Analysis of risk factors for the development of thrombotic complications in antiphospholipid antibody positive lupus patients

Abstract

The objective of this study was to characterize risk factors for thrombotic events in lupus patients. A total of 272 lupus patients were followed up for five years during which the presence of aPL antibodies [anticardiolipin (aCL), anti-beta2-glycoprotein I (aβ2GPI) and lupus anticoagulant (LAC)] were determined, and all thrombotic incidents and antithrombotic therapy-related data were collected. At baseline, three groups were constituted, an aPL–group with 107 aPL negative patients, an aPL+ group with 81 aPL positive patients without clinical thrombosis and a secondary antiphospholipid syndrome (APS) group with 84 aPL+ patients who met the Sapporo criteria. LAC was more common in the APS than the aPL+ group (32.1% versus 9.9%, P < 0.001). The prevalence of clinical thrombotic events was significantly higher when all three types of aPL were present compared to only aCL positive cases. During follow up, aPL appeared in 7.5% of the aPL - group, and 2.8% of this group had thrombotic complications. In the aPL + group, thrombotic events reoccurred in 1.9% of those receiving antithrombotic prophylaxis and 6.9% of those without primary prophylaxis. Despite anticoagulant therapy, thrombotic events reoccurred in 8.3% of the APS group. These findings indicate that LAC, constant and cumulative presence of aPL and previous thrombosis are positive predictors for the development of thrombotic complication in lupus patients.

Keywords

SLE antiphospholipid antibodies antiphospholipid syndrome primary prophylaxis thrombosis

Get full access to this article

View all access options for this article.

References

Hughes GR. Thrombosis, abortion, cerebral disease, and the lupus anticoagulant . Br Med J 1983; 287: 1088–1089 .

Wilson WA , Gharavi AE , Koike T et al. International consensus statement on preliminary classification for definite antiphospholipid syndrome . Arthritis Rheum 1999; 42: 1309–1311 .

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

Hochberg M. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus . Arthritis Rheum 1997; 40: 1725–1743 .

Louizu S , Mackworth-Young CG , Cofiner C , Walpoprt MJ . Heterogeneity of binding reactivity to different phospholipids of antibodies from patients with systemic lupus erythematosus (SLE) and with syphilis . Clin Exp Immunol 1990; 80: 171–176 .

Viard JP , Amoura Z , Bach JF . Association of anti-beta2-gylcoprotein I antibodies with lupus-type circulating anticoagulant and thrombosis in systemic lupus erythematosus . Am J Med 1992; 93: 181–186 .

Sheonfeld Y , Meroni PL . The beta-2-glycoprotein I and antiphospholipid antibodies . Clin Exp Rheumatol 1992; 10: 205–209 .

Matsuura E , Igarashi Y , Yasuda T , Triplett DA , Koike T . Anticardiolipin antibodies recognize beta-2-gylcoprotein I structure altered by intercating with oxygen modified solid phase surface . J Exp Med 1994; 179: 457–462 .

Lakos G , Kiss E , Regeczy N et al. Anti-prothrombin and anti-annexin V antibodies imply a risk of thrombosis in patients with systemic lupus erythematosus . J Rheumatol 2000; 27: 924–929 .

10.

Matsuura E , Kobayashi K , Koike T , Shoenfeld Y . Autoantibody mediated atherosclerosis . Autoimmun Rev 2002; 1: 348–353 .

11.

Gharavi AE , Wilson W , Pierangeli S . The molecular basis of antiphospholipid syndrome . Lupus 2003; 12: 579–583 .

12.

Bick RL , Baker WF . Antiphospholipid syndrome and thrombosis . Semin Thromb Hemost 1999; 25: 333–350 .

13.

Somers E , Magder LS , Petri M . Antiphospholipid antibodies and incidence of venous thrombosis in a cohort of patients with systemic lupus erythematosus . J Rheumatol 2002; 29: 2531–2536 .

14.

De Bandt M , Benali K , Guillevin L et al. Longitudinal determination of antiphospholipid antibodies lupus patients without previous manifestations of antiphospholipid syndrome. A prospective study . J Rheumatol 1999; 26: 91–96 .

15.

Soltesz P , Veres K , Lakos G , Kiss E , Muszbek L , Szegedi G . Evaluation of clinical and laboratory features of antiphospholipid syndrome: a retrospective study of 637 patients . Lupus 2003; 12: 302–307 .

16.

Urfer C , Pichler WJ , Halbling A . Antiphospholipid antibodies syndrome: follow-up of patients with a high antiphospholipid antibody titer . Schweitz Med Wochenschr 1996; 126: 2136–2140 .

17.

