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Thromb Haemost 2000; 84(04): 653-656
DOI: 10.1055/s-0037-1614082
Review Article
Schattauer GmbH

Antibodies to β2-Glycoprotein I Associated with Antiphospholipid Syndrome Suppress the Inhibitory Activity of Tissue Factor Pathway Inhibitor

Irene Salemink
1   From the Department of Biochemistry, Maastricht University, Maastricht, The Netherlands
,
Ron Blezer
1   From the Department of Biochemistry, Maastricht University, Maastricht, The Netherlands
,
George M. Willems
2   Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
,
Monica Galli
3   Department of Haematology, Ospedali Riuniti, Bergamo, Italy
,
Edouard Bevers
1   From the Department of Biochemistry, Maastricht University, Maastricht, The Netherlands
,
Theo Lindhout
1   From the Department of Biochemistry, Maastricht University, Maastricht, The Netherlands
› Author AffiliationsThis work was supported by Grant 902-26-154 from the Dutch Organization for Scientific Research (NWO).
Further Information

Publication History

Received 07 February 2000

Accepted after revision 04 May 2000

Publication Date:
11 December 2017 (online)

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Summary

Anionic phospholipid membranes have a dual role in blood coagulation: they are essential for the initiation and propagation as well as for the limitation and termination of the blood coagulation process. Patients with the anti-phospholipid syndrome (APS) carrying antibodies against complexes of anionic phospholipids and plasma proteins, show in vitro inhibited phospholipid dependent coagulation reactions, whereas in vivo the presence of these antibodies is associated with an increased risk of thrombosis. In this study we focussed on the effects of these anti-phospholipid antibodies on the regulation of TF-mediated factor Xa (FXa) generation in plasma. We hypothesized that anti-phospholipid antibodies interfere with the phospholipiddependent inhibition by tissue factor pathway inhibitor (TFPI) of TFinduced coagulation. Indeed, total-IgG, anti-cardiolipin-IgG (aCL) and anti-β2GPI-IgG, isolated from patient plasmas, all stimulated TF-induced FXa generation in normal plasma. This enhanced FXa generation was not observed when the patient’s IgG was depleted of anti-β2GPI-IgG or when normal plasma was depleted of β2GPI or TFPI. Taken together, these data indicate that antibodies to β2GPI, circulating in patients with APS, suppress TFPI-dependent inhibition of TF-induced coagulation, which results in an increased FXa generation.

