Risk of venous and arterial thrombosis according to type of antiphospholipid antibodies in adults without systemic lupus erythematosus: a systematic review and meta-analysis

Autoimmun Rev. 2014 Jun;13(6):595-608. doi: 10.1016/j.autrev.2013.11.004. Epub 2014 Jan 11.


Aim: To evaluate the magnitude of venous and arterial thrombosis risk associated with antiphospholipid antibodies (APLs) in adults without systemic lupus erythematosus (SLE).

Methods: Case-control and cohort studies were selected from the MEDLINE and Cochrane Library databases. Two investigators independently extracted data on study design, patient characteristics, venous and arterial events and exposure to APLs, including lupus anticoagulant (LA), anticardiolipin (aCL), anti-β2 Glycoprotein I (β2GpI), anti-prothrombin (aPT), anti-phosphatidyl serine (aPS), and anti-phosphatidyl ethanolamine (aPE).

Results: 30 studies were included (16,441 patients). The odds ratio (OR) for venous thrombosis was 6.14 (95% confidence interval [CI] 2.74-13.8) in LA-positive patients (5 studies, 1650 patients) and 1.46 (CI 1.06-2.03) in aCL-positive patients (12 studies, 5375 patients). None of the associations with more recently identified APLs was significant, but fewer studies were available. For arterial thrombosis, the OR for LA and aCL was 3.58 (CI 1.29-9.92) and 2.65 (CI 1.75-4.00) respectively. The associations between β2GpI, aPT and aPS and the risk of arterial thrombosis were also significant, the OR being 3.12 (CI 1.51-6.44), 2.95 (CI 1.31-6.66) and 6.00 (CI 3.07-11.7), respectively. Owing to the heterogeneity of cut-off values for each APL assay, we were unable to perform any sensitivity analysis to determine the optimal value. The presence of low-quality studies may have led to overestimation of the magnitude of the associations.

Conclusions: LA and aCL were significantly associated with an increased risk of thrombosis, especially arterial, in patients without SLE. Systematic thromboprophylaxis in high-risk patients with APL should be evaluated.

Keywords: Anti-phospholipid antibodies; Antiphospholipid syndrome; Arterial thrombosis; Deep venous thrombosis; Meta-analysis; Pulmonary embolism.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Antibodies, Antiphospholipid / analysis
  • Antibodies, Antiphospholipid / immunology*
  • Antiphospholipid Syndrome / complications
  • Antiphospholipid Syndrome / immunology*
  • Case-Control Studies
  • Cohort Studies
  • Humans
  • Lupus Coagulation Inhibitor
  • Lupus Erythematosus, Systemic / complications
  • Lupus Erythematosus, Systemic / immunology
  • Risk Factors
  • Thrombosis / immunology*
  • beta 2-Glycoprotein I


  • Antibodies, Antiphospholipid
  • Lupus Coagulation Inhibitor
  • beta 2-Glycoprotein I