Impact of thromboplastin reagents on monitoring INR in a patient with triple-positive antiphospholipid syndrome: a case report.

Introduction: 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.

Case: 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.

Conclusions: 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.