Antiphospholipid Antibodies: Laboratory and Pathogenetic Aspects

REFERENCES

• McNeil H P, Chesterman C N, Krilis S A. Immunology and clinical importance of antiphospholipid antibodies. Adv Immunol 1991; 49: 193–280
   PubMed Web of Science ®Google Scholar
• Wasserman A, Neisser A, Bruck C. Eine serodiagnostische reaktion bei syphilis. Deutsche Med Wochenschr 1906; 32: 745–746
   Google Scholar
• Pangborn M C. A new serologically active phospholipid from beef heart. Proc Soc Exp Biol Med 1941; 48: 484–486
   Google Scholar
• Moore J E, Mohr C F. Biologically false-positive tests for syphilis. JAMA 1952; 150: 463–473
   Google Scholar
• Moore J E, Lutz W B. Natural history of systemic lupus erythematosus: approach to its study through chronic biologic false positive reactors. J Chron Dis 1955; 1: 297–316
   PubMedGoogle Scholar
• Conley M R, Hartmann R C. A hemorrhagic disorder caused by circulating anticoagulant in patients with disseminated lupus erythematosus. J Lab Clin Invest 1952; 31: 621–622
   Google Scholar
• Loeliger A. Prothrombin as co-factor of the circulating anticoagulant in systemic lupus erythematosus?. Thromb Diath Haemorrh 1959; 3: 237–256
   Google Scholar
• Bowie E J, Thompson J H, Jr., Pascuzzi C A, Owen C A, Jr. Thrombosis in systemic lupus erythematosus despite circulating anticoagulants. J Lab Clin Med 1963; 62: 416–430
   PubMed Web of Science ®Google Scholar
• Feinstein D I, Rapaport S I. Acquired inhibitors of blood coagulation. Prog Hemost Thromb 1972; 1: 75–95
   PubMedGoogle Scholar
• Davis S, Furie B C, Griffin J H, Furie B, Willey R. Circulating inhibitors of blood coagulation associated with procainamide-induce lupus erythematosus. Am J Hematol 1978; 4: 401–407
   PubMedGoogle Scholar
• Zarrabi M H, Zucker S, Miller F, Derman R M, Romano G S, Hartnett J A, Varma A O. Immunologic and coagulation disorders in chlorpromazine-treated patients. Ann Intern Med 1979; 91: 194–199
   PubMed Web of Science ®Google Scholar
• Brodeur G M, O'Neil P J, Williams J A. Acquired inhibitors of coagulation in nonhemophiliac children. J Pediatr 1980; 96: 439–441
   PubMed Web of Science ®Google Scholar
• Bloom E J, Abrams D I, Rodgers G. Lupus anticoagulant in the acquired immunodeficiency syndrome. JAMA 1986; 256: 491–493
   PubMed Web of Science ®Google Scholar
• Petrovas C, Vlachoyiannopoulos P G, Kordossis T, Moutsopoulos H M. Anti-phospholipid antibodies in HIV infection and SLE with or without anti-phospholipid syndrome: comparisons of phospholipid specificity, avidity and reactivity with beta2-GPI. J Autoimmun 1999; 13: 347–355
   PubMedGoogle Scholar
• Hassoun A, Al Kadhimi Z, Cervia J. HIV infection and antiphospholipid antibody: literature review and link to the antiphospholipid syndrome. AIDS Patient Care STDS 2004; 18: 333–340
   PubMedGoogle Scholar
• Gardlund B. The lupus inhibitor in thromboembolic disease and intrauterine death in the absence of systemic lupus. Acta Med Scand 1984; 215: 293–298
   PubMedGoogle Scholar
• Lechner K. Acquired inhibitors in nonhemophiliac patients. Haemostasis 1974; 3: 65–93
   PubMedGoogle Scholar
• Alagille D, Crosnier J, Soulier J P. Anticoagulant circulant a activite thromboplastique. Rev Fr Etud Clin Biol 1956; 1: 335–345
   PubMedGoogle Scholar
• Nilsson I M, Astedt B, Hedner U, Berezin D. Intrauterine death and circulating anticoagulant (antithromboplastin). Acta Med Scand 1975; 197: 153–159
   PubMedGoogle Scholar
• Harris E N, Gharavi A E, Boey M L, Patel B M, Mackworth-Young C G, Loizou S, Hughes G R. Anticardiolipin antibodies: detection by radioimmunoassay and association with thrombosis in systemic lupus erythematosus. Lancet 1983; 2: 1211–1214
   PubMed Web of Science ®Google Scholar
• Loizou S, McCrea J D, Rudge A C, Reynolds R, Boyle C C, Harris E N. Measurement of anti-cardiolipin antibodies by an enzyme-linked immunosorbent assay (ELISA): standardization and quantitation of results. Clin Exp Immunol 1985; 62: 738–745
   PubMed Web of Science ®Google Scholar
• Hughes G R, Harris N N, Gharavi A E. The anticardiolipin syndrome. J Rheumatol 1986; 13: 486–489
   PubMed Web of Science ®Google Scholar
• Harris E N, Baguley E, Asherson R A, Hughes G RV. Clinical and serological features of the antiphospholipid syndrome. J Rheumatol 1987; 26: 19
   Google Scholar
• Asherson R A. A “primary” antiphospholipid syndrome?. J Rheumatol 1988; 15: 1742–1746
   PubMed Web of Science ®Google Scholar
• Mackworth-Young C G, Loizou S, Walport M J. Primary antiphospholipid syndrome: features of patients with raised anticardiolipin antibodies and no other disorder. Ann Rheum Dis 1989; 48: 362–367
   PubMedGoogle Scholar
• Alarcon-Segovia D, Sanchez-Guerrero J. Primary antiphospholipid syndrome. J Rheumatol 1989; 16: 482–488
   PubMed Web of Science ®Google Scholar
• Asherson R A, Khamashta M A, Ordi-Ros J, Derksen R H, Machin S J, Barquinero J, Outt H H, Harris E N, Vilardell-Torres M, Hughes G R. The “primary" antiphospholipid syndrome: major clinical and serological features. Medicine (Baltimore) 1989; 68: 366–374
   PubMed Web of Science ®Google Scholar
• McNeil H P, Chesterman C N, Krilis S A. Anticardiolipin antibodies and lupus anticoagulants comprise separate antibody subgroups with different phospholipid binding characteristics. Br J Haematol 1989; 73: 506–513
   PubMed Web of Science ®Google Scholar
• McNeil H P, Simpson R J, Chesterman C N, Krilis S A. Anti-phospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: beta 2-glycoprotein I (apolipoprotein H). Proc Natl Acad Sci USA 1990; 87: 4120–4124
   PubMed Web of Science ®Google Scholar
• Schousboe I. beta 2-Glycoprotein I: a plasma inhibitor of the contact activation of the intrinsic blood coagulation pathway. Blood 1985; 66: 1086–1091
   PubMed Web of Science ®Google Scholar
• Galli M, Comfurius P, Maassen C, Hemker H C, de Baets M H, Breda-Vriesman P J, Barbui T, Zwaal R F, Bevers E M. Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor. Lancet 1990; 335: 1544–1547
   PubMed Web of Science ®Google Scholar
• Matsuura E, Igarashi Y, Fujimoto M, Ichikawa K, Suzuki T, Sumida T, Yasuda T, Koike T. Heterogeneity of anticardiolipin antibodies defined by the anticardiolipin cofactor. J Immunol 1992; 148: 3885–3891
   PubMed Web of Science ®Google Scholar
• Oosting J D, Derksen R H, Entjes H T, Bouma B N, de Groot P G. Lupus anticoagulant activity is frequently dependent on the presence of beta 2-glycoprotein I. Thromb Haemost 1992; 67: 499–502
   PubMed Web of Science ®Google Scholar
• Roubey R A, Pratt C W, Buyon J P, Winfield J B. Lupus anticoagulant activity of autoimmune antiphospholipid antibodies is dependent upon beta 2-glycoprotein I. J Clin Invest 1992; 90: 1100–1104
   PubMedGoogle Scholar
• Wilson W A, Gharavi A E, Koike T, Lockshin M D, Branch D W, Piette J C, Brey R, Derksen R, Harris E N, Hughes G R, Triplett D A, Khamashta M A. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthritis Rheum 1999; 42: 1309–1311
   PubMed Web of Science ®Google Scholar
• Miyakis S, Lockshin M D, Atsumi T, Branch D W, Brey R L, Cervera R, Derksen R H, De Groot P G, Koike T, Meroni P L, Reber G, Shoenfeld Y, Tincani A, Vlachoyiannopoulos P G, Krilis S A. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006; 4: 295–306
   PubMed Web of Science ®Google Scholar
• Roubey R A. Antigenic specificities of antiphospholipid autoantibodies: implications for clinical laboratory testing and diagnosis of the antiphospholipid syndrome. Lupus 1996; 5: 425–430
   PubMed Web of Science ®Google Scholar
• Roubey R A. Immunology of the antiphospholipid syndrome: antibodies, antigens, and autoimmune response. Thromb Haemost 1999; 82: 656–661
   PubMed Web of Science ®Google Scholar
• Reber G, Arvieux J, Comby E, Degenne D, de Moerloose P, Sanmarco M, Potron G. Multicenter evaluation of nine commercial kits for the quantitation of anticardiolipin antibodies. The Working Group on Methodologies in Haemostasis from the GEHT (Groupe d'Etudes sur l'Hemostase et la Thrombose). Thromb Haemost 1995; 73: 444–452
   PubMed Web of Science ®Google Scholar
• Galli M, Luciani D, Bertolini G, Barbui T. Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature. Blood 2003; 101: 1827–1832
   PubMed Web of Science ®Google 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: 2717–2723
   PubMed Web of Science ®Google Scholar
• Sanmarco M, Alessi M C, Harle J R, Sapin C, Aillaud M F, Gentile S, Juhan-Vague I, Weiller P J. Antibodies to phosphatidylethanolamine as the only antiphospholipid antibodies found in patients with unexplained thromboses. Thromb Haemost 2001; 85: 800–805
   PubMed Web of Science ®Google Scholar
• Brey R L, Cote S A, McGlasson D L, Triplett D A, Barna L K. Effects of repeated freeze-thaw cycles on anticardiolipin antibody immunoreactivity. Am J Clin Pathol 1994; 102: 586–588
   PubMedGoogle Scholar
• Hughes J R, Davies J A, Prentice C R. The effect of different microtitre plates on the enzyme-linked immunosorbent assay (ELISA) for anticardiolipin antibodies (ACAs). Thromb Res 1996; 84: 217–222
   PubMedGoogle Scholar
• Cabral A R, Cabiedes J, Alarcon-Segovia D. Tween 20 detaches cardiolipin from ELISA plates and makes anticardiolipin antibodies undetectable regardless of the presence of beta 2-glycoprotein-I. J Immunol Methods 1994; 175: 107–114
   PubMed Web of Science ®Google Scholar
• Samarkos M, Asherson R A, Loizou S. The clinical significance of IgA antiphospholipid antibodies. J Rheumatol 2001; 28: 694–697
   PubMedGoogle Scholar
• Samarkos M, Davies K A, Gordon C, Loizou S. Clinical significance of IgA anticardiolipin and anti-beta(2)-GP1 antibodies in patients with systemic lupus erythematosus and primary antiphospholipid syndrome. Clin Rheumatol 2006; 25: 199–204
   PubMed Web of Science ®Google Scholar
• Tajima C, Suzuki Y, Mizushima Y, Ichikawa Y. Clinical significance of immunoglobulin A antiphospholipid antibodies: possible association with skin manifestations and small vessel vasculitis. J Rheumatol 1998; 25: 1730–1736
   PubMedGoogle Scholar
• Samarkos M, Davies K A, Gordon C, Walport M J, Loizou S. IgG subclass distribution of antibodies against beta(2)-GP1 and cardiolipin in patients with systemic lupus erythematosus and primary antiphospholipid syndrome, and their clinical associations. Rheumatology (Oxford) 2001; 40: 1026–1032
   PubMedGoogle Scholar
• Passam F, Krilis S. Laboratory tests for the antiphospholipid syndrome: current concepts. Pathology 2004; 36: 129–138
   PubMed Web of Science ®Google Scholar
• Harris E N, Gharavi A E, Patel S P, Hughes G R. Evaluation of the anti-cardiolipin antibody test: report of an international workshop held 4 April 1986. Clin Exp Immunol 1987; 68: 215–222
   PubMed Web of Science ®Google Scholar
• Loizou S, Walport M J, Davies K A. The antiphospholipid syndrome in infectious diseases. The Antiphospholipid Syndrome, R A Asherson, R Cervera, J C Piette, Y Shoenfeld. CRC Press, Boca Raton 1996; 267–284
   Google Scholar
