Skip to main content
SpringerLink
Log in
Book cover

Hughes Syndrome pp 291–306Cite as

Lupus Anticoagulants: Mechanistic and Diagnostic Considerations

  • Chapter

  • 727 Accesses

Keywords

  • Systemic Lupus Erythematosus
  • Lupus Anticoagulant
  • Tissue Factor Pathway Inhibitor
  • Anticardiolipin Antibody
  • Diagnostic Consideration

These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

This is a preview of subscription content, access via your institution.

Chapter
USD   29.95
Price excludes VAT (Canada)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (Canada)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   119.99
Price excludes VAT (Canada)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (Canada)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Moore JE, Mohr CF. Biologically false-positive serologic tests for syphilis: type, incidence, and cause. JAMA 1952;150:467–473.

    CAS  Google Scholar 

  2. Moore JE, Lutz WB. The natural history of systemic lupus erythematosus: an approach to its study through chronic biologic false-positive reactions. J Chronic Dis 1955;1:297–316.

    CrossRef  PubMed  CAS  Google Scholar 

  3. Conley CL, Hartmann RC. A hemorrhagic disorder caused by circulating anticoagulant in patients with disseminated lupus erythematosus. J Clin Invest 1952;31:621–622.

    Google Scholar 

  4. Feinstein DI, Rapaport SI. Acquired inhibitors of blood coagulation. Prog Haemost Thromb 1972;1:75–95.

    CAS  Google Scholar 

  5. Bowie EJW, Thompson JH Jr, Pascuzzi CA, Owen CA Jr. Thrombosis in systemic lupus erythematosus despite circulating anticoagulants. J Lab Clin Med 1963;62:416–430.

    PubMed  CAS  Google Scholar 

  6. Laurell AB, Nilsson IM. Hypergammaglobulinaemia, circulating anticoagulant, and biologic false positive Wassermann reaction: a study of 2 cases. J Lab Clin Med 1957;49:694–707.

    PubMed  CAS  Google Scholar 

  7. Thiagarajan P, Shapiro SS, De Marco L. Monoclonal immunoglobulin M coagulation inhibitor with phospholipid specificity. Mechanism of lupus anticoagulant. J Clin Invest 1980;66:397–405.

    PubMed  CAS  Google Scholar 

  8. Harris EN, Gharavi AE, Boey ML, et al. Anticardiolipin antibodies: detection by radioimmunoassay and association with thrombosis in systemic lupus erythematosus. Lancet 1983;ii:1211–1214.

    CrossRef  Google Scholar 

  9. Triplett DA, Brandt JT, 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  CAS  Google Scholar 

  10. Love PE, Santoro SA. Antiphospholipid antibodies: anticardiolipin and the lupus anticoagulant in systemic lupus erythematosus (SLE) and in non-SLE disorders. Ann Intern Med 1990;112:682–698.

    PubMed  CAS  Google Scholar 

  11. Hughes GRV, Harris EN, Gharavi AE. The anticardiolipin syndrome. J Rheumatol 1986;13:486–489.

    PubMed  CAS  Google Scholar 

  12. Alarcon-Segovia D, Sanchez-Guerrero J. Primary antiphospholipid syndrome. J Rheumatol 1989;16:482–488.

    PubMed  CAS  Google Scholar 

  13. McNeil HP, Simpson RJ, Chesterman CN, Krilis SA. 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 U S A 1990;87:4120–4124.

    CrossRef  PubMed  CAS  Google Scholar 

  14. Galli M, Comfurius P, Maassen C, et al. Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor. Lancet 1990;335:1544–1547.

    CrossRef  PubMed  CAS  Google Scholar 

  15. Matsuura E, Igarashi Y, Fujimoto M, Ichikawa K, Koike T. Anticardiolipin cofactor(s) and differential diagnosis of autoimmune disease. Lancet 1990;336:177–178.

