The Prevalence and Clinical Significance of Heritable Thrombophilia in Antiphospholipid Antibody Positive Patients: Descriptive Results from the Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) Registry

Emre Sahin¹, Maria Efthymiou², Danieli Andrade³, Megan Barber⁴, Maria Tektonidou⁵, Vittorio Pengo⁶, Massimo Radin⁷, Jose Pardos-Gea⁸, MARIA ANGELES AGUIRRE ZAMORANO⁹, Nina Kello¹⁰, Diana Paredes-Ruiz¹¹, H Michael Belmont¹², Paul Fortin¹³, Denis WAHL¹⁴, Ware Branch¹⁵, Maria Gerosa¹⁶, Guilherme Ramires de Jesus¹⁷, Zhuoli Zhang¹⁸, Tatsuya Atsumi¹⁹, Giulia Pazzola²⁰, Laura Andreoli²¹, Ali Duarte-Garcia²², Esther Rodriguez-Almaraz²³, Michelle Petri²⁴, Ricard Cervera²⁵, Bahar Artim Esen²⁶, Guillermo Pons-Estel²⁷, Hui Shi²⁸, Jason S. Knight²⁹, Rohan Willis³⁰, Maria Laura Bertolaccini³¹, Hannah Cohen³² and Doruk Erkan¹, ¹Hospital for Special Surgery, New York, NY, ²University College London, London, United Kingdom, ³University of Sao Paulo, São Paulo, São Paulo, Brazil, ⁴Division of Rheumatology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada, ⁵National and Kapodistrian University of Athens, Athens, Greece, ⁶Padova University Hospital, Padova, Italy, ⁷University of Turin, Turin, Turin, Italy, ⁸Vall d’Hebron University Hospital, Barcelona, Spain, ⁹Rheumatology service/Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/ Reina Sofia University Hospital/ University of Cordoba, Spain, Córdoba, Spain, ¹⁰Northwell Health, Brooklyn, NY, ¹¹Biobizkaia Health Research Institute, Barakaldo, Spain, ¹²NYU School of Medicine, New York, NY, ¹³Centre ARThrite - CHU de Québec - Université Laval, Quebec, QC, Canada, ¹⁴University of Lorraine, Nancy, France, ¹⁵University of Utah Health Sciences Center, Salt Lake City, UT, ¹⁶University of Milan, Milano, Italy, ¹⁷Universidade do Estado do Rio de Janeiro, Rio De Janeiro, Rio de Janeiro, Brazil, ¹⁸Peking University First Hospital, Beijing, Beijing, China (People's Republic), ¹⁹Hokkaido University, Sapporo, Japan, ²⁰Rheumatology Unit, Azienda USL IRCCS di Reggio Emilia, Reggio Emilia, Italy, ²¹University of Brescia, Brescia, Brescia, Italy, ²²Mayo Clinic, Rochester, MN, ²³Hospital Universitario ¹² de Octubre, Madrid, Spain, ²⁴Johns Hopkins University School of Medicine, Timonium, MD, ²⁵Hospital Clinic Barcelona, Barcelona, Spain, ²⁶Istanbul University, Istanbul, Istanbul, Turkey, ²⁷Centro Regional de Enfermedades Autoinmunes y Reumáticas, GO-CREAR, Rosario, Argentina, Rosario, Argentina, ²⁸Shanghai Jiaotong University Affiliated Ruijin Hospital, Shanghai, China (People's Republic), ²⁹University of Michigan, Ann Arbor, MI, ³⁰University of Texas Medical Branch, Galveston, TX, ³¹King's College London, London, United Kingdom, ³²University College London Hospitals NHS Foundation Trust, London, United Kingdom

