The DOI matches its Crossref record; 64 of the 66 references it cites were found in a registry or an index.
Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature
Abstract
To formally establish the risk of lupus anticoagulants and anticardiolipin antibodies for arterial and venous thrombosis, we ran a MEDLINE search of the literature from 1988 to 2000. Studies were selected for their case-control (11), prospective (9), cross-sectional (3), and ambispective (2) design. They provided or enabled us to calculate the odds ratio with 95% confidence interval (CI) of lupus anticoagulants and/or anticardiolipin antibodies for thrombosis in 4184 patients and 3151 controls. Studies were grouped according to the antibody investigated. Five studies compared lupus anticoagulants with anticardiolipin antibodies: the odds ratio with 95% CI of lupus anticoagulants for thrombosis was always significant. None of them found anticardiolipin antibodies were associated with thrombosis. Four studies analyzed only lupus anticoagulants: the odds ratio with 95% CI was always significant. The risk of lupus anticoagulants was independent of the site and type of thrombosis, the presence of systemic lupus erythematosus, and the coagulation tests employed to detect them. Sixteen studies served to assess 28 associations between anticardiolipin antibodies and thrombosis: the odds ratio with 95% CI was significant in 15 cases. Anticardiolipin titer correlated with the odds ratio of thrombosis. In conclusion, the detection of lupus anticoagulants and, possibly, of immunoglobulin G (IgG) anticardiolipin antibodies at medium or high titers helps to identify patients at risk for thrombosis. However, to take full advantage of the conclusions provided by the available evidence, there is an urgent need to harmonize investigational methods.
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In the citing paper
“These results confirm and validate several previous reports that have implicated these antibodies in the pathogenesis of APS [9, 10, 12, 13, 29, 30], but they also add to the growing body of evidence that shows inconsistent associations between aPL-associated autoantibodies and anamnestic thrombotic risk [3, 16].”
From Cardiovascular risk factors are major determinants of thrombotic risk in patients with the lupus anticoagulant (2017) · cites this paper as [29]
In the citing paper
“It is now clear that LA positivity is associated with TEs.22”
From Incidence of a first thromboembolic event in asymptomatic carriers of high-risk antiphospholipid antibody profile: a multicenter prospective study (2011) · cites this paper as [22]
In the citing paper
“It is well known that LA positivity is more strongly associated with both arterial and venous thrombosis than either aCL or anti-β2-glycoprotein I antibodies [8, 9].”
From Antiphospholipid patterns predict risk of thrombosis in systemic lupus erythematosus (2021) · cites this paper as [9]
In the citing paper
“Large studies found that IgM aCL and IgM anti-β2-glycoprotein I are not associated with thrombotic events [9–13].”
From Antiphospholipid patterns predict risk of thrombosis in systemic lupus erythematosus (2021) · cites this paper as [9]
In the citing paper
“Similarly, in a systematic review, aCL IgM was not predictive for thrombosis [9].”
From Antiphospholipid patterns predict risk of thrombosis in systemic lupus erythematosus (2021) · cites this paper as [9]
In the citing paper
“In most studies, it has been shown that in SLE, LA is the main predictor of thrombosis [9, 27–29].”
From Antiphospholipid patterns predict risk of thrombosis in systemic lupus erythematosus (2021) · cites this paper as [9]
In the citing paper
“Patients with persistent aPL with or without APS are at increased risk of future thrombotic events, LA positivity having the strongest association with these events.3”
From Lupus anticoagulant test persistence over time and its associations with future thrombotic events (2022) · cites this paper as [3]
In the citing paper
“Patients with persistent aPL with or without APS are at increased risk of future thrombotic events, LA positivity having the strongest association with these events.3”
From Lupus anticoagulant test persistence over time and its associations with future thrombotic events (2022) · cites this paper as [3]
In the citing paper
“Additional antibodies, most notably anticardiolipin antibodies (aCL) and anti–glycoprotein-I antibodies (aβ2GPI), were later identified and associated with thrombosis and recurrent spontaneous abortions.2-4”
From Lupus anticoagulant test persistence over time and its associations with future thrombotic events (2022) · cites this paper as [3]
In the citing paper
“Notably, most prior efforts to risk-stratify patients for future thrombotic events have used the patients’ aPL status from the first measurement or early in the observation period and have not analyzed changes over time.3,7,8”
From Lupus anticoagulant test persistence over time and its associations with future thrombotic events (2022) · cites this paper as [3]
In the citing paper
“This contention is supported by meta-analyses showing that the presence of aCL and ab2GPI alone are poorly associated with thromboembolic events [6,7].”
