{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:54:30Z","timestamp":1792457670028,"version":"4.5.0"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T00:00:00Z","timestamp":1757980800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T00:00:00Z","timestamp":1757980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Immunol Res"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Efficient utilization of healthcare resources, including laboratory testing, is crucial for environmental sustainability and cost-effectiveness. The diagnosis of APS requires the presence of at least one clinical event (either an objectively confirmed thrombotic event and\/or pregnancy complication) and detection of one or more aPL (lupus anticoagulant [LA], IgG\/IgM anticardiolipin [aCL], and\/or IgG\/IgM anti-\u03b22 glycoprotein-1 [a\u03b22GPI]). However, inappropriate requests for aPL tests contribute to unnecessary healthcare expenses and environmental impact. This study evaluates the appropriateness of aPL testing in a clinical setting. A retrospective analysis was conducted on 642 patients attending the San Giovanni Di Dio Hospital, Florence (11\/2023\u201302\/2024). Diagnostic suspicion underlying aPL test requests were classified as appropriate, inappropriate, or unevaluable using a scoring system based on clinical recommendations. Appropriateness assessment was performed independently by two researchers and reconciled with a third expert. Patient demographics, test results, and the specialty of the physicians ordering aPL were recorded and analyzed. Of the 642 queries, 36% were deemed appropriate, 42% inappropriate, and 22% unevaluable. Family physicians accounted for 53% of all test requests but exhibited the highest rate of inappropriate requests (44%). Rheumatologists, internal medicine physicians, and gynecologists demonstrated better adherence to recommendations (with 34%, 30%, and 18% of inappropriate requests, respectively). Only 4.9% of patients underwent comprehensive aPL testing per international standards (Sidney criteria). Among the 115 aPL-positive cases, multiple antibody positivity was more common in appropriate test requests. Inappropriate requests often stemmed from conditions without established links to APS, such as alopecia, hypercholesterolemia, and dysmenorrhea. A considerable proportion of aPL testing in routine practice lacks clinical justification, reflecting variability in guideline adherence across specialties. Inappropriate testing increases healthcare costs, specialist referrals, and environmental burdens. Improved education, adherence to diagnostic recommendations, and sustainable practices are critical to optimizing APS testing and resource utilization.<\/jats:p>","DOI":"10.1007\/s12026-025-09682-x","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T19:27:40Z","timestamp":1758050860000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Optimizing antiphospholipid antibody testing: a real-world analysis of appropriateness and resource utilization"],"prefix":"10.1007","volume":"73","author":[{"given":"Silvia Grazietta","family":"Foddai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Infantino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariangela","family":"Manfredi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Pavia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Benucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Li Gobbi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Radin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Cecchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Barinotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Savino","family":"Sciascia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,16]]},"reference":[{"key":"9682_CR1","unstructured":"Brundtland GH. Our common future: report of the world commission on environment and development. Geneva: UN-Dokument A\/42\/427; 1987."