• Forastiero R, Martinuzzo M, Adamczuk Y, Carreras L O. Occurrence of anti-prothrombin and anti-beta2-glycoprotein I antibodies in patients with history of thrombosis. J Lab Clin Med 1999; 134: 610–615
   PubMedGoogle Scholar
• Asherson R A, Cervera R. Antiphospholipid antibodies and infections. Ann Rheum Dis 2003; 62: 388–393
   PubMed Web of Science ®Google Scholar
• Tektonidou M G, Vlachoyiannopoulos P G. Antiphospholipid syndrome triggered by thalidomide in a patient with discoid lupus erythematosus. Lupus 2003; 12: 723–724
   PubMedGoogle Scholar
• Levy R A, de Meis E, Pierangeli S. An adapted ELISA method for differentiating pathogenic from nonpathogenic aPL by a beta 2 glycoprotein I dependency anticardiolipin assay. Thromb Res 2004; 114: 573–577
   PubMed Web of Science ®Google Scholar
• Tincani A, Allegri F, Sanmarco M, Cinquini M, Taglietti M, Balestrieri G, Koike T, Ichikawa K, Meroni P, Boffa M C. Anticardiolipin antibody assay: a methodological analysis for a better consensus in routine determinations—a cooperative project of the European Antiphospholipid Forum. Thromb Haemost 2001; 86: 575–583
   PubMed Web of Science ®Google Scholar
• Tincani A, Allegri F, Balestrieri G, Reber G, Sanmarco M, Meroni P, Boffa M C. Minimal requirements for antiphospholipid antibodies ELISAs proposed by the European Forum on antiphospholipid antibodies. Thromb Res 2004; 114: 553–558
   PubMed Web of Science ®Google Scholar
• Hoefner D M, Yeo K T. Lot-to-lot inconsistency of anticardiolipin reagents. Clin Chem 2002; 48: 1625–1626
   PubMedGoogle Scholar
• Wong R C, Gillis D, Adelstein S, Baumgart K, Favaloro E J, Hendle M J, Homes P, Pollock W, Smith S, Steele R H, Sturgess A, Wilson R J. Consensus guidelines on anti-cardiolipin antibody testing and reporting. Pathology 2004; 36: 63–68
   PubMed Web of Science ®Google Scholar
• Harris E N. Special report. The Second International Anti-cardiolipin Standardization Workshop/the Kingston Anti-Phospholipid Antibody Study (KAPS) group. Am J Clin Pathol 1990; 94: 476–484
   PubMed Web of Science ®Google Scholar
• Harris E N, Pierangeli S, Birch D. Anticardiolipin wet workshop report. Fifth International Symposium on antiphospholipid antibodies. Am J Clin Pathol 1994; 101: 616–624
   PubMed Web of Science ®Google Scholar
• Pierangeli S S, Stewart M, Silva L K, Harris E N. An antiphospholipid wet workshop: 7th International Symposium on Antiphospholipid Antibodies. J Rheumatol 1998; 25: 156–160
   PubMedGoogle Scholar
• Wong R, Favaloro E, Pollock W, Wilson R, Hendle M, Adelstein S, Baumgart K, Homes P, Smith S, Steele R, Sturgess A, Gillis D. A multi-centre evaluation of the intra-assay and inter-assay variation of commercial and in-house anti-cardiolipin antibody assays. Pathology 2004; 36: 182–192
   PubMed Web of Science ®Google Scholar
• Favaloro E J, Silvestrini R, Mohammed A. Clinical utility of anticardiolipin antibody assays: high inter-laboratory variation and limited consensus by participants of external quality assurance programs signals a cautious approach. Pathology 1999; 31: 142–147
   PubMedGoogle Scholar
• Robert J M, Macara L M, Chalmers E A, Smith G C. Inter-assay variation in antiphospholipid antibody testing. BJOG 2002; 109: 348–349
   PubMed Web of Science ®Google Scholar
• Favaloro E J, Silvestrini R. Assessing the usefulness of anticardiolipin antibody assays: a cautious approach is suggested by high variation and limited consensus in multilaboratory testing. Am J Clin Pathol 2002; 118: 548–557
   PubMed Web of Science ®Google Scholar
• Audrain M A, Colonna F, Morio F, Hamidou M A, Muller J Y. Comparison of different kits in the detection of autoantibodies to cardiolipin and beta2glycoprotein 1. Rheumatology (Oxford) 2004; 43: 181–185
   PubMed Web of Science ®Google Scholar
• Kutteh W H, Franklin R D. Assessing the variation in antiphospholipid antibody (APA) assays: comparison of results from 10 centers. Am J Obstet Gynecol 2004; 191: 440–448
   PubMedGoogle Scholar
• Favaloro E J, Wong R C, Silvestrini R, McEvoy R, Jovanovich S, Roberts-Thomson P. A multilaboratory peer assessment quality assurance program-based evaluation of anticardiolipin antibody, and beta2-glycoprotein I antibody testing. Semin Thromb Hemost 2005; 31: 73–84
   PubMed Web of Science ®Google Scholar
• Ichikawa K, Tsutsumi A, Atsumi T, Matsuura E, Kobayashi S, Hughes G R, Khamashta M A, Koike T. A chimeric antibody with the human gamma1 constant region as a putative standard for assays to detect IgG beta2-glycoprotein I-dependent anticardiolipin and anti-beta2-glycoprotein I antibodies. Arthritis Rheum 1999; 42: 2461–2470
   PubMed Web of Science ®Google Scholar
• Kilpatrick D C. Factors affecting cardiolipin antibody assays: modification with polyethylene glycol compound. Br J Haematol 1998; 100: 52–57
   PubMedGoogle Scholar
• Greaves M, Cohen H, MacHin S J, Mackie I. Guidelines on the investigation and management of the antiphospholipid syndrome. Br J Haematol 2000; 109: 704–715
   PubMed Web of Science ®Google Scholar
• Triplett D A. Antiphospholipid antibodies. Arch Pathol Lab Med 2002; 126: 1424–1429
   PubMed Web of Science ®Google Scholar
• Wong R C, Adelstein S, Gillis D, Favaloro E J. Development of consensus guidelines for anticardiolipin and lupus anticoagulant testing. Semin Thromb Hemost 2005; 31: 39–48
   PubMedGoogle Scholar
• Arvieux J, Roussel B, Jacob M C, Colomb M G. Measurement of anti-phospholipid antibodies by ELISA using beta 2-glycoprotein I as an antigen. J Immunol Methods 1991; 143: 223–229
   PubMed Web of Science ®Google Scholar
• Ebeling F, Pettersson T, Muukkonen L, Vahtera E, Rasi V. Beta-2-glycoprotein I antibodies in patients with thrombosis. Scand J Clin Lab Invest 2003; 63: 111–118
   PubMedGoogle Scholar
• Lee E Y, Lee C K, Lee T H, Chung S M, Kim S H, Cho Y S, Yoo B, Moon H B. Does the anti-beta2-glycoprotein I antibody provide additional information in patients with thrombosis?. Thromb Res 2003; 111: 29–32
   PubMedGoogle Scholar
• Nash M J, Camilleri R S, Kunka S, Mackie I J, Machin S J, Cohen H. The anticardiolipin assay is required for sensitive screening for antiphospholipid antibodies. J Thromb Haemost 2004; 2: 1077–1081
   PubMed Web of Science ®Google Scholar
• Faden D, Tincani A, Tanzi P, Spatola L, Lojacono A, Tarantini M, Balestrieri G. Anti-beta 2 glycoprotein I antibodies in a general obstetric population: preliminary results on the prevalence and correlation with pregnancy outcome. Anti-beta2 glycoprotein I antibodies are associated with some obstetrical complications, mainly preeclampsia-eclampsia. Eur J Obstet Gynecol Reprod Biol 1997; 73: 37–42
   PubMed Web of Science ®Google Scholar
• Lee R M, Branch D W, Silver R M. Immunoglobulin A anti-beta2-glycoprotein antibodies in women who experience unexplained recurrent spontaneous abortion and unexplained fetal death. Am J Obstet Gynecol 2001; 185: 748–753
   PubMed Web of Science ®Google Scholar
• Cabiedes J, Cabral A R, Alarcon-Segovia D. Clinical manifestations of the antiphospholipid syndrome in patients with systemic lupus erythematosus associate more strongly with anti-beta 2-glycoprotein-I than with antiphospholipid antibodies. J Rheumatol 1995; 22: 1899–1906
   PubMed Web of Science ®Google Scholar
• Abreu I, Pierangeli S, Harris E N. Comparison of three assays for the detection of antiphospholipid antibodies and anti-b2 glycoprotein I antibodies. Lupus 1998; 7: S211
   PubMedGoogle Scholar
• Pierangeli S S, Gharavi A E, Harris E N. Testing for antiphospholipid antibodies: problems and solutions. Clin Obstet Gynecol 2001; 44: 48–57
   PubMedGoogle Scholar
• Helbert M, Bodger S, Cavenagh J, D'Cruz D, Thomas J M, MacCallum P. Optimising testing for phospholipid antibodies. J Clin Pathol 2001; 54: 693–698
   PubMed Web of Science ®Google Scholar
• Meroni P L, Tincani A. Should our approach to the anticardiolipin assay change 20 years after its discovery?. J Thromb Haemost 2004; 2: 1074–1076
   PubMedGoogle Scholar
• Matsuura E, Igarashi Y, Yasuda T, Triplett D A, Koike T. Anticardiolipin antibodies recognize beta 2-glycoprotein I structure altered by interacting with an oxygen modified solid phase surface. J Exp Med 1994; 179: 457–462
   PubMed Web of Science ®Google Scholar
• Roubey R A, Eisenberg R A, Harper M F, Winfield J B. “Anticardiolipin” autoantibodies recognize beta 2-glycoprotein I in the absence of phospholipid. Importance of Ag density and bivalent binding. J Immunol 1995; 154: 954–960
   PubMed Web of Science ®Google Scholar
• Tincani A, Spatola L, Prati E, Allegri F, Ferremi P, Cattaneo R, Meroni P, Balestrieri G. The anti-beta2-glycoprotein I activity in human anti-phospholipid syndrome sera is due to monoreactive low-affinity autoantibodies directed to epitopes located on native beta2-glycoprotein I and preserved during species' evolution. J Immunol 1996; 157: 5732–5738
   PubMedGoogle Scholar
• Tsutsumi A, Ichikawa K, Matsuura E, Sawada K I, Koike T. Heterogeneous behavior of anti-beta2-glycoprotein I antibodies on various commercially available enzyme immunoassay plates coated with beta2-glycoprotein I. J Rheumatol 2000; 27: 391–396
   PubMed Web of Science ®Google Scholar
• Arvieux J, Darnige L, Hachulla E, Roussel B, Bensa J C, Colomb M G. Species specificity of anti-beta 2 glycoprotein I autoantibodies and its relevance to anticardiolipin antibody quantitation. Thromb Haemost 1996; 75: 725–730
   PubMedGoogle Scholar
• Hunt J E, Simpson R J, Krilis S A. Identification of a region of beta 2-glycoprotein I critical for lipid binding and anti-cardiolipin antibody cofactor activity. Proc Natl Acad Sci USA 1993; 90: 2141–2145
   PubMedGoogle Scholar
• Sanmarco M, Bardin N, Blank M, Pascal V, Christine A M, Dignat-George F, Shoenfeld Y, Harle J R. Heterogeneity of anti-beta2-glycoprotein I antibodies. A factor of variability in test results. Thromb Haemost 2005; 93: 80–87
   PubMedGoogle Scholar
• Drouvalakis K A, Buchanan R R. Microtitre plate and assay buffer alter detection of antiphosphatidylethanolamine antibodies in lupus anticoagulant positive plasma. Thromb Res 1999; 94: 205–212
   PubMedGoogle Scholar
• Reber G, Schousboe I, Tincani A, Sanmarco M, Kveder T, de Moerloose P, Boffa M C, Arvieux J. Inter-laboratory variability of anti-beta2-glycoprotein I measurement. A collaborative study in the frame of the European Forum on Antiphospholipid Antibodies Standardization Group. Thromb Haemost 2002; 88: 66–73
   PubMed Web of Science ®Google Scholar
• Cucnik S, Ambrozic A, Bozic B, Skitek M, Kveder T. Anti-beta2-glycoprotein I ELISA: methodology, determination of cut-off values in 434 healthy Caucasians and evaluation of monoclonal antibodies as possible international standards. Clin Chem Lab Med 2000; 38: 777–783
   PubMed Web of Science ®Google Scholar
• Erickson E N, Jr., Najmey S S, Keil L B, El Kadi H S, DeBari V A. Reference calibrators for IgG antibodies to beta2-glycoprotein I: preparation, properties and availability to investigators. Clin Chem 1996; 42: 1116–1117
   PubMedGoogle Scholar
