Download PDF
Thromb Haemost 1998; 79(01): 42-45
DOI: 10.1055/s-0037-1614216
Review Article
Schattauer GmbH

Anti-β2 Glycoprotein I Antibodies and Platelet Activation in Patients with Antiphospholipid Antibodies: Association with Increased Excretion of Platelet-Derived Thromboxane Urinary Metabolites

Ricardo Forastiero
1   From the University Institute of Biomedical Sciences, Favaloro Foundation, Buenos Aires, Argentina
,
Marta Martinuzzo
1   From the University Institute of Biomedical Sciences, Favaloro Foundation, Buenos Aires, Argentina
,
Luis O. Carreras
1   From the University Institute of Biomedical Sciences, Favaloro Foundation, Buenos Aires, Argentina
,
Jacques Maclouf
1   From the IFR Circulation-Lariboisière, U348 INSERM, Paris, France
› Author Affiliations
Further Information

Publication History

Received 14 March 1997

Accepted after resubmission 14 August 1997

Publication Date:
08 December 2017 (online)

Also available at
    Permissions and Reprints

Summary

Platelet activation may contribute to the increased risk of thrombotic complications in patients with antiphospholipid antibodies (aPL). The increased urinary excretion of 11-dehydro-thromboxane B2 (11-DH-TXB2) reported in patients with lupus anticoagulant (LA) and/or anticardiolipin antibodies (aCL) reflects in vivo platelet activation. However the majority of autoimmune aPL are directed to β2 glycoprotein I (β2GPI) or prothrombin (II). We investigated the relationship of these antibodies with 11-DH-TXB2 urinary excretion in 34 patients with aPL. The urinary 11-DH-TXB2 was measured by EIA after extraction on octadecyl columns and purification on silica gel columns, which was validated by thin-layer chromatography/EIA procedure. A significantly increased excretion of 11-DH-TXB2 was found in aPL patients as compared to 18 normal controls (p <0.01). But no differences were seen in the excretion of 11-DH-TXB2 between patients with or without LA, or aCL. The number of patients with anti-II antibodies was too small to draw any conclusion. In contrast, patients with anti-β2GPI antibodies IgG at moderate/high titre (group A, n = 14) had higher levels of urinary 11-DH-TXB2 than those at low titre or negative (group B, n = 20) (p = 0.01). The group A of patients presented an increase in 11-DH-TXB2 compared to controls (p <0.001), but no statistically significant difference was found between patients from the group B and normal controls. A correlation between levels of urinary 11-DH-TXB2 and titre of antibodies was only found for anti-β2GPI-IgG (rs = 0.51, p <0.005). Our data show that the observed platelet activation in aPL patients is related to the presence of antibodies reacting with β2GPI.

 

