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Cited by 88Systemic Lupus Erythematosus ResearchVasculitis and related conditionsBlood Coagulation and Thrombosis Mechanisms

Characteristics of Patients With Antiphospholipid Antibody Positivity in the APS ACTION International Clinical Database and Repository

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Sevim, Ecem, Zisa, Diane, Andrade, Danieli, Sciascia, Savino, Pengo, Vittorio, Tektonidou, Maria G., Ugarte, Amaia, Gerosa, Maria +20 more·2022·Arthritis Care & Research
DOI 10.1002/acr.24468PMC PMC10725727
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Abstract

Objective: To describe the baseline characteristics of patients with positivity for antiphospholipid antibodies (aPLs) who were enrolled in an international registry, the Antiphospholipid Syndrome (APS) Alliance for Clinical Trials and International Networking (APS ACTION) clinical database and repository, overall and by clinical and laboratory subtypes. Methods: The APS ACTION registry includes adults who persistently had positivity for aPLs. We evaluated baseline sociodemographic and aPL‐related (APS classification criteria and “non‐criteria”) characteristics of patients overall and in subgroups (aPL‐positive without APS, APS overall, thrombotic APS only, obstetric APS only, and both thrombotic APS/obstetric APS). We assessed baseline characteristics of patients tested for the presence of three aPLs (lupus anticoagulant [LAC] test, anticardiolipin antibody [aCL], and anti–β 2‐glycoprotein I [anti‐β 2 GPI]) antibodies by aPL profiles (LAC only, single, double, and triple aPL positivity). Results: The 804 aPL‐positive patients assessed in the present study had a mean age of 45 ± 13 years, were 74% female, and 68% White; additionally, 36% had other systemic autoimmune diseases. Of these 804 aPL‐positive patients, 80% were classified as having APS (with 55% having thrombotic APS, 9% obstetric APS, and 15% thrombotic APS/obstetric APS). In the overall cohort, 71% had vascular thrombosis, 50% with a history of pregnancy had obstetric morbidity, and 56% had experienced at least one non‐criteria manifestation. Among those with three aPLs tested (n = 660), 42% were triple aPL–positive. While single–, double–, and triple aPL–positive subgroups had similar frequencies of vascular, obstetric, and non‐criteria events, these events were lowest in the single aPL subgroup, which consisted of aCLs or anti‐β 2 GPI only. Conclusion: Our study demonstrates the heterogeneity of aPL‐related clinical manifestations and laboratory profiles in a multicenter international cohort. Within single aPL positivity, LAC may be a major contributor to clinical events. Future prospective analyses, using standardized core laboratory aPL tests, will help clarify aPL risk profiles and improve risk stratification.

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  • aCL are generally regarded as less symptomatic than LA or aB2GPI.

    “which implies that aCL are generally regarded as less symptomatic than their conventional aPL counterparts.”

    From Single or triple positivity for antiphospholipid antibodies in “carriers” or symptomatic patients: Untangling the knot (2021) · cites this paper as [5]

    The Discussion (page not provided) says LAC positivity may be a stronger risk factor for thrombosis and pregnancy morbidity than positivity for either aCL or anti-β2GPI. It does not say that aCL is less symptomatic than anti-β2GPI, so it supports only the comparison with LAC. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • In the literature, among aPL, isolated LA and aB2GPI are generally found to be associated with higher thrombotic risk than aCL.

    “In the literature, 5-­ 8 among the aPL, isolated LA and aB2GPI are generally found to be associated with higher thrombotic risk than aCL.”

    From Single or triple positivity for antiphospholipid antibodies in “carriers” or symptomatic patients: Untangling the knot (2021) · cites this paper as [5]

    The Results (page not available in our copy) report that patients with isolated LAC positivity had the highest proportion of vascular events among the single-positive groups. The Discussion says LAC may carry greater thrombosis risk than either aCL or anti-β2GPI. It does not establish that isolated anti-β2GPI carries greater thrombotic risk than aCL. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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References 48 · Cited by 88

