Evaluation of clinical and laboratory features of antiphospholipid syndrome: a retrospective study of 637 patients

Abstract

We retrospectively analysed the data of 1519 antiphospholipid antibody (APLA) positive patients between 1986 and 1999. Among them 637 were considered to have antiphospholipid syndrome (APS) based on the 1999 preliminary classification criteria, while 704 patients had no clinical signs of the syndrome. Our aim was to compare the autoantibody profile and clinical characteristics of primary and secondary APS, moreover to evaluate the associations between different APLA and specific symptoms attributable to APS. In our results, the APLA profiles for primary and SLE-associated secondary APS were similar. Among the evaluated clinical symptoms, cerebrovascular thrombosis was found to be more frequent in the SLE-associated, than in the primary APS group (P = 0.04). We identified important differences in the clinical profile of patient populations with various types of APLA. Venous thrombosis occurred more frequently in subjects with lupus anticoagulant (LA), than in those with IgG or IgM type ACLA (P < 0.0001), while coronary, carotid and peripheral artery thrombosis occurred more often in subjects with IgG or IgM ACLA (P < 0.0001). These findings may support the role of antibodies to cardiolipin or its cofactor, b2glycoprotein I (b2-GPI) in the initiation and progression of atherosclerosis. Cerebrovascular thrombosis was detected in larger proportion of LA or IgG ACLA-positive patients compared with to IgM ACLA-positive subjects, while the occurrence of foetal loss was similar in all three groups.

Keywords

consensus criteria anticardiolipin antibodies lupus anticoagulant primary APS secondary APS

Get full access to this article

View all access options for this article.

References

Hughes GRV , Harris EN , Gharavi AE. The anticardiolipin syndrome . J Rheumatol 1986; 13: 486-489 .

Harris EN , Baguley E , Asherson RA , Hughes GRV. Clinical and serological features of the antiphospholipid syndrome (APS) (Abstract .) Br J Rheumatol 1987; 26 (Suppl 2): 19-19 .

Asherson RA , Khamashta MA , Ordi-Ros J. The ‘primary’ antiphospholipid syndrome: major clinical and serological features . Medicine (Baltimore) 1989; 68: 366-372 .

Asherson RA , Cervera R. ‘Primary’, ‘secondary’ and other variants of the antiphospholipid syndrome . Lupus 1994; 3: 293-298 .

Hughes GRV. The antiphospholipid syndrome: ten years on . Lancet 1993; 342: 341-344 .

Asherson RA. The catastrophic antiphospholipid syndrome . J Rheumatol 1992; 19: 508-512 .

Asherson RA et al. Catastrophic antiphospholipid syndrome. Clinical and laboratory features of 50 patients . Medicine (Baltimore) 1998; 77: 195-207 .

Harris EN , Gharavi AE , Boey ML. Anticardiolipin antibodies: detection by radioimmunoassay and association with thrombosis in systemic lupus erythematosus . Lancet 1983; ii: 1211-1214 .

Loizou S et al. Measurement of anticardiolipin antibodies by enzyme-linked immunosorbent assay (ELISA). Standardisation and quantitation of results . Clin Exp Immunol 1985; 62: 738-745 .

10.

Harris EN , Gharavi AE , Patel SP , Hughes GRV. Evaluation of the anti-cardiolipin antibody test: report of an international workshop held 4 April 1986 . Clin Exp Immunol 1987; 68: 215-222 .

11.

Exner T , Triplett DA , Taberner D , Machin SJ. Guidelines for testing and revised criteria for lupus anticoagulant . Thromb Haemost 1991; 65: 320-322 .

12.

Brandt JT , Triplett DA , Alving B , Scharrer I. Criteria for the diagnosisof lupus anticoagulants: an update . Thromb Haemost 1995; 74: 1185-1190 .

13.

Roubey RAS. Immunology of the antiphospholipid antibody syndrome . Arthritis Rheum 1996; 39: 1444-1454 .

14.

Viard JP , Amoura Z , Bach JF. Association of anti-b2-glycoprotein I antibodies with lupus-type circulating anticoagulant and thrombosis in systemic lupus erythematosus . Am J Med 1992; 93: 181-186 .

15.

Bevers EM et al. Lupus anticoagulant IgG’s (LA) are not directed to phospholipids only, but to a complex of lipid-bound human prothrombin . Thromb Haemost 1991; 66: 629-632 .

16.

