Lupus Anticoagulants and Their Relationship with the Inhibitors against Coagulation Factor VIII: Considerations on the Differentiation between the 2 Circulating Anticoagulants
Abstract
Lupus anticoagulants (LAs) are a heterogeneous group of immunoglobulins directed against negatively charged phospholipids in complex with proteins [β2-glycoprotein I (β2GPI), prothrombin and others] (1). LAs prolong phospholipid-dependent coagulation tests and are associated with increased risk of thrombosis and fetal loss (1). There are other types of anti-phospholipid (aPL) antibodies with or without LA activity that are detected by ELISAs that use as capture antigen cardiolipin, β2GPI, or prothrombin (1). Although the exact distribution of the 2 types of antibodies is unknown, it is widely accepted that LAs and aPL antibodies coexist in a large number of patients classified as having the antiphospholipid syndrome. The relationship of these factors to inhibitors of individual coagulation factors seen in other conditions is controversial. Among the inhibitors of individual coagulation factors, those that inhibit factor VIII (anti-FVIII) are the most frequent, with an estimated incidence of 30% in patients with severe hemophilia A (2). They may also occur in nonhemophiliacs, producing a clinical condition known as acquired hemophilia (2). Anti-FVIII inhibitors bind to FVIII over a period of time and are associated with the risk of bleeding (3). Although LA and anti-FVIII inhibitors are dissimilar in terms of target and clinical presentation, they are somewhat related, as both of them prolong the phospholipid-dependent coagulation tests. Over the years there has been much deba…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Some factor VIII inhibitors show a behavior similar to LA in confirmatory tests.
“Furthermore, some factor VIII inhibitors show a behavior similar to LA in confirmatory tests [100].”
From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [100]
Cites
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
Verbruggen, B., Nováková, I. R. O., Wessels, H. M. C., Boezeman, J. B. M., van den Berg, H. M., & Mauser‐Bunschoten, E. P. (1995) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1653759 · Cited by 652 · see citing works
Brandt, J. T., Barna, L. K., & Triplett, D. A. (1995) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1649988 · Cited by 231 · see citing works
Allegri, F., Sanmarco, M., Cinquini, M., Taglietti, M., Balestrieri, G., Koike, T., Ichikawa, K., Meroni, P. L., Boffa, M. C., & Tincani, A. (2001) · Thrombosis and Haemostasis · doi:10.1055/s-0037-1616089 · Cited by 182 · see citing works
Self-citationPathogenic antibodies to coagulation factors. Part one: Factor VIII and Factor IX
Lollar, P. (2004) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2004.00802.x · Cited by 141 · see citing works
Tincani, A., Spatola, L., Prati, E., Allegri, F., Ferremi, P., Cattaneo, R., Meroni, P. L., & Balestrieri, G. (1996) · The Journal of Immunology · doi:10.4049/jimmunol.157.12.5732 · Cited by 133 · see citing works
Self-citationA Hexagonal (II) Phase Phospholipid Neutralization Assay for Lupus Anticoagulant Identification
Triplett, D. A., Barna, L. K., & Unger, G. A. (1993) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1649671 · Cited by 132 · see citing works
Antiphospholipid Syndrome: Diagnostic Aspects of Lupus Anticoagulants
Arnout, J. (2001) · Thrombosis and Haemostasis · doi:10.1055/s-0037-1616204 · Cited by 121 · see citing works
