Predictive value of persistent versus transient antiphospholipid antibody subtypes for the risk of thrombotic events in pediatric patients with systemic lupus erythematosus
Abstract
Study objectives were to determine, in children with systemic lupus erythematosus (SLE), (1) the association of antiphosholipid antibody (APLA) subtypes with thrombotic events (TEs) and (2) the predictive value of persistent versus transient antibodies for TEs. This is a cohort study of 58 SLE children in whom lupus anticoagulants (LAs), anticardiolipin antibodies (ACLAs), anti-beta2-glycoprotein-I (anti-beta2-GPI), and antiprothrombin (anti-PT) were assessed on at least 2 occasions (more than 3 months apart). Antibodies were classified as persistent (positive on at least 2 occasions) or transient (positive once). Outcomes were symptomatic TEs confirmed by objective radiographic tests identified retrospectively and prospectively. Seven of the 58 patients (12%) had 10 TEs; 5 patients had TEs during prospective follow-up. Persistent LAs showed the strongest association with TEs (P < .001). Persistent ACLAs (P = .003) and anti-beta2-GPI (P = .002) were significantly associated with TEs; anti-PT (P = .063) showed a trend. Persistent or transient LAs and anti-beta2-GPI showed similar strength of association, while ACLAs and anti-PT were no longer associated with TEs. Positivity for multiple APLA subtypes showed stronger associations with TEs than for individual APLA subtypes because of improved specificity. Lupus anticoagulant is the strongest predictor of the risk of TEs; other APLA subtypes provide no additional diagnostic value. Anticardiolipin antibodies and anti-PT require serial testing because only persistent antibodies are associated with TEs.
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For transiently positive antibodies, the strength of the association with thrombosis decreased for aCL and aPT, but remained the same for LA and anti-β2-glycoprotein I.
“For transiently positive antibodies, the strength of the association with thrombosis decreased for aCL and aPT, but remained the same for LA and anti-β2-glycoprotein I.”
From Antiphospholipid patterns predict risk of thrombosis in systemic lupus erythematosus (2021) · cites this paper as [45]
Male et al. found, in multivariate analyses, that LA was the strongest predictor of thrombosis, even if grouping patients with one or two positive tests.
“Male et al. [45] found, in multivariate analyses, that LA was the strongest predictor of thrombosis, even if grouping patients with one or two positive tests.”
From Antiphospholipid patterns predict risk of thrombosis in systemic lupus erythematosus (2021) · cites this paper as [45]
Cites
The 1982 revised criteria for the classification of systemic lupus erythematosus
Tan, E. M., Cohen, A. S., Fries, J. F., Masi, A. T., Mcshane, D. J., Rothfield, N. F., Schaller, J. G., Talal, N., & Winchester, R. J. (1982) · Arthritis & Rheumatism · doi:10.1002/art.1780251101 · Cited by 14,519 · see citing works
Derivation of the sledai. A disease activity index for lupus patients
Bombardier, C., Gladman, D. D., Urowitz, M. B., Caron, D., Chang, C. H., Austin, A., Bell, A., Bloch, D. A., Corey, P. N., Decker, J. L., et al. (1992) · Arthritis & Rheumatism · doi:10.1002/art.1780350606 · Cited by 4,570 · see citing works
Brandt, J. T., Triplett, D. A., Alving, B. M., & Scharrer, I. (1995) · PubMed · Cited by 1,164 · see citing works
Brandt, J. T., Triplett, D. A., Alving, B., & Scharrer, I. (1995) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1649901 · Cited by 993 · see citing works
Galli, M., Luciani, D., Bertolini, G., & Barbui, T. (2003) · Blood · doi:10.1182/blood-2002-02-0441 · Cited by 974 · cited 7× · see citing works
“The first was a meta-analysis including 18 studies in adult patients with SLE demonstrating that LA shows stronger association with TEs than ACLAs.1 A more recent systematic review included 25 studies in adult patients with or without SLE.10 The review confirmed LAs as a strong risk factor for TEs but did not find une…”
