Download PDF
Thromb Haemost 1988; 59(01): 080-085
DOI: 10.1055/s-0038-1642570
Review Article
Schattauer GmbH Stuttgart

Thrombosis Associated with Antiphospholipid Antibodies Cannot Be Explained by Effects on Endothelial and Platelet Prostanoid Synthesis

Paula Hasselaar
1   The Department of Haematology, University Hospital Utrecht, The Netherlands
2   The Department of Internal Medicine (Division of Immunopathology), University Hospital Utrecht, The Netherlands
,
Ronald H W M Derksen
2   The Department of Internal Medicine (Division of Immunopathology), University Hospital Utrecht, The Netherlands
,
Laya Blokzijl
1   The Department of Haematology, University Hospital Utrecht, The Netherlands
2   The Department of Internal Medicine (Division of Immunopathology), University Hospital Utrecht, The Netherlands
,
Philip G de Groot
1   The Department of Haematology, University Hospital Utrecht, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 24 August 1987

Accepted after revision 09 October 1987

Publication Date:
18 April 2018 (online)

Also available at
  PDF Download  Permissions and Reprints

Summary

The effect of 23 antiphospholipid antibody positive SLE sera, 4 antiphospholipid antibody negative SLE sera and 17 control sera on endothelial prostacyclin and platelet thromboxane A? production was studied. Endothelial cells and platelets were stimulated with different agonists. Depending on the stimulus used, 4-19% of the SLE sera inhibited the prostacyclin release, whereas 4-28% enhanced prostacyclin production. Our data suggest that the pathophysiological mechanisms underlying decreased prostacyclin production are heterogeneous. Follow-up of two patients showed that prostacyclin inhibitory activity was variable in time. Platelet thromboxane production was normal nr increased, but never decreased in the presence of the SLE sera. An imbalance in thromboxane A2/prostacyclin ratio was present in some patients, but did not correlate with a history of thrombosis. We conclude that, in general, interference of antiphospholipid antibodies with endoihelial or platelet prostanoid synthesis does not explain the occurrence of thromboembolic manifestations in antiphospholipid antibody positive SLE patients.

Keywords

Antiphospholipid antibodies - Systemic lupus erythematosus - Platelet - Endothelial cells - Prostanoid synthesis
 