From Clinical course of high‐risk patients diagnosed with antiphospholipid syndrome (2010) · cites this paper as [6]
In the citing paper
“Although a positive LAC is considered to be a strong risk factor for thrombosis in APS, 10,11”
From Clinical Relevance of Isolated Lupus Anticoagulant Positivity in Patients with Thrombotic Antiphospholipid Syndrome (2021) · cites this paper as [10]
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“[46] Lupus anticoagulant was found to have the strongest association with thrombosis, whereas only medium and high titers of ACA IgG were linked to thrombosis.”
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de Groot, P. G., & Derksen, R. H. W. M. (2005) · Current Opinion in Infectious Diseases · doi:10.1097/01.qco.0000168379.01272.53 · Cited by 18
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“An overview of clinical studies indicated that the presence of LAC correlates better with thromboembolic complications than the presence of aCL antibodies [4].”
BackgroundLaboratory Evaluation of Antiphospholipid Antibodies in Patients With Venous Thromboembolism
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“In fact, when association analysis was restricted to patients without a positive LAC, which confers the highest thrombotic risk among aPL [33], the strength of co-occurrence of aPS/PT with ischaemic events, thrombocytopenia and Libman–Sacks’ endocarditis was no more significant, possibly suggesting that LAC and aPS/PT…”
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“LA appears to be the strongest predictor of thrombosis [17–19]; conversely, aCL and ab2GP1 are associated with a lower risk of thrombotic events.”
Bernardi, M., Spadafora, L., Andaloro, S., Piscitelli, A., Fornaci, G., Intonti, C., Fratta, A. E., Hsu, C.-E., Kaziród-Wolski, K., Metsovitis, T., et al. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13113064 · Cited by 16
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Sniecinski, R. M., Hursting, M. J., Paidas, M. J., & Levy, J. H. (2010) · Anesthesia & Analgesia · doi:10.1213/ane.0b013e3181ff0f7f · Cited by 13
Bhattarai, A., Shah, S., Bagherieh, S., et al. (2022) · International Journal of Clinical Practice · doi:10.1155/2022/5369001 · Cited by 14
“While lupus anticoagulants present paradoxically prolonged coagulation tests on one hand, a strong risk of arterial and venous thrombosis exists on the other [97].”
Cardiovascular events in patients with antiphospholipid antibodies: Strategies of prevention
Tufano, A., Guida, A., Minno, M. N. D. D., Gregorio, A. M. D., Cerbone, A. M., & Minno, G. D. (2010) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2009.10.016 · Cited by 14
Jordan, N., & D’Cruz, D. P. (2015) · Arthritis Care & Research · doi:10.1002/acr.22723 · Cited by 14
“This lack of association may be explained by previous data demonstrating that LAC is a more specific predictor for a diagnosis of APS than aCL, and is therefore probably contributing to damage accumulation to a greater extent than aCL (23).”
ResultPrevention of Pregnancy Complications in Antiphospholipid Syndrome
Czwalinna, A., & Bergmann, F. (2020) · Hämostaseologie · doi:10.1055/a-1113-0689 · Cited by 14
Grypiotis, P., Ruffatti, A., Pengo, V., et al. (2006) · Journal of Clinical Laboratory Analysis · doi:10.1002/jcla.20093 · Cited by 14
“A correlation between the presence of LA and an increased risk of thrombosis has been reported (12).”
BackgroundHigh Titer of Anticardiolipin Antibody Is Associated with First-Ever Ischemic Stroke in Taiwan
Lien, L., Chen, W., Chiu, H., Pan, W., Chen, J.-R., & Bai, C. (2006) · Cerebrovascular Diseases · doi:10.1159/000094008 · Cited by 14
“Taken together with our results (4.4p and 1.2p for stroke patients and controls, respectively), this indicates that Asians have a lower prevalence of high positive aCL IgG in both stroke cases (p = 0.0066) and controls (p 4 Table 4. Prevalence of a higher titer of aCL IgG in non-Asians and Asians T04 Meta-analysis res…”
ResultInfluentialShovman, O., Gilburd, B., Barzilai, O., Langevitz, P., & Shoenfeld, Y. (2007) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-007-0001-3 · Cited by 13
“In contrast, SLE apparently did not influence the risk of thrombosis attributed to aCL antibodies [15].”