Research works printed but not linked: 38

  1. [2]Barbhaiya M, Andrade D, Bertolaccini M, Erkan D. Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION). In: Erkan D, Lockshin MD, editors. Antiphospholipid Syndrome: Current Research Highlights and Clinical Insights. Cham: Springer International Publishing; 2017. p. 267– 76.
  2. [3]Levine J, Branch, DW, Rauch J. The antiphospholipid syndrome. N Engl J Med 2002; 346: 752– 63. 11882732
  3. [4]Cervera R, Serrano R, Pons-Estel G, Ceberio-Hualde L, Shoenfeld Y, Ramón E, Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients. Ann Rheum Dis 2014; 74: 1011– 8. 24464962
  4. [5]Abdel-Wahab N, Lopez-Olivio M, Pinto-Patarroyo G, Suarez-Almazor M. Systematic re of case reports of antiphospholipid syndrome following infection. Lupus 2016; 25: 1520– 31. 27060064 PMC7508159
  5. [6]Reinstein E, Shoenfeld Y. Antiphospholipid syndrome and cancer. Clin Rev Allergy Immunol 2007; 32: 184– 7. 17916991
  6. [7]Pengo V, Biasiolo A, Pegoraro C, Cucchini U, Noventa F, Iliceto S. Antibody profiles for the diagnosis of antiphospholipid syndrome. Thromb Haemost 2005; 93: 1147– 52. 15968401
  7. [9]Yelnik C, Urbanski G, Drumez E, Sobanski V, Maillard H, Lanteri A, Persistent triple antiphospholipid antibody positivity as a strong risk factor of first thrombosis, in a long-term follow-up study of patients without history of thrombosis or obstetrical morbidity. Lupus 2017; 26: 163– 9. 27432808
  8. [11]Ünlü O, Zuily S, Erkan D. The clinical significance of antiphospholipid antibodies in systemic lupus erythematosus. Eur J Rheumatol 2016; 3: 75– 84. 27708976 PMC5042235
  9. [12]Duarte-García A, Pham MM, Crowson CS, Amin S, Moder KG, Pruthi RK, The epidemiology of antiphospholipid syndrome: a population-based study. Arthritis Rheumatol 2019; 71: 1545– 52. 30957430 PMC6717037
  10. [14]Harris P, Taylor R, Thielke R, Payne J, Gonzalez N, Conde J. Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Infor 2009; 42. PMC2700030 18929686
  11. [15]Asherson R, Cervera R, de Groot P, Erkan D, Boffa M-C, Piette JC. Catastrophic antiphospholipid syndrome: international consensus statement on classification criteria and treatment guidelines. Lupus 12: 530– 4. 12892393
  12. [16]Unlu O, Domingues V, de Jesús GR, Zuily S, Espinosa G, Cervera R, Definition and epidemiology of antiphospholipid syndrome. In: Erkan D, Lockshin MD, editors. Antiphospholipid Syndrome: Current Research Highlights and Clinical Insights. Cham: Springer International Publishing; 2017. p. 147– 69.
  13. [17]Blank M, Cohen J, Toder V, Shoenfeld Y. Induction of anti-phospholipid syndrome in naive mice with mouse lupus monoclonal and human polyclonal anti-cardiolipin antibodies. Proc Natl Acad Sci U S A 1991; 88: 3069– 73. 2014226 PMC51386
  14. [19]Zuily S, Wahl D. Pulmonary hypertension in antiphospholipid syndrome. Curr Rheumatol Rep 2015; 17: 478. 25604574
  15. [20]Tektonidou MG, Varsou N, Kotoulas G, Antoniou A, Moutsopoulos HM. Cognitive deficits in patients with antiphospholipid syndrome: association with clinical, laboratory, and brain magnetic resonance imaging findings. Arch Intern Med 2006; 166: 2278– 84. 17101948
  16. [21]Abreu MM, Danowski A, Wahl DG, Amigo MC, Tektonidou M, Pacheco MS, The relevance of “non-criteria” clinical manifestations of antiphospholipid syndrome: 14th International Congress on Antiphospholipid Antibodies Technical Task Force Report on Antiphospholipid Syndrome Clinical Features. Autoimmun Rev 2015; 14: 401– 14. 25641203
  17. [22]Zuily S, Clerc-Urmes I, Wahl D, Erkan D. Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) Clinical Database and Repository Cluster Analysis for Identification of Different Clinical Phenotypes Among Antiphospholipid Antibody-Positive Patients. Lupus 2016; 25: 74– 5.
  18. [23]Zuily S, Clerc-Urmes I, Chighizola C, Baumann C, Wahl D, Meroni P, Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) clinical database and repository cluster analysis for the identification of different clinical phenotypes among antiphospholipid antibody-positive female patients with a history of pregnancy. Lupus 2016; 25: 61.26306740
  19. [24]Garcia D, Erkan D. Diagnosis and management of the antiphospholipid syndrome. N Engl J Med 2018; 378: 2010– 21. 29791828