BackgroundInfluentialGalli, M., Luciani, D., Bertolini, G., & Barbui, T. (2003) · Blood · doi:10.1182/blood-2002-11-3334 · Cited by 413 · see citing works
Roubey, R. A. S. (1994) · Blood · doi:10.1182/blood.v84.9.2854.2854 · Cited by 331 · see citing works
Roubey, R. A. S., Eisenberg, R. A., Harper, M. F., & Winfield, J. B. (1995) · The Journal of Immunology · doi:10.4049/jimmunol.154.2.954 · Cited by 329 · see citing works
Heterogeneity of anticardiolipin antibodies defined by the anticardiolipin cofactor
Matsuura, E., Igarashi, Y., Fujimoto, M., Ichikawa, K., Suzuki, T., Sumida, T., Yasuda, T., & Koike, T. (1992) · The Journal of Immunology · doi:10.4049/jimmunol.148.12.3885 · Cited by 322 · see citing works
Antibody profiles for the diagnosis of antiphospholipid syndrome
Biasiolo, A., Pegoraro, C., Cucchini, U., Noventa, F., Iliceto, S., & Pengo, V. (2005) · Thrombosis and Haemostasis · doi:10.1160/th04-12-0839 · Cited by 318 · see citing works
Wahl, D., Guillemin, F., de Maistre, E., Perret, C., Lecompte, T., & Thibaut, G. (1997) · Lupus · doi:10.1177/096120339700600510 · Cited by 284 · cited 3× · see citing works
“Testing for LAs was performed according to the criteria of the Subcommittee on APLA of the International Society of Thrombosis and Haemostasis24 as previously described in detail19: (1) screening assays included the kaolin clotting time, dilute activated partial thromboplastin time (aPTT), dilute prothrombin time, and…”
MethodResultHorbach, D. A., van Oort, E., Donders, R. C. J. M., Derksen, R. H. W. M., & de Groot, P. G. (1996) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1650686 · Cited by 246 · see citing works
Anticardiolipin response in acute infections
Vaarala, O., Palosuo, T., Kleemola, M., & Aho, K. (1986) · Clinical Immunology and Immunopathology · doi:10.1016/0090-1229(86)90046-2 · Cited by 231 · see citing works
Arvieux, J., Darnige, L., Caron, C., Reber, G., Bensa, J., & Colomb, M. G. (1995) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1649891 · Cited by 210 · see citing works
Tsutsumi, A., Matsuura, E., Ichikawa, K., Fujisaku, A., Mukai, M., Kobayashi, S., & Koike, T. (1996) · Arthritis & Rheumatism · doi:10.1002/art.1780390905 · Cited by 192 · see citing works
Measurement of anti-phospholipid antibodies by ELISA using β2-glycoprotein I as an antigen
Arvieux, J., Roussel, B., Jacob, M., & Colomb, M. G. (1991) · Journal of Immunological Methods · doi:10.1016/0022-1759(91)90047-j · Cited by 187 · see citing works
Anti β2 glycoprotein I antibodies: detection and association with thrombosis
Martinuzzo, M. E., Forastiero, R. R., & Carreras, L. O. (1995) · British Journal of Haematology · doi:10.1111/j.1365-2141.1995.tb03317.x · Cited by 163 · see citing works
Forastiero, R. R., Martinuzzo, M. E., Cerrato, G. S., Kordich, L., & Carreras, L. O. (1997) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1657678 · Cited by 146 · see citing works
Clinical significance of lupus anticoagulants in children
Male, C., Lechner, K., Eichinger, S., et al. (1999) · The Journal of Pediatrics · doi:10.1016/s0022-3476(99)70416-6 · Cited by 144 · see citing works
Self-citationAntibodies to Prothrombin Imply a Risk of Myocardial Infarction in Middle-Aged Men
Vaarala, O., Puurunen, M. K., Mänttäri, M., Manninen, V., Aho, K., & Palosuo, T. (1996) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1650296 · Cited by 130 · see citing works
Antiphospholipid-protein antibodies: Laboratory detection and clinical relevance
Triplett, D. A. (1995) · Thrombosis Research · doi:10.1016/0049-3848(95)00001-1 · Cited by 126 · see citing works
Long, A. A., Ginsberg, J. S., Brill-Edwards, P., Johnston, M., Turner, C., Denburg, J. A., Bensen, W. G., Cividino, A., Andrew, M., & Hirsh, J. (1991) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1646452 · Cited by 120 · cited 7× · see citing works
“However, there was no consistent association between a specific APLA subtype or isotype and either an arterial or venous TE.”
