Varju Lóránt, Bagoly Zsuzsa, Ajzner Éva, Orbán-Kálmándi Rita, Kádár Anna Zsófia, Nevelős Judit, Ilonczai Péter
Department of Hematology, Szabolcs-Szatmár-Bereg County Teaching Hospitals, András Jósa Hospital, Nyíregyháza, Hungary.
Kálmán Laki Doctorate School, University of Debrecen, Debrecen, Hungary.
Front Immunol. 2025 Jul 31;16:1591029. doi: 10.3389/fimmu.2025.1591029. eCollection 2025.
Antiphospholipid syndrome (APS) is an autoimmune disease characterized by a hypercoagulable state and recurrent thromboembolism (TE). Patients with triple-positive antiphospholipid antibodies (APAs) are at the highest risk of TE. As standard treatment for these patients, oral anticoagulation therapy (OAT) with vitamin K antagonists (VKAs) is widely used, but inaccurate International Normalized Ratio (INR) measurement due to APA interference can complicate monitoring.
Here we report the case of a 19-year-old male patient, with a history of submassive pulmonary embolism at the age of 13. Thrombophilia investigations confirmed type II antithrombin deficiency (Budapest 3 heterozygous) combined with triple-positive APS. He received sustained VKA (warfarin) therapy, but his INR values showed strikingly different results when monitored in two different laboratories (INR 3-4 vs. INR >8 on multiple occasions). Therefore, we aimed to investigate the impact of different thromboplastin reagents on INR values in this triple-positive APS patient receiving VKA therapy. INR measurements were performed using animal-derived (rabbit brain-derived) and recombinant thromboplastins. The effect of purified patient IgG concentrates was examined on INR values using antiphospholipid antibody-negative plasma mixtures. Chromogenic FXa activity (CFXa) was also measured to assess the true anticoagulant effect of VKA.
INR values measured using recombinant thromboplastin reagent were consistently higher and less reliable in high APA-titer conditions compared to rabbit brain-derived reagent. CFXa results were more consistent with INR values obtained using rabbit brain-derived thromboplastin. Rabbit brain-derived thromboplastin, less sensitive to APA interference, provided reliable INR monitoring for this high-risk patient. We recommend choosing thromboplastin reagents without interference to APAs, to optimize OAT monitoring in similar cases of patients with high APA-titers.
抗磷脂综合征（APS）是一种自身免疫性疾病，其特征为高凝状态和复发性血栓栓塞（TE）。抗磷脂抗体（APAs）三联阳性的患者发生TE的风险最高。作为这些患者的标准治疗方法，维生素K拮抗剂（VKAs）的口服抗凝治疗（OAT）被广泛使用，但由于APA干扰导致国际标准化比值（INR）测量不准确会使监测变得复杂。
在此，我们报告一例19岁男性患者的病例，该患者在13岁时曾发生次大面积肺栓塞。血栓形成倾向检查证实为II型抗凝血酶缺乏（布达佩斯3型杂合子）合并APAs三联阳性。他接受了持续的VKA（华法林）治疗，但在两个不同实验室监测时，其INR值显示出显著不同的结果（多次测量时INR为3 - 4与INR >8）。因此，我们旨在研究不同的凝血活酶试剂对该接受VKA治疗的APAs三联阳性患者INR值的影响。使用动物源性（兔脑源性）和重组凝血活酶进行INR测量。使用抗磷脂抗体阴性的血浆混合物检测纯化的患者IgG浓缩物对INR值的影响。还测量了发色底物法FXa活性（CFXa）以评估VKA的真正抗凝效果。
与兔脑源性试剂相比，在高APA滴度条件下，使用重组凝血活酶试剂测量的INR值始终更高且可靠性更低。CFXa结果与使用兔脑源性凝血活酶获得的INR值更一致。兔脑源性凝血活酶对APA干扰较不敏感，为该高危患者提供了可靠的INR监测。我们建议选择不受APA干扰的凝血活酶试剂，以优化类似高APA滴度患者的OAT监测。