• Bevers E M, Galli M, Barbui T, Comfurius P, Zwaal R F. Lupus anticoagulant IgG's (LA) are not directed to phospholipids only, but to a complex of lipid-bound human prothrombin. Thromb Haemost 1991; 66: 629–632
   PubMed Web of Science ®Google Scholar
• Fleck R A, Rapaport S I, Rao L V. Anti-prothrombin antibodies and the lupus anticoagulant. Blood 1988; 72: 512–519
   PubMed Web of Science ®Google Scholar
• Freyssinet J M, Toti-Orfanoudakis F, Ravanat C, Grunebaum L, Gauchy J, Cazenave J P, Wiesel M L. The catalytic role of anionic phospholipids in the activation of protein C by factor Xa and expression of its anticoagulant function in human plasma. Blood Coagul Fibrinolysis 1991; 2: 691–698
   PubMedGoogle Scholar
• Galli M, Bevers E M, Comfurius P, Barbui T, Zwaal R F. Effect of antiphospholipid antibodies on procoagulant activity of activated platelets and platelet-derived microvesicles. Br J Haematol 1993; 83: 466–472
   PubMed Web of Science ®Google Scholar
• Arvieux J, Darnige L, Caron C, Reber G, Bensa J C, Colomb M G. Development of an ELISA for autoantibodies to prothrombin showing their prevalence in patients with lupus anticoagulants. Thromb Haemost 1995; 74: 1120–1125
   PubMed Web of Science ®Google Scholar
• Matsuda J, Saitoh N, Gotoh M, Kawasugi K, Gohchi K, Tsukamoto M. Phosphatidyl serine-dependent antiprothrombin antibody is exclusive to patients with lupus anticoagulant. Br J Rheumatol 1996; 35: 589–591
   PubMedGoogle Scholar
• Atsumi T, Ieko M, Bertolaccini M L, Ichikawa K, Tsutsumi A, Matsuura E, Koike T. 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: 1982–1993
   PubMed Web of Science ®Google Scholar
• Amengual O, Atsumi T, Koike T. Specificities, properties, and clinical significance of antiprothrombin antibodies. Arthritis Rheum 2003; 48: 886–895
   PubMed Web of Science ®Google Scholar
• Galli M, Beretta G, Daldossi M, Bevers E M, Barbui T. Different anticoagulant and immunological properties of anti-prothrombin antibodies in patients with antiphospholipid antibodies. Thromb Haemost 1997; 77: 486–491
   PubMed Web of Science ®Google Scholar
• Atsumi T, Amengual O, Yasuda S, Koike T. Antiprothrombin antibodies—are they worth assaying?. Thromb Res 2004; 114: 533–538
   PubMedGoogle Scholar
• Triplett D A. Many faces of lupus anticoagulants. Lupus 1998; 7: S18–S22, Suppl 2
   Google Scholar
• Schultz D R. Antiphospholipid antibodies: basic immunology and assays. Semin Arthritis Rheum 1997; 26: 724–739
   PubMedGoogle Scholar
• Roubey R A. Autoantibodies to phospholipid-binding plasma proteins: a new view of lupus anticoagulants and other “antiphospholipid” autoantibodies. Blood 1994; 84: 2854–2867
   PubMed Web of Science ®Google Scholar
• Arnout J. Antiphospholipid syndrome: diagnostic aspects of lupus anticoagulants. Thromb Haemost 2001; 86: 83–91
   PubMed Web of Science ®Google Scholar
• Arnout J, Wittevrongel C, Vanrusselt M, Hoylaerts M, Vermylen J. Beta-2-glycoprotein I dependent lupus anticoagulants form stable bivalent antibody beta-2-glycoprotein I complexes on phospholipid surfaces. Thromb Haemost 1998; 79: 79–86
   PubMedGoogle Scholar
• Willems G M, Janssen M P, Pelsers M M, Comfurius P, Galli M, Zwaal R F, Bevers E M. Role of divalency in the high-affinity binding of anticardiolipin antibody-beta 2-glycoprotein I complexes to lipid membranes. Biochemistry 1996; 35: 13833–13842
   PubMed Web of Science ®Google Scholar
• Takeya H, Mori T, Gabazza E C, Kuroda K, Deguchi H, Matsuura E, Ichikawa K, Koike T, Suzuki K. Anti-beta2-glycoprotein I (beta2GPI) monoclonal antibodies with lupus anticoagulant-like activity enhance the beta2GPI binding to phospholipids. J Clin Invest 1997; 99: 2260–2268
   PubMed Web of Science ®Google Scholar
• Arnout J, Vermylen J. Mechanism of action of beta2-glycoprotein I-dependent lupus anticoagulants. Lupus 1998; 7: S23–S28, Suppl 2
   PubMedGoogle Scholar
• Brandt J T, Triplett D A, Alving B, Scharrer I. Criteria for the diagnosis of lupus anticoagulants: an update. On behalf of the Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the ISTH. Thromb Haemost 1995; 74: 1185–1190
   PubMed Web of Science ®Google Scholar
• Brandt J T, Barna L K, Triplett D A. Laboratory identification of lupus anticoagulants: results of the Second International Workshop for Identification of Lupus Anticoagulants. On behalf of the Subcommittee on Lupus Anticoagulants/Antiphospholipid Antibodies of the ISTH. Thromb Haemost 1995; 74: 1597–1603
   PubMed Web of Science ®Google Scholar
• Alving B M, Baldwin P E, Richards R L, Jackson B J. The dilute phospholipid APTT: a sensitive assay for verification of lupus anticoagulants. Thromb Haemost 1985; 54: 709–712
   PubMedGoogle Scholar
• Exner T, Rickard K A, Kronenberg H. A sensitive test demonstrating lupus anticoagulant and its behavioural patterns. Br J Haematol 1978; 40: 143–151
   PubMed Web of Science ®Google Scholar
• Thiagarajan P, Pengo V, Shapiro S S. The use of the dilute Russell viper venom time for the diagnosis of lupus anticoagulants. Blood 1986; 68: 869–874
   PubMed Web of Science ®Google Scholar
• Dragoni F, Minotti C, Palumbo G, Faillace F, Redi R, Bongarzoni V, Avvisati G. As compared to kaolin clotting time, silica clotting time is a specific and sensitive automated method for detecting lupus anticoagulant. Thromb Res 2001; 101: 45–51
   PubMedGoogle Scholar
• Schleider M A, Nachmann R L, Jaffe E A, Coleman M. A clinical study of the lupus anticoagulant. Blood 1976; 48: 499–509
   PubMed Web of Science ®Google Scholar
• Rooney A M, McNally T, Mackie I J, Machin S J. The Taipan snake venom time: a new test for lupus anticoagulant. J Clin Pathol 1994; 47: 497–501
   PubMedGoogle Scholar
• Triplett D A, Stocker K F, Unger G A, Barna L K. The Textarin/Ecarin ratio: a confirmatory test for lupus anticoagulants. Thromb Haemost 1993; 70: 925–931
   PubMedGoogle Scholar
• Petri M, Nelson L, Weimer F, Anderson D, Darlington T, Corash L. The automated modified Russell viper venom time test for the lupus anticoagulant. J Rheumatol 1991; 18: 1823–1825
   PubMedGoogle Scholar
• Chantarangkul V, Tripodi A, Arbini A, Mannucci P M. Silica clotting time (SCT) as a screening and confirmatory test for detection of the lupus anticoagulants. Thromb Res 1992; 67: 355–365
   PubMed Web of Science ®Google Scholar
• Galli M, Finazzi G, Bevers E M, Barbui T. Kaolin clotting time and dilute Russell's viper venom time distinguish between prothrombin-dependent and beta 2-glycoprotein I-dependent antiphospholipid antibodies. Blood 1995; 86: 617–623
   PubMed Web of Science ®Google Scholar
• Wisloff F, Jacobsen E M, Liestol S. Laboratory diagnosis of the antiphospholipid syndrome. Thromb Res 2003; 108: 263–271
   Google Scholar
• Guidelines on testing for the lupus anticoagulant. Lupus Anticoagulant Working Party on behalf of the BCSH Haemostasis and Thrombosis Task Force. J Clin Pathol 1991; 44: 885–889, [No authors listed]
   PubMed Web of Science ®Google Scholar
• O'Neill A I, Ibrahim K M, Des Parkin J. Automation of the Kaolin Clotting Time. Pathology 1992; 24: 12–14
   PubMed Web of Science ®Google Scholar
• Kelsey P R, Stevenson K J, Poller L. The diagnosis of lupus anticoagulants by the activated partial thromboplastin time–the central role of phosphatidyl serine. Thromb Haemost 1984; 52: 172–175
   PubMedGoogle Scholar
• Rosove M H, Ismail M, Koziol B J, Runge A, Kasper C K. Lupus anticoagulants: improved diagnosis with a kaolin clotting time using rabbit brain phospholipid in standard and high concentrations. Blood 1986; 68: 472–478
   PubMed Web of Science ®Google Scholar
• Howard M A, Firkin B G. Investigations of the lupus-like inhibitor by-passing activity of platelets. Thromb Haemost 1983; 50: 775–779
   PubMedGoogle Scholar
• Triplett D A, Brandt J T, Kaczor D, Schaeffer J. Laboratory diagnosis of lupus inhibitors: a comparison of the tissue thromboplastin inhibition procedure with a new platelet neutralization procedure. Am J Clin Pathol 1983; 79: 678–682
   PubMed Web of Science ®Google Scholar
• Arnout J, Huybrechts E, Vanrusselt M, Vermylen J. A new lupus anticoagulant neutralization test based on platelet-derived vesicles. Br J Haematol 1992; 80: 341–346
   PubMedGoogle Scholar
• Rauch J, Tannenbaum M, Janoff A S. Distinguishing plasma lupus anticoagulants from anti-factor antibodies using hexagonal (II) phase phospholipids. Thromb Haemost 1989; 62: 892–896
   PubMed Web of Science ®Google Scholar
• Triplett D A, Barna L K, Unger G A. A hexagonal (II) phase phospholipid neutralization assay for lupus anticoagulant identification. Thromb Haemost 1993; 70: 787–793
   PubMedGoogle Scholar
• Le Querrec A, Arnout J, Arnoux D, Borg J Y, Caron C, Darnige L, Delahousse B, Reber G, Sie P. Quantification of lupus anticoagulants in clinical samples using anti-beta2GP1 and anti-prothrombin monoclonal antibodies. Thromb Haemost 2001; 86: 584–589
   PubMedGoogle Scholar
• Simmelink M J, Derksen R H, Arnout J, De Groot P G. A simple method to discriminate between beta2-glycoprotein I-and prothrombin-dependent lupus anticoagulants. J Thromb Haemost 2003; 1: 740–747
   PubMed Web of Science ®Google Scholar
• Detection of lupus like anticoagulant: current laboratory practice in the United Kingdom. The Lupus Anticoagulant Working Party. J Clin Pathol 1990; 43: 73–75
   PubMedGoogle Scholar
• Laboratory heterogeneity of the lupus anticoagulant: a multicentre study using different clotting assays on a panel of 78 samples. Hemostasis Committee of the “Societe Francaise de Biologie Clinique.”. Thromb Res 1992; 66: 349–364, [No authors listed]
   PubMedGoogle Scholar
• Comparison of a standardized procedure with current laboratory practices for the detection of lupus anticoagulant in France. Working Group on Hemostasis of the Societe Francaise de Biologie Clinique. Thromb Haemost 1993; 70: 781–786
   PubMedGoogle Scholar
• Jennings I, Kitchen S, Woods T A, Preston F E, Greaves M. Potentially clinically important inaccuracies in testing for the lupus anticoagulant: an analysis of results from three surveys of the UK National External Quality Assessment Scheme (NEQAS) for Blood Coagulation. Thromb Haemost 1997; 77: 934–937
   PubMedGoogle Scholar
• Arnout J, Meijer P, Vermylen J. Lupus anticoagulant testing in Europe: an analysis of results from the first European Concerted Action on Thrombophilia (ECAT) survey using plasmas spiked with monoclonal antibodies against human beta2-glycoprotein I. Thromb Haemost 1999; 81: 929–934
   PubMed Web of Science ®Google Scholar
• Jennings I, Greaves M, Mackie I J, Kitchen S, Woods T A, Preston F E. Lupus anticoagulant testing: improvements in performance in a UK NEQAS proficiency testing exercise after dissemination of national guidelines on laboratory methods. Br J Haematol 2002; 119: 364–369
   PubMedGoogle Scholar
• Brandt J T, Triplett D A, Rock W A, Bovill E G, Arkin C F. Effect of lupus anticoagulants on the activated partial thromboplastin time. Results of the College of American Pathologists survey program. Arch Pathol Lab Med 1991; 115: 109–114