},{"key":"9682_CR2","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1038\/s41598-024-83880-9","volume":"15","author":"M Zhang","year":"2025","unstructured":"Zhang M, Wang Y, Hu S, Wu Y. Causal relationships between air pollution and common autoimmune diseases: a two-sample Mendelian randomization study. Sci Rep. 2025;15:135.","journal-title":"Sci Rep"},{"issue":"1","key":"9682_CR3","first-page":"3","volume":"38","author":"JB Lopez","year":"2017","unstructured":"Lopez JB, Jackson D, Gammie A, Badrick T. Reducing the environmental impact of clinical laboratories. Clin Biochem Rev. 2017;38(1):3\u201311.","journal-title":"Clin Biochem Rev"},{"issue":"4","key":"9682_CR4","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1515\/cclm-2022-1092","volume":"61","author":"M Frag\u00e3o-Marques","year":"2023","unstructured":"Frag\u00e3o-Marques M, Ozben T. Digital transformation and sustainability in healthcare and clinical laboratories. Clinical Chemistry and Laboratory Medicine (CCLM). 2023;61(4):627\u201333.","journal-title":"Clinical Chemistry and Laboratory Medicine (CCLM)"},{"key":"9682_CR5","doi-asserted-by":"publisher","first-page":"1526","DOI":"10.1056\/NEJMoa021933","volume":"349","author":"MR Arbuckle","year":"2003","unstructured":"Arbuckle MR, McClain MT, Rubertone MV, Scofield RH, Dennis GJ, James JA, Harley JB. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med. 2003;349:1526\u201333.","journal-title":"N Engl J Med"},{"key":"9682_CR6","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1177\/0961203313515763","volume":"23","author":"N Pan","year":"2014","unstructured":"Pan N, Amigues I, Lyman S, Duculan R, Aziz F, Crow MK, Kirou KA. A surge in anti-dsDNA titer predicts a severe lupus flare within six months. Lupus. 2014;23:293\u20138.","journal-title":"Lupus"},{"key":"9682_CR7","doi-asserted-by":"publisher","unstructured":"Alyami MB, Hakeem MN, Fadil AI, Jee BA, ElAbbasy HM, Ankawi G. Frequency of repeating antinuclear antibody testing: when less is more. Cureus. 2024;16(1):e52347. https:\/\/doi.org\/10.7759\/cureus.52347.","DOI":"10.7759\/cureus.52347"},{"key":"9682_CR8","doi-asserted-by":"publisher","unstructured":"Andreoli L, Pregnolato F, Burlingame RW, Fanelli V, Allegri F, Radice A, Corace C, Sinico RA, Tincani A, Meroni PL. L'evoluzione da sindrome da anticorpi antifosfolipidi primaria a lupus eritematoso sistemico: possono gli anticorpi anti-nucleosomi essere predittivi? [Primary antiphospholipid syndrome evolving into systemic lupus erythematosus: may antinucleosome antibodies be predictive?]. Reumatismo. 2008;60(3):185\u201391. https:\/\/doi.org\/10.4081\/reumatismo.2008.185.","DOI":"10.4081\/reumatismo.2008.185"},{"key":"9682_CR9","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1111\/j.1538-7836.2006.01753.x","volume":"4","author":"S Miyakis","year":"2006","unstructured":"Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derkesen RHWM, De Groot PG, Koike T, Meroni PL, Reber G, Shoenfeld Y, Tincani A, Vlachoyiannopoulos PG, Krilis SA. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost J Thromb Haemost. 2006;4:295\u2013306.","journal-title":"J Thromb Haemost J Thromb Haemost"},{"key":"9682_CR10","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1038\/nrrheum.2011.52","volume":"7","author":"PL Meroni","year":"2011","unstructured":"Meroni PL, Borghi MO, Raschi E, Tedesco F. Pathogenesis of antiphospholipid syndrome: understanding the antibodies. Nat Rev Rheumatol. 2011;7:330\u20139.","journal-title":"Nat Rev Rheumatol"},{"key":"9682_CR11","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1038\/nrrheum.2017.124","volume":"13","author":"S Sciascia","year":"2017","unstructured":"Sciascia S, Amigo MC, Roccatello D, Khamashta M. Diagnosing antiphospholipid syndrome: \u201cextra-criteria\u201d manifestations and technical advances. Nat Rev Rheumatol. 2017;13:548\u201360.","journal-title":"Nat Rev Rheumatol"},{"key":"9682_CR12","doi-asserted-by":"crossref","unstructured":"Schreiber K, Sciascia S, de Groot PG, Devreese K, Jacobsen S, Ruiz-Irastroza G, Salmon JE, Shoenfeld Y, Shovman O, Hunt BJ. Antiphospholipid syndrome. Nat Rev Dis Primers. 2018;4:17103.","DOI":"10.1038\/nrdp.2018.5"},{"issue":"10","key":"9682_CR13","doi-asserted-by":"publisher","first-page":"1687","DOI":"10.1002\/art.42624","volume":"75","author":"M Barbhaiya","year":"2023","unstructured":"Barbhaiya M, Zuily S, Naden R, Hendry A, Manneville F, Amigo MC, Amoura Z, Andrade D, Andreoli L, Artim-Esen B, Atsumi T, Avcin T, Belmont MH, Bertolaccini ML, Branch DW, Carvalheiras G, Casini A, Cervera R, Cohen H, Costedoat-Chalumeau N, et al. 2023 ACR\/EULAR antiphospholipid syndrome classification criteria. Arthritis Rheumatol. 