Meeting: ACR Convergence 2025

Keywords: antiphospholipid syndrome, Cardiovascular, risk factors

Session Information

Date: Sunday, October 26, 2025

Title: (0115–0144) Antiphospholipid Syndrome Poster

Session Type: Poster Session A

Session Time: 10:30AM-12:30PM

Background/Purpose: Although antiphospholipid antibodies (aPL) are well-established risk factors for thrombosis, heritable thrombophilias (HT) are also associated with venous thromboembolism (VTE). The latter includes deficiencies of the naturally occurring anticoagulants (antithrombin, protein C, and protein S), and factor V Leiden (FVL) and prothrombin (PT) G20210A gene mutations. Methylene tetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms are not considered part of the HT screen in clinical practice. The primary objective of this ongoing study was to determine the prevalence of HT in persistently aPL-positive patients. Secondly, we analyzed the association between thrombosis and HT in aPL-positive patients, individually and in combination. TRANSLATE with xEnglishArabicHebrewPolishBulgarianHindiPortugueseCatalanHmong DawRomanianChinese SimplifiedHungarianRussianChinese TraditionalIndonesianSlovakCzechItalianSlovenianDanishJapaneseSpanishDutchKlingonSwedishEnglishKoreanThaiEstonianLatvianTurkishFinnishLithuanianUkrainianFrenchMalayUrduGermanMalteseVietnameseGreekNorwegianWelshHaitian CreolePersian TRANSLATE with COPY THE URL BELOW BackEMBED THE SNIPPET BELOW IN YOUR SITE Enable collaborative features and customize widget: Bing Webmaster PortalBack This page is in English Translate to Turkish AfrikaansAlbanianAmharicArabicArmenianAzerbaijaniBengaliBulgarianCatalanCroatianCzechDanishDutchEnglishEstonianFinnishFrenchGermanGreekGujaratiHaitian CreoleHebrewHindiHungarianIcelandicIndonesianItalianJapaneseKannadaKazakhKhmerKoreanKurdish (Kurmanji)LaoLatvianLithuanianMalagasyMalayMalayalamMalteseMaoriMarathiMyanmar (Burmese)NepaliNorwegianPashtoPersianPolishPortuguesePunjabiRomanianRussianSamoanSimplified ChineseSlovakSlovenianSpanishSwedishTamilTeluguThaiTraditional ChineseTurkishUkrainianUrduVietnameseWelsh Always translate English to Turkish Never translate English Never translate www.abstractscorecard.com

Methods: A web-based data capture system is used to store patient demographics and aPL-related medical history in APS ACTION registry. Inclusion criteria are positive aPL, based on the Revised Sapporo Antiphospholipid Syndrome (APS) classification criteria, tested at least twice within one year prior to enrollment. Patients are followed every 12±3 months with clinical data and blood collection. For this cross-sectional analysis, baseline data were used including demographic, clinical, and HT laboratory (either center-reported [CR] or APS ACTION United Kingdom Core Laboratory [CL] data (following testing in the CL)). When evaluating the results of the HT included (see Table 1), CL were used over CR if both were available; Chi square or Fisher’s exact tests were used for comparisons. TRANSLATE with xEnglishArabicHebrewPolishBulgarianHindiPortugueseCatalanHmong DawRomanianChinese SimplifiedHungarianRussianChinese TraditionalIndonesianSlovakCzechItalianSlovenianDanishJapaneseSpanishDutchKlingonSwedishEnglishKoreanThaiEstonianLatvianTurkishFinnishLithuanianUkrainianFrenchMalayUrduGermanMalteseVietnameseGreekNorwegianWelshHaitian CreolePersian TRANSLATE with COPY THE URL BELOW BackEMBED THE SNIPPET BELOW IN YOUR SITE Enable collaborative features and customize widget: Bing Webmaster PortalBack This page is in English Translate to Turkish AfrikaansAlbanianAmharicArabicArmenianAzerbaijaniBengaliBulgarianCatalanCroatianCzechDanishDutchEnglishEstonianFinnishFrenchGermanGreekGujaratiHaitian CreoleHebrewHindiHungarianIcelandicIndonesianItalianJapaneseKannadaKazakhKhmerKoreanKurdish (Kurmanji)LaoLatvianLithuanianMalagasyMalayMalayalamMalteseMaoriMarathiMyanmar (Burmese)NepaliNorwegianPashtoPersianPolishPortuguesePunjabiRomanianRussianSamoanSimplified ChineseSlovakSlovenianSpanishSwedishTamilTeluguThaiTraditional ChineseTurkishUkrainianUrduVietnameseWelsh Always translate English to Turkish Never translate English Never translate www.abstractscorecard.com

