The factor V Leiden mutation, high factor VIII, and high plasminogen activator inhibitor activity: etiologies for sporadic miscarriage

The factor V Leiden mutation, high factor VIII, and high plasminogen activator inhibitor activity: etiologies for sporadic miscarriage
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DOI:
10.1016/j.metabol.2005.04.024
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发表时间:
2005-10-01
影响因子:
9.8
通讯作者:
Wang, P
Wang, P
中科院分区:
医学1区
文献类型:
--
作者:
Glueck, CJ;Pranikoff, J;Wang, P

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我们假设,血栓形成性G1691 A因子V莱顿基因突变是一个常见的显着原因散发性妊娠早期流产。我们比较了92例(85例白色,5例黑人,2例其他)有1次或1次以上妊娠和1次流产(143例活产,92例流产)的女性(病例)和380例(355例白色,21例黑人,4例其他)有1次或1次以上妊娠和0次流产(964例活产)的女性对照组(355例白人,21例黑人,4例其他)的血栓形成和低纤溶。我们使用聚合酶链反应技术来表征血栓形成基因突变(G1691 A V Leiden [FV],G20210 A凝血酶原,C677 T/A1298 C MTHFR)和低纤溶基因突变(纤溶酶原激活物抑制剂[派-1]活性4G 4G)。我们进行了血栓形成倾向(同型半胱氨酸、抗心磷脂抗体[ACLA]免疫球蛋白G和免疫球蛋白M、狼疮抗凝剂、因子VIII、因子XI、蛋白C、总蛋白和游离蛋白S、抗凝血酶III)和低纤维蛋白溶解(纤溶酶原激活物抑制剂活性[PAI-Fx]、脂蛋白[a])的血清学测量。在380例对照中,6例(1.6%)具有FV杂合性,12例杂合和2例纯合FV病例(15.2% [14/92]; P = 21.1 U/mL),63例病例中有21例(33%),152例对照中有27例(18%)(P = 0.013)。48例病例中有15例(31%)的因子VIII较高(> 150%),而103名对照中有19例(18%)(P = 0.079)。通过Logistic回归分析,以年龄和因子VIII(分类[ 150%])为解释变量,以组(病例,对照)为因变量,校正年龄后,高因子VIII是流产的重要预测因子(比值比,3.28; 95%置信区间,1.34-8.04; P = 0.01)。在血栓形成倾向和低纤溶指标方面无其他组间差异(P > 0.05)。在不明原因的早期散发性流产后,我们建议测量FV突变、PAI-Fx和VIII因子,这些因素是散发性流产的病因。(c)2005年爱思唯尔公司All rights reserved.
We hypothesized that the thrombophilic G1691A factor V Leiden gene mutation was a common significant cause of sporadic first trimester miscarriage. We compared thrombophilia and hypofibrinolysis in 92 women (85 white, 5 black, 2 other) with 1 or more pregnancies and 1 miscarriage (143 live births, 92 miscarriages) (cases) and in 380 female controls (355 white, 21 black, 4 other) with 1 or more pregnancies and 0 miscarriages (964 live births). We used polymerase chain reaction techniques to characterize thrombophilic gene mutations (G1691A V Leiden [FV], G20210A prothrombin, C677T/A1298C MTHFR) and hypofibrinolytic gene mutations (plasminogen activator inhibitor [PAI-1] activity 4G4G). We carried out serologic measures of thrombophilia (homocysteine, anticardiolipin antibodies [ACLA] immunoglobulin G and immunoglobulin M, lupus anticoagulant, factor VIII, factor XI, protein C, total and free protein S, antithrombin III) and hypofibrinolysis (plasminogen activator inhibitor activity [PAI-Fx], lipoprotein[a]). Of the 380 controls, 6 (1.6%) had FV heterozygosity vs 12 heterozygous and 2 homozygous FV cases (15.2% [14/92]; P = 21.1 U/mL) in 21 (33%) of 63 cases vs 27 (18%) of 152 controls (P =.013). Factor VIII was high (> 150%) in 15 (31%) of 48 cases vs 19 (18%) of 103 controls (P =.079). By logistic regression, with age and factor VIII (categorical [ 150%]) as explanatory variables and group (cases, controls) as the dependent variable, after adjusting for age, high factor VIII was a significant predictor for miscarriage (odds ratio, 3.28; 95% confidence interval, 1.34-8.04; P =.0 1). There were no other group differences (P >.05) in measures of thrombophilia and hypofibrinolysis. After unexplained sporadic first trimester miscarriage, we suggest that measurements be done of the FV mutation, PAI-Fx, and factor VIII, etiologies for sporadic miscarriage. (c) 2005 Elsevier Inc. All rights reserved.