Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature

Abstract

To formally establish the risk of lupus anticoagulants and anticardiolipin antibodies for arterial and venous thrombosis, we ran a MEDLINE search of the literature from 1988 to 2000. Studies were selected for their case-control (11), prospective (9), cross-sectional (3), and ambispective (2) design. They provided or enabled us to calculate the odds ratio with 95% confidence interval (CI) of lupus anticoagulants and/or anticardiolipin antibodies for thrombosis in 4184 patients and 3151 controls. Studies were grouped according to the antibody investigated. Five studies compared lupus anticoagulants with anticardiolipin antibodies: the odds ratio with 95% CI of lupus anticoagulants for thrombosis was always significant. None of them found anticardiolipin antibodies were associated with thrombosis. Four studies analyzed only lupus anticoagulants: the odds ratio with 95% CI was always significant. The risk of lupus anticoagulants was independent of the site and type of thrombosis, the presence of systemic lupus erythematosus, and the coagulation tests employed to detect them. Sixteen studies served to assess 28 associations between anticardiolipin antibodies and thrombosis: the odds ratio with 95% CI was significant in 15 cases. Anticardiolipin titer correlated with the odds ratio of thrombosis. In conclusion, the detection of lupus anticoagulants and, possibly, of immunoglobulin G (IgG) anticardiolipin antibodies at medium or high titers helps to identify patients at risk for thrombosis. However, to take full advantage of the conclusions provided by the available evidence, there is an urgent need to harmonize investigational methods. IntroductionAntiphospholipid antibodies are a heterogeneous family of immunoglobulins that includes, among others, lupus anticoagulants and anticardiolipin antibodies. Lupus anticoagulants behave as acquired inhibitors of coagulation, prolonging phospholipid-dependent in vitro coagulation tests, 1 and anticardiolipin antibodies are measured by immunoassay, utilizing cardiolipin or other anionic phospholipids in solid phase. 2 Despite their name, antiphospholipid antibodies do not recognize phospholipids, but plasma proteins bound to suitable anionic (not necessarily phospholipid) surfaces. Among these, ␤ 2 -glycoprotein I 3,4 and prothrombin 5 are the most widely investigated antigenic targets. Most anticardiolipin antibodies need ␤ 2 -glycoprotein I to react with cardiolipin in immunoassays. 4 Specific subgroups of anti-␤ 2 -glycoprotein I 6 and antiprothrombin 7 antibodies are responsible for the lupus anticoagulant activity in phospholipid-dependent coagulation tests. Clinical interest in antiphospholipid antibodies is due to their relation with arterial and venous thrombosis in the antiphospholipid syndrome. Two forms of antiphospholipid syndrome have been described: a "primary" syndrome, 8 with no evidence of an underlying disease, and a "secondary" syndrome, mainly in the setting of systemic lupus erythematosus. 9 Thromboembolic events are reported in approximately one third of a...

Thrombotic recurrences and bleeding events in APS vascular patients: A review from the literature and a comparison with the APS Piedmont Cohort

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Aspirin for primary thrombosis prevention in the antiphospholipid syndrome: A randomized, double‐blind, placebo‐controlled trial in asymptomatic antiphospholipid antibody–positive individuals

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The antiphospholipid syndrome: a large elephant with many parts or an elusive chameleon disguised by many colours?

“…aCL and anti-β2GPI). The differing sensitivity and specificity of the liquid-phase and solid-phase aPL assays for clinical features of APS [37,38] may thus affect the likelihood of APS being diagnosed.…”