Lupus anticoagulants and anti-phospholipid antibodies as risk factors for a first episode of ischemic stroke.

Abstract

Antiphospholipid antibodies (aPLA) and lupus anticoagulant (LAC) were shown to precipitate thromboembolic events. Their association with ischemic stroke remains to be seen. We investigated the contribution of LAC, and antibodies directed against the phospholipids cardiolipin (aCL), phosphatidylserine (aPS), and the phospholipid-dependent cofactors beta2-glycoprotein I and annexin V, to the risk for ischemic stroke. LAC and antibody levels were measured in 208 stroke patients and 203 age- and gender-matched control subjects. Positive LAC resulted in an increased risk for stroke [OR (95% CI) = 8.1 (2.4-27.5)]. Significant elevation in aPS IgG, aCL IgM and aCL IgG titers, and increased prevalence of elevated aPS IgG, aCL IgM and aCL IgG (based on P95 cutoff values of healthy individuals) were seen in patients. aPS IgG was associated with cardioembolic, whereas aCL IgG and IgM were elevated in lacunar, atherosclerotic and cardioembolic, and LAC positivity was documented only in lacunar stroke subtypes. The co-presence of LAC with a positive aCL IgM/IgG or aPS IgG did not affect the overall risk for stroke. Multivariate analysis confirmed the association of positive LAC with stroke [aOR (95% CI) = 9.7 (1.8-52.5)], and demonstrated a clear gradation of increasing risk of stroke associated with the four categories of aCL IgG and aPS IgG, and identified aCL IgM P95 as independent predictors of stroke after adjusting for potentially confounding covariates. Our study demonstrates that the presence of LAC, and elevated aCL IgG and aPS IgG antibodies are risk factors for stroke.