Results: Of 1,252 patients recruited as of January 2025, 741 (59%) had at least one CR and/or CL HT result (female: 515 [70%]; mean age at registry entry: 55±13.5; thrombotic APS: 456 [62%]; triple aPL-positive: 273 [37%], lupus anticoagulant with/without aCL or aβ2GPI: 308 [42%]). The prevalence of each HT and the association with vascular events are shown in Tables 1 and 2, respectively. Homozygosity for the MTHFR C677T and A1286 polymorphisms were reported in 20 (6%) and 4 (1%), respectively, with high homocysteine in 2/20 with MTHFR C677T and none with MTHFR A1298C. In the subgroup analysis of 316 (43%) patients, we compared those with at least one abnormal HT result (n: 86; excluding heterozygous HT) and those with normal results for all HT assessed (n=230); the former group had significantly more VTE, but not arterial, events (p=0.015) (Table 3). TRANSLATE with xEnglishArabicHebrewPolishBulgarianHindiPortugueseCatalanHmong DawRomanianChinese SimplifiedHungarianRussianChinese TraditionalIndonesianSlovakCzechItalianSlovenianDanishJapaneseSpanishDutchKlingonSwedishEnglishKoreanThaiEstonianLatvianTurkishFinnishLithuanianUkrainianFrenchMalayUrduGermanMalteseVietnameseGreekNorwegianWelshHaitian CreolePersian TRANSLATE with COPY THE URL BELOW BackEMBED THE SNIPPET BELOW IN YOUR SITE Enable collaborative features and customize widget: Bing Webmaster PortalBack This page is in English Translate to Turkish AfrikaansAlbanianAmharicArabicArmenianAzerbaijaniBengaliBulgarianCatalanCroatianCzechDanishDutchEnglishEstonianFinnishFrenchGermanGreekGujaratiHaitian CreoleHebrewHindiHungarianIcelandicIndonesianItalianJapaneseKannadaKazakhKhmerKoreanKurdish (Kurmanji)LaoLatvianLithuanianMalagasyMalayMalayalamMalteseMaoriMarathiMyanmar (Burmese)NepaliNorwegianPashtoPersianPolishPortuguesePunjabiRomanianRussianSamoanSimplified ChineseSlovakSlovenianSpanishSwedishTamilTeluguThaiTraditional ChineseTurkishUkrainianUrduVietnameseWelsh Always translate English to Turkish Never translate English Never translate www.abstractscorecard.com

Conclusion: Based on our large-scale international cohort, up to six percent of persistently aPL-positive patients may have one or more heritable thrombophilia (antithrombin, protein C, or protein S deficiencies, FVL or PT G20210A), which may increase the risk of VTE. Our preliminary results have limitations, including reporting/selection bias, and the lack of information on testing methodology/confirmation and factors that may affect results of naturally occurring anticoagulants, e.g. anticoagulation and pregnancy/puerperium. However, these results and the relatively high frequency of HT in the general population highlight the potential additive risk of HT in aPL-positive patients that may be contributory in the stratification and management of such patients. TRANSLATE with xEnglishArabicHebrewPolishBulgarianHindiPortugueseCatalanHmong DawRomanianChinese SimplifiedHungarianRussianChinese TraditionalIndonesianSlovakCzechItalianSlovenianDanishJapaneseSpanishDutchKlingonSwedishEnglishKoreanThaiEstonianLatvianTurkishFinnishLithuanianUkrainianFrenchMalayUrduGermanMalteseVietnameseGreekNorwegianWelshHaitian CreolePersian TRANSLATE with COPY THE URL BELOW BackEMBED THE SNIPPET BELOW IN YOUR SITE Enable collaborative features and customize widget: Bing Webmaster PortalBack This page is in English Translate to Turkish AfrikaansAlbanianAmharicArabicArmenianAzerbaijaniBengaliBulgarianCatalanCroatianCzechDanishDutchEnglishEstonianFinnishFrenchGermanGreekGujaratiHaitian CreoleHebrewHindiHungarianIcelandicIndonesianItalianJapaneseKannadaKazakhKhmerKoreanKurdish (Kurmanji)LaoLatvianLithuanianMalagasyMalayMalayalamMalteseMaoriMarathiMyanmar (Burmese)NepaliNorwegianPashtoPersianPolishPortuguesePunjabiRomanianRussianSamoanSimplified ChineseSlovakSlovenianSpanishSwedishTamilTeluguThaiTraditional ChineseTurkishUkrainianUrduVietnameseWelsh Always translate English to Turkish Never translate English Never translate www.abstractscorecard.com

Table 1. Prevalence of Heritable Thrombophilia and Methylene tetrahydrofolate reductase (MTHFR) C677T and A1298C Polymorphisms Among APS ACTION Registry Patients

Table 2. The Frequency of Arterial/Venous Thrombosis is Patients with Individual Heritable Thrombophilia and Methylene tetrahydrofolate reductase (MTHFR) C677T and A1298C Polymorphisms Among APS ACTION Registry Patients (those with heterozygous MTHFR polymorphisms were not included)

Table 3. Comparison of Arterial and Venous Events Between Patients With and Without Heritable Thrombophilia (HT) Among APS ACTION Registry Patients (those with MTHFR polymorphisms were not included)