    CrossRef  PubMed  CAS  Google Scholar 

  16. Roubey RAS, Eisenberg RA, Harper MF, Winfield JB. “Anticardiolipin” autoantibodies recognize β2-glycoprotein I in the absence of phospholipid. Importance of Ag density and bivalent binding. J Immunol 1995;154:954–960.

    PubMed  CAS  Google Scholar 

  17. Roubey RA. Update on antiphospholipid antibodies. Curr Opin Rheumatol 2000;12:374–378.

    CrossRef  PubMed  CAS  Google Scholar 

  18. Arnout J, Wittevrongel C, Vermylen J. Phospholipid-binding proteins and the antiphospholipid syndrome: a role for complement factor H? Thromb Haemost 1997;(suppl):1.

    Google Scholar 

  19. Forastiero RR, Martinuzzo ME, Broze GJ. High titers of autoantibodies to tissue factor pathway inhibitor are associated with the antiphospholipid syndrome. J Thromb Haemost 2003;1:718–724.

    CrossRef  PubMed  CAS  Google Scholar 

  20. Caronti B, Calderaro C, Alessandri C, et al. Beta2-glycoprotein I (beta2-GPI) mRNA is expressed by several cell types involved in anti-phospholipid syndrome-related tissue damage. Clin Exp Immunol 1999;115:214–219.

    CrossRef  PubMed  CAS  Google Scholar 

  21. Lozier J, Takahashi N, Putnam FW. Complete amino acid sequence of human plasma beta 2-glycoprotein I. Proc Natl Acad Sci U S A 1984;81:3640–3644.

    CrossRef  PubMed  CAS  Google Scholar 

  22. Steinkasserer A, Barlow PN, Willis AC, et al. Activity, disulphide mapping and structural modelling of the fifth domain of human beta 2-glycoprotein I. FEBS Lett 1992;313:193–197.

    CrossRef  PubMed  CAS  Google Scholar 

  23. Bouma B, de Groot PG, van den Elsen JM, et al. Adhesion mechanism of human beta(2)-glycoprotein I to phospholipids based on its crystal structure. EMBO J 1999;18:5166–5174.

    CrossRef  PubMed  CAS  Google Scholar 

  24. Schwarzenbacher R, Zeth K, Diederichs K, Gries A, Kostner GM, Laggner P, Prassl R. Crystal structure of human beta2-glycoprotein I: implications for phospholipid binding and the antiphospholipid syndrome. EMBO J 1999;18:6228–6239.

    CrossRef  PubMed  CAS  Google Scholar 

  25. Ohkura N, Hagihara Y, Yoshimura T, Goto Y, Kato H. Plasmin can reduce the function of human beta2 glycoprotein I by cleaving domain V into a nicked form. Blood 1998;91:4173–4179.

    PubMed  CAS  Google Scholar 

  26. Mann K. Prothrombin and thrombin. In: Colman RW, Hirsch J, Marder VJ, Slzman EW, eds. Hemostasis and thrombosis: basic principles and clinical practice. Philadelphia: J.B. Lippincott; 1994:184–199.

    Google Scholar 

  27. Harper MF, Hayes PM, Lentz B, Roubey RAS. Characterization of β2-glycoprotein I binding to phospholipid membranes. Thromb Haemost 1998;80:610–614.

    PubMed  CAS  Google Scholar 

  28. Willems GM, Janssen MP, Pelsers MMAL, et al. Role of divalency in the high-affinity binding of anticardiolipin antibody-β2-glycoprotein I complexes to lipid membranes. Biochemistry 1996;35:13833–13842.

    CrossRef  PubMed  CAS  Google Scholar 

  29. Takeya H, Mori T, Gabazza EC, et al. Anti-β2-Glycoprotein I (β2GPIÒ) monoclonal antibodies with lupus anticoagulant-like activity enhance the β2GPI binding to phospholipids. J Clin Invest 1997;99:2260–2268.

    CrossRef  PubMed  CAS  Google Scholar 

  30. 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.

    PubMed  CAS  Google Scholar 

  31. Galli M, Comfurius P, Barbui T, Zwaal RF, Bevers EM. Anticoagulant activity of beta 2-glycoprotein I is potentiated by a distinct subgroup of anticardiolipin antibodies. Thromb Haemost 1992;68:297–300.