Reber, G., Schousboe, I., Tincani, A., Sanmarco, M., Kveder, T., de Moerloose, P., Boffa, M., & Arvieux, J. (2002) · PubMed · Cited by 119 · see citing works
Roles of Platelets and Factor XI in the Initiation of Blood Coagulation by Thrombin
Walsh, P. (2001) · Thrombosis and Haemostasis · doi:10.1055/s-0037-1616203 · Cited by 96 · 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
Inhibitors in hemophilia patients: Current status and management
Aledort, L. M. (1994) · American Journal of Hematology · doi:10.1002/ajh.2830470312 · Cited by 86 · see citing works
Horbach, D. A., van Oort, E., Derksen, R. H. W. M., & de Groot, P. G. (1998) · PubMed · Cited by 72 · see citing works
The Contribution of Anti-prothrombin-antibodies to Lupus Anticoagulant Activity
van Oort, E., Derksen, R. H. W. M., de Groot, P. G., & Horbach, D. A. (1998) · Thrombosis and Haemostasis · doi:10.1055/s-0037-1615066 · Cited by 71 · see citing works
Tripodi, A., Chantarangkul, V., Clerici, M., & Mannucci, P. M. (2002) · PubMed · Cited by 62 · see citing works
Self-citationChantarangkul, V., Tripodi, A., Arbini, A., & Mannucci, P. M. (1992) · Thrombosis Research · doi:10.1016/0049-3848(92)90266-d · Cited by 52 · see citing works
Self-citationAlsaeed, A., Makris, M., Malía, R. G., Preston, F. E., & Greaves, M. (1994) · British Journal of Haematology · doi:10.1111/j.1365-2141.1994.tb05126.x · Cited by 49 · see citing works
Laboratory Diagnosis of Lupus Anticoagulants for Patients on Oral Anticoagulant Treatment
Chantarangkul, V., Clerici, M., Mannucci, P. M., & Tripodi, A. (2002) · Thrombosis and Haemostasis · doi:10.1055/s-0037-1613259 · Cited by 43 · see citing works
Self-citationAssays for Detection of Antiphospholipid Antibodies
Triplett, D. A. (1994) · Lupus · doi:10.1177/096120339400300415 · Cited by 37 · see citing works
Acquired haemophilia A: errors in the diagnosis
Kazmi, M. A., Pickering, W., Smith, M. P., Holland, L. J., & Savidge, G. F. (1998) · Blood Coagulation & Fibrinolysis · doi:10.1097/00001721-199810000-00009 · Cited by 36 · see citing works
Anti-factor VIII Inhibitors and Lupus Anticoagulants in Haemophilia A Patients
Blanco, A. N., Cardozo, M. A., Candela, M., Santarelli, M. T., Bianco, R. P., & Lazzari, M. A. (1997) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1656029 · Cited by 35 · see citing works
Lupus anticoagulant, anticardiolipin antibodies, and human immunodeficiency virus in haemophilia.
Cohen, H., Mackie, I. J., Anagnostopoulos, N. I., Savage, G., & Machin, S. J. (1989) · Journal of Clinical Pathology · doi:10.1136/jcp.42.6.629 · Cited by 35 · see citing works
Exner, T., Papadopoulos, G., & Koutts, J. (1990) · Blood Coagulation & Fibrinolysis · doi:10.1097/00001721-199008000-00002 · Cited by 33 · see citing works
Diagnostic Methodologies for Circulating Anticoagulants
Exner, T. (1995) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1642699 · Cited by 32 · see citing works
Simultaneous occurrence of lupus anticoagulant and factor VIII inhibitors
Triplett, D. A. (1997) · American Journal of Hematology · doi:10.1002/(sici)1096-8652(199711)56:3 · Cited by 19 · see citing works
Simultaneous occurrence of lupus anticoagulant, factor VIII inhibitor and localized pemphigoid
Biron, C., Durand, L., Lemkecher, T., Dauverchain, J., Meunier, L., Mevnadier, J., & Schved, J. (1996) · American Journal of Hematology · doi:10.1002/1096-8652(199603)51:3 · Cited by 18 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
How we diagnose the antiphospholipid syndrome
