Beheiri A, Langer C, Düring C, Krümpel A, Thedieck S, Nowak-Göttl U
Department of Paediatric Haematology/Oncology, Univ. Children's Hospital, Münster, Germany.
J Thromb Haemost. 2007 Jun;5(6):1179-84. doi: 10.1111/j.1538-7836.2007.02534.x.
alpha(2)-Macroglobulin (alpha2MG) is a broad-spectrum protease inhibitor that is known to neutralize alpha-thrombin, 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 alpha2MG in children with venous thromboembolism [VTE: paradoxical embolism causing ischemic stroke (IS) or deep-vein thrombosis (DVT)].
alpha2MG 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 alpha2MG and prothrombotic risk factors [factor V G1691A, prothrombin G20210A, raised lipoprotein (a)] between patients and controls and to evaluate the interaction between elevated alpha2MG 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.
alpha2MG 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 alpha2MG levels, with a gradual increase per mg dL(-1). In addition, when elevated alpha2MG 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 alpha2MG levels (IS, 5.9/1.9-18.3; DVT, 7.2/2.1-24.4).
The procoagulant properties of elevated alpha2MG levels independently increase the odds of stroke and DVT in white children.
α2-巨球蛋白（α2MG）是一种广谱蛋白酶抑制剂，已知可中和α-凝血酶、纤溶酶和活化蛋白C，这表明它具有抗凝和促凝特性。本研究旨在评估α2MG在患有静脉血栓栓塞症[VTE：导致缺血性中风（IS）或深静脉血栓形成（DVT）的反常栓塞]儿童中的作用。
将白人患者急性VTE发作后测得的α2MG水平与年龄和性别匹配的健康对照者的数据进行比较。此外，为了比较患者与对照者中α2MG升高率和血栓形成前危险因素[因子V G1691A、凝血酶原G20210A、升高的脂蛋白（a）]，并评估α2MG水平升高与其他血栓形成倾向之间的相互作用，使用逻辑回归模型估计比值比（OR）以及95%置信区间（CI）。该模型针对年龄和纤维蛋白原进行了调整。
患者的α2MG水平显著高于对照者（320/139 - 524对302/109 - 406；P = 0.005）。在患者组（IS n = 103；DVT n = 92）中，随着α2MG水平升高，有症状血栓栓塞的风险显著增加，每毫克分升（-1）逐渐升高。此外，当将α2MG水平>第90百分位数升高与低于临界值的值进行比较时，在多变量分析中纳入既定的血栓形成前危险因素，患者经纤维蛋白原调整的α2MG水平的OR/95%CI显著升高（IS，5.9/1.9 - 18.3；DVT，7.2/2.1 - 24.4）。
α2MG水平升高的促凝特性独立增加了白人儿童中风和DVT的几率。