Disclosures: E. Sahin: None; M. Efthymiou: None; D. Andrade: None; M. Barber: AstraZeneca, 1, GlaxoSmithKlein(GSK), 1; M. Tektonidou: None; V. Pengo: None; M. Radin: None; J. Pardos-Gea: None; M. AGUIRRE ZAMORANO: None; N. Kello: None; D. Paredes-Ruiz: None; H. Belmont: None; P. Fortin: AbbVie/Abbott, 1, AstraZeneca, 1, Moderna, 1, Roche, 1; D. WAHL: None; W. Branch: UCB, 5; M. Gerosa: None; G. Ramires de Jesus: None; Z. Zhang: AbbVie/Abbott, 1, 6, Amgen, 6, BMS, 1, Eisai, 5, 6, Eli Lilly, 6, GSK, 6, Novartis, 6, Rongchang Pharmaceutials, 6, Xiansheng Pharmaceutials, 6; T. Atsumi: None; G. Pazzola: None; L. Andreoli: Pfizer, 2, UCB, 2; A. Duarte-Garcia: None; E. Rodriguez-Almaraz: None; M. Petri: Amgen, 2, AnaptysBio, 2, Annexon Bio, 2, AstraZeneca, 2, 5, Atara Biosciences, 2, Aurinia, 2, 5, Autolus, 2, Bain Capital, 2, Baobab Therapeutics, 2, Biocryst, 2, Biogen, 2, Boxer Capital, 2, Cabaletto Bio, 2, Caribou Biosciences, 2, CTI Clinical Trial and Consulting Services, 2, CVS Health, 2, Dualitybio, 2, Eli Lilly, 2, 5, EMD Serono, 2, Emergent, 2, Escient Pharmaceuticals, 2, Exagen, 5, Exo Therapeutics, 2, Gentibio, 2, GlaxoSmithKlein(GSK), 2, 5, iCell Gene Therapeutics, 2, Innovaderm Research, 2, IQVIA, 2, Janssen, 5, Kezar Life Sciences, 2, Kira Pharmaceuticals, 2, Nexstone Immunology, 2, Nimbus Lakshmi, 2, Novartis, 2, Ono Pharma, 2, PPD Development, 2, Proviant, 2, Regeneron, 2, Seismic Therapeutic, 2, Senti Biosciences, 2, Sinomab Biosciences, 2, Steritas, 2, Takeda, 2, Tenet Medicines, 2, TG Therapeutics, 2, UCB, 2, Variant Bio, 2, Worldwide Clinical Trials, 2, Zydus, 2; R. Cervera: None; B. Artim Esen: None; G. Pons-Estel: AstraZeneca, 1, 6, GlaxoSmithKlein(GSK), 1, 6, Janssen, 1, 6; H. Shi: None; J. Knight: BioCryst, 2, Ouro Medicines, 2, Roche, 2, Roivant Sciences, 2, Visterra, 2; R. Willis: None; M. Bertolaccini: None; H. Cohen: GlaxoSmithKlein(GSK), 6, Roche, 2, Roivant, 2; D. Erkan: Chugai, 5, GlaxoSmithKlein(GSK), 1, 5, 6, Merida Biosciences, 2, NIH, 5, Roche, 1, Roivant Sciences, 2, Star Therapeutics, 1, Up-To-Date, 9.

To cite this abstract in AMA style:

Sahin E, Efthymiou M, Andrade D, Barber M, Tektonidou M, Pengo V, Radin M, Pardos-Gea J, AGUIRRE ZAMORANO M, Kello N, Paredes-Ruiz D, Belmont H, Fortin P, WAHL D, Branch W, Gerosa M, Ramires de Jesus G, Zhang Z, Atsumi T, Pazzola G, Andreoli L, Duarte-Garcia A, Rodriguez-Almaraz E, Petri M, Cervera R, Artim Esen B, Pons-Estel G, Shi H, Knight J, Willis R, Bertolaccini M, Cohen H, Erkan D. The Prevalence and Clinical Significance of Heritable Thrombophilia in Antiphospholipid Antibody Positive Patients: Descriptive Results from the Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) Registry [abstract]. Arthritis Rheumatol. 2025; 77 (suppl 9). https://acrabstracts.org/abstract/the-prevalence-and-clinical-significance-of-heritable-thrombophilia-in-antiphospholipid-antibody-positive-patients-descriptive-results-from-the-antiphospholipid-syndrome-alliance-for-clinical-trials/. Accessed .

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