Meta-analysis of the risk of venous thrombosis in individuals with antiphospholipid antibodies without underlying autoimmune disease or previous thrombosis

Abstract

Patients with systemic lupus erythematosus (SLE) and antiphospholipid antibodies (aPL) are at a greater risk for venous thromboembolism (VTE) than SLE patients without these antibodies. For patients without SLE there is a controversy about the risk associated with these antibodies and about their prognostic significance. We reviewed the degree of evidence and describe the odds ratio for VTE associated with aPL, namely the lupus anticoagulant (LA) and anticardiolipin antibodies (aCL), in patients without SLE. The study was a meta-analysis of seven observational studies of risk for antiphospholipid associated venous thromboembolism (VTE), excluding SLE patients. The strategies to identify published research included a computerized literature search and the review of citations in primarily relevant articles for the period 1983 to 1997. A summary of study characteristics and a critical appraisal of study quality were done. Summary odds ratios were obtained conducted using a random and a fixed effects-model. The overall odds ratio for aCL associated VTE obtained by fixed-effects model was 1.56 (95% CI, 1.10—2.24) and 1.64 (95% CI, 0.93—2.89) by random-effects model. The heterogeneity of these results appeared to be due in part to the detection limit of the aCL assay: the odds ratio was 3.21 (95% CI, 1.11—9.28) with both models when high titres only were considered. The overall odds ratio for LA associated VTE was 11.1 (95% CI, 3.81—32.3). In conclusion meta-analysis of the risk for antiphospholipid associated thrombosis demonstrated a higher risk in patients with the LA than in other patients. This risk was also higher than in patients with aCL even when high titres only were considered.

Keywords

anticardiolipin antibodies lupus anticoagulant antiphospholipid antibodies Hughes' syndrome venous thrombosis

Get full access to this article

View all access options for this article.

References

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

Khamashta MA , Asherson RA . Hughes syndrome: antiphospholipid antibodies move closer to thrombosis in 1994 . Br J Rheum 1995; 34: 493–497 .

Gharavi AE , Wilson WA . The syndrome of thrombosis, thrombocytopenia, and recurrent spontaneous abortions associated with antiphospholipid antibodies: Hughes syndrome . Lupus 1996; 5: 343–344 .

Asherson RA et al. The ‘primary’ antiphospholipid syndrome: major clinical and serological features . Medicine (Balt) 1989; 68: 366–374 .

Derksen RHWM , De Groot PG , Kater L , Nieuwenhuis HK . Patients with antiphospholipid antibodies and venous thrombosis should receive long term anticoagulant treatment . Ann Rheum Dis 1993; 52: 689–692 .

Khamashta MA et al. The management of thrombosis in the antiphospholipid-antibody syndrome . N Engl J Med 1995; 332: 993–997 .

Rosove MH , Brewer PMC . Antiphospholipid thrombosis: clinical course after the first thrombotic event in 70 patients . Ann Intern Med 1992; 117: 303–308 .

Horbach DA et al. Lupus anticoagulant is the strongest risk factor for both venous and arterial thrombosis in patients with systemic lupus erythematosus . Thromb Haemost 1996; 76: 916–924 .

Puurunen M , Vaarala O , Julkunen H , Aho K , Palosuo T . Antibodies to phospholipid-binding plasma proteins and occurence of thrombosis in patients with systemic lupus erythematosus . Clin Immunol Immunopathol 1996; 80: 16–22 .

10.

Wahl DG et al. Risk for venous thrombosis related to antiphospholipid antibodies in systemic lupus erythematosus: a meta-analysis . Lupus 1997; 6: 467–473 .

11.

Ginsburg KS et al. Anticardiolipin antibodies and the risk for ischemic stroke and venous thrombosis . Ann Intern Med 1992; 117: 997–1002 .

12.

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

13.

Oger E et al. Association between IgM anticardiolipin antibodies and deep venous thrombosis in patients without systemic lupus erythematosus . Lupus 1997; 6: 455–461 .

14.

McCrae KR . Antiphospholipid associated thrombosis: a consensus for treatment? Lupus 1996; 5: 560–570 .

15.

Cook DJ , Guyatt GH , Laupacis A , Sackett DL , Goldberg RJ . Clinical recommendations using levels of evidence for antithrombotic agents . Chest 1995; 108: 227S–30S .

16.

Gabriel SE , Jaakkimainen L , Bombardier C . Risk for serious gastrointestinal complications related to use of nonsteroidal antiinflammatory drugs . A meta-analysis. Ann Intern Med 1991; 115: 787–796 .

17.

Thiagarajan P , Pengo V , Shapiro SS . The use of the dilute Russell viper venom time for the diagnosis of lupus anticoagulants . Blood 1986; 68: 869–874 .

18.

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

19.

Triplett DA . Assays for detection of antiphospholipid antibodies . Lupus 1994; 3: 281–287 .

20.

Loizou S et al. Measurement of anticardiolipin antibodies by an enzyme linked immunosorbent assay (ELISA): standardization and quantitation of results . Clin Exp Immunol 1986; 62: 738–745 .

21.

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

22.

Harris EN . The second international anticardiolipin standardization workshop/the Kingston antiphospholipid antibody study (KAPS) group . Am J Clin Pathol 1990; 94: 476–484 .

23.

Harris EN . Anticardiolipin wet workshop report. Fifth International Symposium on Antiphospholipid Antibodies . Am J Clin Pathol 1994; 101: 616–624 .

24.

Gardner MJ , Gardner S , Winter PD . Confidence interval analysis (CIA). Microcomputer program manual. London: BMJ Publishing Group , 1992.

25.

DerSimonian R , Laird N . Meta-analysis in clinical trials . Controlled Clin Trials 1986; 7: 177–188 .

26.

Greenland S . Quantitative methods in the review of epidemiologic literature . Epidemiol Rev 1987; 9: 1–30 .

27.

Breslow NE , Day NE . Statistical Methods in Cancer Research, Vol. 1. The Analysis of Case-Control Studies. Davis W. Lyon: IARC , 1980.

28.

Gahlinger PM , Abramson JH . Computer Programs for Epidemiologic Analysis. PEPI Version 2. Stone Mountain, Georgia: USD Inc , 1995.

29.

Simioni P et al. Deep venous thrombosis and lupus anticoagulant. A case-control study . Thromb Haemost 1996; 76: 187–189 .

30.

Bongard O , Reber G , Bounameaux H , de Moerloose P . Anticardiolipin antibodies in acute venous thromboembolism . Thromb Haemost 1992; 67: 724–724 .

31.

Fijnheer R , de Valk B , Punt J , Muller HP . Antiphospholipid antibodies in patients with thromboembolic disease: a prospective controlled study . Lupus 1994; 3: 361–361 .

32.

Simioni P et al. Lupus anticoagulant and antiphospholipid antibodies in outpatients with clinically suspected DVT . Lupus 1994; 3: 361–361 .

33.

Reber G et al. Multicenter evaluation of nine commercial kits for the quantitation of anticardiolipin antibodies . Thromb Haemost 1995; 73: 444–452 .

34.

Piette JC . 1996 diagnostic and classification criteria for the antiphospholipid/cofactors syndrome: a ‘mission impossible?’ Lupus 1996; 5: 354–363 .

35.

Galli M et al. Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor . Lancet 1990; 335: 1544–1547 .

36.

Violi F , Ferro D , Valesini G . Thrombosis in the antiphospholipid syndrome . N Engl J Med 1995; 333: 665–665 .