“Lupus” Anticoagulant and Thrombosis – Possible Role of Inhibition of Prostacyclin Formation

Summary

A “lupus” anticoagulant was discovered in 14 patients over a one year period. Only three of them had systemic lupus erythematosus. Bleeding manifestations were only present in one patient with concomitant severe thrombocytopenia. In contrast, eight patients had a history of thrombosis; five of them presented repeated thrombotic episodes. Obstetrical complications (recurrent abortion, fetal death, or intrauterine growth retardation) were observed in six patients. An inhibitory effect of plasma on the production of prostacyclin by vascular tissue was detected in eight patients, six of whom had thrombosis. We suggest that inhibition of prostacyclin formation could play a major role in the pathogenesis of thrombosis and obstetrical problems in some patients with this type of anticoagulant, even in the absence of systemic lupus erythematosus.

Keywords

“Lupus” anticoagulant - Thrombosis - Prostacyclin

• References

• 1 Veltkamp JJ, Kerkhoven P, Loeliger EA. Circulating anticoagulant in disseminated lupus erythematosus. Haemostasis 1973; 1974; 2: 253-259
• 2 Thiagarajan P, Shapiro SS, De Marco L. Monoclonal immunoglobulin M lambda coagulation inhibitor with phospholipid specificity. Mechanism of a lupus anticoagulant. J Clin Invest 1980; 66: 397-405
• 3 Feinstein DI, Rapaport SI. Acquired inhibitors of blood coagulation. Prog Hemost Thromb 1972; 1: 75-95
• 4 Exner T, Rickard KA, Kronenberg H. A sensitive test demonstrating lupus anticoagulant and its behavioural patterns. Br J Haematol 1978; 40: 143-151
• 5 Boxer M, Ellman L, Carvalho A. The lupus anticoagulant. Arthritis Rheum 1976; 19: 1244-1248
• 6 Schleider MA, Nachman RL, Jaffe EA, Coleman M. A clinical study of the lupus anticoagulant. Blood 1976; 48: 499-509
• 7 Conley CL, Hartmann RC. A haemorrhagic disorder caused by circulating anticoagulant in patients with disseminated lupus erythematosus. J Clin Invest 1952; 31: 621-622
• 8 Lechner K. Acquired inhibitors in nonhemophilic patients. Haemostasis 1974; 3: 65-93
• 9 Mueh JR, Herbst KD, Rapaport SI. Thrombosis in patients with the lupus anticoagulant. Ann Intern Med 1980; 92: 156-159
• 10 Margolius Jr A, Jackson DP, Ratnoff OD. Circulating anticoagulants: a study of 40 cases and a review of the literature. Medicine (Baltimore) 1961; 40: 145-202
• 11 Bowie EW, Thompson JH, Cascuzzi PA, Owen GA. Thrombosis in SLE despite circulating anticoagulants. J Lab Clin Med 1963; 62: 416-430
• 12 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
• 13 Moneada S, Higgs EA, Vane JR. Human arterial and venous tissues generate prostacyclin (prostaglandin X), a potent inhibitor of platelet aggregation. Lancet 1977; 1: 18-20
• 14 Carreras LO, Vermylen J, Spitz B, van Assche A. “Lupus” anticoagulant and inhibition of prostacyclin formation in patients with repeated abortion, intrauterine growth retardation and intrauterine death. Br J Obstet Gynaecol 1981; 88: 890-894
• 15 Clauvel JP, Sultan Y. Anticoagulant circulant et syndrome de Willebrand au cours du lupus érythémateux disséminé. Actual Hématol 1977; 11: 109-121
• 16 Dubois EL, Tallman E, Wonka RA. Chlorpromazine-induced systemic lupus erythematosus. JAMA 1972; 221: 595-596
• 17 Williams H, Laurent R, Gibson T. The lupus coagulation inhibitor and venous thrombosis: a report of four cases. Clin Lab Haematol 1980; 1: 139-144
• 18 Manoharan A, Gibson L, Rush B, Feery BJ. Recurrent venous thrombosis with a “lupus” coagulation inhibitor in the absence of systemic lupus. Aust N Z J Med 1977; 7: 638-641
• 19 Nilsson IM, Astedt B, Hedner U, Berezin D. Intrauterine death and circulating anticoagulant (“antithromboplastin”). Acta Med Scand 1975; 197: 153-159
• 20 Soulier JP, Boffa MC. Avortements à répétition, thrombose et anticoagulant circulant anti-thromboplastine. Nouv Presse Méd 1980; 9: 859-864
• 21 Firkin BG, Howard MA, Radford N. Possible relationship between lupus inhibitor and recurrent abortion in young women. Lancet 1980; 2: 366
• 22 Marchesi D, Parbtani A, Frampton G, Livio M, Remuzzi G, Cameron JS. Thrombotic tendency in systemic lupus erythematosus. Lancet 1981; 1: 719
• 23 McVerry BA, Machin SJ, Parry H, Goldstone AH. Reduced prostacyclin activity in systemic lupus erythematosus. Ann Rheum Dis 1980; 39: 524-525
• 24 Slater D. “Lupus” and prostacyclin formation. Lancet 1981; 1: 393
• 25 Bamford DS, Jogee M, Williams KI. Prostacyclin formation by the pregnant human myometrium. Br J Obstet Gynaecol 1980; 87: 214-215
• 26 Lewis PJ, Boylan P, Friedman LA, Hensby CN, Downing I. Prostacyclin in pregnancy. Br Med J 1980; 280: 1581-1582
• 27 Remuzzi G, Misiani R, Muratore D, Marchesi D, Livio M, Schieppati A, Mecca G, DeGaetano G, Donati MB. Prostacyclin and human foetal circulation. Prostaglandins 1979; 18: 341-348
• 28 Remuzzi G, Marchesi D, Zoja C, Muratore D, Mecca G, Misiani R, Rossi E, Barbato M, Capetta P, Donati MB, de Gaetano G. Reduced umbilical and placental vascular prostacyclin in severe pre-eclampsia. Prostaglandins 1980; 20: 105-110
• 29 Carreras LO, Defreyn G, van Houtte E, Vermylen J, van Assche A. Prostacyclin and pre-eclampsia. Lancet 1981; 1: 442
• 30 Bussolino F, Benedetto C, Massobrio M, Camussi G. Maternal vascular prostacyclin activity in pre-eclampsia. Lancet 1980; 2: 702