Download PDF
Thromb Haemost 1986; 55(03): 309-313
DOI: 10.1055/s-0038-1661553
Original Article
Schattauer GmbH Stuttgart

An IgM Lupus Anticoagulant that Neutralizes the Enhancing Effect of Phospholipid on Purified Endothelial Thrombomodulin Activity-A Mechanism for Thrombosis

J-M Freyssinet
1   The Laboratoire de Biologie et de Pharmacologie des Interactions du Sang avec les Vaisseaux et les Biomatériaux, Centre Régional de Transfusion Sanguine, Strasbourg, France
,
Marie-Louise Wiesel
1   The Laboratoire de Biologie et de Pharmacologie des Interactions du Sang avec les Vaisseaux et les Biomatériaux, Centre Régional de Transfusion Sanguine, Strasbourg, France
,
Josiane Gauchy
1   The Laboratoire de Biologie et de Pharmacologie des Interactions du Sang avec les Vaisseaux et les Biomatériaux, Centre Régional de Transfusion Sanguine, Strasbourg, France
,
B Boneu
2   The Laboratoire d’Hemostase, Centre Regional de Transfusion Sanguine, Hôpital Purpan, Toulouse, France
,
J-P Cazenave
1   The Laboratoire de Biologie et de Pharmacologie des Interactions du Sang avec les Vaisseaux et les Biomatériaux, Centre Régional de Transfusion Sanguine, Strasbourg, France
› Author Affiliations
Further Information

Publication History

Received 29 October 1985

Accepted after revision 03 March 1986

Publication Date:
18 July 2018 (online)

  PDF Download  Permissions and Reprints

Summary

An anticoagulant activity was isolated from the plasma of a patient with a strong lupus-like anticoagulant using gel filtration by high performance liquid chromatography. IgM were detected in this anticoagulant fraction which exhibited specificity towards 50% phosphatidylcholine - 50% phosphatidylserine vesicles and cardiolipin. These phospholipids were able to produce an apparent 3-fold enhancement of purified human protein C activation by human a-thrombin in the presence of purified human placenta thrombomodulin. In the absence of phospholipid, the anticoagulant fraction had no effect on thrombomodulin activity. The anticoagulant fraction could neutralize the enhancement of thrombomodulin activity by phospholipid in a dose-dependent manner. This study suggests that the neutralization of phospholipid might result in a reduced activation of protein C which could be responsible for the occurrence of thrombotic complications in a proportion of patients with lupus anticoagulants.

