Clinical characteristics and prognosis of patients with antiphospholipid antibodies based on cluster analysis: an 8-year cohort study
Open accessAbstract
Background: Antiphospholipid syndrome (APS) is an autoimmune disease characterized by persistent antiphospholipid antibodies (aPLs) positivity with a wide manifestation spectrum. A risk stratification is needed for management guidance and prognosis assessment. We aimed to identify phenotypes among aPL-positive patients and assess the prognosis of each phenotype. Methods: This was a single-center, prospective cohort study of aPL-positive patients presented to Peking Union Medical College Hospital from 2012 to 2020. Demographic characteristics, aPL-related manifestations, cardiovascular risk factors, and antibodies profiles were recorded. The primary endpoint was defined as a combination of newly onset thrombosis, major bleeding events, non-criteria manifestations, and all-cause death. Hierarchical cluster analysis and Kaplan-Meier survival analysis were performed. Results: Four clusters among 383 patients (70.2% female; mean age 37.7 years) were identified. Cluster 1 ( n = 138): patients with systemic lupus erythematosus (SLE) and non-criteria manifestations; cluster 2 ( n = 112): patients with multiple cardiovascular risk factors; cluster 3 ( n = 83): female patients with obstetric morbidity; cluster 4 ( n = 50): patients with isolated lupus anticoagulant (LA) positivity. Non-criteria manifestations were found aggregated with SLE from cluster analysis of variables. Cluster 3 showed the best outcome, while cluster 2 suffered highest frenquency of newly onset arterial thrombosis. Conclusions: We identified 4 clinical phenotypes of aPL-positive patients. Non-criteria manifestations may indicate underlying SLE, for which immunosuppressive therapy besides anticoagulation may be necessary. Patients with isolated LA positivity suffered similar risks with secondary APS and patients with multiple cardiovascular risk factors. Attention should be paid to male patients, and the screening of cardiovascular risk factors should never be ignored.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Most triple-positivity studies report LA testing as positive without distinguishing between dRVVT and APTT and single-assay positivity or only perform dRVVT.
“Of note is that many studies on triple positivity merely report patients as being positive for LA without assessing dRVVT and APTT results separately [10,[23][24][25][26][27][28][29], or even use only 1 assay [7,8,12].”
From Triple-positive antiphospholipid syndrome does not guarantee positivity in each lupus anticoagulant assay (2023) · cites this paper as [12]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Aringer, M., Costenbader, K., Daikh, D., Brinks, R., Mosca, M., Ramsey‐Goldman, R., Smolen, J. S., Wofsy, D., Boumpas, D. T., Kamen, D. L., et al. (2019) · Arthritis & Rheumatology · doi:10.1002/art.40930 · Cited by 2,677 · see citing works
Cervera, R., Piette, J., Font, J., Khamashta, M. A., Shoenfeld, Y., Camps, M. T., Jacobsen, S., Lakos, G., Tincani, A., Kontopoulou‐Griva, I., et al. (2002) · Arthritis & Rheumatism · doi:10.1002/art.10187 · Cited by 2,156 · cited 2× · see citing works
“In addition to thrombotic events and recurrent obstetric losses, aPLs were also associated with a higher prevalence of thrombocytopenia, hemolytic anemia, heart valve disease, livedo reticularis, aPL-related nephropathy, and cognitive impairment, referred to “non-criteria manifestations”, which led to disease exacerba…”
BackgroundEULAR recommendations for the management of antiphospholipid syndrome in adults
Tektonidou, M. G., Andreoli, L., Limper, M., Amoura, Z., Cervera, R., Costedoat-Chalumeau, N., Cuadrado, M. J., Dörner, T., Ferrer-Oliveras, R., Hambly, K., et al. (2019) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2019-215213 · Cited by 1,261 · cited 1× · see citing works
“LA positivity was defined as one of the high-risk aPLs profiles according to the EULAR recommendations [22] and was assigned of 4 points in the Global Anti-Phospholipid Syndrome Score (GAPSS) [15].”