    PubMed  CAS  Google Scholar 

  32. Hunt J, Krilis S. The fifth domain of beta 2-glycoprotein I contains a phospholipid binding site (Cys281-Cys288) and a region recognized by anticardiolipin antibodies. J Immunol 1994;152:653–659.

    PubMed  CAS  Google Scholar 

  33. George J, Gilburd B, Hojnik M, et al. Target recognition of beta2-glycoprotein I (beta2GPI)-dependent anticardiolipin antibodies: evidence for involvement of the fourth domain of beta2GPI in antibody binding. J Immunol 1998;160:3917–3923.

    PubMed  CAS  Google Scholar 

  34. Iverson GM, Victoria EJ, Marquis DM. Anti-beta2 glycoprotein I (beta2GPI) autoantibodies recognize an epitope on the first domain of beta2GPI. Proc Natl Acad Sci U S A 1998;95:15542–15546.

    CrossRef  PubMed  CAS  Google Scholar 

  35. McNeeley PA, Dlott JS, Furie RA, et al. Beta2-glycoprotein I-dependent anticardiolipin antibodies preferentially bind the amino terminal domain of beta2-glycoprotein I. Thromb Haemost 2001;86:590–595.

    PubMed  CAS  Google Scholar 

  36. Iverson GM, Matsuura E, Victoria EJ, Cockerill KA, Linnik MD. The orientation of beta-2-GPI on the plate is important for the binding of anti-beta2gpi autoantibodies by ELISA. J Autoimmun 2002;18:289–297.

    CrossRef  PubMed  Google Scholar 

  37. Horbach DA, van Oort E, Derksen RH, de Groot PG. The contribution of anti-prothrombin-antibodies to lupus anticoagulant activity — discrimination between functional and non-functional antiprothrombin-antibodies. Thromb Haemost 1998;79:790–795.

    PubMed  CAS  Google Scholar 

  38. Rao LV, Hoang AD, Rapaport SI. Mechanism and effects of the binding of lupus anticoagulant IgG and prothrombin to surface phospholipid. Blood 1996;88:4173–4182.

    PubMed  CAS  Google Scholar 

  39. Simmelink MJ, Horbach DA, Derksen RH, 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;113:621–629.

    CrossRef  PubMed  CAS  Google Scholar 

  40. Field SL, Chesterman CN, Dai YP, Hogg PJ. Lupus antibody bivalency is required to enhance prothrombin binding to phospholipid. J Immunol 2001;166:6118–6125.

    PubMed  CAS  Google Scholar 

  41. Akimoto T, Akama T, Kono I, Sumida T. Relationship between clinical features and binding domains of anti-prothrombin autoantibodies in patients with systemic lupus erythematosus and antiphospholipid syndrome. Lupus 1999;8:761–766.

    CrossRef  PubMed  CAS  Google Scholar 

  42. Puurunen M, Manttari M, Manninen V, Palosuo T, Vaarala O. Antibodies to prothrombin crossreact with plasminogen in patients developing myocardial infarction. Br J Haematol 1998;100:374–379.

    CrossRef  PubMed  CAS  Google Scholar 

  43. Jones DW, Nicholls PJ, Donohoe S, Gallimore MJ, 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.

    CAS  Google Scholar 

  44. Galli M, Luciani D, Bertolini G, Barbui T. Lupus anticoagulants are stronger risk factors of thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome. A systematic review of the literature. Blood 2003;101:1827–1832.

    CrossRef  PubMed  CAS  Google Scholar 

  45. Bevers EM, Comfurius P, Dekkers DW, Zwaal RF. Lipid translocation across the plasma membrane of mammalian cells. Biochim Biophys Acta 1999;1439:317–330.

