{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T08:01:12Z","timestamp":1792569672069,"version":"4.5.0"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case<\/jats:title><jats:p>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\u20134 vs. INR &amp;gt;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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1591029","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T06:08:12Z","timestamp":1753942092000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Impact of thromboplastin reagents on monitoring INR in a patient with triple-positive antiphospholipid syndrome: a case report"],"prefix":"10.3389","volume":"16","author":[{"given":"L\u00f3r\u00e1nt","family":"Varju","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsuzsa","family":"Bagoly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c9va","family":"Ajzner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Orb\u00e1n-K\u00e1lm\u00e1ndi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Zs\u00f3fia","family":"K\u00e1d\u00e1r","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judit","family":"Nevel\u0151s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e9ter","family":"Ilonczai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1111\/j.1538-7836.2006.01753.x","article-title":"International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS)","volume":"4","author":"Miyakis","year":"2006","journal-title":"J Thromb Haemost"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2017.07.006","article-title":"Diagnosis and management of the antiphospholipid syndrome","volume":"31","author":"Chaturvedi","year":"2017","journal-title":"Blood Rev"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtha.2024.10.022","article-title":"An update on laboratory detection and interpretation of antiphospholipid antibodies for diagnosis of antiphospholipid syndrome: guidance from the ISTH-SSC Subcommittee on Lupus Anticoagulant\/Antiphospholipid Antibodies","volume":"23","author":"Devreese","year":"2025","journal-title":"J Thromb Haemost"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2023-224609","article-title":"ACR\/EULAR antiphospholipid syndrome classification criteria","volume":"82","author":"Barbhaiya","year":"2023","journal-title":"Ann Rheum Dis"},{"key":"B5","doi-asserted-by":"publisher","first-page":"17103","DOI":"10.1038\/nrdp.2017.103","article-title":"Antiphospholipid syndrome","volume":"4","author":"Schreiber","year":"2018","journal-title":"Nat Rev Dis Primers"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2016.07.028","article-title":"APS - Diagnostics and challenges for the future","volume":"15","author":"Pengo","year":"2016","journal-title":"Autoimmun Rev"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-03-340232","article-title":"Incidence of a first thromboembolic event in asymptomatic carriers of high-risk antiphospholipid antibody profile: a multicenter prospective study","volume":"118","author":"Pengo","year":"2011","journal-title":"Blood"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ker139","article-title":"Risk factors for pregnancy failure in patients with anti-phospholipid syndrome treated with conventional therapies: a multicentre, case-control study","volume":"50","author":"Ruffatti","year":"2011","journal-title":"Rheumatol (Oxford)"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2009.03674.x","article-title":"Clinical course of high-risk patients diagnosed with antiphospholipid syndrome","volume":"8","author":"Pengo","year":"2010","journal-title":"J Thromb Haemost"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.16431","article-title":"Diagnosis and management of the antiphospholipid syndrome","volume":"378","author":"Garcia","year":"2018","journal-title":"N Engl J Med"},{"key":"B11","doi-asserted-by":"crossref","DOI":"10.1111\/bjh.16431","article-title":"What is the appropriate anticoagulation strategy for thrombotic antiphospholipid syndrome","volume":"189","author":"Arachchillage","year":"2020","journal-title":"Br J Haematol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2018.04.009","article-title":"Increased risk of thrombosis in antiphospholipid syndrome patients treated with direct oral anticoagulants. 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