BackgroundResultInfluentialReber, G., Schousboe, I., Tincani, A., Sanmarco, M., Kveder, T., de Moerloose, P., Boffa, M., & Arvieux, J. (2002) · PubMed · Cited by 119 · see citing works
Thromboembolism in paediatric lupus patients
Levy, D. M., Massicotte, M. P., Harvey, E. A., et al. (2003) · Lupus · doi:10.1191/0961203303lu458oa · Cited by 112 · see citing works
Berube, C., Mitchell, L. G., Silverman, E. D., David, M., Saint‐Cyr, C., Laxer, R. M., Adams, M., Vegh, P., & Andrew, M. E. (1998) · Pediatric Research · doi:10.1203/00006450-199809000-00014 · Cited by 108 · see citing works
Self-citationGinsberg, J., Brill-Edwards, P. A., Johnston, M., Denburg, J. A., Andrew, M., Burrows, R. F., Bensen, W., Cividino, A. A., & Long, A. A. (1992) · Blood · doi:10.1182/blood.v80.4.975.975 · Cited by 93 · see citing works
Inter-laboratory Variability of Anti-β2-glycoprotein I Measurement
Schousboe, I., Tincani, A., Sanmarco, M., Kveder, T., de Moerloose, P., Boffa, M., Arvieux, J., & Reber, G. (2002) · Thrombosis and Haemostasis · doi:10.1055/s-0037-1613156 · Cited by 90 · see citing works
Bertolaccini, M. L., Atsumi, T., Khamashta, M. A., Amengual, O., & Hughes, G. R. V. (1998) · PubMed · Cited by 89 · see citing works
Forastiero, R. R., Martinuzzo, M. E., Kordich, L., & Carreras, L. O. (1996) · PubMed · Cited by 84 · see citing works
Male, C., Mitchell, L. G., Julian, J. A., et al. (2001) · Blood · doi:10.1182/blood.v97.4.844 · Cited by 77 · see citing works
Self-citationForastiero, R. R., Martinuzzo, M. E., Kordich, L., & Carreras, L. O. (1996) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1650354 · Cited by 72 · see citing works
Sebastiani, G. D., Galeazzi, M., Tincani, A., Pietté, J. C., Font, J., Allegri, F., Mathieu, A., Smolen, J. S., Garrido, E. D. R., Fernández‐Nebro, A., et al. (1999) · Scandinavian Journal of Rheumatology · doi:10.1080/03009749950155320 · Cited by 71 · see citing works
Sanmarco, M., Soler, C., Christides, C., Raoult, D., Weiller, P. J., Gérolami, V., & Bernard, D. J. (1997) · Journal of Laboratory and Clinical Medicine · doi:10.1016/s0022-2143(97)90004-4 · Cited by 67 · see citing works
Clinical signification of lupus anticoagulant in children
Male, C. (1999) · Jornal de Pediatria · Cited by 67 · see citing works
Self-citationClinical importance of persistence of anticardiolipin antibodies in systemic lupus erythematosus.
Ishii, Y., Nagasawa, K., Mayumi, T., & Niho, Y. (1990) · Annals of the Rheumatic Diseases · doi:10.1136/ard.49.6.387 · Cited by 66 · see citing works
Muñoz, F. J., Reverter, J. C., Font, J., Tàssies, D., Cervera, R., Espinosa, G., Carmona, F., Balasch, J., Ordinas, A., & Ingelmo, M. (2000) · PubMed · Cited by 56 · see citing works
Nojima, J., Kuratsune, H., Suehisa, E., Futsukaichi, Y., Yamanishi, H., Machii, T., Kitani, T., Iwatani, Y., & Kanakura, Y. (2001) · British Journal of Haematology · doi:10.1046/j.1365-2141.2001.02950.x · Cited by 54 · see citing works
von Scheven, E., Glidden, D. V., & Elder, M. E. (2002) · Arthritis Care & Research · doi:10.1002/art.10510 · Cited by 53 · see citing works
Heterogeneity and Immunochemical Properties of Anti-β2-glycoprotein I Autoantibodies
Regnault, V., HACHULLA, E., Darnige, L., et al. (1998) · Thrombosis and Haemostasis · doi:10.1055/s-0037-1615218 · Cited by 44 · see citing works
Sebastiani, G. D., Galeazzi, M., Tincani, A., Pietté, J. C., Font, J., Allegri, F., Mathieu, A., Smolen, J. S., Garrido, E. D. R., Fernández‐Nebro, A., et al. (1999) · Scandinavian Journal of Rheumatology · doi:10.1080/03009749950155328 · Cited by 43 · see citing works
Out, H. J., van Vliet, M., de Groot, P. G., & Derksen, R. H. (1992) · Annals of the Rheumatic Diseases · doi:10.1136/ard.51.3.353 · Cited by 42 · see citing works
Lee, S., Cho, M. L., Joo, Y.-S., Kim, W. U., Hong, Y. S., Min, J., Lee, S. H., Park, S. H., Cho, C. S., & Kim, H. (2001) · PubMed · Cited by 41 · see citing works
CLASSIFICATION CRITERIA FOR ANTIPHOSPHOLIPID SYNDROME
