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Thromb Haemost 1989; 61(02): 175-177
DOI: 10.1055/s-0038-1646554
Original Article
Schattauer GmbH Stuttgart

Impaired Fibrinolysis as an Essential Contribution to Thrombosis in Patients with Lupus Anticoagulant

D A Tsakiris
1   The Coagulation and Fibrinolysis Laboratory, Kantonsspital Basel, Switzerland
,
G A Marbet
1   The Coagulation and Fibrinolysis Laboratory, Kantonsspital Basel, Switzerland
,
P E Makris
2   The A’Medical Propaedeutic Department, Aristotelian University of Thessaloniki, Greece
,
L Settas
2   The A’Medical Propaedeutic Department, Aristotelian University of Thessaloniki, Greece
,
F Duckert
1   The Coagulation and Fibrinolysis Laboratory, Kantonsspital Basel, Switzerland
› Institutsangaben
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Publikationsverlauf

Received 15. Juni 1988

Accepted after revision 26. September 1988

Publikationsdatum:
30. Juni 2018 (online)

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Summary

Lupus anticoagulants (LA) are IgG or IgM antibodies against phospholipids which in vivo represent an important thrombophilic factor despite their in vitro anticoagulant activity. We investigated the fibrinolytic system of 20 patients with connective tissue disease and positive LA, compared to a control group of 24 age- and disease-matched patients without LA. There was no statistically significant difference of alpha2-antiplasmin, plasminogen, fibrinogen, t-PA activity, D-dimers and heparin cofactor II, between the two groups. Although t-PA was uniformly low in both groups, plasminogen activator inhibitor activity (PAI) was significantly higher in LA cases (p <0.001). Increased PAI levels represent an inhibitory factor of the fibrinolytic defense mechanism, which together with other functional deviations may contribute to the thrombophilic tendency of LA patients.

Keywords

Lupus anticoagulant - Fibrinolysis - Plasminogen activator inhibitor - Tissue plasminogen activator - Alpha2-antiplasmin - Plasminogen - D-dimers - Heparin cofactor II - Antithrombin III - C4 complement component
 

