title: The factor V Leiden mutation, high factor VIII, and high plasminogen activator inhibitor activity: etiologies for sporadic miscarriage.
abstract: 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 < .0001). Plasminogen activator inhibitor activity was high (> or =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 [< or =150%, >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 = .01). 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.
authors.affiliation: Cholesterol Center, Department of Medicine, Jewish Hospital of Cincinnati, Cincinnati, OH 45229, USA. glueckch@healthall.com
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Glueck
authors.forename: Joel
authors.initials: J
authors.lastname: Pranikoff
authors.forename: Dawit
authors.initials: D
authors.lastname: Aregawi
authors.forename: Mofiz
authors.initials: M
authors.lastname: Haque
authors.forename: Binghua
authors.initials: B
authors.lastname: Zhu
authors.forename: Trent
authors.initials: T
authors.lastname: Tracy
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
mesh_terms: D000022:Abortion, Spontaneous / Q000097:blood / Q000209:etiology* / Q000235:genetics; D015992:Body Mass Index; D005165:Factor V / Q000235:genetics*; D005169:Factor VIII / Q000032:analysis*; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D009154:Mutation; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D011247:Pregnancy; D019851:Thrombophilia / Q000150:complications
chemical_list: D017395:Plasminogen Activator Inhibitor 1; C095381:factor V Leiden; D005165:Factor V; D005169:Factor VIII