Key words

Tissue factor - TFPI - FXa generation - anti-β2-glycoprotein I
 

  • References

  • 1 Rapaport SI, Rao LVM. The tissue factor pathway: how it has become a “primaballerina”. Thromb Haemost 1995; 74: 7-17.
    PubMedGoogle Scholar
  • 2 Broze GJ. The role of tissue factor pathway inhibitor in a revised coagulation cascade. Semin Hematol 1992; 29: 159-69.
    PubMedGoogle Scholar
  • 3 Kazama Y. The importance of the binding of Factor Xa to phospholipids in the inhibitory mechanism of tissue factor pathway inhibitor: the transmembrane and cytoplasmic domains of tissue factor are not essential for the inhibitory action of tissue factor pathway inhibitor. Thromb Haemost 1997; 77: 492-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 4 Salemink I, Franssen J, Willems GM, Hemker HC, Lindhout T. Inhibition of tissue factor: factor VIIa-catalyzed factor X activation by factor Xa: tissue factor pathway inhibitor. A rotating disc study on the effect of phospholipid membrane composition. J Biol Chem 1999; 274: 28225-32.
    CrossrefPubMedGoogle Scholar
  • 5 Rauch J. Lupus anticoagulant antibodies: recognition of phospholipidbinding protein complex. Lupus 1998; 07: S29-S31.
    PubMedGoogle Scholar
  • 6 Hughes GRV. Thrombosis, abortion, cerebral disease and the lupus anticoagulant. Br Med J 1983; 287: 1088-9.
    CrossrefPubMedGoogle Scholar
  • 7 Feinstein DI. Lupus anticoagulant, thrombosis and fetal loss. N Engl J Med 1985; 313: 1348-50.
    CrossrefPubMedGoogle Scholar
  • 8 Shapiro SS. The lupus anticoagulant/antiphospholipid syndrome. Annu Rev Med 1996; 47: 533-53.
    CrossrefPubMedGoogle Scholar
  • 9 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
  • 10 Loizou S, McCrea JD, Rudge AC, Reynolds R, Boyle CC, Harris EN. Measurement of anti-cardiolipin antibodies by an enzyme-linked immunosorbent assay (ELISA): standardization and quantitation of results. Clin Exp Immunol 1985; 62: 738-44.
    PubMedGoogle Scholar
  • 11 Brandt JT, Triplett DA, Alving B, Scharrer I. Criteria for the diagnosis of lupus anticoagulant: an update. Thromb Haemost 1995; 74: 1185-90.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 12 Sandset PM, Abildgaard U, Pettersen M. A sensitive assay of extrinsic pathway inhibitor (EPI) in plasma and plasma fractions. Thromb Res 1987; 47: 389-400.
    CrossrefPubMedGoogle Scholar
  • 13 Bach R, Gentry R, Nemerson Y. Factor VII binding to tissue factor in reconstituted phospholipid vesicles: induction of cooperativity by phosphatidylserine. Biochemistry 1986; 25: 4007-20.
    CrossrefPubMedGoogle Scholar
  • 14 Wurm H. β2-glycoprotein I (apolipoprotein H) interactions with phospholipid vesicles. Int J Biochem 1984; 16: 511-5.
    CrossrefPubMedGoogle Scholar
  • 15 DiScipio RG, Hermodson MA, Yates SG, Davie EW. A comparison of human prothrombin, factor IX (Christmas factor), factor X (Stuart factor), and protein S. Biochemistry 1977; 16: 698-706.
    CrossrefPubMedGoogle Scholar
  • 16 Diaz-Collier JA, Palmier MO, Kretzmer KK, Bishop BF, Combs RG, Obukowicz MG, Frazier RB, Bild GS, Joy WD, Hill SR, Duffin KL, Gustafson ME, Junger KD, Grabner RW, Galluppi GR, Wun TC. Refold and characterization of recombinant tissue factor pathway inhibitor expressed in Escherichia coli. Thromb Haemost 1994; 71: 339-46.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Galli M, Comfurius P, Maassen C, Hemker HC, de Baets MH, van Breda PJVriesman, Barbui T, Zwaal RF, Bevers EM. Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor. Lancet 1990; 335: 1544-7.
    CrossrefPubMedGoogle Scholar
  • 18 Willems GM, Janssen MP, Pelsers MM, Comfurius P, Galli M, Zwaal RFA, Bevers E. Role of divalency in the high-affinity binding of anticardiolipin antibody-β2-glycoprotein I complexes to lipid membranes. Biochemistry 1996; 35: 13833-42.
    CrossrefPubMedGoogle Scholar
  • 19 Pieters J, Lindhout T. The limited importance of factor Xa inhibition to the anticoagulant property of heparin in thromboplastin-activated plasma. Blood 1988; 72: 2048-52.
    PubMedGoogle Scholar
  • 20 Shi W, Chong BH, Hogg PJ, Chesterman CN. Anticardiolipin antibodies block the inhibition by β2-glycoprotein 1 of the factor Xa generating activity. Thromb Haemost 1993; 70: 342-5.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 21 Pieters J, Lindhout T, Hemker HC. In situ generated thrombin is the only enzyme that effectively activates factor VIII and Factor V in thromboplastin-activated plasma. Blood 1989; 74: 1021-4.
    PubMedGoogle Scholar
  • 22 Lindhout T, Franssen J, Willems G. Kinetics of the inhibition of tissue factor-factor VIIa by tissue factor pathway inhibitor. Thromb Haemost 1995; 74: 910-5.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 23 Baugh RJ, Broze GJ, Krishnaswamy S. Regulation of extrinsic pathway factor Xa formation by tissue factor pathway inhibitor. J Biol Chem 1998; 273: 4378-86.
    CrossrefPubMedGoogle Scholar
  • 24 Galli M, Comfurius P, Barbui T, Zwaal RFA, Bevers EM. Anticoagulant activity of -β2-glycoprotein I is potentiated by a distinct subgroup of anticardiolipin antibodies. Thromb Haemost 1992; 68: 297-300.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Pengo V, Brocco T, Biasiolo A, Rampazzo P, Carraro P, Zamarchi R. Procoagulant effect of anti-β22-glycoprotein I antibodies with lupus anticoagulant activity. Blood 1999; 94: 3814-9.
    PubMedGoogle Scholar
  • 26 Willems GM, Janssen MP, Salemink I, Wun TC, Lindhout T. Transient high affinity binding of tissue factor pathway inhibitor-factor Xa complexes to negatively charged phospholipid membranes. Biochemistry 1998; 37: 3321-8.
    CrossrefPubMedGoogle Scholar
  • 27 Salemink I, Franssen J, Willems GM, Hemker HC, Li AG, Wun TC, Lindhout T. Factor Xa cleavage of tissue factor pathway inhibitor is associated with loss of anticoagulant activity. Thromb Haemost 1998; 80: 273-80.
    Article in Thieme ConnectPubMedGoogle Scholar