McClain MT , Arbuckle MR , Heilen LD et al. The prevalence, onset and clinical significance of antiphospholipid antibodies prior to diagnosis of systemic lupus erythematosus . Arthitis Rheum 2004; 50: 1226–1232 .

18.

Gomez-Puerta JA , Martin H , Amigo MC et al. Long-term follow-up in 128 patients with primary antiphospholipid syndrome: do they develop lupus? Medicine (Baltimore) 2005; 84: 225–230 .

19.

Petri M. Evidence-based management of thrombosis in the antiphospholipid antibody syndrome . Curr Rheumatol Rep 2003; 5: 370–373 .

20.

Crowther MA , Ginsberg JS , Julian J et al. A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome . N Engl J Med 2003; 349: 1133–1138 .

21.

Derksen RH , De Groot PG , Kappelle LJ . Low dose aspirin after ischemic stroke associated with antiphospholipid syndrome . Neurology 2003; 61: 111–114 .

22.

Ruiz-Irastorza G , Khamashta MA , Hughes GR . Treatment of pregnancy loss in Hughes syndrome: a critical update . Autoimmunity Rev 2002; 1: 298–304 .

23.

Khamashta MA , Shoenfeld Y . Antiphospholipid syndrome: a consensus for treatment? Lupus 2003; 12: 495-495 .

24.

Alargon-Segovia D , Boffa MC , Branch W et al. Prophylaxis of the antiphospholipid syndrome: a consensus report . Lupus 2003; 12: 499–503 .

25.

Miyakis S , Lockshin MD , Astumi T et al. International consensus statement on an update of the classification criteria dor definite antiphospholipid syndrome (APS) . J Thromb Haemost 2006; 4: 295–306 .

26.

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

27.

Lakos G , Kiss E , Regeczy N et al. Isotype distribution and clinical relevance of anti-beta2-glycoprotein I (β2-GPI) antibodies: importance of IgA isotype . Clin Exp Immunol 1999; 117: 574–579 .

28.

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

29.

Sanna G , Bertolaccini ML , Cuadrado MJ et al. Neuropsychiatric manifestations in systemic lupus erythematosus: prevalence and association with antiphospholipid antibodies . J Rheumatol 2003; 30: 985–992 .

30.

Cervera R , Piette JC , Font J et al. for the Euro-Phospholipid Project Group. Antiphospholipid syndrome. Clinical and immunologic manifestations and patterns of disease expression in a cohort of 1000 patients . Arthritis Rheum 2002; 46: 1019–1027 .

31.

Danowski A , Kickler TS , Petri M . Anti-β2-glycoprotein I: Prevalence, clinical correlations, and importance of persistent positivity in patients with antiphospholipid syndrome and systemic lupus ertyhematosus . J Rheumatol 2006; 33: 1775–1779 .

32.

Mari I , Gilburd B , Blank M , Shoenfeld Y . Anti-cariolipin and anti-β2-glycoprotein I (β2GP-I) antibody assays as screening for anti-phospholipid syndrome , Human Antibodies 2003; 12: 57–62 .

33.

Ruiz-Irastorza G , Khamashta MA , Castellino G , Hughes GRV . Systemic lupus erythematosus . Lancet 2001; 357: 1027–1032 .

34.

Shah NM , Khamashta MA , Atsumi T , Hughes GR . Outcome of patients with anticardiolipin antibodies: a 10 year follow-up of 52 patients . Lupus 1998; 7: 3–6 .

35.

Meroni PL , Moia M , Derksen RH et al. Venous thromboembolism in the antiphospholipid syndrome management guidelines for secondary prophylaxis . Lupus 2003; 12: 504–507 .

36.

Brey RL , Chapman J , Leine SR et al. Stroke and the antiphospho-lipid syndrome: consensus meet Taormina 2002 . Lupus 2003; 12: 508–513 .

37.

Lockshin MD , Erkan D . Treatment of antiphospholipid syndrome . N Engl J Med 2003; 349: 1177–1179 .

38.

Asherson RA , Cervera R . The antiphospholipid syndrome: multiple faces beyond the classical presentation . Autoimm Rev 2003; 2: 140–151 .

39.

Tincani A , Branch W , Levy RA et al. Treatment of pregnant patients with antiphospholipid syndrome . Lupus 2003; 12: 524–529 .

40.

Lockshin M , Tenedios F , Petri M et al. Cardiac disease in the antiphospholipid syndrome: recommendations for treatment. Committee consensus report . Lupus 2003; 12: 518–523 .

41.

Galli M , Barbui T . Antiphospholipid antibodies and thrombosis: strength of association . Hematol J 2003; 4: 180–186 .

42.

Zandman-Goddard G , Blank M , Sherer Y et al. 10th International congress on antiphospholipid antibodies – summary . Autoimm Rev 2003; 2: 79–85 .