Association of osteonecrosis in systemic lupus erythematosus with abnormalities of fibrinolysis

Abstract

Patients with systemic lupus erythematosus (SLE) are at an increased risk of developing osteonecrosis (ON). Twenty-six patients with SLE were studied. Fifteen of these had ON and 11 did not. The latter were used as control subjects. Various coagulation analytes including antithrombin III (ATIII) activity, protein C activity, protein S activity, a2-antiplasmin activity, anticardiolipin antibodies (aCL), plasminogen activator inhibitor (PAI-1) activity and tissue type plasminogen activator (tPA) antigen were measured using citrated plasma samples from the patients. A significant proportion (80%) of patients had at least one laboratory abnormality that has been associated with a thrombotic predisposition. ON was significantly associated with elevated levels of PAI-1 activity; it was also associated with elevated PAI-1/tPA ratio. There was no association between ON of SLE and abnormalities of the other measured coagulation analytes. These results suggest that defective fibrinolysis seems to be operative in the pathogenesis of ON associated with SLE. The defect appears to involve an imbalance between tPA and its inhibitor, PAI-1. This imbalance could represent an important risk factor in the pathogenesis of ON.

Keywords

osteonecrosis fibrinolysis systemic lupus erythematosus

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References

Weiner ES , Abeles M . Aseptic necrosis and glucocorticosteroids in systemic lupus erythematosus: a reevaluation . J Rheumatology 1989; 16: 604–608 .

Zizic TM et al. Corticosteroid therapy associated with ischemic necrosis of bone in systemic lupus erythematosus . Am J Med 1985; 79: 596–604 .

Glueck CJ et al. Hypofibrinolysis: a common major cause of osteonecrosis . Am J Hematol 1994; 45: 156–166 .

Glueck CJ et al. Familial high plasminogen activator inhibitor, a new pathophysiologic cause of osteonecrosis . Thromb Haemost 1993; 69: 460–465 .

Veldhuizen PJV et al. Decreased fibrinolytic potential in patients with idiopathic vascular necrosis and transient osteoporosis of the hip . Am J Hematol 1993; 44: 243–248 .

Jones JP . Intravascular coagulation and osteonecrosis . Clin Orthop Res 1992; 277: 41–52 .

Ficat RP , Arlet J . Ischemia and Bone Necrosis. Williams and Wilkins: Baltimore , 1980.

Angele's-Cano E , Sultan Y , Clauvel JP . Predisposing factors to thrombosis in systemic lupus erythematosus: possible relation to endothelial cell damage . J Lab Clin Med 1979; 94: 312–323 .

S'anchez-Medal L , Lisker R . Circulating anticoagulants in disseminated lupus erythematosus . Acta Haematol (Basel) 1963; 5: 284–289 .

10.

Mueh JR , Herbst KD , Rapaport SI . Thrombosis in patients with lupus anticoagulant . Ann Intern Med 1980; 92: 156–159 .

11.

Bryan MA et al. Indications of vascular endothelial cell dysfunction in systemic lupus erythematosus . Ann Rheum Dis 1987; 46: 741–745 .

12.

Dorsch CA , Meyerhoff J . Mechanisms of abnormal platelet aggregation in systemic lupus erythematosus . Arthritis Rheum 1982; 25: 966–973 .

13.

Regan MG , Lackner H , Karpatkin S . Platelet function and coagulation profile in lupus erythematosus . Ann Intern Med 1974; 81: 462–468 .

14.

Ruiz-Arguelles GJ , Ruiz-Arguelles A , Deleze M . Acquired protein C deficiency in a patient with primary antiphospholipid syndrome: relationship to reactivity of the anticardiolipid antibody to thrombomodulin . J Rheum 1989; 16: 381–383 .

15.

Ginsberg JS et al. Acquired free protein S deficiency is associated with antiphospholipid antibodies and increased thrombin generation in patients with systemic lupus erythematosus . Am J Med 1995; 98: 379–383 .

16.

Ruiz-Arguelles GJ , Ruiz-Arguelles A , Alarcon-Segovia D . Natural anticoagulants in systemic lupus erythematosus: relationship of deficiencies to antiphospholipid antibodies, recent thrombosis and the antiphospholipid syndrome. J Rheum (in press).

17.

Carreras LO , Vermylen JG . Lupus anticoagulant and thrombosis: possible role of inhibition of prostacyclin formation . Lancet 1981; i: 244–244 .

18.

Guillermo J et al. Disturbances in tissue plasminogen activator/ plasminogen activator inhibitor (tPA/PAI) system in systemic lupus erythematosus . Am J Hematol 1991; 37: 37–39 .

19.

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: 962–976 .

20.

Chu P et al. Abnormal fibrinolytic activity in systemic lupus erythematosus and possible mechanisms . Br J Rheumatol 1988; 27: 436–439 .

21.

Judado M , Paramo JA , Gutierrez-Pimentel , Rocha E . Fibrinolytic potential and antiphospholipid antibodies in systemic lupus erythematosus and other connective tissue disorders . Thromb Haemost 1992; 68: 516–520 .

22.

Asherson RA et al. Avascular necrosis of bone and antiphospholipid antibodies in systemic lupus erythematosus . J Rheumatol 1993; 20: 284–288 .

23.

Migliaresi S et al. Avascular osteonecrosis in patients with SLE: relation to corticosteroid therapy and anticardiolipin antibodies . Lupus 1994; 3: 37–41 .

24.

Hess EV . The uniform data base for rheumatic diseases . Arthritis Rheum 1979; 22: 1029–1033 .

25.

Tan EM et al. The 1982 revised criteria for the classification of systemic lupus erythematosus . Arthritis Rheum 1982; 25: 1271–1277 .

26.

Blomgren SE , Condemi JJ , Vaughan JH . Procainamide-induced lupus erythematosus: clinical and laboratory observations . Am J Med 1972; 52: 338–348 .

27.

Wayne L et al. Effect of PAI-1 levels on the molar concentrations of active tissue plasminogen activator (t-PA) and t-PA/PAI-1 complex in plasma . Blood 1990; 76: 930–937.28–28

28.

Nilsson IM et al. Severe thrombotic disease in a young man with bone marrow and skeletal changes and with a high content of an inhibitor in the fibrinolytic system . Acta Med Scand 1961; 169: 323–337 .

29.

Newland JR , Haire WD . Elevated plasminogen activator inhibitor levels found in patients with malignant conditions . Am J Clin Pathol 1991; 96: 602–604 .

30.

Simpson HCR et al. Hypertriglyceridemia and hypercoagulability. Lancet April 1983; 786–789.

31.

Colucci M , Paramo JA , Collen D . Generation in plasma of a fast-acting inhibitor of plasminogen activator in response to endotoxin stimulation . J Clin Invest 1985; 75: 818–824 .

32.

Awada H et al. Fibrinolysis abnormalities in systemic lupus erythematosus and their relation to vasculitis . J Lab Clin Med 1988; 111: 229–236 .

33.

Munkvad S , Gram J , Jespersen J . Depressed plasma fibrinolytic activity in a group of patients with connective tissue diseases . Scand J Rheumatol 1989; 18: 277–282 .

34.

Gladman DD et al. Venous syndromes and pulmonary embolism in systemic lupus erythematosus . Ann Rheum Dis 1980; 39: 340–343 .

35.

Harris EN , Gharani AE , Hughes GRV . Antiphospholipid antibodies . Clin Rheum Dis 1985; 11: 591–609 .

36.

Park AL et al. The thrombotic diasthesis associated with presence of antiphospholipid antibodies may be due to low levels of free protein S . Am J Med 1992; 93: 49–56 .