{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T14:29:55Z","timestamp":1766068195094,"version":"build-2065373602"},"reference-count":28,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T00:00:00Z","timestamp":1754956800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: The role of direct oral anticoagulants (DOACs) vs. vitamin K antagonists (VKAs) in preventing recurrent thrombosis in patients with antiphospholipid syndrome (APS) remains uncertain. Using real-world data, we aimed to evaluate the effectiveness and internal validity of a digital twin (DT) approach for modeling thrombotic recurrence risk in APS patients treated with DOACs or VKAs. Methods: We conducted a multicenter observational study that included thrombotic APS patients treated with DOACs or VKAs. Clinical data were used to generate DT via conditional generative adversarial networks (CGANs), incorporating a directed acyclic graph (DAG) to preserve causal relationships. Validation metrics included absolute standardized mean differences (ASMD), mean ASMD (MASMD), and Spearman correlation matrices to assess structural fidelity. Treatment effects were estimated in a CGAN-conditioned cohort matched on key covariates. Results: Eighty-nine thrombotic APS patients were included: 70 (78.7%) received VKAs and 19 (21.3%) received DOACs. Thrombotic recurrences occurred in 5 DOAC patients (26.3%) and 17 AVK patients (24.3%). The CGAN-generated synthetic cohort closely mirrored the original data (MASMD = 0.073 \u00b1 0.041), with 85.4% of pairwise correlations differing by &lt;0.1 in absolute value. In the conditioned DT cohort, predicted recurrence was 24.2% for DOACs and 19.9% for VKAs. Recurrence risk increased with antibody burden, reaching 41.3% in triple-positive patients and 46.8% in those with index arterial thrombosis treated with DOACs. Conclusions: DT technology accurately replicated the clinical structure of APS patients, supporting its application for simulating counterfactual scenarios and estimating individualized treatment effects.<\/jats:p>","DOI":"10.3390\/jcm14165716","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T16:30:36Z","timestamp":1755016236000},"page":"5716","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Digital Twin Strategy to Predict Thrombotic Recurrence in Antiphospholipid Syndrome Patients Treated with Direct Oral Anticoagulants vs. Vitamin K Antagonists Using Data from Real-World Populations"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2293-9644","authenticated-orcid":false,"given":"Miguel \u00c1ngel","family":"Casado-Suela","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Hospital Universitario Infanta Leonor, 28031 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3357-4038","authenticated-orcid":false,"given":"Juan","family":"Torres-Macho","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Universitario Infanta Leonor, 28031 Madrid, Spain"},{"name":"Department of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aida","family":"Izquierdo-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Universitario de Fuenlabrada, 28942 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3832-8170","authenticated-orcid":false,"given":"Cristina Luc\u00eda","family":"Ancos-Aracil","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Universitario de Fuenlabrada, 28942 Madrid, Spain"},{"name":"Venous Thromboembolism Unit, Hospital Universitario de Fuenlabrada, 28942 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Ferreira-Burguillos","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Universitario de Fuenlabrada, 28942 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Madro\u00f1al-Cerezo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Universitario de Fuenlabrada, 28942 Madrid, Spain"},{"name":"Venous Thromboembolism Unit, Hospital Universitario de Fuenlabrada, 28942 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamar","family":"Talav\u00e1n-Za\u00f1\u00f3n","sequence":"additional","affiliation":[{"name":"Clinical Analysis Laboratory, Hospital Universitario Infanta Leonor, 28031 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adela","family":"Casta\u00f1eda-Mata","sequence":"additional","affiliation":[{"name":"Clinical Analysis Laboratory, Hospital Universitario de Fuenlabrada, 28942 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Escobar-Curbelo","sequence":"additional","affiliation":[{"name":"Artificial Intelligence, 11012 C\u00e1diz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Mart\u00ednez","family":"de la Casa-Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Hospital Universitario Gregorio Mara\u00f1\u00f3n, 28007 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Ruiz-Nav\u00edo","sequence":"additional","affiliation":[{"name":"Hospital Universitario Infanta Leonor, 28031 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Bustamante-Fermosel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Universitario Infanta Leonor, 28031 Madrid, Spain"},{"name":"Department of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1061-0200","authenticated-orcid":false,"given":"Anabel","family":"Franco-Moreno","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Universitario Infanta Leonor, 28031 Madrid, Spain"},{"name":"Venous Thromboembolism Unit, Hospital Universitario Infanta Leonor, 28031 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1002\/art.42624","article-title":"The 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