   PubMed Web of Science ®Google Scholar
• Andrews P A, Frampton G, Cameron J S. Antiphospholipid syndrome and systemic lupus erythematosus. Lancet 1993; 342: 988–989
   PubMed Web of Science ®Google Scholar
• Tripodi A, Biasiolo A, Chantarangkul V, Pengo V. Lupus anticoagulant (LA) testing: performance of clinical laboratories assessed by a national survey using lyophilized affinity-purified immunoglobulin with LA activity. Clin Chem 2003; 49: 1608–1614
   PubMedGoogle Scholar
• Roussi J, Roisin J P, Goguel A. Lupus anticoagulants: first French interlaboratory Etalonorme survey. Am J Clin Pathol 1996; 105: 788–793
   PubMedGoogle Scholar
• Sletnes K E, Gravem K, Wisloff F. Preparation of plasma for the detection of lupus anticoagulants and antiphospholipid antibodies. Thromb Res 1992; 66: 43–53
   PubMedGoogle Scholar
• Brien W F, Schaus M R, Cooper K E, O'Keefe B T, Inwood M. Lupus anticoagulant testing: effect of the platelet count on the activated partial thromboplastin time. Br J Biomed Sci 1993; 50: 114–116
   PubMedGoogle Scholar
• Exner T. Conceptions and misconceptions in testing for lupus anticoagulants. J Autoimmun 2000; 15: 179–183
   PubMed Web of Science ®Google Scholar
• Chantarangkul V, Tripodi A, Clerici M, Bressi C, Mannucci P M. Laboratory diagnosis of lupus anticoagulants–effect of residual platelets in plasma, assessed by Staclot LA and silica clotting time. Thromb Haemost 2002; 87: 854–858
   PubMedGoogle Scholar
• McGlasson D L, Ledford M, Barna L, Best H A, Hickman J R. Rapid removal of platelets from plasma utilizing the Hepcheck heparin removal filter. Blood Coagul Fibrinolysis 1997; 8: 16–20
   PubMedGoogle Scholar
• Schjetlein R, Wisloff F. Detection of lupus anticoagulant: an evaluation of routines for preparation and storage of plasma. Thromb Res 1995; 79: 135–140
   PubMedGoogle Scholar
• Reber G, Roisin J P, Migaud M, de Moerloose P. Comparison of a platelet neutralization procedure with a hexagonal phase phospholipid neutralization assay as confirmatory tests for the presence of lupus anticoagulants. Thromb Res 1994; 73: 131–135
   PubMedGoogle Scholar
• Martin B A, Branch D W, Rodgers G M. Sensitivity of the activated partial thromboplastin time, the dilute Russell's viper venom time, and the kaolin clotting time for the detection of the lupus anticoagulant: a direct comparison using plasma dilutions. Blood Coagul Fibrinolysis 1996; 7: 31–38
   PubMedGoogle Scholar
• Derksen R H, de Groot P G. Tests for lupus anticoagulant revisited. Thromb Res 2004; 114: 521–526
   PubMedGoogle Scholar
• Vlachoyiannopoulos P G, Beigbeder G, Dueymes M, Youinou P, Hunt J E, Krilis S A, Moutsopoulos H M. Antibodies to phosphatidylethanolamine in antiphospholipid syndrome and systemic lupus erythematosus: their correlation with anticardiolipin antibodies and beta 2 glycoprotein-I plasma levels. Autoimmunity 1993; 16: 245–249
   PubMed Web of Science ®Google Scholar
• Merkel P A, Chang Y, Pierangeli S S, Harris E N, Polisson R P. Comparison between the standard anticardiolipin antibody test and a new phospholipid test in patients with connective tissue diseases. J Rheumatol 1999; 26: 591–596
   PubMed Web of Science ®Google Scholar
• Santiago M, Martinelli R, Ko A, Reis E A, Fontes R D, Nascimento E G, Pierangeli S, Espinola R, Gharavi A. Anti-beta2 glycoprotein I and anticardiolipin antibodies in leptospirosis, syphilis and Kala-azar. Clin Exp Rheumatol 2001; 19: 425–430
   PubMed Web of Science ®Google Scholar
• Stewart M W, McKay T, Schwind P, Gordon P A. Rapid detection of anticardiolipin antibodies. Am J Hematol 1998; 57: 315–319
   PubMedGoogle Scholar
• Stewart M W, Etches W S, Russell A S, Percy J S, Johnston C A, Chew C K, Gordon P A. Detection of antiphospholipid antibodies by flow cytometry: rapid detection of antibody isotype and phospholipid specificity. Thromb Haemost 1993; 70: 603–607
   PubMedGoogle Scholar
• Pierangeli S S, Silva L K, Harris E N. A flow cytometric assay for the detection of antiphospholipid antibodies. Am Clin Lab 1999; 18: 18–19
   PubMedGoogle Scholar
• Sheng Y, Hanly J G, Reddel S W, Kouts S, Guerin J, Koike T, Ichikawa K, Sturgess A, Krilis S A. Detection of ‘antiphospholipid’ antibodies: a single chromogenic assay of thrombin generation sensitively detects lupus anticoagulants, anticardiolipin antibodies, plus antibodies binding beta(2)-glycoprotein I and prothrombin. Clin Exp Immunol 2001; 124: 502–508
   PubMedGoogle Scholar
• Katano K, Aoki A, Sasa H, Ogasawara M, Matsuura E, Yagami Y. beta 2-Glycoprotein I-dependent anticardiolipin antibodies as a predictor of adverse pregnancy outcomes in healthy pregnant women. Hum Reprod 1996; 11: 509–512
   PubMed Web of Science ®Google Scholar
• Kutteh W H. Antiphospholipid antibodies and reproduction. J Reprod Immunol 1997; 35: 151–171
   PubMedGoogle Scholar
• Juby A G, Davis P. Prevalence and disease associations of certain autoantibodies in elderly patients. Clin Invest Med 1998; 21: 4–11
   PubMed Web of Science ®Google Scholar
• Manoussakis M N, Tzioufas A G, Silis M P, Pange P J, Goudevenos J, Moutsopoulos H M. High prevalence of anti-cardiolipin and other autoantibodies in a healthy elderly population. Clin Exp Immunol 1987; 69: 557–565
   PubMed Web of Science ®Google Scholar
• Fields R A, Toubbeh H, Searles R P, Bankhurst A D. The prevalence of anticardiolipin antibodies in a healthy elderly population and its association with antinuclear antibodies. J Rheumatol 1989; 16: 623–625
   PubMed Web of Science ®Google Scholar
• Richaud-Patin Y, Cabiedes J, Jakez-Ocampo J, Vidaller A, Llorente L. High prevalence of protein-dependent and protein-independent antiphospholipid and other autoantibodies in healthy elders. Thromb Res 2000; 99: 129–133
   PubMedGoogle Scholar
• Alarcon-Segovia D. Clinical manifestations of the antiphospholipid syndrome. J Rheumatol 1992; 19: 1778–1781
   PubMed Web of Science ®Google Scholar
• Cervera R, Piette J C, Font J, Khamashta M A, Shoenfeld Y, Camps M T, Jacobsen S, Lakos G, Tincani A, Kontopoulou-Griva I, Galeazzi M, Meroni P L, Derksen R H, de Groot P G, Gromnica-Ihle E, Baleva M, Mosca M, Bombardieri S, Houssiau F, Gris J C, Quere I, Hachulla E, Vasconcelos C, Roch B, Fernandez-Nebro A, Boffa M C, Hughes G R, Ingelmo M. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum 2002; 46: 1019–1027
   PubMed Web of Science ®Google Scholar
• Amigo M C, Garcia-Torres R, Robles M, Bochicchio T, Reyes P A. Renal involvement in primary antiphospholipid syndrome. J Rheumatol 1992; 19: 1181–1185
   PubMed Web of Science ®Google Scholar
• Spronk P E, Bootsma H, Nikkels P G, Kallenberg C G. A new class of lupus nephropathy associated with antiphospholipid antibodies. Br J Rheumatol 1994; 33: 686–687
   PubMedGoogle Scholar
• Nochy D, Daugas E, Droz D, Beaufils H, Grunfeld J P, Piette J C, Bariety J, Hill G. The intrarenal vascular lesions associated with primary antiphospholipid syndrome. J Am Soc Nephrol 1999; 10: 507–518
   PubMed Web of Science ®Google Scholar
• Loizou S, Samarkos M, Norsworthy P J, Cazabon J K, Walport M J, Davies K A. Significance of anticardiolipin and anti-beta(2)-glycoprotein I antibodies in lupus nephritis. Rheumatology (Oxford) 2000; 39: 962–968
   PubMedGoogle Scholar
• Ohtomo Y, Nagaoka R, Watanabe H, Kaneko K, Ohyama S, Yamashiro Y. Non-lupus nephropathy associated with antiphospholipid antibodies. Pediatr Nephrol 2000; 15: 136–138
   PubMedGoogle Scholar
• Daugas E, Nochy D, Huong D L, Duhaut P, Beaufils H, Caudwell V, Bariety J, Piette J C, Hill G. Antiphospholipid syndrome nephropathy in systemic lupus erythematosus. J Am Soc Nephrol 2002; 13: 42–52
   PubMedGoogle Scholar
• Nochy D, Daugas E, Hill G, Grunfeld J P. Antiphospholipid syndrome nephropathy. J Nephrol 2002; 15: 446–461
   PubMedGoogle Scholar
• Fakhouri F, Noel L H, Zuber J, Beaufils H, Martinez F, Lebon P, Papo T, Chauveau D, Bletry O, Grunfeld J P, Piette J C, Lesavre P. The expanding spectrum of renal diseases associated with antiphospholipid syndrome. Am J Kidney Dis 2003; 41: 1205–1211
   PubMedGoogle Scholar
• Vlachoyiannopoulos P G, Kanellopoulos P, Tektonidou M, Moutsopoulos H M. Renal involvement in antiphospholipid syndrome. Nephrol Dial Transplant 2001; 16: S60–S62, Suppl 6
   PubMedGoogle Scholar
• Tektonidou M G, Sotsiou F, Nakopoulou L, Vlachoyiannopoulos P G, Moutsopoulos H M. Antiphospholipid syndrome nephropathy in patients with systemic lupus erythematosus and antiphospholipid antibodies: prevalence, clinical associations, and long-term outcome. Arthritis Rheum 2004; 50: 2569–2579
   PubMedGoogle Scholar
• Thiagarajan P. Atherosclerosis, autoimmunity, and systemic lupus erythematosus. Circulation 2001; 104: 1876–1877
   PubMed Web of Science ®Google Scholar
• Asanuma Y, Oeser A, Shintani A K, Turner E, Olsen N, Fazio S, Linton M F, Raggi P, Stein C M. Premature coronary-artery atherosclerosis in systemic lupus erythematosus. N Engl J Med 2003; 349: 2407–2415
   PubMed Web of Science ®Google Scholar
• Vlachoyiannopoulos P G, Kanellopoulos P G, Ioannidis J P, Tektonidou M G, Mastorakou I, Moutsopoulos H M. Atherosclerosis in premenopausal women with antiphospholipid syndrome and systemic lupus erythematosus: a controlled study. Rheumatology (Oxford) 2003; 42: 645–651
   PubMed Web of Science ®Google Scholar
• Vlachoyiannopoulos P G, Samarkos M. Peripheral vascular disease in antiphospholipid syndrome. Thromb Res 2004; 114: 509–519
   PubMedGoogle Scholar
• Tektonidou M G, Ioannidis J P, Moyssakis I, Boki K A, Vassiliou V, Vlachoyiannopoulos P G, Kyriakidis M K, Moutsopoulos H M. Right ventricular diastolic dysfunction in patients with anticardiolipin antibodies and antiphospholipid syndrome. Ann Rheum Dis 2001; 60: 43–48
   PubMed Web of Science ®Google Scholar
• Tektonidou M G, Malagari K, Vlachoyiannopoulos P G, Kelekis D A, Moutsopoulos H M. Asymptomatic avascular necrosis in patients with primary antiphospholipid syndrome in the absence of corticosteroid use: a prospective study by magnetic resonance imaging. Arthritis Rheum 2003; 48: 732–736
   PubMed Web of Science ®Google Scholar
• Vianna J L, Khamashta M A, Ordi-Ros J, Font J, Cervera R, Lopez-Soto A, Tolosa C, Franz J, Selva A, Ingelmo M. Comparison of the primary and secondary antiphospholipid syndrome: a European Multicenter Study of 114 patients. Am J Med 1994; 96: 3–9
   PubMed Web of Science ®Google Scholar
• Furie B, Furie B C. Molecular basis of blood coagulation. Hematology, 4th Ed, R Hoffman, E J Benz, Jr., S J Shattil, B Furie, H J Cohen, L E Silberstein, P McGlave. Elsevier, Philadelphia 2005; 1931–1953
   Google Scholar
• Schwartz M L, Pizzo S V, Hill R L, McKee P A. The subunit structures of human plasma and platelet factor XIII (fibrin-stabilizing factor). J Biol Chem 1971; 246: 5851–5854
   PubMed Web of Science ®Google Scholar
• Lorand L, Jeong J M, Radek J T, Wilson J. Human plasma factor XIII: subunit interactions and activation of zymogen. Methods Enzymol 1993; 222: 22–35