Lakos G et al. Anti-prothrombin and anti-annexin V antibodies imply a risk of thrombosis in patients with systemic autoimmune diseases . J Rheumatol 2000; 27: 924-929 .

17.

Hunt JE et al. A phospholipid-b2 glycoprotein I complex is an antigen for anticardiolipin antibodies occuring in autoimmune disease but not with infection . Lupus 1992; 1: 83-90 .

18.

McNally T et al. The use of an anti-b2-glycoprotein-Iassay for discrimination between anticardiolipin antibodies associated with infection and increased risk of thrombosis . Br J Haematol 1995; 91: 471-473 .

19.

Pierangeli SS et al. Induction of thrombosis in a mouse model by IgG, IgM and IgA immunoglobulinsfrom patients with the antiphospholipid syndrome . Thromb Haemost 1995; 74: 1361-1367 .

20.

Blank M et al. Immunization with anticardiolipin cofactor (beta-2- glycoprotein I) induces experimental antiphospholipid syndrome in naive mice . J Autoimmun 1994; 7: 441-455 .

21.

Martinuzzo M et al. Activated protein C resistance in patients with anti-beta 2-glycoprotein I antibodies . Blood Coagul Fibrinol 1996; 7: 702-704 .

22.

Branch DW , Rodgers GA. Induction of endothelial cell tissue factor activity by sera from patients with antiphospholipidsyndrome: a possible mechanism of thrombosis . Am J Obstet Gynecol 1993; 168: 206-210 .

23.

Arnout J. The pathogenesis of the antiphospholipid syndrome: a hypothesis based on parallelism with heparin-induced thrombocytopenia . Thromb Haemost 1996; 75: 536-541 .

24.

Wilson WA et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome . Arthritis Rheum 1999; 42: 309-311 .

25.

Bick RL , Baker WF. Antiphospholipid syndrome and thrombosis . Seminars Thromb Haemost 1999; 25: 333-349 .

26.

Harris EN et al. Thrombosis, recurrent fetal loss, and thrombocytopenia. Predictive value of the anticardiolipin antibody test . Arch Intern Med 1986; 146: 2153-2156 .

27.

Cervera R et al. Antiphospholipid syndrome: clinical and immunological manifestations and patterns of disease expression in a cohort of 1,000 patients . Arthritis Rheum 2002; 46: 1019-1027 .

28.

Font J et al. The ‘primary’ antiphospholipid syndrome: Antiphospholipid antibody pattern and clinical features of a series of 23 patients . Autoimmunity 1991; 9: 69-75 .

29.

Vianna JL et al. Comparison of the primary and secondary antiphospholipid syndrome. A European multicenter study of 114 patients . Am J Med 1994; 96: 3-9 .

30.

Haider YS , Roberts WC. Coronary arterial disease in systemic lupus erythematosus: quantification of degrees of narrowing in 22 necropsy patients (21 women) aged 16 to 37 years . Am J Med 1981; 70: 775-781 .

31.

Ilowite NT. Hyperlipidaemia and the rheumatic diseases . Curr Opin Rheumatol 1996; 8: 455-458 .

32.

Manzi S. inflammation-mediated rheumatic diseases and atherosclerosis . Ann Rheum Dis 2000; 59: 321-325 .

33.

Swadzba J et al. Anticardiolipin, anti-b(2)-glycoprotein I, antiprothrombin antibodies and lupus anticoagulant in patients with systemic lupus erythematosus with a history of thrombosis . J Rheumatol 1997; 24: 1710-1715 .

34.

Finazzi G et al. Natural history and risk factors for thrombosis in 360 patients with antiphospholipid antibodies: a four-year prospective study from the Italian registry . Am J Med 1996; 100: 530-536 .

35.

Ginsberg JS et al. Antiphospholipid antibodies and venous thromboembolism . Blood 1995; 86: 3685-3691 .

36.

Horbach DA et al. Lupus anticoagulant is the strongest risk factor for both venous and arterial thrombosis in patients with systemic lupus erythematosus. Comparison between different assays for the detection of antiphospholipid antibodies . Thromb Haemost 1996; 76: 916-924 .

37.

Sherer Y et al. Coronary calcium and anti-cardiolipin antibody are elevated in patients with typical chest pain . Am J Cardiol 2000; 86: 1306-1311 .

38.

George J , Shoenfeld Y , Harats D. The involvement of b2-glycoprotein I(b2-GPI) in human and murine atherosclerosis . J Autoimmun 1999; 13: 57-60 .