MethodRuffatti, A., Del Ross, T., Ciprian, M., Bertero, M. T., Salvatore, S., Scarpato, S., Montecucco, C., Rossi, S., Caramaschi, P., Biasi, D., et al. (2011) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2010.142042 · Cited by 184 · see citing works
Reynaud, Q., Lega, J.-C., Mismetti, P., Chapelle, C., Wahl, D., Cathébras, P., & Laporte, S. (2014) · Autoimmunity Reviews · doi:10.1016/j.autrev.2013.11.004 · Cited by 179 · see citing works
Flagged first, then by citations
Research works printed but not linked: 25
- [1]Oliveira DC Correia A Oliveira C The issue of the antiphospholipid antibody syndrome J Clin Med Res 2020 12 5 286 292 10.14740/jocmr4154 32489503 PMC7239578 · DOI
- [2]Lopes MRU, Danowski A, Funke A, Rêgo J, Levy R, Andrade DCO. Update on antiphospholipid antibody syndrome. Rev Assoc Med Bras (1992). 2017;63(11):994-9. 10.1590/1806-9282.63.11.994. 29451664 · DOI
- [3]Buttari B Profumo E Capozzi A Saso L Sorice M Riganò R Post-translational modifications of proteins in antiphospholipid antibody syndrome Crit Rev Clin Lab Sci 2019 56 8 511 525 10.1080/10408363.2019.1650714 31448653 · DOI
- [5]Ünlü O Zuily S Erkan D The clinical significance of antiphospholipid antibodies in systemic lupus erythematosus Eur J Rheumatol 2016 3 2 75 84 10.5152/eurjrheum.2015.0085 27708976 PMC5042235 · DOI
- [6]Ogata Y Fujieda Y Sugawara M Morbidity and mortality in antiphospholipid syndrome based on cluster analysis: a 10-year longitudinal cohort study Rheumatology (Oxford) 2021 60 3 1331 1337 10.1093/rheumatology/keaa542 32944779 · DOI
- [7]Sciascia S Radin M Cecchi I Identifying phenotypes of patients with antiphospholipid antibodies: results from a cluster analysis in a large cohort of patients Rheumatology (Oxford) 2021 60 3 1106 1113 10.1093/rheumatology/kez596 31840749 · DOI · Paper page
- [8]Zuily S, Clerc-Urmès I, Bauman C, et al. Cluster analysis for the identification of clinical phenotypes among antiphospholipid antibody-positive patients from the APS ACTION Registry. Lupus. 2020:961203320940776. 10.1177/0961203320940776. PMC8216235 32703117 · DOI
- [9]Miyakis S Lockshin MD Atsumi T International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS) J Thromb Haemost 2006 4 2 295 306 10.1111/j.1538-7836.2006.01753.x 16420554 · DOI · Paper page
- [11]Schreiber K Sciascia S de Groot PG Antiphospholipid syndrome Nat Rev Dis Primers 2018 4 17103 10.1038/nrdp.2017.103 29321641 · DOI
- [12]Amigo MC What do we know about the cardiac valve lesion in the antiphospholipid syndrome (APS)? Lupus. 2014 23 12 1259 1261 10.1177/0961203314534307 25228720 · DOI
- [13]Malika Charrad NG Boiteau V Niknafs A NbClust: an R package for determining the relevant number of clusters in a data set J Stat Softw 2014 61 6 1 36 10.1016/j.ultrasmedbio.2019.11.004 · DOI
- [14]Krause I Blank M Fraser A The association of thrombocytopenia with systemic manifestations in the antiphospholipid syndrome Immunobiology. 2005 210 10 749 754 10.1016/j.imbio.2005.10.005 16325493 · DOI
- [15]Stojanovich L Kontic M Djokovic A Association between systemic non-criteria APS manifestations and antibody type and level: results from the Serbian national cohort study Clin Exp Rheumatol 2013 31 2 234 242 23306109
- [16]Unlu O Erkan D Barbhaiya M 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 2019 71 1 134 141 10.1002/acr.23584 PMC6484425 29669399 · DOI
- [17]Vianna JL Khamashta MA Ordi-Ros J Comparison of the primary and secondary antiphospholipid syndrome: a European Multicenter Study of 114 patients Am J Med 1994 96 1 3 9 10.1016/0002-9343(94)90108-2 8304360 · DOI
- [18]Kampolis C Tektonidou M Moyssakis I Tzelepis GE Moutsopoulos H Vlachoyiannopoulos PG Evolution of cardiac dysfunction in patients with antiphospholipid antibodies and/or antiphospholipid syndrome: a 10-year follow-up study Semin Arthritis Rheum 2014 43 4 558 565 10.1016/j.semarthrit.2013.07.016 24012042 · DOI
- [19]Vreede AP Bockenstedt PL Knight JS Antiphospholipid syndrome: an update for clinicians and scientists Curr Opin Rheumatol 2017 29 5 458 466 10.1097/bor.0000000000000410 28538012 PMC5813838 · DOI · Paper page