2023;75(10):1687\u2013702.","journal-title":"Arthritis Rheumatol."},{"key":"9682_CR14","doi-asserted-by":"publisher","unstructured":"Tektonidou MG, Andreoli L, Limper M, Amoura Z, Cervera R, Costedoat-Chalumeau N, Cuadrado MJ, D\u00f6rner T, Ferrer-Oliveras R, Hambly K, Khamashta MA, King J, Marchiori F, Meroni PL, Mosca M, Pengo V, Raio L, Ruiz-Irastorza G, Shoenfeld Y, Stojanovich L, Svenungsson E, Wahl D, Tincani A, Ward MM. EULAR recommendations for the management of antiphospholipid syndrome in adults. Ann Rheum Dis. 2019;78(10):1296\u2013304. https:\/\/doi.org\/10.1136\/annrheumdis-2019-215213.","DOI":"10.1136\/annrheumdis-2019-215213"},{"issue":"6","key":"9682_CR15","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1136\/annrheumdis-2021-221733","volume":"81","author":"GC Doros","year":"2022","unstructured":"Doros GC, Vedder D, Houben E, Boekel L, Atzeni F, Badreh S, Boumpas DT, Brodin N, Bruce IN, Gonz\u00e1lez-Gay M\u00c1, Jacobsen S, Kerekes G, Marchiori F, Mukhtyar C, Ramos-Casals M, Sattar N, Schreiber K, Sciascia S, Svenungsson E, Szekanecz Z, Tausche AK, Tyndall A, van Halm V, Voskuyl A, Macfarlane GJ, Ward MM, Nurmohamed MT, Tektonidou MG. EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal diseases, including systemic lupus erythematosus and antiphospholipid syndrome. Ann Rheum Dis. 2022;81(6):768\u201379. https:\/\/doi.org\/10.1136\/annrheumdis-2021-221733.","journal-title":"Ann Rheum Dis"},{"key":"9682_CR16","doi-asserted-by":"publisher","first-page":"2828","DOI":"10.1111\/jth.15047","volume":"18","author":"KMJ Devreese","year":"2020","unstructured":"Devreese KMJ, de Groot PG, de Laat B, Erkan D, Favaloro EJ, Mackie I, Martinuzzo M, Ortel TL, Pengo V, Rand JH, Tripodi A, Wahl D, Cohen H. Guidance from the Scientific and Standardization Committee for lupus anticoagulant\/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis: update of the recommendations for lupus anticoagulant detection and interpretation. J Thromb Haemost. 2020;18:2828\u201339.","journal-title":"J Thromb Haemost"},{"key":"9682_CR17","doi-asserted-by":"publisher","first-page":"2319","DOI":"10.1002\/art.34380","volume":"64","author":"M Satoh","year":"2012","unstructured":"Satoh M, Chan EKL, Ho LA, Rose KM, Parks CG, Cohn RD, et al. Prevalence and sociodemographic correlates of antinuclear antibodies in the United States. Arthritis Rheum. 2012;64:2319\u201327.","journal-title":"Arthritis Rheum"},{"key":"9682_CR18","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1002\/art.41214","volume":"72","author":"GE Dinse","year":"2020","unstructured":"Dinse GE, Parks CG, Weinberg CR, Co CA, Wilkerson J, Zeldin DC, et al. Increasing prevalence of antinuclear antibodies in the United States. Arthritis Rheumatol. 2020;72:1026\u201335.","journal-title":"Arthritis Rheumatol"},{"key":"9682_CR19","doi-asserted-by":"crossref","unstructured":"Eyal Reinstein 1 YS. Antiphospholipid syndrome and cancer. Clin Rev Allergy Immunol 2007;32:184\u20137.","DOI":"10.1007\/s12016-007-0003-1"},{"key":"9682_CR20","doi-asserted-by":"publisher","unstructured":"Gomez-Flores M, Herrera-Argaez G, Vazquez-Martinez O, Herz-Ruelas M, Ocampo-Candiani J, Villarreal-Martinez A, Galarza-Delgado DA, Hernandez-Galarza I, Chavez-Alvarez S. Cutaneous manifestations of antiphospholipid syndrome. Lupus. 2021;30(4):541\u201348. https:\/\/doi.org\/10.1177\/0961203321990100.","DOI":"10.1177\/0961203321990100"},{"key":"9682_CR21","doi-asserted-by":"publisher","unstructured":"Zhang J, Li C, Han X, Chen Z, Adhikari BK, Wang Y, Wang Y, Sun J. The digestive system involvement of antiphospholipid syndrome: pathophysiology, clinical characteristics, and treatment strategies. Ann Med. 2021;53(1):1328\u201339. https:\/\/doi.org\/10.1080\/07853890.2021.1962964.","DOI":"10.1080\/07853890.2021.1962964"},{"key":"9682_CR22","doi-asserted-by":"publisher","unstructured":"Saccone G, Berghella V, Maruotti GM, Ghi T, Rizzo G, Simonazzi G, Rizzo N, Facchinetti F, Dall'Asta A, Visentin S, Sarno L, Xodo S, Bernabini D, Monari F, Roman A, Eke AC, Hoxha A, Ruffatti A, Schuit E, Martinelli P; PREGNANTS (PREGNancy in women with ANTiphospholipid Syndrome) working group. Antiphospholipid antibody profile based obstetric outcomes of primary antiphospholipid syndrome: the PREGNANTS study. Am J Obstet Gynecol. 