Risk Factors for Thrombosis and the Beneficial Effect of Aspirin in Patients with Antiphospholipid Antibodies (aPL).

Introduction: Some subjects with aPL remain healthy while others develop thrombosis. We hypothesize that coexisting risk factors (inherited or acquired) may influence the incidence and rate of arterial and venous thrombosis in these individuals.

Methods: After institutional review aboard approval, subjects with two positive aPL tests (lupus anticoagulant, IgG or IgM anticardiolipin antibodies) at least 3 weeks apart were identified and invited to participate in a one-time study visit conducted at three medical centers. Consenting subjects were interviewed and/or their medical chart reviewed for definitive evidence of thrombotic events and documentation of risk (inherited and acquired) factors thought to determine outcome (thrombosis) in aPL. Inherited risk factor evaluation included testing for Factor V Leiden (FVL), prothrombin gene (3′PTG) and methyltetrahydrofolate reductase (MTHFR) gene polymorphisms. Acquired risk factors evaluated included estrogen therapy, hypertension, hyperlipidemia, tobacco use, and diabetes mellitus. In addition, subjects were also queried regarding the use of daily aspirin, non-steroidal anti-inflammatory agents, and/or hydroxychloroquine, currently and at the time of thrombosis; subjects without thrombosis were contacted one year later to document if any thrombotic events had occurred in the interim. Statistical analysis included the chi-square test of significance, and summary odds ratios (OR) for venous and arterial thrombosis calculated using the Mantel-Haenszel method.

Results: 222 patients (157 females, 65 males) with aPL were included in our multi-center study. 83/222 (37.4%) patients with aPL had venous thromboembolic disease (VTE), and 90/222 (40.5%) subjects had documented evidence of arterial thrombosis. In patients with aPL and VTE, the presence of either FVL or 3′PTG polymorphism was associated with a higher risk of thrombosis (OR: 2.88, 95% CI: 1.01–8.24; p < 0.05, chi-square). No specific acquired risk factors for venous thrombosis were identified. In contrast, significant risk factors for arterial thrombosis included hypertension, hyperlipidemia, and tobacco use, with an OR (95% CI) of 3.57 (1.78–7.17), 3.45 (1.61–7.38) and 2.35 (1.12–4.93) respectively, and inherited hypercoagulable states were not associated with an increased incidence of arterial thrombosis. Furthermore, daily aspirin intake appeared to have a favorable impact on the risk of venous (OR (benefit): 0.04, 95% CI: 0.01–0.3; p = 0.002, chi-square) and arterial thrombotic events (OR (benefit): 0.42, 95% CI: 0.19–0.96; p = 0.01, chi-square).

Conclusions: These results confirm our earlier finding that inherited thrombophilic states (FVL and 3′PTG) confer an additional risk of VTE in patients with aPL, and that hypertension, hyperlipidemia, and tobacco use appear to be risk factors for arterial thrombosis. In addition, aspirin use appears to protect from both venous and arterial thrombosis in patients with aPL. Awaiting future controlled trials aimed at evaluating the independent beneficial effect of aspirin, our results suggest that patients with aPL should be encouraged to take a daily aspirin, and adhere to optimal antihypertensive therapy, smoking cessation, and cholesterol lowering measures. Such disease modifying strategies may decrease their incidence of venous and arterial thrombotic events.