    PubMed  CAS  Google Scholar 

  46. Heemskerk JW, Bevers EM, Lindhout T. Platelet activation and blood coagulation. Thromb Haemost 2002;88:186–193.

    PubMed  CAS  Google Scholar 

  47. Siljander P, Farndale RW, Feijge MA, et al. Platelet adhesion enhances the glycoprotein VI-dependent procoagulant response: involvement of p38 MAP kinase and calpain. Arterioscler Thromb Vasc Biol 2001;21:618–627.

    PubMed  CAS  Google Scholar 

  48. Rosove MH, Brewer PMC. Antiphospholipid thrombosis: clinical course after the first thrombotic event in 70 patients. Ann Intern Med 1992;117:303–308.

    PubMed  CAS  Google Scholar 

  49. Esmon CT. Regulation of blood coagulation. Biochim Biophys Acta 2000;1477:349–360.

    PubMed  CAS  Google Scholar 

  50. 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.

    PubMed  CAS  Google Scholar 

  51. Salemink I, Blezer R, Willems GM, Galli M, Bevers E, Lindhout T. Antibodies to beta2-glycoprotein I associated with antiphospholipid syndrome suppress the inhibitory activity of tissue factor pathway inhibitor. Thromb Haemost 2000;84:653–656.

    PubMed  CAS  Google Scholar 

  52. Safa O, Hensley K, Smirnov MD, Esmon CT, Esmon NL. Lipid oxidation enhances the function of activated protein C. J Biol Chem 2001;276:1829–1836.

    CrossRef  PubMed  CAS  Google Scholar 

  53. Field SL, Hogg PJ, Daly EB, et al. Lupus anticoagulants form immune complexes with prothrombin and phospholipid that can augment thrombin production in flow. Blood 1999;94:3421–3431.

    PubMed  CAS  Google Scholar 

  54. Arnout J. The pathogenesis of the antiphospholipid syndrome: a hypothesis based on parallelisms with heparin-induced thrombocytopenia. Thromb Haemost 1996;75:536–541.

    PubMed  CAS  Google Scholar 

  55. Vermylen J, Hoylaerts MF, Arnout J. Antibody-mediated thrombosis. Thromb Haemost 1997;78:420–426.

    PubMed  CAS  Google Scholar 

  56. Jankowski M, Vreys I, Wittevrongel C, et al. Thrombogenicity of beta-2-glycoprotein I dependent antiphospholipid antibodies in a photochemically induced thrombosis model in the hamster. Blood 2003;101:157–162.

    CrossRef  PubMed  CAS  Google Scholar 

  57. Lutters BC, Derksen RH, Tekelenburg WL, Lenting PJ, Arnout J, De Groot PG. Dimers of 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.

    CrossRef  PubMed  CAS  Google Scholar 

  58. Brandt JT, Triplett DA, Alving B, Scharrer I. Criteria for the diagnosis of lupus anticoagulants: an update. Thromb Haemost 1995;74:1185–1190.

    PubMed  CAS  Google Scholar 

  59. Male C, Lechner K, Speiser W, Pabinger I. Transient lupus anticoagulants in children: stepwise disappearance of diagnostic features. Thromb Haemost 2000;83:174–175.

    PubMed  CAS  Google Scholar 

  60. Le Querrec A, Arnout J, Arnoux D, et al. Quantification of lupus anticoagulants in clinical samples using anti-beta2GP1 and anti-prothrombin monoclonal antibodies. Thromb Haemost 2001;86:584–589.

    PubMed  Google Scholar 

  61. Arnout J. Antiphospholipid syndrome: diagnostic aspects of lupus anticoagulants. Thromb Haemost 2001;86:83–91.

    PubMed  CAS  Google Scholar 

  62. Somers E, Magder LS, Petri M. Antiphospholipid antibodies and incidence of venous thrombosis in a cohort of patients with systemic lupus erythematosus. J Rheumatol 2002;29:2531–2536.

    PubMed  CAS  Google Scholar 

  63. Finazzi G, Brancaccio V, Moia M, et al. Natural history and risk factors for thrombosis in 360 patients with antiphospholipid antibodies: a four-year prospective study from the Italian Registry. Am J Med 1996;100:530–536.