2017;216(5):525.e1\u201325.e12. https:\/\/doi.org\/10.1016\/j.ajog.2017.01.026.","DOI":"10.1016\/j.ajog.2017.01.026"},{"key":"9682_CR23","doi-asserted-by":"publisher","unstructured":"de Jes\u00fas GR, Benson AE, Chighizola CB, Sciascia S, Branch DW. 16th International Congress on Antiphospholipid Antibodies Task Force report on obstetric antiphospholipid syndrome. SAGE PublicationsSage UK: London, England; 2020; 29: 52, 1601\u201315. https:\/\/doi.org\/10.1177\/0961203320954520.","DOI":"10.1177\/0961203320954520"},{"key":"9682_CR24","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1136\/annrheumdis-2015-208840","volume":"75","author":"CG Skorpen","year":"2016","unstructured":"Skorpen CG, Hoeltzenbein M, Tincani A, Fischer-Betz R, Elefant E, Chambers C, et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis. 2016;75:795\u2013810.","journal-title":"Ann Rheum Dis"},{"key":"9682_CR25","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1136\/annrheumdis-2016-209770","volume":"76","author":"L Andreoli","year":"2017","unstructured":"Andreoli L, Bertsias GK, Agmon-Levin N, Brown S, Cervera R, Costedoat-Chalumeau N, et al. EULAR recommendations for women\u2019s health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and\/or antiphospholipid syndrome. Ann Rheum Dis. 2017;76:476\u201385.","journal-title":"Ann Rheum Dis"},{"key":"9682_CR26","doi-asserted-by":"publisher","unstructured":"Zare S, Meidani Z, Shirdeli M, Nabovati E. Laboratory test ordering in inpatient hospitals: a systematic review on the effects and features of clinical decision support systems. BMC Med Inform Decis Mak. 2021;21(1):20. https:\/\/doi.org\/10.1186\/s12911-020-01384-8.","DOI":"10.1186\/s12911-020-01384-8"},{"key":"9682_CR27","doi-asserted-by":"publisher","unstructured":"Cadamuro J, Gaksch M, Wiedemann H, Lippi G, von Meyer A, Pertersmann A, Auer S, Mrazek C, Kipman U, Felder TK, Oberkofler H, Haschke-Becher E. Are laboratory tests always needed? Frequency and causes of laboratory overuse in a hospital setting. Clin Biochem. 2018;54:85\u201391. https:\/\/doi.org\/10.1016\/j.clinbiochem.2018.01.024.","DOI":"10.1016\/j.clinbiochem.2018.01.024"},{"issue":"Suppl 2","key":"9682_CR28","doi-asserted-by":"publisher","first-page":"ii11","DOI":"10.1136\/bmjqs-2012-001616","volume":"22","author":"DE Newman-Toker","year":"2013","unstructured":"Newman-Toker DE, McDonald KM, Meltzer DO. How much diagnostic safety can we afford, and how should we decide? A health economics perspective. BMJ Qual Saf. 2013;22(Suppl 2):ii11-20.","journal-title":"BMJ Qual Saf"},{"issue":"1","key":"9682_CR29","first-page":"315179","volume":"2014","author":"M Mahler","year":"2014","unstructured":"Mahler M, Meroni PL, Bossuyt X, Fritzler MJ. Current concepts and future directions for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies. J Immunol Res J Immunol Res. 2014;2014(1):315179.","journal-title":"J Immunol Res J Immunol Res"}],"container-title":["Immunologic Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12026-025-09682-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12026-025-09682-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12026-025-09682-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T07:29:50Z","timestamp":1770190190000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12026-025-09682-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,16]]},"references-count":29,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["9682"],"URL":"https:\/\/doi.org\/10.1007\/s12026-025-09682-x","relation":{},"ISSN":["0257-277X","1559-0755"],"issn-type":[{"value":"0257-277X","type":"print"},{"value":"1559-0755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,16]]},"assertion":[{"value":"12 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 August 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 September 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was conducted in accordance with the Declaration of Helsinki; informed consent\u00a0was obtained from all individuals included in this study, or their legal guardians or wards.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"N\/A.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"130"}}