Giannakopoulos, B., Passam, F. H., Ioannou, Y., & Krilis, S. A. (2008) · Blood · doi:10.1182/blood-2007-12-129627 · Cited by 186 · see citing works
Laboratory Diagnosis of Acquired Hemophilia A: Limitations, Consequences, and Challenges
Werwitzke, S., Scharf, R., & Tiede, A. (2014) · Seminars in Thrombosis and Hemostasis · doi:10.1055/s-0034-1390004 · Cited by 114 · see citing works
Antiphospholipid syndrome: laboratory detection, mechanisms of action and treatment
Tripodi, A., de Groot, P. G., & Pengo, V. (2011) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2011.02362.x · Cited by 113 · see citing works
Self-citationAntiphospholipid Antibodies Affect Human Endometrial Angiogenesis1
Simone, N. D., Nicuolo, F. D., D’Ippolito, S., Castellani, R., Tersigni, C., Caruso, A., Meroni, P. L., & Marana, R. (2010) · Biology of Reproduction · doi:10.1095/biolreprod.110.083410 · Cited by 100 · see citing works
Self-citationFighting COVID-19: Integrated Micro- and Nanosystems for Viral Infection Diagnostics
Qin, Z., Peng, R., Baravik, I. K., & Liu, X. (2020) · Matter · doi:10.1016/j.matt.2020.06.015 · Cited by 94 · see citing works
Patients with antiphospholipid syndrome display endothelial perturbation
Cugno, M., Borghi, M. O., Lonati, L. M., Ghiadoni, L., Gerosa, M., Grossi, C., Angelis, V. D., Magnaghi, G., Tincani, A., Mari, D., et al. (2009) · Journal of Autoimmunity · doi:10.1016/j.jaut.2009.07.004 · Cited by 89 · see citing works
Self-citationSimone, N. D., Tersigni, C., Cardaropoli, S., Franceschi, F., Nicuolo, F. D., Castellani, R., Bugli, F., de Waure, C., Cavaliere, A. F., Gasbarrini, A., et al. (2016) · Helicobacter · doi:10.1111/hel.12347 · Cited by 84 · see citing works
Laboratory Testing for Lupus Anticoagulants: A Review of Issues Affecting Results
Tripodi, A. (2007) · Clinical Chemistry · doi:10.1373/clinchem.2007.089524 · Cited by 81 · see citing works
Self-citationImprovements in Factor VIII Inhibitor Detection: From Bethesda to Nijmegen
Verbruggen, B., van Heerde, W. L., & Gorkom, B. A. P. L. (2009) · Seminars in Thrombosis and Hemostasis · doi:10.1055/s-0029-1245107 · Cited by 78 · 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
Qi, Y., Geib, T., Schorr, P., Meier, F., & Volmer, D. A. (2014) · Rapid Communications in Mass Spectrometry · doi:10.1002/rcm.7075 · Cited by 60 · see citing works
Werwitzke, S., Geisen, U., Nowak‐Göttl, U., Eichler, H., Stephan, B., Scholz, U., Holstein, K., Klamroth, R., Knöbl, P., Huth‐Kühne, A., et al. (2016) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.13304 · Cited by 55 · see citing works
Simone, N. D., Marana, R., Castellani, R., Nicuolo, F. D., D’Alessio, M. C., Raschi, E., Borghi, M. O., Chen, P. P., Sanguinetti, M., Caruso, A., et al. (2010) · Arthritis & Rheumatism · doi:10.1002/art.27361 · Cited by 54 · see citing works
Self-citationDiagnosis and quantification of factor VIII inhibitors
Verbruggen, B. (2009) · Haemophilia · doi:10.1111/j.1365-2516.2008.01924.x · Cited by 50 · see citing works
Antiphospholipid antibodies: Paradigm in transition
Horstman, L. L., Jy, W., Bidot, C., Ahn, Y. S., Kelley, R. E., Zivadinov, R., Maghzi, A. H., Etemadifar, M., Mousavi, S. A., & Minagar, A. (2009) · Journal of Neuroinflammation · doi:10.1186/1742-2094-6-3 · Cited by 46 · see citing works
Testing for lupus anticoagulants: all that a clinician should know
Tripodi, A. (2009) · Lupus · doi:10.1177/0961203308101436 · Cited by 41 · see citing works
Self-citationManagement of acquired haemophilia A
Scharf, R. E., Dobbelstein, C. E., Werwitzke, S., & Tiede, A. (2015) · Hämostaseologie · doi:10.5482/hamo-14-11-0064 · Cited by 33 · see citing works
