Manukyan D, Rossmann H, Schulz A, Zeller T, Pfeiffer N, Binder H, et al. Distribution of antiphospholipid antibodies in a large population-based German cohort. Clin Chem Lab Med 2016;54:1663–70.Web of ScienceGoogle Scholar
Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006;4:295–306.CrossrefPubMedGoogle Scholar
Rodriguez-Garcia V, Ioannou Y, Fernandez-Nebro A, Isenberg DA, Giles IP. Examining the prevalence of non-criteria anti-phospholipid antibodies in patients with anti-phospholipid syndrome: a systematic review. Rheumatology (Oxford) 2015;54:2042–50.CrossrefPubMedGoogle Scholar
Galli M, Luciani D, Bertolini G, Barbui T. Anti-beta 2-glycoprotein I, antiprothrombin antibodies, and the risk of thrombosis in the antiphospholipid syndrome. Blood 2003;102:2717–23.CrossrefPubMedGoogle Scholar
Simmelink MJ, Horbach DA, Derksen RH, Meijers JC, Bevers EM, Willems GM, et al. Complexes of anti-prothrombin antibodies and prothrombin cause lupus anticoagulant activity by competing with the binding of clotting factors for catalytic phospholipid surfaces. Br J Haematol 2001;113:621–9.CrossrefPubMedGoogle Scholar
Haj-Yahia S, Sherer Y, Blank M, Kaetsu H, Smolinsky A, Shoenfeld Y. Anti-prothrombin antibodies cause thrombosis in a novel qualitative ex-vivo animal model. Lupus 2003;12:364–9.CrossrefGoogle Scholar
Vega-Ostertag M, Liu X, Kwan-Ki H, Chen P, Pierangeli S. A human monoclonal antiprothrombin antibody is thrombogenic in vivo and upregulates expression of tissue factor and E-selectin on endothelial cells. Br J Haematol 2006;135:214–9.PubMedCrossrefGoogle Scholar
Yang YH, Chang CJ, Chuang YH, Hsu HY, Chen PP, Chiang BL. Identification of anti-prothrombin antibodies in the anti-phospholipid syndrome that display the prothrombinase activity. Rheumatology (Oxford) 2010;49:34–42.PubMedCrossrefGoogle Scholar
Pregnolato F, Chighizola CB, Encabo S, Shums Z, Norman GL, Tripodi A, et al. Anti-phosphatidylserine/prothrombin antibodies: an additional diagnostic marker for APS? Immunol Res 2013;56:432–8.PubMedWeb of ScienceCrossrefGoogle Scholar
Sciascia S, Sanna G, Murru V, Roccatello D, Khamashta MA, Bertolaccini ML. Anti-prothrombin (aPT) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies and the risk of thrombosis in the antiphospholipid syndrome. A systematic review. Thromb Haemost 2014;111:354–64.PubMedCrossrefGoogle Scholar
Zhang S, Wu Z, Li J, Li P, Chen S, Wen X, et al. Clinical performance of antibodies to prothrombin and thrombin in Chinese patients with antiphospholipid syndrome: potential interest in discriminating patients with thrombotic events and non-thrombotic events. Rheumatol Int 2017;37:579–84.Web of SciencePubMedCrossrefGoogle Scholar
Bertolaccini ML, Atsumi T, Koike T, Hughes GR, Khamashta MA. Antiprothrombin antibodies detected in two different assay systems. Prevalence and clinical significance in systemic lupus erythematosus. Thromb Haemost 2005;93:289–97.PubMedGoogle Scholar
Bertolaccini ML, Amengual O, Andreoli L, Atsumi T, Chighizola CB, Forastiero R, et al. 14th International Congress on Antiphospholipid Antibodies Task Force. Report on antiphospholipid syndrome laboratory diagnostics and trends. Autoimmun Rev 2014;13:917–30.CrossrefWeb of SciencePubMedGoogle Scholar
Hoxha A, Ruffatti A, Mattia E, Meneghel L, Tonello M, Salvan E, et al. Relationship between antiphosphatidylserine/prothrombin and conventional antiphospholipid antibodies in primary antiphospholipid syndrome. Clin Chem Lab Med 2015;53:1265–70.PubMedWeb of ScienceGoogle Scholar
Devreese KM, Pierangeli SS, de Laat B, Tripodi A, Atsumi T, Ortel TL, et al. Testing for antiphospholipid antibodies with solid phase assays: guidance from the SSC of the ISTH. J Thromb Haemost 2014;12:792–5.Web of ScienceCrossrefPubMedGoogle Scholar
Institute CaLS. User verification of performance for precision and trueness; approved guidelines. 2nd ed. Wayne, PA: Clinical and Laboratory Standards Institute, 2005Google Scholar
Sciascia S, Khamashta MA, Bertolaccini ML. New tests to detect antiphospholipid antibodies: antiprothrombin (aPT) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies. Curr Rheumatol Rep 2014;16:415.Web of SciencePubMedCrossrefGoogle Scholar
