Abstract
Background: Antibodies binding to domain I of beta(2)-glycoprotein I (aDI) and activated protein C (APC) resistance are associated with an increased risk of thrombosis in cross-sectional studies. The objective of this study was to assess their predictive value for future thromboembolic events in patients with antiphospholipid antibodies (aPL) or antiphospholipid syndrome.
Methods: This prospective multicenter cohort study included consecutive patients with aPL or systemic lupus erythematosus. We followed 137 patients (43.5 +/- 15.4 year old; 107 women) for a mean duration of 43.1 +/- 20.7 months.
Results: We detected aDI IgG antibodies by ELISA in 21 patients. An APC sensitivity ratio (APCsr) was determined using a thrombin generation-based test. The APCsr was higher in patients with anti-domain I antibodies demonstrating APC resistance (0.75 +/- 0.13 vs 0.48 +/- 0.20, P <0.0001). In univariate analysis, the hazard ratio (HR) for thrombosis over time was higher in patients with aDI IgG (3.31 [95% CI, 1.15-9.52]; P = 0.03) and patients with higher APC resistance (APCsr >95th percentile; HR, 6.07 [95% CI, 1.69-21.87]; P = 0.006). A sensitivity analysis showed an increased risk of higher aDI IgG levels up to HR 5.61 (95% CI, 1.93-16.31; P = 0.01). In multivariate analysis, aDI IgG (HR, 3.90 [95% CI, 1.33-11.46]; P = 0.01) and APC resistance (HR, 4.98 [95% CI, 1.36-18.28]; P = 0.02) remained significant predictors of thrombosis over time.
Conclusions: Our study shows that novel tests for antibodies recognizing domain I of beta(2)-glycoprotein I and functional tests identifying APC resistance are significant predictors of thrombosis over time and may be useful for risk stratification.
Original language | English |
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Pages (from-to) | 1242-1252 |
Number of pages | 11 |
Journal | Journal of Applied Laboratory Medicine |
Volume | 5 |
Issue number | 6 |
DOIs | |
Publication status | Published - Nov 2020 |
Keywords
- CLASSIFICATION CRITERIA
- LUPUS ANTICOAGULANTS
- REVISED CRITERIA
- 1ST EPISODE
- RISK
- GENERATION
- STANDARDIZATION
- AUTOANTIBODIES
- ASSOCIATION
- RECOGNIZE