Summary. Objective: a 2 -Macroglobulin (a2MG) is a broadspectrum protease inhibitor that is known to neutralize athrombin, plasmin, and activated protein C, which suggests that it has anticoagulant as well as procoagulant properties. The present study was conducted to evaluate the role of a2MG in children with venous thromboembolism [VTE: paradoxical embolism causing ischemic stroke (IS) or deep-vein thrombosis (DVT)]. Methods: a2MG levels measured after acute VTE onset in white patients were compared with data obtained from age-and gender-matched healthy controls. In addition, to compare the rate of elevated a2MG and prothrombotic risk factors [factor V G1691A, prothrombin G20210A, raised lipoprotein (a)] between patients and controls and to evaluate the interaction between elevated a2MG levels and other thrombophilias, odds ratios (ORs) together with 95% confidence intervals (CIs) were estimated using a logistic regression model. The model was adjusted for age and fibrinogen. Results: a2MG levels were significantly higher in patients than in controls (320/139-524 vs. 302/109-406; P = 0.005). In the group of patients (IS n = 103; DVT n = 92), the risk of symptomatic thromboembolism was significantly increased with elevated a2MG levels, with a gradual increase per mg dL )1. In addition, when elevated a2MG levels > 90th percentile were compared with values below the cut-off, including established prothrombotic risk factors in the multivariate analysis, patients had a significantly increased OR/95% CI for fibrinogen-adjusted a2MG levels (IS, 5.9/1.9-18.3; DVT, 7.2/2.1-24.4). Conclusions: The procoagulant properties of elevated a2MG levels independently increase the odds of stroke and DVT in white children.
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