Wilson, W. A. (2001) · Rheumatic Disease Clinics of North America · doi:10.1016/s0889-857x(05)70216-7 · Cited by 41 · see citing works
Donohoe, S., Mackie, I. J., Isenberg, D. A., & Machin, S. J. (2001) · British Journal of Haematology · doi:10.1046/j.1365-2141.2001.02716.x · Cited by 38 · see citing works
Erickson, E., Najmey, S. S., KEIL, L. B., et al. (1996) · Clinical Chemistry · doi:10.1093/clinchem/42.7.1116 · Cited by 26 · see citing works
Kaburaki, J., Kuwana, M., Yamamoto, M., et al. (1995) · Lupus · doi:10.1177/096120339500400609 · Cited by 23 · see citing works
The Evaluation of Clotting Times in the Laboratory Detection of Lupus Anticoagulants
Jacobsen, E. M., Barna, L. K., Taylor, J., Triplett, D. A., & Wislöff, F. (2001) · Thrombosis Research · doi:10.1016/s0049-3848(01)00365-6 · Cited by 22 · see citing works
Tsutsumi, A., Ichikawa, K., Matsuura, E., Sawada, K., & Koike, T. (2000) · PubMed · Cited by 17 · see citing works
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MIYAKIS, S., LOCKSHIN, M. D., ATSUMI, T., BRANCH, D. W., BREY, R. L., CERVERA, R., DERKSEN, R. H. W. M., DE GROOT, P. G., KOIKE, T., MERONI, P. L., et al. (2006) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2006.01753.x · Cited by 7,203 · see citing works
A systematic review of secondary thromboprophylaxis in patients with antiphospholipid antibodies
Ruiz‐Irastorza, G., Hunt, B. J., & Khamashta, M. A. (2007) · Arthritis Care & Research · doi:10.1002/art.23109 · Cited by 324 · see citing works
Invitation to a debate on the serological criteria that define the antiphospholipid syndrome
GALLI, M., REBER, G., DE MOERLOOSE, P., & DE GROOT, P. G. (2008) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2008.02862.x · Cited by 85 · see citing works
Laboratory diagnosis of the antiphospholipid syndrome: a plethora of obstacles to overcome
Devreese, K., & Hoylaerts, M. F. (2009) · European Journal Of Haematology · doi:10.1111/j.1600-0609.2009.01243.x · Cited by 78 · see citing works
Martinez-Berriotxoa, A., Ruiz-Irastorza, G., Egurbide, M.-V., Garmendia, M., Gabriel Erdozain, J., Villar, I., & Aguirre, C. (2007) · Lupus · doi:10.1177/0961203307083316 · Cited by 77 · see citing works
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Amory, C. F., Levine, S. R., Brey, R. L., Gebregziabher, M., Tuhrim, S., Tilley, B. C., Simpson, A.-C. C., Sacco, R. L., Mohr, J. P., & Collaborators, F. T. A.-W. (2015) · Cerebrovascular Diseases · doi:10.1159/000441362 · Cited by 31 · see citing works
- Authors
- Male, C., Foulon, D., Hoogendoorn, H., Vegh, P., Silverman, E., David, M., & Mitchell, L.
- Affiliations
- Hospital for Sick Children (CA)
- From the Children's Hospital, Medical University of Vienna, Austria; Henderson Research Centre, McMaster University, Hamilton, ON; Hospital for Sick Children, Toronto, ON; Hôpital Ste Justine, Montreal, QC; and Stollery Children's Hospital, Edmonton, AB, Canada.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2005-12-15
- Volume
- 106
- Issue
- 13
- Pages
- 4152-4158
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W1963752281
- Cited by
- 106
- References
- 49
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 6 · 2020: 5 · 2019: 4 · 2017: 4 · 2016: 9 · 2015: 3 · 2014: 5 · 2013: 3 · 2012: 10
- FWCI
- 4.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- 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
- systemic lupus erythematosus, pediatric lupus, antiphospholipid antibodies, thrombotic complications, lupus anticoagulant, anticardiolipin antibodies, anti-beta2-glycoprotein I antibodies, anti-prothrombin antibodies, thrombosis risk prediction
- MeSH terms
- Adolescent, Adult, Child, Child, Preschool, Female, Humans, Lupus Erythematosus, Systemic, Male, Predictive Value of Tests, Prospective Studies, Retrospective Studies, Risk Factors, Thrombosis, Time Factors, Cohort Studies, Antibodies, Antiphospholipid
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