  • References

  • 1 Harris EN. The antiphospholipid syndrome – an introduction.. In: Phospholipid-Binding Antibodies.. Harris EN, Exner T, Hughes GRV, Asherson RA. eds. Boca Raton, Florida (USA): CRC Press; 1991: 373-86.
    Google Scholar
  • 2 Carreras LO, Forastiero RR. Pathogenic role of antiprotein-phospholipid antibodies.. Haemostasis 1996; 26: 340-57.
    PubMedGoogle Scholar
  • 3 Carreras LO, Defreyn G, Machin SJ, Vermylen J, Deman R, Spitz B, Van Assche A. Recurrent arterial thrombosis, repeated intrauterine death and »lupus« anticoagulant. Detection of an immunoglobulin interfering with prostacyclin formation.. Lancet 1981; 1: 244-6.
    PubMedGoogle Scholar
  • 4 Schörer AE, Wickham NWR, Watson KV. Lupus anticoagulant induces a selective defect in thrombin-mediated endothelial prostacyclin release and platelet aggregation.. Br J Haematol 1989; 71: 399-407.
    PubMedGoogle Scholar
  • 5 Watson KV, Schörer AE. Lupus anticoagulant inhibition of in vitro prostacyclin release is associated with a thrombosis-prone subset of patients.. Am J Med 1991; 90: 47-53.
    CrossrefPubMedGoogle Scholar
  • 6 Martinuzzo ME, Maclouf J, Carreras LO, Lévy Toledano S. Antiphospholipid antibodies enhance thrombin-induced platelet activation and thromboxane formation.. Thromb Haemost 1993; 70: 667-71.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Catella F, FitzGerald GA. Paired analysis of urine thromboxane B2 metabolites in humans.. Thromb Res 1987; 47: 647-56.
    CrossrefPubMedGoogle Scholar
  • 8 Arfors L, Vesterqvist O, Johnsson H, Gréen K. Increased thromboxane formation in patients with antiphospholipid syndrome.. Eur J Clin Invest 1990; 20: 607-12.
    PubMedGoogle Scholar
  • 9 Lellouche F, Martinuzzo M, Said P, Maclouf J, Carreras LO. Imbalance of thromboxane/prostacyclin biosynthesis in patients with lupus anticoagulant.. Blood 1991; 78: 2894-9.
    PubMedGoogle Scholar
  • 10 Galli M, Comfurius P, Maassen C, Hemker HC, de Baets MH, van BredaVriesman PJC, Barbui T, Zwaal RFA, Bevers EM. Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor.. Lancet 1990; 335: 1544-7.
    CrossrefPubMedGoogle Scholar
  • 11 McNeil HP, Simpson RJ, Chesterman CN, Krilis SA. Antiphospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: β2-glycoprotein I (apolipoprotein H).. Proc Natl Acad Sci USA 1990; 87: 4120-4.
    CrossrefPubMedGoogle Scholar
  • 12 Arvieux J, Darnige L, Caron C, Reber G, Bensa JC, Colomb MG. Development of an ELISA for autoantibodies to prothrombin showing their prevalence in patients with lupus anticoagulants.. Thromb Haemost 1995; 74: 1120-5.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Martinuzzo ME, Forastiero RR, Carreras LO. Anti β2-glycoprotein I: Detection and association with thrombosis.. Br J Haematol 1995; 89: 397-402.
    CrossrefPubMedGoogle Scholar
  • 14 Viard JP, Amoura Z, Bach JF. Association of anti β2-glycoprotein I antibodies with lupus-type circulating anticoagulant and thrombosis in systemic lupus erythematosus.. Am J Med 1992; 93: 181-6.
    CrossrefPubMedGoogle Scholar
  • 15 Forastiero RR, Martinuzzo ME, Cerrato GS, Kordich LC, Carreras LO. Relationship of anti β2-glycoprotein I and anti prothrombin antibodies to thrombosis and pregnancy loss in patients with antiphospholipid antibodies.. Thromb Haemost 1997; 78: 1008-15.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Pengo V, Biasiolo A, Brocco T, Tonetto S, Ruffatti A. Autoantibodies to phospholipid-binding plasma proteins in patients with thrombosis and phospholipid-reactive antibodies.. Thromb Haemost 1996; 75: 721-4.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Vaarala O, Puurunen M, Mänttäri M, Manninen V, Aho K, Palosuo T. Antibodies to prothrombin imply a risk of myocardial infarction in middle-aged men.. Thromb Haemost 1996; 75: 456-9.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Forastiero RR, Cerrato GS, Carreras LO. Evaluation of recently described tests for detection of the lupus anticoagulant.. Thromb Haemost 1994; 72: 728-33.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Brandt JT, Triplett DA, Alving B, Scharrer I. Criteria for the diagnosis of lupus anticoagulants: An update.. Thromb Haemost 1995; 74: 1185-90.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 20 Harris EN. The Second International Anticardiolipin Standardization Workshop/The Kingston Antiphospholipid Antibody (KAPS) Study Group.. Am J Clin Pathol 1990; 94: 476-84.
    CrossrefPubMedGoogle Scholar
  • 21 Pradelles P, Grassi J, Maclouf J. Enzyme immunoassays of eicosanoids using acetylcholine esterase as label: An alternative to radioimmunoassay.. Anal Chem 1985; 57: 1170-3.
    CrossrefPubMedGoogle Scholar
  • 22 Lellouche F, Fradin A, FitzGerald G, Maclouf J. Enzyme immunoassay measurement of the urinary metabolites of thromboxane A2 and prostacyclin.. Prostaglandins 1990; 40: 297-310.
    CrossrefPubMedGoogle Scholar
  • 23 Patrono C, Ciabattoni G, Remuzzi G, Gotti E, Bombardieri S, Di Minno O, Tartarelli GA, Simonetti BM, Pierucci A. Functional significance of renal prostacyclin and thromboxane A2 production in patients with systemic lupus erythematosus.. J Clin Invest 1985; 76: 1011-8.
    CrossrefPubMedGoogle Scholar
  • 24 Forastiero RR, Martinuzzo ME, Kordich LC, Carreras LO. Reactivity to β2-glycoprotein I clearly differentiates anticardiolipin antibodies from anti-phospholipid syndrome and syphilis.. Thromb Haemost 1996; 75: 717-20.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Campbell AL, Pierangeli SS, Wellhausen S, Harris EN. Comparison of the effects of anticardiolipin antibodies from patients with the antiphospholipid syndrome and with syphilis on platelet activation and aggregation.. Thromb Haemost 1995; 73: 529-34.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 26 Lin YL, Wang CT. Activation of human platelets by the rabbit anticardiolipin antibodies.. Blood 1992; 80: 3135-43.
    PubMedGoogle Scholar
  • 27 Balestrieri G, Tincani A, Spatola L, Allegri F, Prati E, Cattaneo R, Valesini G, Del Papa N, Meroni P. Anti-beta2-glycoprotein I antibodies: a marker of antiphospholipid syndrome?. Lupus 1995; 4: 122-30.
    CrossrefPubMedGoogle Scholar
  • 28 Roubey RAS, Maldonado MA, Byrd SN. Comparison of an enzyme-linked immunosorbent assay for antibodies to β2-glycoprotein I and a conventional anticardiolipin immunoassay.. Arthritis Rheum 1996; 39: 1606-9.
    CrossrefPubMedGoogle Scholar
  • 29 Shi W, Chong BH, Chesterman CN. Beta 2-glycoprotein I is a requirement for anticardiolipin antibodies binding to activated platelets: differences with lupus anticoagulants.. Blood 1993; 81: 1255-62.
    PubMedGoogle Scholar
  • 30 Arvieux J, Roussel B, Pouzol P, Colomb MG. Platelet activating properties of murine monoclonal antibodies to beta 2-glycoprotein I.. Thromb Haemost 1993; 70: 336-41.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 31 Arnout J. The pathogenesis of the antiphospholipid syndrome: A hypothesis based on parallelisms with heparin-induced thrombocytopenia.. Thromb Haemost 1996; 75: 536-41.
    Article in Thieme ConnectPubMedGoogle Scholar