- [20]Abreu MM Danowski A Wahl DG 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 5 401 414 10.1016/j.autrev.2015.01.002 25641203 · DOI
- [21]Brakkan SK Hald EM Mathiesen EB Competing risk of atherosclerotic risk factors for arterial and venous thrombosis in a general population: the Tromso study Arterioscler Thromb Vasc Biol 2012 32 2 487 491 10.1161/atvbaha.111.237545 22075253 · DOI
- [23]Zhang Y Bai L Shi M Features and risk factors of carotid atherosclerosis in a population with high stroke incidence in China Oncotarget. 2017 8 34 57477 57488 10.18632/oncotarget.15415 28915687 PMC5593659 · DOI
- [24]Cinoku II Mavragani CP Moutsopoulos HM Atherosclerosis: beyond the lipid storage hypothesis. The role of autoimmunity Eur J Clin Investig 2020 50 2 e13195 10.1111/eci.13195 31868918 · DOI
- [25]Zhao TX Mallat Z Targeting the immune system in atherosclerosis: JACC State-of-the-Art Review J Am Coll Cardiol 2019 73 13 1691 1706 10.1016/j.jacc.2018.12.083 30947923 · DOI
- [26]Conley C, Hartmann RC. A hemorrhagic disorder caused by circulating anticoagulant in patients with disseminated lupus erythematosus. J Clin Investig. 1952;31(2). 10.15557/JoU.2020.0032. · DOI
- [27]Rasool ZS Tiwari V Biochemistry, Lupus anticoagulant StatPearls 2021 Treasure Island StatPearls PublishingCopyright © 2021, StatPearls Publishing LLC 31335077
- [28]Tripodi A Laboratory testing for lupus anticoagulants: a review of issues affecting results Clin Chem 2007 53 9 1629 1635 10.1373/clinchem.2007.089524 17712001 · DOI · Paper page
Cited by
Sorted by citations
Devreese, K. M. J., Bertolaccini, M. L., Branch, D. W., de Laat, B., Erkan, D., Favaloro, E. J., Pengo, V., Ortel, T. L., Wahl, D., & Cohen, H. (2025) · Journal of Thrombosis and Haemostasis · doi:10.1016/j.jtha.2024.10.022 · Cited by 92 · see citing works
Moore, G. W., Foxton, E., Platton, S., Yartey, N., White, D., & MacDonald, S. G. (2023) · Journal of Thrombosis and Haemostasis · doi:10.1016/j.jtha.2023.08.009 · Cited by 6 · see citing works
Analytical dilemmas in lupus anticoagulant detection
Moore, G. W. (2023) · Exploration of Immunology · doi:10.37349/ei.2023.00104 · Cited by 5 · see citing works
Lupus Anticoagulant Testing in Challenging Situations: Navigating Complexities
Devreese, K. M. J. (2026) · International Journal of Laboratory Hematology · doi:10.1111/ijlh.14490 · Cited by 2 · see citing works
- Authors
- Qi, W., Zhao, J., Huang, C., Jiang, N., Li, J., Wu, C., Zhang, S., Hu, C., Xu, D., Wang, Q., Li, M., Tian, X., Zhao, Y., & Zeng, X.
- Affiliations
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Ministry of Education of the People's Republic of China (CN)
- Corresponding author
- Zeng, Xiaofeng
- ORCID
- Venue
- Arthritis Research & Therapy
- Published
- 2022-06-11
- Volume
- 24
- Issue
- 1
- Pages
- 140-140
- ISSN
- 1478-6354 (ISSN-L)
- 1478-6362
- PMC
- PMC9188169
- OpenAlex
- W4282931044
- Cited by
- 32
- References
- 5
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 8 · 2023: 8 · 2022: 1
- FWCI
- 4.55
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Arthritis Research & Therapy (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Chinese Academy of Medical Sciences (2017YFC0907601, 2019-I2M-2-008)
- Beijing Municipal Science and Technology Commission (Z201100005520023, No. Z201100005520023, Z201100005520027, 2019-I2M-2-008)
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Vasculitis and related conditions
- Health Sciences › Medicine › Pathology and Forensic Medicine › Systemic Sclerosis and Related Diseases
- Keywords
- antiphospholipid syndrome, antiphospholipid antibodies, clinical phenotype, risk stratification, systemic lupus erythematosus, lupus anticoagulant, arterial thrombosis, cardiovascular risk factors, obstetric morbidity, prognosis, immunosuppressive therapy
- MeSH terms
- Female, Humans, Lupus Erythematosus, Systemic, Male, Pregnancy, Prognosis, Prospective Studies, Thrombosis, Cohort Studies, Lupus Coagulation Inhibitor, Antiphospholipid Syndrome, Antibodies, Antiphospholipid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