   PubMedGoogle Scholar
• Mosesson M W. Fibrinogen and fibrin polymerization: appraisal of the binding events that accompany fibrin generation and fibrin clot assembly. Blood Coagul Fibrinolysis 1997; 8: 257–267
   PubMed Web of Science ®Google Scholar
• Ichinose A, McMullen B A, Fujikawa K, Davie E W. Amino acid sequence of the b subunit of human factor XIII, a protein composed of ten repetitive segments. Biochemistry 1986; 25: 4633–4638
   PubMedGoogle Scholar
• Nicholson-Weller A, Zaia J, Raum M G, Coligan J E. Decay accelerating factor (DAF) peptide sequences share homology with a consensus sequence found in the superfamily of structurally related complement proteins and other proteins including haptoglobin, factor XIII, beta 2-glycoprotein I, and the IL-2 receptor. Immunol Lett 1987; 14: 307–311
   PubMedGoogle Scholar
• Tokunaga F, Miyata T, Nakamura T, Morita T, Kuma K, Miyata T, Iwanaga S. Lipopolysaccharide-sensitive serine-protease zymogen (factor C) of horseshoe crab hemocytes. Identification and alignment of proteolytic fragments produced during the activation show that it is a novel type of serine protease. Eur J Biochem 1987; 167: 405–416
   PubMedGoogle Scholar
• Lorand L, Maldonado N, Fradera J, Atencio A C, Robertson B, Urayama T. Haemorrhagic syndrome of autoimmune origin with a specific inhibitor against fibrin stabilizing factor (factor XIII). Br J Haematol 1972; 23: 17–27
   PubMed Web of Science ®Google Scholar
• Lorand L, Velasco P T, Rinne J R, Amare M, Miller L K, Zucker M L. Autoimmune antibody (IgG Kansas) against the fibrin stabilizing factor (factor XIII) system. Proc Natl Acad Sci USA 1988; 85: 232–236
   PubMedGoogle Scholar
• Fukue H, Anderson K, McPhedran P, Clyne L, McDonagh J. A unique factor XIII inhibitor to a fibrin-binding site on factor XIIIA. Blood 1992; 79: 65–74
   PubMed Web of Science ®Google Scholar
• Milner G R, Holt P J, Bottomley J, Maciver J E. Practolol therapy associated with a systemic lupus erythematosus-like syndrome and an inhibitor to factor XIII. J Clin Pathol 1977; 30: 770–773
   PubMed Web of Science ®Google Scholar
• Lorand L, Velasco P T, Hill J M, Hoffmeister K J, Kaye F J. Intracranial hemorrhage in systemic lupus erythematosus associated with an autoantibody against factor XIII. Thromb Haemost 2002; 88: 919–923
   PubMedGoogle Scholar
• Chiarantini E, Valanzano R, Liotta A A, Cellai A P, Ilari I, Prisco D, Antonucci E, Tonelli F, Abbate R. Persistence of hemostatic alterations in patients affected by Crohn's disease after bowel surgery. Thromb Res 1997; 87: 539–546
   PubMedGoogle Scholar
• Sjober K, Eriksson S, Tenngart B, Roth E B, Leffler H, Stenberg P. Factor XIII and tissue transglutaminase antibodies in coeliac and inflammatory bowel disease. Autoimmunity 2002; 35: 357–364
   PubMed Web of Science ®Google Scholar
• Mann K G, Jenny R J, Krishnaswamy S. Cofactor proteins in the assembly and expression of blood clotting enzyme complexes. Annu Rev Biochem 1988; 57: 915–956
   PubMed Web of Science ®Google Scholar
• Verwilghen R, Verstraete M, Vandenbroucke J. [Anti-thrombin specific antibodies of equine origin; description of a case where such antibodies developed following repeated injections of thrombin.]. Rev Hematol 1953; 8: 273–275
   PubMedGoogle Scholar
• Korochkin I M, Verbitskaia I A, Tugutov A N, Miagkova M A, Polevaia O I. [Thrombin and anti-thrombin antibody levels in the blood of patients with acute myocardial infarction]. Kardiologiia 1990; 30: 45–48
   PubMedGoogle Scholar
• Zehnder J L, Leung L L. Development of antibodies to thrombin and factor V with recurrent bleeding in a patient exposed to topical bovine thrombin. Blood 1990; 76: 2011–2016
   PubMed Web of Science ®Google Scholar
• Costa J M, Fiessinger J N, Capron L, Aiach M. Partial characterization of an autoantibody recognizing the secondary binding site(s) of thrombin in a patient with recurrent spontaneous arterial thrombosis. Thromb Haemost 1992; 67: 193–199
   PubMedGoogle Scholar
• Hwang K K, Grossman J M, Visvanathan S, Chukwuocha R U, Woods V L, Jr., Le D T, Hahn B H, Chen P P. Identification of anti-thrombin antibodies in the antiphospholipid syndrome that interfere with the inactivation of thrombin by antithrombin. J Immunol 2001; 167: 7192–7198
   PubMedGoogle Scholar
• Blanchard R A, Furie B C, Kruger S F, Waneck G, Jorgensen M J, Furie B. Immunoassays of human prothrombin species which correlate with functional coagulant activities. J Lab Clin Med 1983; 101: 242–255
   PubMedGoogle Scholar
• Oosting J D, Derksen R H, Bobbink I W, Hackeng T M, Bouma B N, de Groot P G. Antiphospholipid antibodies directed against a combination of phospholipids with prothrombin, protein C, or protein S: an explanation for their pathogenic mechanism?. Blood 1993; 81: 2618–2625
   PubMed Web of Science ®Google Scholar
• Field S L, Chesterman C N, Hogg P J. Dependence on prothrombin for inhibition of activated protein C activity by lupus antibodies. Thromb Haemost 2000; 84: 1132–1133
   PubMedGoogle Scholar
• Nojima J, Kuratsune H, Suehisa E, Kawasaki T, Machii T, Kitani T, Iwatani Y, Kanakura Y. Acquired activated protein C resistance is associated with the co-existence of anti-prothrombin antibodies and lupus anticoagulant activity in patients with systemic lupus erythematosus. Br J Haematol 2002; 118: 577–583
   PubMedGoogle Scholar
• Simmelink M J, Horbach D A, Derksen R H, Meijers J C, Bevers E M, Willems G M, De Groot P G. 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: 621–629
   PubMed Web of Science ®Google Scholar
• Galli M, Willems G M, Rosing J, Janssen R M, Govers-Riemslag J W, Comfurius P, Barbui T, Zwaal R F, Bevers E M. Anti-prothrombin IgG from patients with anti-phospholipid antibodies inhibits the inactivation of factor Va by activated protein C. Br J Haematol 2005; 129: 240–247
   PubMedGoogle Scholar
• van Dieijen G, Tans G, Rosing J, Hemker H C. The role of phospholipid and factor VIIIa in the activation of bovine factor X. J Biol Chem 1981; 256: 3433–3442
   PubMed Web of Science ®Google Scholar
• Pittman D D, Kaufman R J. Proteolytic requirements for thrombin activation of anti-hemophilic factor (factor VIII). Proc Natl Acad Sci USA 1988; 85: 2429–2433
   PubMed Web of Science ®Google Scholar
• Radcliffe R D, Barton P G. Comparisons of the molecular forms of activated bovine factor X. Products of activation with Russell's viper venom, insoluble trypsin, sodium citrate, tissue factor, and the intrinsic system. J Biol Chem 1973; 248: 6788–6795
   PubMedGoogle Scholar
• Sanders N L, Bajaj S P, Zivelin A, Rapaport S I. Inhibition of tissue factor/factor VIIa activity in plasma requires factor X and an additional plasma component. Blood 1985; 66: 204–212
   PubMed Web of Science ®Google Scholar
• Broze G J, Jr., Miletich J P. Characterization of the inhibition of tissue factor in serum. Blood 1987; 69: 150–155
   PubMed Web of Science ®Google Scholar
• Rapaport S I. Inhibition of factor VIIa/tissue factor-induced blood coagulation: with particular emphasis upon a factor Xa-dependent inhibitory mechanism. Blood 1989; 73: 359–365
   PubMed Web of Science ®Google Scholar
• Forastiero R R, Martinuzzo M E, Lu L, Broze G J. Autoimmune antiphospholipid antibodies impair the inhibition of activated factor X by protein Z/protein Z-dependent protease inhibitor. J Thromb Haemost 2003; 1: 1764–1770
   PubMed Web of Science ®Google Scholar
• Sinha D, Seaman F S, Koshy A, Knight L C, Walsh P N. Blood coagulation factor XIa binds specifically to a site on activated human platelets distinct from that for factor XI. J Clin Invest 1984; 73: 1550–1556
   PubMedGoogle Scholar
• Baird T R, Walsh P N. The interaction of factor XIa with activated platelets but not endothelial cells promotes the activation of factor IX in the consolidation phase of blood coagulation. J Biol Chem 2002; 277: 38462–38467
   PubMedGoogle Scholar
• Jacobson D M, Lewis J H, Bontempo F A, Spero J A, Ragni M V, Reinmuth O M. Recurrent cerebral infarctions in two brothers with antiphospholipid antibodies that block coagulation reactions. Stroke 1986; 17: 98–102
   PubMedGoogle Scholar
• Clyne L P, Farber L R, Chopyk R L. Procainamide-induced circulating anticoagulants in a congenitally-deficient factor XI patient. Folia Haematol Int Mag Klin Morphol Blutforsch 1989; 116: 239–244
   PubMedGoogle Scholar
• Halbmayer W M, Haushofer A, Schon R, Mannhalter C, Strohmer E, Baumgarten K, Fischer M. The prevalence of moderate and severe FXII (Hageman factor) deficiency among the normal population: evaluation of the incidence of FXII deficiency among 300 healthy blood donors. Thromb Haemost 1994; 71: 68–72
   PubMedGoogle Scholar
• Schousboe I, Rasmussen M S. Synchronized inhibition of the phospholipid mediated autoactivation of factor XII in plasma by beta 2-glycoprotein I and anti-beta 2-glycoprotein I. Thromb Haemost 1995; 73: 798–804
   PubMed Web of Science ®Google Scholar
• Gallimore M J, Jones D W, Winter M. Factor X II determinations in the presence and absence of phospholipid antibodies. Thromb Haemost 1998; 79: 87–90
   PubMedGoogle Scholar
• Jones D W, Gallimore M J, Winter M. An automated chromogenic peptide substrate assay for coagulation factor XII. Blood Coagul Fibrinolysis 1998; 9: 183–187
   PubMedGoogle Scholar
• Jones D W, Gallimore M J, Harris S L, Winter M. Antibodies to factor XII associated with lupus anticoagulant. Thromb Haemost 1999; 81: 387–390
   PubMedGoogle Scholar
• Jones D W, Gallimore M J, MacKie I J, Harris S L, Winter M. Reduced factor XII levels in patients with the antiphospholipid syndrome are associated with antibodies to factor XII. Br J Haematol 2000; 110: 721–726
   PubMedGoogle Scholar
• Jones D W, MacKie I J, Gallimore M J, Winter M. Antibodies to factor XII and recurrent fetal loss in patients with the anti-phospholipid syndrome. Br J Haematol 2001; 113: 550–552
   PubMedGoogle Scholar
• Iinuma Y, Sugiura-Ogasawara M, Makino A, Ozaki Y, Suzumori N, Suzumori K. Coagulation factor XII activity, but not an associated common genetic polymorphism (46C/T), is linked to recurrent miscarriage. Fertil Steril 2002; 77: 353–356
   PubMedGoogle Scholar
• Jones D W, Nicholls P J, Donohoe S, Gallimore M J, Winter M. Antibodies to factor XII are distinct from antibodies to prothrombin in patients with the anti-phospholipid syndrome. Thromb Haemost 2002; 87: 426–430
   PubMedGoogle Scholar
• Kitchens C S. The contact system. Arch Pathol Lab Med 2002; 126: 1382–1386
   PubMed Web of Science ®Google Scholar
• Takeuchi R, Atsumi T, Ieko M, Amasaki Y, Ichikawa K, Koike T. Suppressed intrinsic fibrinolytic activity by monoclonal anti-beta-2 glycoprotein I autoantibodies: possible mechanism for thrombosis in patients with antiphospholipid syndrome. Br J Haematol 2002; 119: 781–788
   PubMed Web of Science ®Google Scholar
• Sugi T, McIntyre J A. Certain autoantibodies to phosphatidylethanolamine (aPE) recognize factor XI and prekallikrein independently or in addition to the kininogens. J Autoimmun 2001; 17: 207–214