  • References

  • 1 Conley L, Hartman RC. A hemorrhagic disorder caused by a circulating anticoagulant in patients with disseminated lupus erythematosus. J Clin Invest 1952; 31: 621-622
    PubMedGoogle Scholar
  • 2 Lechner K. Lupus anticoagulants and thrombosis. In: Thrombosis and Hemostasis. Verstraete M, Vermylen J, Lijnen HR, Arnout J. (eds) International Society on Thrombosis and Hemostasis; Leuven: 1987. pp 525-547
    Google Scholar
  • 3 Lechner K, Pabinger-Fasching I. Lupus anticoagulants and thrombosis. A study of 25 cases and review of the literature Haemostasis 1985; 15: 254-262
    PubMedGoogle Scholar
  • 4 Sakata Y, Loskutoff DJ, Gladson CL, Hekman CM, Griffin GH. Mechanism of protein C dependent clot lysis: Role of plasminogen activator inhibitor. Blood 1986; 68: 1218-1223
    PubMedGoogle Scholar
  • 5 Van Hinsbergh VW M, Bertina RM, van Wijngaarden A, van Tilburg NA, Emeis JJ, Haverkate E. Activated Protein C decreases plasminogen activator-inhibitor activity in endothelial cell-conditioned medium. Blood 1985; 65: 444-451
    PubMedGoogle Scholar
  • 6 D’Angelo A, Lockhart MS, D’Angelo SV, Taylor Jr FB. Protein S is a cofactor for activated protein C neutralization of an inhibitor of plasminogen activation released from platelets. Blood 1987; 69: 231-237
    PubMedGoogle Scholar
  • 7 Josso F, Prou-Wartelle O. Exploration de l’hemostase. In: Techniques en Hematologie. Alagille D, Josso F, Colombani J, Fine JM. (eds) Flammarion; Paris: 1972. pp 101-208
    Google Scholar
  • 8 Schleider MA, Nachman RL, Jaffe EA, Coleman M. A clinical study of the lupus anticoagulant. Blood 1976; 48: 499-509
    PubMedGoogle Scholar
  • 9 Clauss A. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens. Acta Haematol 1957; 17: 237-246
    CrossrefPubMedGoogle Scholar
  • 10 Abilgaard U, Larsen ML. Assay of dermatan sulphate cofactor (heparin cofactor II) activity in human plasma. Thromb Res 1984; 35: 257-266
    CrossrefPubMedGoogle Scholar
  • 11 Marbet GA, Zbinden B, Duckert F. Konstitutionelle Dysfunktion von Heparinkofaktor II mit venöser Thromboseneigung. Schweiz Med Wschr 1988; 118: 1586-1588
    PubMedGoogle Scholar
  • 12 Elms MJ, Bunce IH, Bundesen PG, Rylatt DB, Welber AJ, Masci PP, Whitaker AN. Rapid detection of cross-linked fibrin degradation products in plasma using monoclonal antibody coated latex particles. Am J Clin Pathol 1986; 85: 360-364
    CrossrefPubMedGoogle Scholar
  • 13 Introduction to Statistics. In: Geigy Scientific Tables. Lentner C. (ed) Ciba Geigy Ltd; Basel: 1982
    Google Scholar
  • 14 Bowie WE J, Thomson JR, Pascuzzi CA, Owen CA. Thrombosis in systemic lupus erythematosus despite circulating anticoagulant. J Clin Invest 1963; 62: 416-430
    PubMedGoogle Scholar
  • 15 Angles-Cano E, Sultan E, Clauvel JP. Predisposing factors to thrombosis in systemic lupus erythematosus. J Lab Clin Med 1979; 2: 312-323
    PubMedGoogle Scholar
  • 16 Nilsson IM, Asted B, Hedner U, Berezin D. Intrauterine death and circulating anticoagulant (antithromboplastin). Acta Med Scand 1975; 197: 153-159
    PubMedGoogle Scholar
  • 17 Branch D, Scott J, Kochenour L, Hershgold E. Obstetric complications associated with the lupus anticoagulant. N Engl J Med 1985; 313: 1322
    CrossrefPubMedGoogle Scholar
  • 18 Carreras LO, Machin SJ, Deman R. et al. Arterial thrombosis, intrauterine death and lupus anticoagulant: Detection of immunoglobulin interfering with prostacyclin formation. Lancet 1982; 1: 244-246
    PubMedGoogle Scholar
  • 19 Rustin MH A, Bull HA, Dowd PM, Isenberg DA, Snaith ML, Machin SJ. Presence of the lupus anticoagulant in patients with systemic lupus erythematosus does not cause inhibition of prostacyclin production. Thromb Haemostas 1987; 58 (01) 390 (Abstr 1428)
    PubMedGoogle Scholar
  • 20 Comp PC, De Bault LE, Esmon NL, Esmon CT. Human thrombomodulin is inhibited by IgG from two patients with nonspecific anticoagulants. Blood 1983; 62: 1099
    PubMedGoogle Scholar
  • 21 Cariou G, Tobelem G, Soria C, Caen J. Inhibition of protein C activation by endothelial cells in the presence of lupus anticoagulant. N Engl J Med 1986; 314: 1193-1194
    CrossrefPubMedGoogle Scholar
  • 22 Freyssinet JM, Wiesel ML, Gauchy J, Boneu B, Cazenave JP. An IgM lupus anticoagulant that neutralizes the enhancing effect of phospholipid on purified endothelial thrombomodulin activity - A mechanism for thrombosis. Thromb Haemostas 1986; 55: 309-313
    PubMedGoogle Scholar
  • 23 Friedman KD, Marlar RA, Gill JC, Endres-Brooks J, Mongomery RR. Protein S deficiency in patients with lupus anticoagulant. Blood 1986; 68: 1210 (Abstr)
    PubMedGoogle Scholar
  • 24 Belch JJ F, Zoma A, MacLaughlin K, Curran L, Capell HA, Forbes CD, Sturrock RD. Fibrinolysis in systemic lupus erythematosus: Effect of des-amino D-Arginin vasopressin infusion. Br J Rheum 1987; 26: 262-266
    CrossrefPubMedGoogle Scholar
  • 25 Moroz LA, MacLean LD, Langleben D. Abnormalities in the cellular phase of blood fibrinolytic activity in systemic lupus erythematosus and in venous thrombembolism. Thromb Res 1986; 43: 595-602
    CrossrefPubMedGoogle Scholar
  • 26 Glas-Greenwalt P, Kant KS, Allen C, Pollak VE. Fibrinolysis in health and disease: Severe abnormalities in systemic lupus erythematosus. J Lab Clin Med 1984; 104: 962-996
    PubMedGoogle Scholar
  • 27 Sprengers ED, Kluft C. Plasminogen activator inhibitors. Blood 1987; 69: 381-387
    PubMedGoogle Scholar
  • 28 Kruithof EK O, Gudinchet A, Bachmann F. Plasminogen activator inhibitor 1 and plasminogen activator inhibitor 2 in various disease states. Thromb Haemostas 1988; 59: 7-12
    PubMedGoogle Scholar
  • 29 Freyssinet JM, Cazenave JP. Lupus-like anticoagulants, modulation of the protein C pathway and thrombosis. Thromb Haemostas 1987; 58: 679-681
    PubMedGoogle Scholar