BackgroundAntiphospholipid Syndrome Review
Eby, C. (2009) · Clinics in Laboratory Medicine · doi:10.1016/j.cll.2009.06.001 · Cited by 14
Laboratory Testing in Pediatric Rheumatology
Mehta, J. (2012) · Pediatric Clinics of North America · doi:10.1016/j.pcl.2012.03.008 · Cited by 14
Favaloro, E. J., & Wong, R. C. W. (2009) · Pathology · doi:10.3109/00313020903257731 · Cited by 14
“This is also in keeping with current evidence, and with the mini-survey of contributing authors mentioned above.(4,8,17,18,22,23) The dRVVT is the most popular current test procedure in use within laboratories worldwide for LA testing and so the related responses of participants was not unexpected.”
ResultIschemic Stroke: An Underestimated Complication of COVID-19
Cao, W., Zhang, C., Wang, H., Wu, Q., Yuan, Y., Chen, J., Geng, S., & Zhang, X. (2021) · Aging and Disease · doi:10.14336/ad.2021.0209 · Cited by 14
“Among aPLs, LAC, the complex of aPL and plasma proteins (mainly β2-glycoproteins), is the greatest risk factor for arterial and venous thrombosis [83] and β2GPI is the main binding cofactor for these antibodies [84].”
BackgroundBećarević, M. B., Stojanovich, L., Ignjatović, S., & Dopsaj, V. (2016) · Clinical Rheumatology · doi:10.1007/s10067-016-3230-0 · Cited by 13
Legault, K., Ugarte, A., Crowther, M. A., & Ruiz‐Irastorza, G. (2016) · Current Rheumatology Reports · doi:10.1007/s11926-016-0573-0 · Cited by 14
Barilaro, G., Coloma, E., Chacur, C. A., Rocca, C. D., Pérez-Isidro, A., Ruiz‐Ortiz, E., Viñas, O., Penella, D. T., Reverter, J. C., Andújar, A. M., et al. (2022) · Autoimmunity Reviews · doi:10.1016/j.autrev.2022.103208 · Cited by 15
Risk Factors for Thrombosis in an African Population
Fall, A. O. T., Proulle, V., Sail, A. S., et al. (2014) · Plasmatology · doi:10.4137/cmbd.s13401 · Cited by 13
Favaloro, E. J., Reben, R., Mohammed, S., & Koutts, J. (2010) · Internal Medicine Journal · doi:10.1111/j.1445-5994.2010.02329.x · Cited by 14
Antiphospholipid antibody: laboratory, pathogenesis and clinical manifestations
Tincani, A., Casu, C., Cartella, S., ZIGLIOLI, T., & Cattaneo, R. (2011) · Reumatismo · doi:10.4081/reumatismo.2010.65 · Cited by 13
Evaluation of a new commercial dilute prothrombin time in the diagnosis of Lupus Anticoagulants
Devreese, K. M. J. (2008) · Thrombosis Research · doi:10.1016/j.thromres.2008.04.005 · Cited by 14
“An overview of clinical studies indicated that the presence of LAC correlates better with thromboembolic complications than the presence of anticardiolipin (aCL) antibodies [4].”
BackgroundHucker, W. J., Chatzizisis, Y. S., Steigner, M. L., Winters, G. L., & Kirshenbaum, J. M. (2014) · Circulation · doi:10.1161/circulationaha.113.007417 · Cited by 15
“6 in the presence of anticardiolipin antibodies alone.(32) Patients who are positive for a lupus anticoagulant, anticardiolipin antibody, and anti–β-2 glycoprotein-1 antibodies (so-called triple-positive patients) are at particularly high risk for rethrombosis.”
BackgroundMethodAntiphospholipid Syndrome: Role of Antiphospholipid Antibodies in Neurology
Dafer, R. M., & Biller, J. (2008) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2007.10.005 · Cited by 13
“LA appears to be the stronger predictor of thrombotic risk for both venous and arterial thrombosis with an odds ratio of thrombosis five to 16 times higher than control [8,9], followed by anti- b2GP1 antibodies, which correlate mainly with arterial thrombosis.”
BackgroundParadoxical Brain Embolism Induced by Mycoplasma pneumoniae Infection with Deep Venous Thrombus
Senda, J., Ito, M., Atsuta, N., et al. (2010) · Internal Medicine · doi:10.2169/internalmedicine.49.3570 · Cited by 13
A functional coagulation test to identify anti-β2-glycoprotein I dependent lupus anticoagulants
Devreese, K. M. J. (2006) · Thrombosis Research · doi:10.1016/j.thromres.2006.06.003 · Cited by 13
Coagulation Parameters in the Patients with Fournier’s Gangrene
Şahin, H., Aflay, U., Kılınç, N., et al. (2005) · International Urology and Nephrology · doi:10.1007/s11255-005-8437-y · Cited by 13
“Circulatuary anticoagulants induced thrombosis much more than bleeding [25].”