  20. [25]Finazzi G, Brancaccio V, Moia M, Ciavarella N, Mazzucconi MG, Schinco P, Natural history and risk factors for thrombosis in 360 patients with antiphospholipid antibodies: a four-year prospective study from the Italian registry. Am J Med 1996; 100: 530– 6. 8644765
  21. [26]Gresele P, Migliacci R, Vedovati MC, Ruffatti A, Becattini C, Facco M, Patients with primary antiphospholipid antibody syndrome and without associated vascular risk factors present a normal endothelial function. Thromb Res 2009; 123: 444– 51. 18617225
  22. [27]Zuily S, de Laat B, Mohamed S, Kelchtermans H, Shums Z, Albesa R, Validity of the global anti-phospholipid syndrome score to predict thrombosis: a prospective multicentre cohort study. Rheumatology (Oxford) 2015; 54: 2071– 5. 26163690
  23. [28]Mustonen P, Lehtonen KV, Javela K, Puurunen M. Persistent antiphospholipid antibody (aPL) in asymptomatic carriers as a risk factor for future thrombotic events: a nationwide prospective study. Lupus 2014; 23: 1468– 76. 25164304
  24. [30]Zuily S, Regnault V, Selton-Suty C, Eschwege V, Bruntz J-F, Bode-Dotto E, Increased risk for heart valve disease associated with antiphospholipid antibodies in patients with systemic lupus erythematosus: meta-analysis of echocardiographic studies. Circulation 2011; 124: 215– 24. 21690492
  25. [31]Domingues V, Magder LS, Petri M. Assessment of the independent associations of IgG, IgM and IgA isotypes of anticardiolipin with thrombosis in SLE. Lupus Sci Med 2016; 3: e000107. 27403332 PMC4932305
  26. [32]Lockshin M, Kim M, Laskin C, Guerra M, Branch D, Merrill J, Prediction of adverse pregnancy outcome by the presence of lupus anticoagulant, but not anticardiolipin antibody, in patients with antiphospholipid antibodies. Arthritis Rheum 2012; 64: 2311– 8. 22275304 PMC3357451
  27. [33]Erkan D, Aguiar CL, Andrade D, Cohen H, Cuadrado MJ, Danowski A, 14th International Congress on Antiphospholipid Antibodies Task Force Report on Antiphospholipid Syndrome Treatment Trends. Autoimmunity Res 2014; 13: 685– 696. 24468415
  28. [36]Erkan D, Vega J, Ramón G, Kozora E, Lockshin MD. A pilot open-label phase II trial of rituximab for non-criteria manifestations of antiphospholipid syndrome. Arthritis Rheum 2013; 65: 464– 71. 23124321
  29. [37]Elazary AS, Klahr P, Hershko A, Dranitzki Z, Rubinow A, Naparstek Y. Rituximab induces resolution of recurrent diffuse alveolar hemorrhage in a patient with primary antiphospholipid antibody syndrome. Lupus 2011; 21: 438– 40. 21993385
  30. [38]Lonze BE, Zachary AA, Magro CM, Desai NM, Orandi BJ, Dagher NN, Eculizumab prevents recurrent antiphospholipid antibody syndrome and enables successful renal transplantation. Am J Transplant 2014; 14: 459– 65. 24400968
  31. [39]Zapantis E, Furie R, Horowitz D. Response to eculizumab in the antiphospholipid antibody syndrome. Ann Rheum Dis 2015; 74: 341.24285491
  32. [40]Rai R, Cohen H, Dave M, Regan L. Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies). BMJ 1997; 314: 253– 7. 9022487 PMC2125731
  33. [41]Kutteh WH. Antiphospholipid antibody-associated recurrent pregnancy loss: treatment with heparin and low-dose aspirin is superior to low-dose aspirin alone. Am J Obstet Gynecol 1996; 174: 1584– 9. 9065133
  34. [42]Farquharson RG, Quenby S, Greaves M. Antiphospholipid syndrome in pregnancy: a randomized, controlled trial of treatment. Obstet Gynecol 2002; 100: 408– 13. 12220757
  35. [45]Zuo Y, Barbhaiya M, Erkan D. Primary thrombosis prophylaxis in persistently antiphospholipid antibody-positive individuals: where do we stand in 2018? Curr Rheumatol Rep 2018; 20: 66. 30203272
  36. [48]Sciascia S, Murru V, Sanna G, Roccatello D, Khamashta MA, Bertolaccini ML. Clinical accuracy for diagnosis of antiphospholipid syndrome in systemic lupus erythematosus: evaluation of 23 possible combinations of antiphospholipid antibody specificities. J Thromb Haemost 2012; 10: 2512– 8. 23025466
  37. [49]Pengo V, Ruffatti A, Tonello M, Cuffaro S, Banzato A, Bison E, Antiphospholipid syndrome: antibodies to Domain 1 of beta2-glycoprotein 1 correctly classify patients at risk. J Thromb Haemost 2015; 13: 782– 7. 25645395
  38. [50]Unlu O, Erkan D, Barbhaiya M, Andrade D, Nascimento I, Rosa R, The impact of systemic lupus erythematosus on the clinical phenotype of antiphospholipid antibody-positive patients: results from the AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal clinical database and repository. Arthritis Care Res (Hoboken) 2019; 71: 134– 41. 29669399 PMC6484425