Keywords

Lupus anticoagulant - Thrombosis - Phospholipid - Thrombomodulin - Protein C
 

  • References

  • 1 Shapiro SS, Thiagarajan P. Lupus anticoagulants. In: Progress in Hemostasis and Thrombosis. Spaet TH. (Ed) Grune and Stratton; Orlando: 1982. 6 263-285
  • 2 Bowie EJ W, Thompson Jr JH, Cascuzzi PA, Owen Jr GA. Thrombosis in systemic lupus erythematosus despite circulating anticoagulants. J Lab Clin Med 1963; 62: 416-430
    PubMedGoogle Scholar
  • 3 Gastineau DA, Kazmier FJ, Nichols WL, Bowie EJ W. Lupus anticoagulant: An analysis of the clinical and laboratory features of 219 cases. Amer J Hematol 1985; 19: 265-275
    CrossrefPubMedGoogle Scholar
  • 4 Lechner K, Pabinger-Fashing I. Lupus anticoagulants and thrombosis. Haemostasis 1985; 15: 254-262
    PubMedGoogle Scholar
  • 5 Cazenave JP, Klein-Soyer C, Beretz A. The vascular endothelium. An important site of blood-tissue exchanges. Inter Angio 1984; 3: 27-32
    PubMedGoogle Scholar
  • 6 Feinstein DI. Lupus anticoagulant, thrombosis, and fetal loss. N Engl J Med 1985; 313: 1348-1350
    CrossrefPubMedGoogle Scholar
  • 7 Carreras LO, Defreyn G, Machin SJ, Vermylen J, Deman R, Spitz B, Van Assche A. Arterial thrombosis, intrauterine death and “lupus” anticoagulant: Detection of immunoglobulin interfering with prostacyclin production. Lancet 1981; 01: 244-246
    PubMedGoogle Scholar
  • 8 Comp PC, DeBault LE, Esmon NL, Esmon CT. Human thrombomodulin is inhibited by IgG from two patients with nonspecific anticoagulants. Blood 1983; 62 (05) (Suppl. 01) 299 Abstr
    PubMedGoogle Scholar
  • 9 Jackson CM, Nemerson Y. Blood coagulation. Annu Rev Biochem 1980; 49: 765-811
    CrossrefPubMedGoogle Scholar
  • 10 Zwall RFA. Membrane and lipid involvement in blood coagulation. Biochim Biophys Acta 1978; 515: 163-205
    CrossrefPubMedGoogle Scholar
  • 11 Thiagarajan P, Shapiro SS, De Marco L. Monoclonal immunoglobulin MX coagulation inhibitor with phospholipid specificity. Mechanism of a lupus anticoagulant. J Clin Invest 1980; 66: 397-405
    CrossrefPubMedGoogle Scholar
  • 12 Harris EN, Gharavi EA, Boey ML, Patel BM, Mackworth-Young CG, Loizou S, Hughes GV R. Anticardiolipin antibodies: Detection by radioimmunoassay and association with thrombosis in systemic lupus erythematosus. Lancet 1983; 2: 1211-1214
    PubMedGoogle Scholar
  • 13 Esmon CT, Owen WG. Identification of an endothelial cell cofactor for thrombin-catalyzed activation of protein C. Proc Natl Acad Sci USA 1981; 78: 2249-2252
    CrossrefPubMedGoogle Scholar
  • 14 Stenflo J. Structure and function of protein C. Semin Thromb Hemostasis 1984; 10: 109-121
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Walker FJ. Regulation of activated protein C by protein S. The role of phospholipid in factor Va inactivation. J Biol Chem 1981; 256: 11128-11131
    PubMedGoogle Scholar
  • 16 Griffin JH. Clinical studies of protein C. Semin Thromb Hemostasis 1984; 10: 162-166
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Comp PC, Esmon CT. Recurrent venous thromboembolism in patients with a partial deficiency of protein S. N Engl J Med 1984; 311: 1525-1528
    CrossrefPubMedGoogle Scholar
  • 18 Schwarz HP, Fischer M, Hopmeier P, Batard MA, Griffin JH. Plasma protein S deficiency in familial thrombotic disease. Blood 1984; 64: 1297-1300
    PubMedGoogle Scholar
  • 19 Freyssinet JM, Gauchy J, Spaethe R, Fritsche R, Cazenave JP. Effects of concanavalin A and phospholipases A2and C on thrombomodulin and thromboplastin activities extracted from human placenta. Thromb Haemostas 1985; 54: 83 Abstr
    PubMedGoogle Scholar
  • 20 Freyssinet JM, Brami B, Gauchy J, Cazenave JP. Coextraction of thrombomodulin and tissue factor from human placenta: Effects of concanavalin A and phospholipid environment on activity. Thromb Haemostas 1986; 55: 112-118
    PubMedGoogle Scholar
  • 21 Esmon CT, Esmon NL, Johnson AE, DeBault L, Galvin J. Cellular control of protein C activation. Thromb Haemostas 1985; 54: 234 Abstr
    PubMedGoogle Scholar
  • 22 Caen J, Larrieu MJ, Samama M. L’Hémostase. Expansion Scientifi-que, Paris 1975
    PubMedGoogle Scholar
  • 23 Esmon NL, Owen WG, Esmon CT. Isolation of a membrane-bound cofactor for thrombin-catalyzed activation of protein C. J Biol Chem 1982; 257: 859-864
    PubMedGoogle Scholar
  • 24 Freyssinet JM, Grunebaum L, Wiesel ML, Cazenave JP, Fritsche R, Greber S, Lampart A, Spaethe R. Production of an antibody against protein C and its use to detect patients with congenital protein C deficiency associated with thrombosis. In: Protein C. Biochemical and Medical Aspects Witt I. (Ed) Walter de Gruyter; Berlin: 1985: 107-116
  • 25 Freyssinet JM, Thevenon D, Souque A, Suscillon M. Reversible inhibition of the in vitro coagulation of human plasma by lectins. Thomb Haemostas 1982; 48: 120-124
    PubMedGoogle Scholar
  • 26 Owen WG, Jackson CM. Activation of prothrombin with Oxyuranus scutellatus scutellatus (taipan snake) venom. Thromb Res 1973; 3: 705-714
    CrossrefPubMedGoogle Scholar
  • 27 Salem HH, Maruyama I, Ishii H, Majerus PW. Isolation and characterization of thrombomodulin from human placenta. J Biol Chem 1984; 259: 12246-12251
    PubMedGoogle Scholar
  • 28 Johnstone A, Thorpe R. Immunochemistry in Practice. Blackwell Scientific Publications, Oxford 1982
    PubMedGoogle Scholar
  • 29 Sakata Y, Curriden S, Lawrence D, Griffin JH, Loskutoff DJ. Activated protein C stimulates the fibrinolytic activity of cultured endothelial cells and decreases anti-activator activity. Proc Natl Acad Sci USA 1985; 82: 1121-1125
    CrossrefPubMedGoogle Scholar
  • 30 Van Hinsberg VW M, Bertina RM, Van Wijngaarden A, Van Tilburg NH, Emeis JJ, Haverkate F. Activated protein C decreases plasminogen activator-inhibitor activity in endothelial cell-conditioned medium. Blood 1985; 65: 444-451
    PubMedGoogle Scholar
  • 31 Angles-Cano E, Sultan Y, Clauvel JP. Predisposing factors to thrombosis in systemic lupus erythematosus. J Lab Clin Med 1979; 94: 312-323
    PubMedGoogle Scholar
  • 32 Soulier JP, Boffa MC. Avortements a repetition, thromboses et anticoagulant circulant anti-thromboplastine: trois observations. Nouv Presse Med 1980; 9: 859-864
    PubMedGoogle Scholar