BackgroundA DNA vaccine for multiple sclerosis
Garren, H. (2008) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.8.10.1539 · Cited by 13
“Antiphospholipid syndrome β 2-glycoprotein I, prothrombin [90]”
Merrill, J. T. (2004) · Lupus · doi:10.1191/0961203304lu2026oa · Cited by 13
Pathogenetic Potential of Antiphospholipid Antibodies
Vlachoyiannopoulos, P. G., & Samarkos, M. (2006) · Future Cardiology · doi:10.2217/14796678.2.3.303 · Cited by 13
“Clinical studies have confirmed that the presence of aPLs, especially of LA, is strongly associated with arterial and venous thrombosis; however, this cannot confirm the pathogenicity of aPLs [29,30].”
BackgroundAudiovestibular Dysfunction Related to Anti-Phospholipid Syndrome: A Systematic Review
Chen, J.-J., Hsu, C., Chen, Y., Chen, T., Zeng, B., & Tseng, P. (2024) · Diagnostics · doi:10.3390/diagnostics14222522 · Cited by 13
Antiphospholipid antibodies in young Indian patients with stroke
Mishra, M., & Rohatgi, S. J. (2009) · Journal of Postgraduate Medicine · doi:10.4103/0022-3859.57387 · Cited by 12
Ahluwalia, J., Sreedharanunni, S., Kumar, N., Masih, J., Bose, S. K., Varma, N., Varma, S., & Singh, S. (2014) · International Journal of Rheumatic Diseases · doi:10.1111/1756-185x.12479 · Cited by 12
ACTION, O. B. O. A., Barbhaiya, M., ANDRADE, D. C. O. D., et al. (2016) · Current Rheumatology Reports · doi:10.1007/s11926-016-0611-y · Cited by 12
Forastiero, R. R., & Martinuzzo, M. E. (2015) · Expert Review of Clinical Immunology · doi:10.1586/1744666x.2015.1080121 · Cited by 12
“The last systematic review published in 2003 [15] included data from 25 evaluable studies recruiting 4184 patients and 3151 controls.”
BackgroundChen, J., Sun, S., Yan, Q., Bao, C., & Fu, Q. (2016) · Clinical Rheumatology · doi:10.1007/s10067-015-3159-8 · Cited by 12
“Risk factors for thromboembolism were collected, including APL profiles (LAC, IgG/IgM aCL, IgG/IgM anti-β2GPI antibodies), APTT, lipid profile, diabetes mellitus, hypertension requiring therapy, nephrotic syndrome, heart valve disease, and use of medications such as corticosteroids, chloroquine (CQ), hydroxychloroquin…”
BackgroundResultInfluentialLatest advances in connective tissue disorders
Rao, V., & Bowman, S. (2013) · Therapeutic Advances in Musculoskeletal Disease · doi:10.1177/1759720x13480280 · Cited by 13
Metadata
- Authors
- Galli, M., Luciani, D., Bertolini, G., & Barbui, T.
- Affiliations
- From the Division of Hematology, Ospedali Riuniti, Bergamo, Italy; and Laboratory of Clinical Epidemiology, Mario Negri Institute, Ranica (Bergamo), Italy.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2003-03-01
- Volume
- 101
- Issue
- 5
- Pages
- 1827-1832
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2044043417
- Cited by
- 972
- References
- 66
- Citations by year
- 2026: 23 · 2025: 22 · 2024: 32 · 2023: 28 · 2022: 34 · 2021: 40 · 2020: 37 · 2019: 39 · 2018: 30 · 2017: 41 · 2016: 57 · 2015: 36 · 2014: 40 · 2013: 41 · 2012: 50
- FWCI
- 8.77
- 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 › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Hematology › Heparin-Induced Thrombocytopenia and Thrombosis
- Keywords
- lupus anticoagulant, anticardiolipin antibodies, antiphospholipid syndrome, thrombosis, arterial thrombosis, venous thrombosis, thrombosis risk factors, systemic lupus erythematosus, antibody titers
- MeSH terms
- Arterial Occlusive Diseases, Autoantigens, Autoimmune Diseases, Cross-Sectional Studies, Glycoproteins, Humans, Myocardial Infarction, Prospective Studies, Prothrombin, Research Design, Risk Factors, Thrombosis, Confidence Intervals, Odds Ratio, Case-Control Studies, Lupus Coagulation Inhibitor, Antiphospholipid Syndrome, Antibodies, Anticardiolipin, Thrombophilia, Venous Thrombosis, Stroke, beta 2-Glycoprotein I
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