Authors
Sevim, E., Zisa, D., Andrade, D., Sciascia, S., Pengo, V., Tektonidou, M. G., Ugarte, A., Gerosa, M., Belmont, H. M., Zamorano, M. A. A., Fortin, P. R., Ji, L., Efthymiou, M., Cohen, H., Branch, D. W., de Jesus, G. R., Andreoli, L., Petri, M., Rodriguez, E., Cervera, R., Knight, J. S., Atsumi, T., Willis, R., Roubey, R., Bertolaccini, M. L., Erkan, D., Barbhaiya, M., & APS ACTION Investigators
Affiliations
  • Hospital for Special Surgery (US)
  • Universidade de São Paulo (BR)
  • University of Turin (IT)
  • University of Padua (IT)
  • National and Kapodistrian University of Athens (GR)
  • Hospital de Cruces (ES)
  • University of Milan (IT)
  • New York University Langone Medical Center New York New York
  • Maimonides Institute for Biomedical Research of Cordoba Cordoba Spain
  • Université Laval (CA)
  • Peking University First Hospital (CN)
  • University College London (GB)
  • Intermountain Healthcare (US)
  • Rio de Janeiro State University Rio de Janeiro Brazil
  • University of Brescia Brescia Italy
  • Johns Hopkins University (US)
  • Hospital Universitario 12 de Octubre Madrid Spain
  • Hospital Clínic de Barcelona (ES)
  • University of Michigan (US)
  • Hokkaido University Hospital (JP)
  • The University of Texas Medical Branch at Galveston (US)
  • University of North Carolina at Chapel Hill (US)
  • St Thomas’ Hospital London UK
Corresponding author
Barbhaiya, Medha
ORCID
Venue
Arthritis Care & Research
Publisher
Wiley
Published
2022-01-25
Volume
74
Issue
2
Pages
324-335
ISSN
  • 0893-7524 (ISSN-L)
  • 2151-464X
  • 2151-4658
DOI
10.1002/acr.24468
PMC
PMC10725727
OpenAlex
W3091092179
Cited by
88
References
48
Citations by year
2026: 14 · 2025: 19 · 2024: 16 · 2023: 20 · 2022: 8 · 2021: 10 · 2020: 1
FWCI
7.35
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Arthritis Care & Research (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Deep Blue (University of Michigan) (submittedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
Funders
  • Canada Research Chairs
  • National Institutes of Health (R01‐AR069572)
  • Rheumatology Research Foundation
Topics
  • Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Vasculitis and related conditions
  • Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
Keywords
antiphospholipid antibodies, antiphospholipid syndrome, lupus anticoagulant, anticardiolipin antibodies, anti-beta2-glycoprotein I antibodies, vascular thrombosis, pregnancy complications, risk stratification, systemic autoimmune diseases
MeSH terms
Adult, Female, Humans, Male, Middle Aged, Registries, Cohort Studies, Antibodies, Antiphospholipid

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