Tiede, A., Zieger, B., & Lisman, T. (2022) · Haemophilia · doi:10.1111/hae.14548 · Cited by 28 · see citing works
Angelis, V. D., Scurati, S., Raschi, E., Liutkus, A., Bélot, A., Borghi, M. O., Meroni, P. L., & Cimaz, R. (2008) · Journal of Autoimmunity · doi:10.1016/j.jaut.2008.11.002 · Cited by 28 · see citing works
Self-citation(2022) · Blood transfusion · doi:10.2450/2022.0238-21 · Cited by 22 · see citing works
Self-citationBlood Coagulation and Thrombotic Disorders following SARS-CoV-2 Infection and COVID-19 Vaccination
Sekulovski, M., Mileva, N. B., Vasilev, G., Miteva, D., Gulinac, M., Peshevska-Sekulovska, M., Chervenkov, L., Batselova, H., Vasilev, G., Tomov, L., et al. (2023) · Biomedicines · doi:10.3390/biomedicines11102813 · Cited by 14 · see citing works
Sahud, M. A., Zhukov, O. S., MO, K., Popov, J. M., & Dlott, J. S. (2012) · Haemophilia · doi:10.1111/j.1365-2516.2012.02781.x · Cited by 14 · see citing works
Diagnostic Challenges on the Laboratory Detection of Lupus Anticoagulant
Tripodi, A. (2021) · Biomedicines · doi:10.3390/biomedicines9070844 · Cited by 14 · see citing works
Self-citationTiede, A., Zieger, B., & Lisman, T. (2020) · Haemophilia · doi:10.1111/hae.14033 · Cited by 12 · see citing works
Lupus Anticoagulant Detection under the Magnifying Glass
Molinari, A. C., Martini, T., Banov, L., Ierardi, A., Leotta, M., Strangio, A., & Santoro, R. C. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12206654 · Cited by 9 · see citing works
“Furthermore, some factor VIII inhibitors show a behavior similar to LA in confirmatory tests [100].”
BackgroundLaer, M. V., Penaloza, A., Stockman, W., Meert, P., Lambert, C., & Hermans, C. R. J. R. (2019) · Blood Coagulation & Fibrinolysis · doi:10.1097/mbc.0000000000000799 · Cited by 7 · see citing works
The Art of Detecting Antibodies against Factor VIII
Tiede, A., & Alberio, L. (2020) · Hämostaseologie · doi:10.1055/a-1223-3353 · Cited by 7 · see citing works
Hemostatic therapy as a management strategy for acquired hemophilia: what does the future hold?
Franchini, M., Schiavulli, M., & Liumbruno, G. M. (2021) · Expert Review of Hematology · doi:10.1080/17474086.2021.1892483 · Cited by 7 · see citing works
The First Case of Postpartum Acquired Hemophilia A in Korea
Lee, J. H., Kim, D., Yoo, K. Y., Choi, Y., Kim, S., & Kim, H. (2011) · Journal of Korean Medical Science · doi:10.3346/jkms.2011.26.9.1247 · Cited by 7 · see citing works
Transient cefuroxime/metronidazole treatment induced factor V antibodies
van den Berg, S. A. A., Verwer, P. E. B., Idema, R. N., & van Guldener, C. (2014) · BMJ Case Reports · doi:10.1136/bcr-2014-205523 · Cited by 4 · see citing works
Ieko, M., Ohmura, K., Naito, S., Yoshida, M., Sasaki, H., Sato, T., Sugawara, N., Takahashi, N., & Ichinose, A. (2023) · Exploration of Immunology · doi:10.37349/ei.2023.00103 · Cited by 4 · see citing works
Detecting and Quantifying Functional Inhibitors in Hemostasis
Verbruggen, B., Nováková, I. R. O., & van Heerde, W. L. (2008) · Wiley eBooks · doi:10.1002/9781444303575.ch20 · Cited by 4 · see citing works
Antiphospholipid Antibody Syndrome-Diagnostic Issues of Lupus Anticoagulants
Tyagi, S., & Ahuja, A. (2016) · Journal of Hematology & Thromboembolic Diseases · doi:10.4172/2329-8790.1000253 · Cited by 3 · see citing works
Ieko, M., Naito, S., Yoshida, M., Ohmura, K., Takahashi, N., Sugawara, N., Kiyohara, K., Shimosegawa, K., & Ichinose, A. (2022) · International Journal of Hematology · doi:10.1007/s12185-022-03392-y · Cited by 3 · see citing works