   PubMedGoogle Scholar
• Shi T, Iverson G M, Qi J C, Cockerill K A, Linnik M D, Konecny P, Krilis S A. Beta 2-Glycoprotein I binds factor XI and inhibits its activation by thrombin and factor XIIa: loss of inhibition by clipped beta 2-glycoprotein I. Proc Natl Acad Sci USA 2004; 101: 3939–3944
   PubMedGoogle Scholar
• Shi T, Giannakopoulos B, Iverson G M, Cockerill K A, Linnik M D, Krilis S A. Domain V of beta2-glycoprotein I binds factor XI/XIa and is cleaved at Lys317-Thr318. J Biol Chem 2005; 280: 907–912
   PubMedGoogle Scholar
• Yang Q, Shi T, Cheyne B, et al. Anti-b2-glycoprotein I antibodies potentiate the inhibitory effects of b2-glycoprotein I on the activation of FXI by FIIa: effect on clipped b2-glycoprotein I. Thromb Res 2004; 114: 608
   Google Scholar
• Cariou R, Tobelem G, Bellucci S, Soria J, Soria C, Maclouf J, Caen J. Effect of lupus anticoagulant on antithrombogenic properties of endothelial cells—inhibition of thrombomodulin-dependent protein C activation. Thromb Haemost 1988; 60: 54–58
   PubMed Web of Science ®Google Scholar
• Ruiz-Arguelles G J, Ruiz-Arguelles A, Deleze M, Alarcon-Segovia D. Acquired protein C deficiency in a patient with primary antiphospholipid syndrome. Relationship to reactivity of anticardiolipin antibody with thrombomodulin. J Rheumatol 1989; 16: 381–383
   PubMedGoogle Scholar
• Oosting J D, Derksen R H, Hackeng T M, van Vliet M, Preissner K T, Bouma B N, de Groot P G. In vitro studies of antiphospholipid antibodies and its cofactor, beta 2-glycoprotein I, show negligible effects on endothelial cell mediated protein C activation. Thromb Haemost 1991; 66: 666–671
   PubMedGoogle Scholar
• Potzsch B, Kawamura H, Preissner K T, Schmidt M, Seelig C, Muller-Berghaus G. Acquired protein C dysfunction but not decreased activity of thrombomodulin is a possible marker of thrombophilia in patients with lupus anticoagulant. J Lab Clin Med 1995; 125: 56–65
   PubMedGoogle Scholar
• Del Papa N, Guidali L, Spatola L, Bonara P, Borghi M O, Tincani A, Balestrieri G, Meroni P L. Relationship between anti-phospholipid and anti-endothelial cell antibodies III: beta 2 glycoprotein I mediates the antibody binding to endothelial membranes and induces the expression of adhesion molecules. Clin Exp Rheumatol 1995; 13: 179–185
   PubMedGoogle Scholar
• Meroni P L, Papa N D, Beltrami B, Tincani A, Balestrieri G, Krilis S A. Modulation of endothelial cell function by antiphospholipid antibodies. Lupus 1996; 5: 448–450
   PubMedGoogle Scholar
• Hanly J G, Hong C, Issekutz A. Beta 2-glycoprotein I and anticardiolipin antibody binding to resting and activated cultured human endothelial cells. J Rheumatol 1996; 23: 1543–1549
   PubMedGoogle Scholar
• Rao L V, Hoang A D, Rapaport S I. Mechanism and effects of the binding of lupus anticoagulant IgG and prothrombin to surface phospholipid. Blood 1996; 88: 4173–4182
   PubMedGoogle Scholar
• Forman S D, Nemerson Y. Membrane-dependent coagulation reaction is independent of the concentration of phospholipid-bound substrate: fluid phase factor X regulates the extrinsic system. Proc Natl Acad Sci USA 1986; 83: 4675–4679
   PubMed Web of Science ®Google Scholar
• George J, Blank M, Levy Y, Meroni P, Damianovich M, Tincani A, Shoenfeld Y. Differential effects of anti-beta2-glycoprotein I antibodies on endothelial cells and on the manifestations of experimental antiphospholipid syndrome. Circulation 1998; 97: 900–906
   PubMed Web of Science ®Google Scholar
• Afek A, Shoenfeld Y, Manor R, Goldberg I, Ziporen L, George J, Polak-Charcon S, Amigo M C, Garcia-Torres R, Segal R, Kopolovic J. Increased endothelial cell expression of alpha3beta1 integrin in cardiac valvulopathy in the primary (Hughes) and secondary antiphospholipid syndrome. Lupus 1999; 8: 502–507
   PubMedGoogle Scholar
• Pierangeli S S, Liu X W, Barker J H, Anderson G, Harris E N. Induction of thrombosis in a mouse model by IgG, IgM and IgA immunoglobulins from patients with the antiphospholipid syndrome. Thromb Haemost 1995; 74: 1361–1367
   PubMed Web of Science ®Google Scholar
• Gharavi A E, Pierangeli S S, Espinola R G, Liu X, Colden-Stanfield M, Harris E N. Antiphospholipid antibodies induced in mice by immunization with a cytomegalovirus-derived peptide cause thrombosis and activation of endothelial cells in vivo. Arthritis Rheum 2002; 46: 545–552
   PubMed Web of Science ®Google Scholar
• Cho C S, Cho M L, Chen P P, Min S Y, Hwang S Y, Park K S, Kim W U, Min D J, Min J K, Park S H, Kim H Y. Antiphospholipid antibodies induce monocyte chemoattractant protein-1 in endothelial cells. J Immunol 2002; 168: 4209–4215
   PubMedGoogle Scholar
• Zhang J, McCrae K R. Annexin A2 mediates endothelial cell activation by antiphospholipid/anti-beta2 glycoprotein I antibodies. Blood 2005; 105: 1964–1969
   PubMed Web of Science ®Google Scholar
• Cederholm A, Svenungsson E, Jensen-Urstad K, Trollmo C, Ulfgren A K, Swedenborg J, Fei G Z, Frostegard J. Decreased binding of annexin v to endothelial cells: a potential mechanism in atherothrombosis of patients with systemic lupus erythematosus. Arterioscler Thromb Vasc Biol 2005; 25: 198–203
   PubMed Web of Science ®Google Scholar
• Dieude M, Senecal J L, Raymond Y. Induction of endothelial cell apoptosis by heat-shock protein 60-reactive antibodies from anti-endothelial cell autoantibody-positive systemic lupus erythematosus patients. Arthritis Rheum 2004; 50: 3221–3231
   PubMed Web of Science ®Google Scholar
• Lopez-Lira F, Rosales Leon L, Monroy Martinez V, Ruiz Ordaz B H. The role of beta2-glycoprotein I (beta(2)GPI) in the activation of plasminogen. Biochim Biophys Acta 2006; 1764: 815–823
   PubMedGoogle Scholar
• Dunoyer-Geindre S, de Moerloose P, Galve-de Rochemonteix B, Reber G, Kruithof E K. NFkappaB is an essential intermediate in the activation of endothelial cells by anti-beta(2)-glycoprotein 1 antibodies. Thromb Haemost 2002; 88: 851–857
   PubMed Web of Science ®Google Scholar
• Raschi E, Testoni C, Bosisio D, Borghi M O, Koike T, Mantovani A, Meroni P L. Role of the MyD88 transduction signaling pathway in endothelial activation by antiphospholipid antibodies. Blood 2003; 101: 3495–3500
   PubMed Web of Science ®Google Scholar
• Espinola R G, Liu X, Colden-Stanfield M, Hall J, Harris E N, Pierangeli S S. E-Selectin mediates pathogenic effects of antiphospholipid antibodies. J Thromb Haemost 2003; 1: 843–848
   PubMed Web of Science ®Google Scholar
• Rand J H, Wu X X, Quinn A S, Chen P P, McCrae K R, Bovill E G, Taatjes D J. Human monoclonal antiphospholipid antibodies disrupt the annexin A5 anticoagulant crystal shield on phospholipid bilayers: evidence from atomic force microscopy and functional assay. Am J Pathol 2003; 163: 1193–1200
   PubMed Web of Science ®Google Scholar
• Chen Q, Stone P R, Woon S T, Ching L M, Hung S, McCowan L M, Chamley L W. Antiphospholipid antibodies bind to activated but not resting endothelial cells: is an independent triggering event required to induce antiphospholipid antibody-mediated disease?. Thromb Res 2004; 114: 101–111
   PubMedGoogle Scholar
• Hasselaar P, Derksen R H, Oosting J D, Blokzijl L, de Groot P G. Synergistic effect of low doses of tumor necrosis factor and sera from patients with systemic lupus erythematosus on the expression of procoagulant activity by cultured endothelial cells. Thromb Haemost 1989; 62: 654–660
   PubMedGoogle Scholar
• Bouma B, de Groot P G, van den Elsen J M, Ravelli R B, Schouten A, Simmelink M J, Derksen R H, Kroon J, Gros P. Adhesion mechanism of human beta(2)-glycoprotein I to phospholipids based on its crystal structure. EMBO J 1999; 18: 5166–5174
   PubMed Web of Science ®Google Scholar
• Guerin J, Sheng Y, Reddel S, Iverson G M, Chapman M G, Krilis S A. Heparin inhibits the binding of beta 2-glycoprotein I to phospholipids and promotes the plasmin-mediated inactivation of this blood protein. Elucidation of the consequences of the two biological events in patients with the anti-phospholipid syndrome. J Biol Chem 2002; 277: 2644–2649
   PubMed Web of Science ®Google Scholar
• Vlachoyiannopoulos P G, Mavragani C P, Bourazopoulou E, Balitsari A V, Routsias J G. Anti-CD40 antibodies in antiphospholipid syndrome and systemic lupus erythematosus. Thromb Haemost 2004; 92: 1303–1311
   PubMed Web of Science ®Google Scholar
• Kotowicz K, Dixon G L, Klein N J, Peters M J, Callard R E. Biological function of CD40 on human endothelial cells: costimulation with CD40 ligand and interleukin-4 selectively induces expression of vascular cell adhesion molecule-1 and P-selectin resulting in preferential adhesion of lymphocytes. Immunology 2000; 100: 441–448
   PubMed Web of Science ®Google Scholar
• Vega-Ostertag M, Harris E N, Pierangeli S S. Intracellular events in platelet activation induced by antiphospholipid antibodies in the presence of low doses of thrombin. Arthritis Rheum 2004; 50: 2911–2919
   PubMedGoogle Scholar
• Pierangeli S S, Vega-Ostertag M, Liu X, Girardi G. Complement activation: a novel pathogenic mechanism in the antiphospholipid syndrome. Ann NY Acad Sci 2005; 1051: 413–420
   PubMedGoogle Scholar
• Pierangeli S S, Girardi G, Vega-Ostertag M, Liu X, Espinola R G, Salmon J. Requirement of activation of complement C3 and C5 for antiphospholipid antibody-mediated thrombophilia. Arthritis Rheum 2005; 52: 2120–2124
   PubMed Web of Science ®Google Scholar
• Girardi G, Berman J, Redecha P, Spruce L, Thurman J M, Kraus D, Hollmann T J, Casali P, Caroll M C, Wetsel R A, Lambris J D, Holers V M, Salmon J E. Complement C5a receptors and neutrophils mediate fetal injury in the antiphospholipid syndrome. J Clin Invest 2003; 112: 1644–1654
   PubMed Web of Science ®Google Scholar
• Martinuzzo M E, Maclouf J, Carreras L O, Levy-Toledano S. Antiphospholipid antibodies enhance thrombin-induced platelet activation and thromboxane formation. Thromb Haemost 1993; 70: 667–671
   PubMed Web of Science ®Google Scholar
• Vazquez-Mellado J, Llorente L, Richaud-Patin Y, Alarcon-Segovia D. Exposure of anionic phospholipids upon platelet activation permits binding of beta 2 glycoprotein I and through it that of IgG antiphospholipid antibodies. Studies in platelets from patients with antiphospholipid syndrome and normal subjects. J Autoimmun 1994; 7: 335–348
   PubMed Web of Science ®Google Scholar
• Silver R K, Mullen T A, Caplan M S, O'Connell P D, Ragin A. Inducible platelet adherence to human umbilical vein endothelium by anticardiolipin antibody-positive sera. Am J Obstet Gynecol 1995; 173: 702–707
   PubMedGoogle Scholar
• Joseph J E, Harrison P, Mackie I J, Isenberg D A, Machin S J. Increased circulating platelet-leucocyte complexes and platelet activation in patients with antiphospholipid syndrome, systemic lupus erythematosus and rheumatoid arthritis. Br J Haematol 2001; 115: 451–459
   PubMed Web of Science ®Google Scholar
• Fanelli A, Bergamini C, Rapi S, Caldini A, Spinelli A, Buggiani A, Emmi L. Flow cytometric detection of circulating activated platelets in primary antiphospholipid syndrome. Correlation with thrombocytopenia and anticardiolipin antibodies. Lupus 1997; 6: 261–267
