Medical Science, Kanazawa University.
Department of Clinical Laboratory, Kanazawa University Hospital.
J Atheroscler Thromb. 2022 Jul 1;29(7):1059-1068. doi: 10.5551/jat.62951. Epub 2021 Jul 30.
Measurement of protein S (PS) activity in patients taking direct oral anticoagulants (DOACs) using reagents based on a clotting assay results in falsely high PS activity, thus masking inherited PS deficiency, which is most frequently seen in the Japanese population. In this study, we investigated the effect of factor Xa (FXa) inhibitors on PS activity using the reagent on the basis of the chromogenic assay, which was recently developed in Japan.
The study enrolled 152 patients (82 males and 70 females; the average age: 68.5±14.0 years) receiving three FXa inhibitors (rivaroxaban, edoxaban, and apixaban). PS activity was measured using the reagents on the basis of the clotting and chromogenic assays.
PS activity measured by the clotting assay reagents exhibited falsely high values depending on the plasma concentrations of FXa inhibitors in patients taking either rivaroxaban or edoxaban. However, none of the three FXa inhibitors affected PS activity when measured using the chromogenic assay.
In patients taking rivaroxaban or edoxaban, inherited PS deficiency is likely missed because the levels of PS activity measured using the reagents based on the clotting assay are falsely high. However, we report that three FXa inhibitors do not affect PS activity measured by the chromogenic assay. When measuring the levels of PS activity in patients undergoing DOACs, the principles of each reagent should be understood. Furthermore, plasma samples must be collected at the time when plasma concentrations of DOACs are lowest or the DOAC-Stop reagent should be used.
使用基于凝固测定法的试剂测量正在服用直接口服抗凝剂（DOAC）的患者的蛋白 S（PS）活性，会导致 PS 活性的假性升高，从而掩盖遗传性 PS 缺乏症，这种缺乏症在日本人群中最为常见。在这项研究中，我们使用最近在日本开发的基于显色测定法的试剂，研究了因子 Xa（FXa）抑制剂对 PS 活性的影响。
本研究纳入了 152 名患者（82 名男性和 70 名女性；平均年龄：68.5±14.0 岁），他们正在服用三种 FXa 抑制剂（利伐沙班、依度沙班和阿哌沙班）。使用基于凝固和显色测定法的试剂测量 PS 活性。
接受利伐沙班或依度沙班治疗的患者的 PS 活性，根据其血浆中 FXa 抑制剂的浓度，用凝固测定法试剂测定时会出现假性升高。然而，用显色测定法测量时，三种 FXa 抑制剂均不影响 PS 活性。
在服用利伐沙班或依度沙班的患者中，由于基于凝固测定法的试剂测量的 PS 活性水平偏高，遗传性 PS 缺乏症可能会被遗漏。然而，我们报告称，三种 FXa 抑制剂不会影响用显色测定法测量的 PS 活性。在测量正在服用 DOAC 的患者的 PS 活性水平时，应该了解每种试剂的原理。此外，必须在 DOAC 浓度最低时采集血浆样本，或者使用 DOAC-Stop 试剂。
