目的:使用基于凝血测定的试剂测量服用直接口服抗凝剂(DOACs)的患者的蛋白S(PS)活性会导致PS活性过高,从而掩盖了遗传性PS缺乏症,这在日本人口中最常见。在这项研究中,我们研究了因子Xa(FXa)抑制剂对PS活性的影响,使用该试剂在显色测定的基础上,这是最近在日本开发的。
方法:该研究纳入了152名接受三种FXa抑制剂(利伐沙班,edoxaban,和阿哌沙班)。基于凝血和显色测定使用试剂测量PS活性。
结果:根据服用利伐沙班或依度沙班的患者中FXa抑制剂的血浆浓度,通过凝血测定试剂测量的PS活性显示出错误的高值。然而,当使用显色测定法测量时,三种FXa抑制剂均不影响PS活性。
结论:服用利伐沙班或依度沙班的患者,遗传性PS缺乏症可能被错过,因为使用基于凝血分析的试剂测量的PS活性水平是错误的高。然而,我们报道了三种FXa抑制剂不影响通过显色测定法测量的PS活性。当测量接受DOAC的患者的PS活性水平时,应该理解每种试剂的原理。此外,必须在DOAC的血浆浓度最低时收集血浆样本,或者应使用DOAC-Stop试剂。
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.