    CrossRef  PubMed  CAS  Google Scholar 

  64. Galli M, Finazzi G, Bevers EM, 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  CAS  Google Scholar 

  65. Galli M, Finazzi G, Norbis F, Marziali S, Marchioli R, Barbui T. The risk of thrombosis in patients with lupus anticoagulants is predicted by their specific coagulation profile. Thromb Haemost 1999;81:695–700.

    PubMed  CAS  Google Scholar 

  66. Nojima J, Kuratsune H, Suehisa E, et al. Anti-prothrombin antibodies combined with lupus anticoagulant activity is an essential risk factor for venous thromboembolism in patients with systemic lupus erythematosus. Br J Haematol 2001;114:647–654.

    CrossRef  PubMed  CAS  Google Scholar 

  67. Zanon E, Saggiorato G, Ramon R, Girolami A, Pagnan A, Prandoni P. Anti-prothrombin antibodies as a potential risk factor of recurrent venous thromboembolism. Thromb Haemost 2004;91:255–258.

    PubMed  CAS  Google Scholar 

  68. Simmelink MJA, Derksen RHWM, Arnout J, de Groot PG. A simple method to discriminate between β2glycoprotein I-and prothrombin-dependent lupus anticoagulants. J Thromb Haemost 2003;1:740–747.

    CrossRef  PubMed  CAS  Google Scholar 

  69. Pengo V, Biasiolo A, Pegoraro C, Iliceto S. A two-step coagulation test to identify anti-beta2-glycoprotein I Lupus anticoagulants. J Thromb Haemost 2004;2:702–707.

    CrossRef  PubMed  CAS  Google Scholar 

  70. Harper MF, Hayes PM, Lentz B, Roubey RAS. Characterization of β2-glycoprotein I binding to phospholipid membranes. Thromb Haemost 1998;80:610–614.

    PubMed  CAS  Google Scholar 

  71. Roussi J, Roisin JP, Goguel A. Lupus anticoagulants. First French Interlaboratory Etalanorme Survey. Am J Clin Pathol 1996;105:788–793.

    PubMed  CAS  Google Scholar 

  72. Jennings I, Kitchen S, Woods TAL, Preston FE, Greaves M. 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.

    PubMed  CAS  Google Scholar 

  73. Gray E, Mackie I, Greaves M. Calibration of the 1st British reference plasma panel for lupus anticoagulants. Br J Haematol 1998;105(suppl 1):97.

    Google Scholar 

  74. Arnout J, Vanrusset M, Wittevrongel C, Vermylen J. Monoclonal antibodies against β-2-glycoprotein I: use as reference material for lupus anticoagulant tests. Thromb Haemost 1998;79:955–958.

    PubMed  CAS  Google Scholar 

  75. Arnout J, Boon D, Vandervoort P, Vanrusselt M, Vermylen J. A monoclonal antibody against prothrombin fragment 2 behaves like a lupus anticoagulant. Lupus 2002;11:550.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centre for Molecular and Vascular Biology, Faculty of Medicine, University of Leuven, Leuven, Belgium

    Jef M. M. C. Arnout PhD & Jos Vermylen MD, PhD

Authors
  1. Jef M. M. C. Arnout PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jos Vermylen MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Lupus Research Unit, St Thomas’ Hospital, London, UK

    M. A. Khamashta MD, FRCP, PhD (Deputy Head) (Deputy Head)

Rights and permissions

Reprints and Permissions

Copyright information

© 2006 Springer-Verlag London Limited

About this chapter

Cite this chapter

Arnout, J.M.M.C., Vermylen, J. (2006). Lupus Anticoagulants: Mechanistic and Diagnostic Considerations. In: Khamashta, M.A. (eds) Hughes Syndrome. Springer, London. https://doi.org/10.1007/1-84628-009-5_24

Download citation

  • DOI: https://doi.org/10.1007/1-84628-009-5_24

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-85233-873-2

  • Online ISBN: 978-1-84628-009-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

search

Navigation