   PubMedGoogle Scholar
• Jankowski M, Vreys I, Wittevrongel C, Boon D, Vermylen J, Hoylaerts M F, Arnout J. Thrombogenicity of beta 2-glycoprotein I-dependent antiphospholipid antibodies in a photochemically induced thrombosis model in the hamster. Blood 2003; 101: 157–162
   PubMed Web of Science ®Google Scholar
• Lutters B C, Derksen R H, Tekelenburg W L, Lenting P J, Arnout J, de Groot P G. Dimers of beta 2-glycoprotein I increase platelet deposition to collagen via interaction with phospholipids and the apolipoprotein E receptor 2'. J Biol Chem 2003; 278: 33831–33838
   PubMed Web of Science ®Google Scholar
• Patrassi G M, Sartori M T, Ruffatti A, Viero M, DiLenardo L, Cazzanello D, Ghirardello A, Boeri G, Saggiorato G, Girolami A. Fibrinolytic pattern in recurrent spontaneous abortions: no relationship between hypofibrinolysis and anti-phospholipid antibodies. Am J Hematol 1994; 47: 266–272
   PubMedGoogle Scholar
• Ruiz-Arguelles G J, Ruiz-Arguelles A, Lobato-Mendizabal E, Diaz-Gomez F, Pacheco-Pantoja E, Drenkard C, Alarcon-Segovia D. Disturbances in the tissue plasminogen activator/plasminogen activator inhibitor (TPA/PAI) system in systemic lupus erythematosus. Am J Hematol 1991; 37: 9–13
   PubMedGoogle Scholar
• Joseph J, Scopelitis E. Seronegative antiphospholipid syndrome associated with plasminogen activator inhibitor. Lupus 1994; 3: 201–203
   PubMedGoogle Scholar
• Cugno M, Dominguez M, Cabibbe M, Bisiani G, Galli M, Angles-Cano E, Agostoni A. Antibodies to tissue-type plasminogen activator in plasma from patients with primary antiphospholipid syndrome. Br J Haematol 2000; 108: 871–875
   PubMedGoogle Scholar
• Ieko M, Sawada K I, Koike T, Notoya A, Mukai M, Kohno M, Wada N, Itoh T, Yoshioka N. The putative mechanism of thrombosis in antiphospholipid syndrome: impairment of the protein C and the fibrinolytic systems by monoclonal anticardiolipin antibodies. Semin Thromb Hemost 1999; 25: 503–507
   PubMedGoogle Scholar
• Ieko M, Ichikawa K, Atsumi T, Takeuchi R, Sawada K I, Yasukouchi T, Koike T. Effects of beta2-glycoprotein I and monoclonal anticardiolipin antibodies on extrinsic fibrinolysis. Semin Thromb Hemost 2000; 26: 85–90
   PubMed Web of Science ®Google Scholar
• Tassies D, Espinosa G, Munoz-Rodriguez F J, Freire C, Cervera R, Monteagudo J, Maragall S, Escolar G, Ingelmo M, Ordinas A, Font J, Reverter J C. The 4G/5G polymorphism of the type 1 plasminogen activator inhibitor gene and thrombosis in patients with antiphospholipid syndrome. Arthritis Rheum 2000; 43: 2349–2358
   PubMedGoogle Scholar
• Eriksson P, Kallin B, van 't Hooft F M, Bavenholm P, Hamsten A. Allele-specific increase in basal transcription of the plasminogen-activator inhibitor 1 gene is associated with myocardial infarction. Proc Natl Acad Sci USA 1995; 92: 1851–1855
   PubMed Web of Science ®Google Scholar
• Yang C D, Hwang K K, Yan W, Gallagher K, Fitz Gerald J, Grossman J M, Hahn B H, Chen P P. Identification of anti-plasmin antibodies in the antiphospholipid syndrome that inhibit degradation of fibrin. J Immunol 2004; 172: 5765–5773
   PubMedGoogle Scholar
• Kolev K, Gombas J, Varadi B, Skopal J, Mede K, Pitlik E, Nagy Z, Machovich R. Immunoglobulin G from patients with antiphospholipid syndrome impairs the fibrin dissolution with plasmin. Thromb Haemost 2002; 87: 502–508
   PubMedGoogle Scholar
• Atsumi T, Khamashta M A, Andujar C, Leandro M J, Amengual O, Ames P R, Hughes G R. Elevated plasma lipoprotein(a) level and its association with impaired fibrinolysis in patients with antiphospholipid syndrome. J Rheumatol 1998; 25: 69–73
   PubMed Web of Science ®Google Scholar
• Miletich J, Sherman L, Broze G, Jr. Absence of thrombosis in subjects with heterozygous protein C deficiency. N Engl J Med 1987; 317: 991–996
   PubMed Web of Science ®Google Scholar
• Tait R C, Walker I D, Reitsma P H, Islam S I, McCall F, Poort S R, Conkie J A, Bertina R M. Prevalence of protein C deficiency in the healthy population. Thromb Haemost 1995; 73: 87–93
   PubMed Web of Science ®Google Scholar
• Mateo J, Oliver A, Borrell M, Sala N, Fontcuberta J. Laboratory evaluation and clinical characteristics of 2,132 consecutive unselected patients with venous thromboembolism—results of the Spanish Multicentric Study on Thrombophilia (EMET-Study). Thromb Haemost 1997; 77: 444–451
   PubMed Web of Science ®Google Scholar
• Crowther M A, Kelton J G. Congenital thrombophilic states associated with venous thrombosis: a qualitative overview and proposed classification system. Ann Intern Med 2003; 138: 128–134
   PubMed Web of Science ®Google Scholar
• Dahlback B, Carlsson M, Svensson P J. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. Proc Natl Acad Sci USA 1993; 90: 1004–1008
   PubMed Web of Science ®Google Scholar
• Marciniak E, Romond E H. Impaired catalytic function of activated protein C: a new in vitro manifestation of lupus anticoagulant. Blood 1989; 74: 2426–2432
   PubMedGoogle Scholar
• Malia R G, Kitchen S, Greaves M, Preston F E. Inhibition of activated protein C and its cofactor protein S by antiphospholipid antibodies. Br J Haematol 1990; 76: 101–107
   PubMed Web of Science ®Google Scholar
• Borrell M, Sala N, de Castellarnau C, Lopez S, Gari M, Fontcuberta J. Immunoglobulin fractions isolated from patients with antiphospholipid antibodies prevent the inactivation of factor Va by activated protein C on human endothelial cells. Thromb Haemost 1992; 68: 268–272
   PubMedGoogle Scholar
• Halbmayer W M, Haushofer A, Schon R, Fischer M. Influence of lupus anticoagulant on a commercially available kit for APC-resistance. Thromb Haemost 1994; 72: 645–646
   PubMedGoogle Scholar
• Tsakiris D A, Settas L, Makris P E, Marbet G A. Lupus anticoagulant—antiphospholipid antibodies and thrombophilia. Relation to protein C—protein S—thrombomodulin. J Rheumatol 1990; 17: 785–789
   PubMedGoogle Scholar
• Lo S C, Salem H H, Howard M A, Oldmeadow M J, Firkin B G. Studies of natural anticoagulant proteins and anticardiolipin antibodies in patients with the lupus anticoagulant. Br J Haematol 1990; 76: 380–386
   PubMedGoogle Scholar
• Rossi E, Gatti L, Guarneri D, Finotto E, Lombardi A, Preda L. Functional protein S in women with lupus anticoagulant inhibitor. Thromb Res 1992; 65: 253–262
   PubMedGoogle Scholar
• Parke A L, Weinstein R E, Bona R D, Maier D B, Walker F J. The thrombotic diathesis associated with the presence of phospholipid antibodies may be due to low levels of free protein S. Am J Med 1992; 93: 49–56
   PubMedGoogle Scholar
• Kordich L C, Forastiero R R, Basilotta E, Porterie P, Carreras L O. Natural inhibitors of blood coagulation and fibrinolysis in patients with lupus anticoagulant. Blood Coagul Fibrinolysis 1992; 3: 765–771
   PubMedGoogle Scholar
• Hudson M, Herr A L, Rauch J, Neville C, Chang E, Ibrahim R, Seguin C, Kassis J, Busque L, Fortin P R. The presence of multiple prothrombotic risk factors is associated with a higher risk of thrombosis in individuals with anticardiolipin antibodies. J Rheumatol 2003; 30: 2385–2391
   PubMedGoogle Scholar
• Costallat L T, Ribeiro C C, Annichino-Bizzacchi J M. Antithrombin, protein S and protein C and antiphospholipid antibodies in systemic lupus erythematosus. Sangre (Barc) 1998; 43: 345–348
   PubMedGoogle Scholar
• Tomas J F, Alberca I, Tabernero M D, Cordero M, Pino-Montes J, Vicente V. Natural anticoagulant proteins and antiphospholipid antibodies in systemic lupus erythematosus. J Rheumatol 1998; 25: 57–62
   PubMedGoogle Scholar
• Pablos J L, Caliz R A, Carreira P E, Atsumi T, Serrano L, Amengual O, Santiago B, Khamashta M A, Hughes G R, Gomez-Reino J J. Risk of thrombosis in patients with antiphospholipid antibodies and factor V Leiden mutation. J Rheumatol 1999; 26: 588–590
   PubMed Web of Science ®Google Scholar
• Chopra N, Koren S, Greer W L, Fortin P R, Rauch J, Fortin I, Senecal J L, Docherty P, Hanly J G. Factor V Leiden, prothrombin gene mutation, and thrombosis risk in patients with antiphospholipid antibodies. J Rheumatol 2002; 29: 1683–1688
   PubMed Web of Science ®Google Scholar
• Kassis J, Neville C, Rauch J, Busque L, Chang E R, Joseph L, Le Comte M, Subang R, Fortin P R. Antiphospholipid antibodies and thrombosis: association with acquired activated protein C resistance in venous thrombosis and with hyperhomocysteinemia in arterial thrombosis. Thromb Haemost 2004; 92: 1312–1319
   PubMed Web of Science ®Google Scholar
• Bokarewa M I, Bremme K, Falk G, Sten-Linder M, Egberg N, Blomback M. Studies on phospholipid antibodies, APC-resistance and associated mutation in the coagulation factor V gene. Thromb Res 1995; 78: 193–200
   PubMedGoogle Scholar
• Munoz-Rodriguez F J, Reverter J C, Font J, Tassies D, Espinosa G, Cervera R, Carmona F, Balsch J, Ingelmo M, Ordinas A. Clinical significance of acquired activated protein C resistance in patients with systemic lupus erythematosus. Lupus 2002; 11: 730–735
   PubMedGoogle Scholar
• Pullmann R, Jr., Skerenova M, Lukac J, Hybenova J, Melus V, Kubisz P, Rovensky J, Pullmann R. Factor V Leiden and prothrombin G20210A mutations and the risk of atherothrombotic events in systemic lupus erythematosus. Clin Appl Thromb Hemost 2004; 10: 233–238
   PubMedGoogle Scholar
• Ruiz-Arguelles G J, Garces-Eisele J, Alarcon-Segovia D, Ruiz-Arguelles A. Activated protein C resistance phenotype and genotype in patients with primary antiphospholipid syndrome. Blood Coagul Fibrinolysis 1996; 7: 344–348
   PubMedGoogle Scholar
• Aznar J, Villa P, Espana F, Estelles A, Grancha S, Falco C. Activated protein C resistance phenotype in patients with antiphospholipid antibodies. J Lab Clin Med 1997; 130: 202–208
   PubMedGoogle Scholar
• Martinuzzo M, Forastiero R, Adamczuk Y, Cerrato G, Carreras L O. Activated protein C resistance in patients with anti-beta 2 glycoprotein I antibodies. Blood Coagul Fibrinolysis 1996; 7: 702–704
   PubMedGoogle Scholar
• Wu J, Zhou Z, Li X, Li X, Chen Y, Wang G, Wang Z. Activated protein C resistance in antiphospholipid thrombosis syndrome. Chin Med J (Engl) 2000; 113: 699–701
   PubMedGoogle Scholar
• Gennari L C, Blanco A N, Alberto M F, Grosso S H, Peirano A A, Lazzari M A. Antiphospholipid antibodies impact the protein C (PC) pathway behavior. Am J Hematol 2002; 71: 128–130
   PubMedGoogle Scholar
• Nojima J, Kuratsune H, Suehisa E, Iwatani Y, Kanakura Y. Acquired activated protein C resistance associated with IgG antibodies against beta2-glycoprotein I and prothrombin as a strong risk factor for venous thromboembolism. Clin Chem 2005; 51: 545–552
   PubMedGoogle Scholar
• Male C, Mitchell L, Julian J, Vegh P, Joshua P, Adams M, David M, Andrew M E. Acquired activated protein C resistance is associated with lupus anticoagulants and thrombotic events in pediatric patients with systemic lupus erythematosus. Blood 2001; 97: 844–849
   PubMed Web of Science ®Google Scholar