Patil, R., S., C., Parihar, A., Mohite, A., & Shetty, S. (2018) · Thrombosis Research · doi:10.1016/j.thromres.2018.10.015 · Cited by 2 · see citing works
Evaluating the Relationship Between Antiphospholipid Antibodies and COVID-19 Severity
Sadeghi, A., Hasanlu, M., Feyzi, A., Mansori, K., Ghodrati, S., & Parsamanesh, N. (2022) · DNA and Cell Biology · doi:10.1089/dna.2022.0293 · Cited by 2 · see citing works
Detecting and Quantifying Acquired Functional Inhibitors in Hemostasis
Verbruggen, B., Dardikh, M., & Gorkom, B. A. P. L. (2013) · Wiley eBooks · doi:10.1002/9781118543467.ch12 · Cited by 2 · see citing works
Clinicohematologic Profile of Patients With Factor VIII Inhibitors
Singh, N., Mishra, P. P., Tyagi, S., Pati, H., Mahapatra, M., Seth, T., & Saxena, R. (2014) · Clinical and Applied Thrombosis/Hemostasis · doi:10.1177/1076029614548720 · Cited by 1 · see citing works
Acquired factor VIII inhibitor and positive lupus anticoagulant testing on silica clotting time
Ip, H. W. A., So, C. C., Leung, Y.-H., Chan, J. ‐., Sin, P., & Lam, C. (2014) · International Journal of Laboratory Hematology · doi:10.1111/ijlh.12260 · Cited by 1 · see citing works
Clotting Factors and Inhibitors: Assays and Interpretation
Meijer, P., Verbruggen, H. W., & Spannagl, M. (2012) · Wiley eBooks · doi:10.1002/9781444398595.ch33
Laboratory Testing for Antiphospholipid Syndrome
Ioannou, Y., & Krilis, S. A. (2011) · Elsevier eBooks · doi:10.1016/b978-0-12-374994-9.10052-x
The coexistence of antiβ2 glycoprotein 1 antibody antibody has no effect on hemophilia A patient
Yu, X., Kong, D., Wang, Z., Yin, J., & Yu, Z. (2022) · Blood Coagulation & Fibrinolysis · doi:10.1097/mbc.0000000000001137
Coagulation Laboratory Testing: Methods and Clinical Interpretation
Zadeh, M. K., Valipour, N., Shams, M., Kohzadi, Z., Varmaghani, B., Samadov, A., Qayumov, M., Safdari, S. M., Beigi, M. B. D., & Dorgalaleh, A. (2026) · Springer eBooks · doi:10.1007/978-3-032-17940-1_13
Lupus anticoagulant: a never-ending story. New insights from anti-prothrombin antibodies
Pengo, V. (2026) · Bleeding Thrombosis and Vascular Biology · doi:10.4081/btvb.2026.469
- Authors
- Tripodi, A., Mancuso, M. E., Chantarangkul, V., Clerici, M., Bader, R., Meroni, P. L., Santagostino, E., & Mannucci, P. M.
- Affiliations
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
- IRCCS Istituto Auxologico Italiano (IT)
- Corresponding author
- Tripodi, Armando
- ORCID
- Venue
- Clinical Chemistry
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-10-01
- Volume
- 51
- Issue
- 10
- Pages
- 1883-1885
- ISSN
- 0009-9147 (ISSN-L)
- 1530-8561
- OpenAlex
- W2137951823
- Cited by
- 44
- References
- 27
- Citations by year
- 2026: 2 · 2023: 3 · 2022: 5 · 2021: 2 · 2020: 3 · 2019: 1 · 2018: 1 · 2016: 3 · 2015: 1 · 2014: 5 · 2013: 1 · 2012: 2
- FWCI
- 0.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Clinical Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Hematology › Hemophilia Treatment and Research
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Keywords
- lupus anticoagulant, factor VIII inhibitors, acquired hemophilia, hemophilia A, antiphospholipid syndrome, antiphospholipid antibodies, beta2-glycoprotein I, prothrombin, coagulation factor inhibitors, diagnostic interference
- MeSH terms
- Adolescent, Adult, Aged, Child, Child, Preschool, Diagnosis, Differential, Factor VIII, Follow-Up Studies, Hemophilia A, Humans, Middle Aged, Lupus Coagulation Inhibitor, 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
