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RATIO study: Lupus anticoagulant risk factor for arterial thrombotic events
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Lupus anticoagulants were associated with an elevated risk for myocardial infarction and ischemic stroke in women younger than 50 years.
Researchers enrolled women admitted to various centers with first ischemic stroke or MI between January 1990 and October 1995 into the Risk of Arterial Thrombosis in Relation to Oral Contraceptives (RATIO) study.
There were 175 participants with ischemic stroke, 203 with MI and 628 controls. Three percent (OR=5.3; 95% CI, 1.4-20.8) of participants with MI, 17% (OR=43.1; 95% CI, 12.2-152.0) with ischemic stroke and 0.6% in the control group had lupus anticoagulant.
Among women with lupus anticoagulant, the OR for MI increased to 21.6 (95% CI, 1.9-242.0) for women who used oral contraceptives and 33.7 (95% CI, 6.0-189.0) for women who smoked. The OR for ischemic stroke increased to 201.0 (95% CI, 22.1-1,828.0) in women who used oral contraceptives and 87.0 (95% CI, 14.5-523.0) in women who smoked.
The risk for ischemic stroke was 2.3 (95% CI, 1.4-3.7) in women with anti-beta 2-glycoprotein I antibodies, whereas the risk for MI was unaffected. Lupus anticoagulant plus any additional antiphospholipid antibody subpopulation did not affect the risk for MI or ischemic stroke, according to researchers.
“Further standardization and reporting of antiphospholipid antibodies assays for research and diagnostic purposes is imperative,” Kathryn Kirchoff-Torress, MD, Senior Vascular Neurology Fellow, and Steven R. Levine, MD, Professor of Neurology, Mount Sinai School of Medicine in New York, said in an accompanying editorial.
“Thrombosis associated with antiphospholipid antibodies is a heterogeneous disorder, and accurate risk assessment is essential for formulation of patient-centered prognosis and treatment,” they said. – by Christen Haigh
Urbanus RT. Lancet Neurol. 2009;doi:10.1016/S1474-4422(09)70239-X.
The consequences of having antiphospholipid antibodies range from mere laboratory curiosity to life- and limb-threatening venous or arterial thrombosis and pregnancy complications such as recurrent fetal loss. The mechanisms underlying these protean clinical manifestations and those that drive the synthesis of antiphospholipid antibodies remain poorly understood.
The study by Urbanus et al lends additional support to the already established view that lupus anticoagulant, and to a lesser extent beta-2-glycoprotein I antibodies, are risk factors for arterial thrombosis, at least in younger women. Like many similar studies, the degree to which these findings can be applied to other patient groups is unknown.
More importantly, however, this study emphasizes the powerful synergistic interaction that may exist between multiple thrombotic risk factors within an individual patient. Clinicians should be mindful of the fact that both arterial and venous thrombosis are multifactorial conditions, and there may thus be a number of potential interventions that could help reduce the risk for thrombotic events.
In the accompanying editorial, Kirchoff-Torres and Levine point out a notable methodological shortcoming of this study. Because subjects were tested only once for antiphospholipid antibodies, and the testing could have been done up to several years after the thrombotic event, it is impossible to know with certainty whether or not the antiphospholipid antibodies were present at the time of the event, or whether the antiphospholipid antibodies were transient or persistent over time. The clinical significance of transient antiphospholipid antibodies and those that occur not in association with a thrombotic event is unclear.
– Mark T. Reding, MD
Director, Center for Bleeding and Clotting Disorders, University of Minnesota, Minneapolis