  • References

  • 1 Harris EN, Gharavi AE, Boey ML, Patel BM, Mackworth-Young CG, Loizou S, Hughes G RV. Anticardiolipin antibodies: detection by radioimmunoassay and association with thrombosis in systemic lupus erythematosus. Lancet 1983; 2: 1211-1214
    PubMedGoogle Scholar
  • 2 Derksen R HW M, Kater L. Lupus anticoagulant: revival of an old phenomenon. Clin Exp Rheumatol 1985; 3: 349-357
    PubMedGoogle Scholar
  • 3 Feinstein DI. Lupus anticoagulant, thrombosis and fetal loss. N Engl J Med 1985; 313: 1348-1350
    CrossrefPubMedGoogle Scholar
  • 4 Derksen R HW M, Bouma BN, Kater L. The striking association between lupus anticoagulant and fetal loss in systemic lupus erythematosus. Arthritis Rheum 1986; 29: 695-696
    PubMedGoogle Scholar
  • 5 Lechner K, Pabinger-Fasching I. Lupus anticoagulants and thrombosis. Haemostas 1985; 15: 254-262
    PubMedGoogle Scholar
  • 6 Carreras LO, Vermylen JG. “Lupus” anticoagulant and thrombosis - Possible role of inhibition of prostacyclin formation. Thromb Haemostas 1982; 48: 38-40
    PubMedGoogle Scholar
  • 7 Moneada S, Higgs EA, Vane JR. Human arterial and venous tissues generate prostacyclin (prostaglandin X), a potent inhibitor of platelet aggregation. Lancet 1977; 1: 18-21
    PubMedGoogle Scholar
  • 8 Hamberg M, Svensson J, Samuelsson B. Thromboxanes: A new group of biologically active compounds derived from prostaglandin eiidoperoxides. Proe Natl Acad Sci USA 1975; 72: 2994-2998
    CrossrefPubMedGoogle Scholar
  • 9 Bunting S, Moneada S, Vane JR. The prostacyclin-thromboxane A2 balance: pathophysiological and therapeutic implications. Br Med Bull 1983; 39: 271-276
    CrossrefPubMedGoogle Scholar
  • 10 Harris EN, Asherson RA, Gharavi AE, Morgan SH, Derue G, Hughes G RV. Thrombocytopenia in SLE and related autoimmune disorders: association with anticardiolipin antibody. Br J Haematol 1985; 59: 227-230
    CrossrefPubMedGoogle Scholar
  • 11 Harris EN, Gharavi AE, Hedge U, Derue G, Morgan SH, Englert H, Chan JK H, Asherson RA, Hughes GR V. Anticardiolipin antibodies in autoimmune thrombocytopenic purpura. Br J Haematol 1985; 59: 231-234
    CrossrefPubMedGoogle Scholar
  • 12 Tan EM, Cohen AS, Fries JF, Masi AT, McShane J, Rothfield NF, Green SchallerJ, Talal N, Winchester RJ. The 1982 revised criteria for the classification of SLE. Arthritis Rheum 1982; 25: 1271-1277
    CrossrefPubMedGoogle Scholar
  • 13 Derksen R HW M, Hasselaar P, Blokzijl L, Gmelig Meyling FH J, de Groot PG. Coagulation screen is more specific than ACA-ELISA in defining a thrombotic subset of lupus patients. Ann Rheum Dis (in press);
    Google Scholar
  • 14 Hjort P, Rapaport SI, Owren PA. A simple specific one-stage prothrombin assay using Russell’s viper venom in cephalin suspension. J Lab Clin Med 1955; 46: 89-97
    PubMedGoogle Scholar
  • 15 Loizou S, McCrea JD, Rudge AC, Reynolds R, Boyle CC, Harris EN. Measurement of anti-cardiolipin antibodies by an enzyme-linked immunosorbent assay (ELISA): standardisation and quantitation of results. Clin exp Immunol 1985; 62: 738-745
    PubMedGoogle Scholar
  • 16 Harris EN, Gharavi AE, Patel SP, Hughes GG R. Evaluation of the anticardiolipin antibody test: report of an international workshop held 4 April 1986. Clin exp Immunol 1987; 68: 215-222
    PubMedGoogle Scholar
  • 17 Jaffe EA, Nachman RL, Becker CG, Minick CR. Culture of human endothelial cells derived from umbilical veins. J Clin Invest 1973; 52: 2745-2756
    CrossrefPubMedGoogle Scholar
  • 18 Willems C, Astaldi GG C, de Groot PG, Janssen MC, Gonsalves MD, Zeijlemaker WP, van Mourik JA, van Aken WG. Media conditioned by cultured human vascular endothelial cells inhibit the growth of vascular smooth muscle cells. Exp Cell Res 1982; 139: 191-197
    CrossrefPubMedGoogle Scholar
  • 19 de Groot PG, Brinkman HIM, Gonsalves MD, Van Mourik IA. The role of thrombin in the regulation of the endothelial prostaglandin production. Biochim Biophys Acta 1985; 846: 342-349
    CrossrefPubMedGoogle Scholar