Galli M, Beretta G, Daldossi M, Bevers EM, Barbui T. Different anticoagulant and immunological properties of anti-prothrombin antibodies in patients with antiphospholipid antibodies. Thromb Haemost 1997;77:486–91.PubMedGoogle Scholar
Atsumi T, Ieko M, Bertolaccini ML, Ichikawa K, Tsutsumi A, Matsuura E, et al. Association of autoantibodies against the phosphatidylserine-prothrombin complex with manifestations of the antiphospholipid syndrome and with the presence of lupus anticoagulant. Arthritis Rheum 2000;43:1982–93.PubMedCrossrefGoogle Scholar
Egerer K, Roggenbuck D, Buttner T, Lehmann B, Kohn A, von Landenberg P, et al. Single-step autoantibody profiling in antiphospholipid syndrome using a multi-line dot assay. Arthritis Res Ther 2011;13:R118.CrossrefPubMedWeb of ScienceGoogle Scholar
Roggenbuck D, Egerer K, von Landenberg P, Hiemann R, Feist E, Burmester GR, et al. Antiphospholipid antibody profiling: time for a new technical approach? Autoimmun Rev 2012;11:821–6.CrossrefWeb of SciencePubMedGoogle Scholar
Hoxha A, Mattia E, Tonello M, Grava C, Pengo V, Ruffatti A. Antiphosphatidylserine/prothrombin antibodies as biomarkers to identify severe primary antiphospholipid syndrome. Clin Chem Lab Med 2017;55:890–8.PubMedWeb of ScienceGoogle Scholar
Vlagea A, Gil A, Cuesta MV, Arribas F, Diez J, Lavilla P, et al. Antiphosphatidylserine/prothrombin antibodies (aPS/PT) as potential markers of antiphospholipid syndrome. Clin Appl Thromb Hemost 2013;19:289–96.PubMedCrossrefGoogle Scholar
Zohoury N, Bertolaccini ML, Rodriguez-Garcia JL, Shums Z, Ateka-Barrutia O, Sorice M, et al. Closing the serological gap in the antiphospholipid syndrome: the value of “Non-criteria” antiphospholipid antibodies. J Rheumatol 2017;44:1597–602.PubMedCrossrefWeb of ScienceGoogle Scholar
Nojima J, Motoki Y, Aoki N, Tsuneoka H, Ichihara K. A novel ELISA system for simultaneous detection of six subclasses of anti-phospholipid antibodies for prediction of thrombotic complications among SLE patients. Thromb Res 2014;133:1135–40.CrossrefWeb of SciencePubMedGoogle Scholar
Zigon P, Cucnik S, Ambrozic A, Kveder T, Semrl SS, Rozman B, et al. Detection of antiphosphatidylserine/prothrombin antibodies and their potential diagnostic value. Clin Dev Immunol 2013;2013:724592.Web of SciencePubMedGoogle Scholar
Sugiura-Ogasawara M, Atsumi T, Ozaki Y, Koike T, Suzumori K. Phosphatidylserine-dependent antiprothrombin antibodies are not useful markers for high-risk women with recurrent miscarriages. Fertil Steril 2004;82:1440–2.PubMedCrossrefGoogle Scholar
Alijotas-Reig J, Ferrer-Oliveras R, Rodrigo-Anoro MJ, Farran-Codina I, Cabero-Roura L, Vilardell-Tarres M. Anti-beta(2)-glycoprotein-I and anti-phosphatidylserine antibodies in women with spontaneous pregnancy loss. Fertil Steril 2010;93:2330–6.PubMedWeb of ScienceCrossrefGoogle Scholar
Opatrny L, David M, Kahn SR, Shrier I, Rey E. Association between antiphospholipid antibodies and recurrent fetal loss in women without autoimmune disease: a metaanalysis. J Rheumatol 2006;33:2214–21.PubMedGoogle Scholar
Forastiero RR, Martinuzzo ME, Cerrato GS, Kordich LC, Carreras LO. Relationship of anti beta2-glycoprotein I and anti prothrombin antibodies to thrombosis and pregnancy loss in patients with antiphospholipid antibodies. Thromb Haemost 1997;78:1008–14.PubMedGoogle Scholar
Peterson LK, Willis R, Harris EN, Branch WD, Tebo AE. Antibodies to phosphatidylserine/prothrombin complex in antiphospholipid syndrome: analytical and clinical perspectives. Adv Clin Chem 2016;73:1–28.PubMedCrossrefWeb of ScienceGoogle Scholar
About the article
Published Online: 2018-03-21
Published in Print: 2018-05-24
Author contributions: SZ, FZ and YL designed the study. SZ, ZW, WZ, JZ, XZ, GLN and YL performed the experiments and analyzed the data. SZ, GLN, FZ and YL wrote the manuscript. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: This work was supported in part by the National Natural Science Foundation of China, Funder ID: 10.13039/501100001809; grant nos. 81373188, 81671618/81172857 (to YL) and 81771661 (to SZ); Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine (CAMS-I2M) grant no. 2017-I2M-3-001 (to SZ and YL); and The National Key Research and Development Program of China grant no. 2016YFC0903900 (to YL).
Employment or leadership: Gary L. Norman is an employee of Inova Diagnostics.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.