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Thromb Haemost 1998; 79(04): 790-795
DOI: 10.1055/s-0037-1615066
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The Contribution of Anti-prothrombin-antibodies to Lupus Anticoagulant Activity

Discrimination between Functional and Non-functional Anti-prothrombin-antibodies
Daniëlle A. Horbach
1   From the Departments of Haematology, The Netherlands
2   From the Rheumatology and Clinical Immunology, University Hospital Utrecht, The Netherlands
3   From the Institute of Biomembranes, Utrecht University, The Netherlands
,
Erica van Oort
1   From the Departments of Haematology, The Netherlands
2   From the Rheumatology and Clinical Immunology, University Hospital Utrecht, The Netherlands
,
Ronald H. W. M. Derksen
2   From the Rheumatology and Clinical Immunology, University Hospital Utrecht, The Netherlands
,
Philip G. de Groot
1   From the Departments of Haematology, The Netherlands
3   From the Institute of Biomembranes, Utrecht University, The Netherlands
› Author AffiliationsThis work was supported in part by grants from “The Dutch League against Rheumatism” (NR 642) and “De Trombosestichting Nederland” (No 94.002).
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Publication History

Received 28 October 1997

Accepted after revision 15 December 1997

Publication Date:
07 December 2017 (online)

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Summary

The presence of lupus anticoagulant (LAC) is strongly correlated with a history of thrombosis in patients with SLE. LAC activity can be caused by anti-prothrombin (FII)- and/or anti-β2glycoprotein I (β2GPI)-antibodies.

In the present study, the contribution of anti-FII-antibodies to LAC activity was measured in 28 LAC positive plasmas. Plasmas were incubated with prothrombin or BSA, immobilized on CNBr-activated Sepharose, to absorb all anti-FII-antibodies. In 4 out of the 28 plasmas LAC activity was completely dependent on anti-FII-antibodies. In 7 out of the 28 plasmas, anti-FII-antibodies did not contribute to LAC activity. These anti-FII-antibodies can be regarded as non-functional antibodies. In the majority (17/28) of the samples, LAC activity within a single plasma was caused by a combination of antibodies with different specificities. Both dRVVT and KCT showed comparable sensitivity for the detection of functional anti-FII-antibodies.

In conclusion, in most samples LAC activity is not caused by anti-FII-antibodies alone but by a combination of different types of antibodies. The presence of LAC activity and anti-FII-antibodies in one plasma does not automatically implicate that these antibodies are responsible for the LAC activity.

 

  • References

  • 1 Horbach DA, Van Oort E, Donders RCJM, Derksen RHWM, De Groot PG. Lupus anticoagulant is the strongest risk factor for both venous and arterial thrombosis in patients with systemic lupus erythematosus – Comparison between different assays for the detection of antiphospholipid antibodies. Thromb Haemost 1996; 76: 916-24.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 Oosting JD, Derksen RHWM, Entjes HTI, Bouma BN, De Groot PG. Lupus anticoagulant activity is frequently dependent on the presence of β2-glycoprotein I. Thromb Haemost 1992; 67: 499-502.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 3 Roubey RAS, Pratt CW, Buyon JP, Winfield JB. Lupus anticoagulant activity of autoimmune antiphospholipid antibodies is dependent upon β2-glyco-protein I. J Clin Invest 1992; 90: 1100-4.
    CrossrefPubMedGoogle Scholar
  • 4 Keeling DM, Wilson AJG, Mackie IJ, Isenberg DA, Machin SJ. Lupus anticoagulant activity of some antiphospholipid antibodies against phospholipid bound β2-glycoprotein I. J Clin Pathol 1993; 46: 665-7.
    CrossrefPubMedGoogle Scholar
  • 5 Takeya H, Mori T, Gabazza EC, Kuroda K, Deguchi H, Matsuura E, Ichikawa K, Koike T, Suzuki K. Anti-β2-glycoprotein I (β2GPI) monoclonal antibodies with lupus anticoagulant-like activity enhance the β2GPI binding to phospholipids. J Clin Invest 1997; 99: 2260-8.
    CrossrefPubMedGoogle Scholar
  • 6 Arnout J, Wittevrongel C, Vermylen J. Murine monoclonal antibodies against beta-2-glycoprotein I with lupus anticoagulant activity. Thromb Haemost 1997; 77: 154 (Abstract).
    PubMedGoogle Scholar
  • 7 Brandt JT. Antibodies to β2-glycoprotein I inhibit phospholipid dependent coagulation reactions. Thromb Haemost 1993; 70: 598-602.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Bevers EM, Galli M, Barbui T, Comfurius P, Zwaal RFA. Lupus anticoagulant IgG’s (LA) are not directed to phospholipids only, but to a complex of lipid-bound human prothrombin. Thromb Haemost 1991; 66: 629-32.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Permpikul P, Rao LVM, Rapaport SI. Functional and binding studies of the roles of prothrombin and β2-glycoprotein I in the expression of lupus anticoagulant activity. Blood 1994; 83: 2878-92.
    PubMedGoogle Scholar
  • 10 Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271-7.
    CrossrefPubMedGoogle Scholar
  • 11 Arnout J, Vanrusselt M, Huybrechts E, Vermylen J. Optimization of the dilute prothrombin time for the detection of the lupus anticoagulant by use of a recombinant tissue thromboplastin. Br J Haematol 1994; 87: 94-9.
    CrossrefPubMedGoogle Scholar
  • 12 Derksen RH, Hasselaar P, Blokzijl L, Gmelig Meyling FH, De Groot PG. Coagulation screen is more specific than the anticardiolipin antibody ELISA in defining a thrombotic subset of lupus patients. Ann Rheum Dis 1988; 47: 364-71.
    CrossrefPubMedGoogle Scholar
  • 13 Koedam JA, Meijers JCM, Sixma JJ, Bouma BN. Inactivation of human factor VIII by activated protein C. Cofactor activity of protein S and protective effect of von Willebrand factor. J Clin Invest 1988; 82: 1236-43.
    CrossrefPubMedGoogle Scholar
  • 14 Haupt H, Schwick HG, Storiko K. [On a hereditary beta-2-glycoprotein I deficiency] Über einen erblichen beta-2-Glykoprotein I-Mangel. Human genetik 1968; 5: 291-3.
    PubMedGoogle Scholar
  • 15 Bajaj SP, Rapaport SI, Prodanos C. A simplified procedure for purification of human prothrombin, factor IX and factor X. Prep Biochem 1981; 11: 397-412.
    PubMedGoogle Scholar
  • 16 Galli M, Finazzi G, Bevers EM, Barbui T. Kaolin clotting time and dilute Russell’s viper venom time distinguish between prothrombin-dependent and β2-glycoprotein I-dependent antiphospholipid antibodies. Blood 1995; 86: 617-23.
    PubMedGoogle Scholar
  • 17 Ginsberg JS, Wells PS, Brill-Edwards P, Donovan D, Moffatt K, Johnston M, Stevens P, Hirsh J. Antiphospholipid antibodies and venous thromboembolism. Blood 1995; 86: 3685-91.
    PubMedGoogle Scholar
  • 18 Rao LVM, Hoang AD, Rapaport SI. Mechanism and effects of the binding of lupus anticoagulant IgG and prothrombin to surface phospholipid. Blood 1996; 88: 4173-82.
    PubMedGoogle Scholar