• Galli M, Ruggeri L, Barbui T. Differential effects of anti-beta2-glycoprotein I and antiprothrombin antibodies on the anticoagulant activity of activated protein C. Blood 1998; 91: 1999–2004
   PubMedGoogle Scholar
• Safa O, Esmon C T, Esmon N L. Inhibition of APC anticoagulant activity on oxidized phospholipid by anti-beta2-glycoprotein I monoclonal antibodies. Blood 2005; 106: 1629–1635
   PubMedGoogle Scholar
• Simmelink M J, Fernandez J A, Derksen R H, Griffin J H, de Groot P G. Low levels of activated protein C in patients with systemic lupus erythematosus do not relate to lupus anticoagulants but to low levels of factor II. Br J Haematol 2002; 117: 676–684
   PubMedGoogle Scholar
• Matsuda J, Gotoh M, Gohchi K, Kawasugi K, Tsukamoto M, Saitoh N. Resistance to activated protein C activity of an anti-beta 2-glycoprotein I antibody in the presence of beta 2-glycoprotein I. Br J Haematol 1995; 90: 204–206
   PubMedGoogle Scholar
• Ieko M, Ichikawa K, Triplett D A, Matsuura E, Atsumi T, Sawada K, Koike T. Beta2-glycoprotein I is necessary to inhibit protein C activity by monoclonal anticardiolipin antibodies. Arthritis Rheum 1999; 42: 167–174
   PubMedGoogle Scholar
• Izumi T, Pound M L, Su Z, Iverson G M, Ortel T L. Anti-beta(2)-glycoprotein I antibody-mediated inhibition of activated protein C requires binding of beta(2)-glycoprotein I to phospholipids. Thromb Haemost 2002; 88: 620–626
   PubMedGoogle Scholar
• Atsumi T, Khamashta M A, Amengual O, Donohoe S, Mackie I, Ichikawa K, Koike T, Hughes G R. Binding of anticardiolipin antibodies to protein C via beta2-glycoprotein I (beta2-GPI): a possible mechanism in the inhibitory effect of antiphospholipid antibodies on the protein C system. Clin Exp Immunol 1998; 112: 325–333
   PubMedGoogle Scholar
• Hwang K K, Yang C D, Yan W, Grossman J M, Hahn B H, Chen P P. A thrombin-cross-reactive anticardiolipin antibody binds to and inhibits the anticoagulant function of activated protein C. Arthritis Rheum 2003; 48: 1622–1630
   PubMedGoogle Scholar
• Toyoshima K, Makino T, Ozawa N, Umeuchi M, Nozawa S. Effect of anticardiolipin antibody in patients with recurrent fetal loss on thrombomodulin-dependent protein C activation. J Clin Lab Anal 1993; 7: 57–59
   PubMedGoogle Scholar
• Freyssinet J M, Wiesel M L, Gauchy J, Boneu B, Cazenave J P. An IgM lupus anticoagulant that neutralizes the enhancing effect of phospholipid on purified endothelial thrombomodulin activity—a mechanism for thrombosis. Thromb Haemost 1986; 55: 309–313
   PubMedGoogle Scholar
• Nojima J, Kuratsune H, Suehisa E, Kawasaki T, Machii T, Kitani T, Iwatani Y, Kanakura Y. Acquired activated protein C resistance associated with anti-protein S antibody as a strong risk factor for DVT in non-SLE patients. Thromb Haemost 2002; 88: 716–722
   PubMedGoogle Scholar
• Hurtado V, Montes R, Gris J C, Bertolaccini M L, Alonso A, Martinez-Gonzalez M A, Khamashta M A, Fukudome K, Lane D A, Hermida J. Autoantibodies against EPCR are found in antiphospholipid syndrome and are a risk factor for fetal death. Blood 2004; 104: 1369–1374
   PubMedGoogle Scholar
• Olee T, Pierangeli S S, Handley H H, Le D T, Wei X, Lai C J, En J, Novotny W, Harris E N, Woods V L, Jr., Chen P P. A monoclonal IgG anticardiolipin antibody from a patient with the antiphospholipid syndrome is thrombogenic in mice. Proc Natl Acad Sci USA 1996; 93: 8606–8611
   PubMedGoogle Scholar
• Bakimer R, Guilburd B, Zurgil N, Shoenfeld Y. The effect of intravenous gamma-globulin on the induction of experimental antiphospholipid syndrome. Clin Immunol Immunopathol 1993; 69: 97–102
   PubMedGoogle Scholar
• Shoenfeld Y, Sherer Y, Blank M. Antiphospholipid syndrome in pregnancy–animal models and clinical implications. Scand J Rheumatol Suppl 1998; 107: 33–36
   PubMedGoogle Scholar
• Robertson S A, Roberts C T, van Beijering E, Pensa K, Sheng Y, Shi T, Krilis S A. Effect of beta2-glycoprotein I null mutation on reproductive outcome and antiphospholipid antibody-mediated pregnancy pathology in mice. Mol Hum Reprod 2004; 10: 409–416
   PubMedGoogle Scholar
• Radway-Bright E L, Inanc M, Isenberg D A. Animal models of the antiphospholipid syndrome. Rheumatology (Oxford) 1999; 38: 591–601
   PubMedGoogle Scholar
• Ichikawa K, Shimada K, Nawata Y, Ishii T, Tomioka H, Yoshida S, Koike T. Monoclonal hybridoma anti-cardiolipin antibodies from SLE mice. Clin Exp Immunol 1988; 74: 110–114
   PubMedGoogle Scholar
• Hashimoto Y, Kawamura M, Ichikawa K, Suzuki T, Sumida T, Yoshida S, Matsuura E, Ikehara S, Koike T. Anticardiolipin antibodies in NZW x BXSB F1 mice. A model of antiphospholipid syndrome. J Immunol 1992; 149: 1063–1068
   PubMed Web of Science ®Google Scholar
• Gharavi A E, Mellors R C, Elkon K B. IgG anti-cardiolipin antibodies in murine lupus. Clin Exp Immunol 1989; 78: 233–238
   PubMed Web of Science ®Google Scholar
• Smith H R, Hansen C L, Rose R, Canoso R T. Autoimmune MRL-1 pr/1 pr mice are an animal model for the secondary antiphospholipid syndrome. J Rheumatol 1990; 17: 911–915
   PubMed Web of Science ®Google Scholar
• Hess D C, Taormina M, Thompson J, Sethi K D, Diamond B, Rao R, Chamberlain C R, Feldman D S. Cognitive and neurologic deficits in the MRL/lpr mouse: a clinicopathologic study. J Rheumatol 1993; 20: 610–617
   PubMedGoogle Scholar
• Hang L M, Izui S, Dixon F J. (NZW x BXSB)F1 hybrid. A model of acute lupus and coronary vascular disease with myocardial infarction. J Exp Med 1981; 154: 216–221
   PubMed Web of Science ®Google Scholar
• Pierangeli S S, Barker J H, Stikovac D, Ackerman D, Anderson G, Barquinero J, Acland R, Harris E N. Effect of human IgG antiphospholipid antibodies on an in vivo thrombosis model in mice. Thromb Haemost 1994; 71: 670–674
   PubMed Web of Science ®Google Scholar
• Pierangeli S S, Harris E N. Antiphospholipid antibodies in an in vivo thrombosis model in mice. Lupus 1994; 3: 247–251
   PubMed Web of Science ®Google Scholar
• Gharavi A E, Pierangeli S S, Gharavi E E, Hua T, Liu X W, Barker J H, Anderson G H, Harris E N. Thrombogenic properties of antiphospholipid antibodies do not depend on their binding to beta2 glycoprotein 1 (beta2GP1) alone. Lupus 1998; 7: 341–346
   PubMedGoogle Scholar
• Blank M, Cohen J, Toder V, Shoenfeld Y. Induction of anti-phospholipid syndrome in naive mice with mouse lupus monoclonal and human polyclonal anti-cardiolipin antibodies. Proc Natl Acad Sci USA 1991; 88: 3069–3073
   PubMed Web of Science ®Google Scholar
• Blank M, Tincani A, Shoenfeld Y. Induction of experimental antiphospholipid syndrome in naive mice with purified IgG antiphosphatidylserine antibodies. J Rheumatol 1994; 21: 100–104
   PubMed Web of Science ®Google Scholar
• Piona A, La Rosa L, Tincani A, Faden D, Magro G, Grasso S, Nicoletti F, Balestrieri G, Meroni P L. Placental thrombosis and fetal loss after passive transfer of mouse lupus monoclonal or human polyclonal anti-cardiolipin antibodies in pregnant naive BALB/c mice. Scand J Immunol 1995; 41: 427–432
   PubMed Web of Science ®Google Scholar
• Holers V M, Girardi G, Mo L, Guthridge J M, Molina H, Pierangeli S S, Espinola R, Xiaowei L E, Mao D, Vialpando C G, Salmon J E. Complement C3 activation is required for antiphospholipid antibody-induced fetal loss. J Exp Med 2002; 195: 211–220
   PubMed Web of Science ®Google Scholar
• Bakimer R, Blank M, Kosashvilli D, Ichikawa K, Khamashta M A, Hughes G R, Koike T, Shoenfeld Y. Antiphospholipid syndrome and the idiotypic network. Lupus 1995; 4: 204–208
   PubMed Web of Science ®Google Scholar
• Bakimer R, Fishman P, Blank M, Sredni B, Djaldetti M, Shoenfeld Y. Induction of primary antiphospholipid syndrome in mice by immunization with a human monoclonal anticardiolipin antibody (H-3). J Clin Invest 1992; 89: 1558–1563
   PubMed Web of Science ®Google Scholar
• Sthoeger Z M, Tartakovsky B, Bentwich Z, Mozes E. Monoclonal anticardiolipin antibodies derived from mice with experimental lupus erythematosus: characterization and the induction of a secondary antiphospholipid syndrome. J Clin Immunol 1993; 13: 127–138
   PubMedGoogle Scholar
• Sthoeger Z M, Mozes E, Tartakovsky B. Anti-cardiolipin antibodies induce pregnancy failure by impairing embryonic implantation. Proc Natl Acad Sci USA 1993; 90: 6464–6467
   PubMed Web of Science ®Google Scholar
• Cohen J, Bakimer R, Blank M, Valesini G, Shoenfeld Y. Pathogenic serum IgG anticardiolipin antibodies and the idiotypic network. Ann Rheum Dis 1993; 52: 742–748
   PubMed Web of Science ®Google Scholar
• Cohen J, Bakimer R, Blank M, Valesini G, Shoenfeld Y. Pathogenic natural anti-cardiolipin antibodies: the experience from monoclonal gammopathy. Clin Exp Immunol 1994; 97: 181–186
   PubMedGoogle Scholar
• Gharavi A E, Sammaritano L R, Wen J, Elkon K B. Induction of antiphospholipid autoantibodies by immunization with beta 2 glycoprotein I (apolipoprotein H). J Clin Invest 1992; 90: 1105–1109
   PubMed Web of Science ®Google Scholar
• Rauch J, Janoff A S. The nature of antiphospholipid antibodies. J Rheumatol 1992; 19: 1782–1785
   PubMedGoogle Scholar
• Aron A L, Cuellar M L, Brey R L, Mckeown S, Espinoza L R, Shoenfeld Y, Gharavi A E. Early onset of autoimmunity in MRL/++ mice following immunization with beta 2 glycoprotein I. Clin Exp Immunol 1995; 101: 78–81
   PubMed Web of Science ®Google Scholar
• Blank M, Faden D, Tincani A, Kopolovic J, Goldberg I, Gilburd B, Allegri F, Balestrieri G, Valesini G, Shoenfeld Y. Immunization with anticardiolipin cofactor (beta-2-glycoprotein I) induces experimental antiphospholipid syndrome in naive mice. J Autoimmun 1994; 7: 441–455
   PubMed Web of Science ®Google Scholar
• Garcia C O, Kanbour-Shakir A, Tang H, Molina J F, Espinoza L R, Gharavi A E. Induction of experimental antiphospholipid antibody syndrome in PL/J mice following immunization with beta 2 GPI. Am J Reprod Immunol 1997; 37: 118–124
   PubMed Web of Science ®Google Scholar
• Silver R M, Pierangeli S S, Gharavi A E, Harris E N, Edwin S S, Salafia C M, Branch D W. Induction of high levels of anticardiolipin antibodies in mice by immunization with beta 2-glycoprotein I does not cause fetal death. Am J Obstet Gynecol 1995; 173: 1410–1415
   PubMedGoogle Scholar
• Pierangeli S S, Liu S W, Anderson G, Barker J H, Harris E N. Thrombogenic properties of murine anti-cardiolipin antibodies induced by beta 2 glycoprotein 1 and human immunoglobulin G antiphospholipid antibodies. Circulation 1996; 94: 1746–1751
   PubMedGoogle Scholar
• Harris E N, Pierangeli S S. Revisiting the anticardiolipin test and its standardization. Lupus 2002; 11: 269–275
   PubMed Web of Science ®Google Scholar
• Reber G, Tincani A, Sanmarco M, de Moerloose P, Boffa M C. Proposals for the measurement of anti-beta2-glycoprotein I antibodies. Standardization group of the European Forum on Antiphospholipid Antibodies. J Thromb Haemost 2004; 2: 1860–1862
   PubMed Web of Science ®Google Scholar
• Brummel K E, Butenas S, Mann K G. An integrated study of fibrinogen during blood coagulation. J Biol Chem 1999; 274: 22862–22870
   PubMedGoogle Scholar