  • 20 Hong SL, McLaughlin NJ, Tzeng C, Patton G. Prostacyclin synthesis and deacvlation of phospholipids in human endothelial cells: comparison of thrombin, histamine and ionophore A23187. Thrombosis Res 1985; 38: 1-10
    CrossrefPubMedGoogle Scholar
  • 21 Weksler BB, Ley CW, Jaffe EA. Stimulation of endothelial cell prostacyclin production by thrombin; trypsin and the ionophore A23187. J Clin Invest 1978; 62: 923-930
    CrossrefPubMedGoogle Scholar
  • 22 Dejana E, Breviario F, Erroi A, Bussolino F, Mussoni L, Gramse M, Pintucci G, Casali B, Dinarello CA, Van DammeJ, Mantovani A. Modulation of endothelial cell functions by different molecular species of interleukin 1. Blood 1987; 69: 695-699
    PubMedGoogle Scholar
  • 23 Hall ER, Papp AC, Seifert WE, Wu KK. Stimulation of endothelial cell prostacyclin formation by interleukin-2. Lymphokine Res 1986; 5: 87-96
    PubMedGoogle Scholar
  • 24 Hong SL, Deykin D. Activation of phospholipases A2 and C in pig aortic endothelial cells synthesizing prostacyclin. J Biol Chem 1982; 257: 7151-7154
    PubMedGoogle Scholar
  • 25 Eldor A, Fridman R, Vlodavsky I, Hy-Am E, Fuks Z, Panet A. Interferon enhances prostacyclin production by cultured vascular endothelial cells. J Clin Invest 1984; 73: 251-257
    CrossrefPubMedGoogle Scholar
  • 26 Nawroth PP, Stern DM, Kaplan KL, Nossel HL. Prostacyclin production by perturbed bovine aortic endothelial cells in culture. Blood 1984; 64: 801-806
    PubMedGoogle Scholar
  • 27 Willems C, de Groot PG, Pool GA, Gonsalvez MS, van Aken WG, van Mourik JA. Arachidonate metabolism in cultured human vascular endothelial cells. Evidence for two prostaglandin synthetic pathways sensitive to acetylsalicylic acid. Biochim Biophys Acta 1982; 713: 581-588
    CrossrefPubMedGoogle Scholar
  • 28 Bamford DS, Jogee M, Williams KI. Prostacyclin formation by the pregnant human myometrium. Br J Obstet Gynaecol 1980; 87: 214-215
    PubMedGoogle Scholar
  • 29 Lewis PJ, Boylan P, Friedman LA, Hensby CN, Downing I. Prostacyclin in pregnancy. Br Med J 1980; 280: 1581-1582
    CrossrefPubMedGoogle Scholar
  • 30 Remuzzi G, Marchesi D, Zoja C, Muratore D, Mecca G, Misiani R, Rossi E, Barbato M, Capotta P, Donati MB, de Gaetano G. Reduced umbilical and placental vascular prostacyclin in severe pre-eclampsia. Prostaglandins 1980; 20: 105-110
    CrossrefPubMedGoogle Scholar
  • 31 Carreras LO, Defreyn G, van Houtte E, Vermylen J, van Assche A. Prostacyclin in pre-eclampsia. Lancet 1981; 1: 442
    PubMedGoogle Scholar
  • 32 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 formation. Lancet 1981; 1: 244-246
    PubMedGoogle Scholar
  • 33 Marchesi D, Parbtani A, Frampton G, Livio M, Remuzzi G, Cameron JS. Thrombotic tendenecy in systemic lupus erythematosus. Lancet 1981; 1: 719
    PubMedGoogle Scholar
  • 34 De Castellarnau C, Vila L, Sancho MJ, Borrell M, Fontcuberta J, Rutllant ML. Lupus anticoagulant, recurrent abortion, and prostacyclin production by cultured smooth muscle cells. Lancet 1983; 2: 1137-1138
    PubMedGoogle Scholar
  • 35 Schorer AE, Watson KV. The “lupus anticoagulant” induces functional changes in endothelial cells and platelets. Thromb Haemostas 1987; 58: 232 (Abstr)
    PubMedGoogle Scholar
  • 36 Violi F, Valesini G, Iuliano L, Ghiselli A, Falco M, Balsano F. Anticardiolipin antibodies and prostacyclin synthesis. Thromb Haemostas 1987; 57: 374
    PubMedGoogle Scholar
  • 37 Jaffe EA, Grulich J, Weksler BB, Hampel G, Watanabe K. Correlation between thrombin-induced prostacyclin production and inositol trisphosphate and cytosolic free calcium levels in cultered human endothelial cells. J Biol Chem 1987; 262: 8557-8565
    PubMedGoogle Scholar
  • 38 Comp PC, De Bault LE, Esmon NE, Esmon CP. Human thrombomodulin is inhibited by IgG from two patients, with nonspecific anticoagulants. Blood 1983; 62: 1099
    PubMedGoogle Scholar
  • 39 Cariou R, Tobe lem 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
  • 40 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