RESUMO
BACKGROUND: Aspirin and low-molecular-weight heparin are prescribed for women with unexplained recurrent miscarriage, with the goal of improving the rate of live births, but limited data from randomized, controlled trials are available to support the use of these drugs. METHODS: In this randomized trial, we enrolled 364 women between the ages of 18 and 42 years who had a history of unexplained recurrent miscarriage and were attempting to conceive or were less than 6 weeks pregnant. We then randomly assigned them to receive daily 80 mg of aspirin plus open-label subcutaneous nadroparin (at a dose of 2850 IU, starting as soon as a viable pregnancy was demonstrated), 80 mg of aspirin alone, or placebo. The primary outcome measure was the live-birth rate. Secondary outcomes included rates of miscarriage, obstetrical complications, and maternal and fetal adverse events. RESULTS: Live-birth rates did not differ significantly among the three study groups. The proportions of women who gave birth to a live infant were 54.5% in the group receiving aspirin plus nadroparin (combination-therapy group), 50.8% in the aspirin-only group, and 57.0% in the placebo group (absolute difference in live-birth rate: combination therapy vs. placebo, -2.6 percentage points; 95% confidence interval [CI], -15.0 to 9.9; aspirin only vs. placebo, -6.2 percentage points; 95% CI, -18.8 to 6.4). Among 299 women who became pregnant, the live-birth rates were 69.1% in the combination-therapy group, 61.6% in the aspirin-only group, and 67.0% in the placebo group (absolute difference in live-birth rate: combination therapy vs. placebo, 2.1 percentage points; 95% CI, -10.8 to 15.0; aspirin alone vs. placebo -5.4 percentage points; 95% CI, -18.6 to 7.8). An increased tendency to bruise and swelling or itching at the injection site occurred significantly more frequently in the combination-therapy group than in the other two study groups. CONCLUSIONS: Neither aspirin combined with nadroparin nor aspirin alone improved the live-birth rate, as compared with placebo, among women with unexplained recurrent miscarriage. (Current Controlled Trials number, ISRCTN58496168.)
Assuntos
Aborto Habitual/prevenção & controle , Anticoagulantes/uso terapêutico , Aspirina/uso terapêutico , Nadroparina/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Adulto , Anticoagulantes/efeitos adversos , Aspirina/efeitos adversos , Contusões/induzido quimicamente , Quimioterapia Combinada/efeitos adversos , Feminino , Humanos , Nascido Vivo , Nadroparina/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Gravidez , Falha de Tratamento , Adulto JovemRESUMO
High levels of thrombin-activatable fibrinolysis inhibitor (TAFI) are a supposed risk factor for thrombosis. However, results from previous studies are conflicting. We assessed the absolute risk of venous and arterial thromboembolism in subjects with high TAFI levels (>126 U/dl) versus subjects with normal levels, and the contribution of other concomitant thrombophilic defects. Relatives from four identical cohort studies in families with either deficiencies of antithrombin, protein C or protein S, prothrombin 20210A, high factor VIII levels, or hyperhomocysteinemia were pooled. Probands were excluded. Of 1,940 relatives, 187 had high TAFI levels. Annual incidences of venous thromboembolism were 0.23% in relatives with high TAFI levels versus 0.26% in relatives with normal TAFI levels (adjusted relative risk [RR] 0.8; 95% confidence interval [CI], 0.5-1.3). For arterial thrombosis these were 0.31% versus 0.23% (adjusted RR 1.4; 95% CI, 0.9-2.2). High levels of factor VIII, IX and XI were observed more frequently in relatives with high TAFI levels. Only high factor VIII levels were associated with an increased risk of venous and arterial thrombosis, independently of TAFI levels. None of these concomitant defects showed interaction with high TAFI levels. High TAFI levels were not associated with an increased risk of venous and arterial thromboembolism in thrombophilic families.
Assuntos
Carboxipeptidase B2/sangue , Doença da Artéria Coronariana/etiologia , Doenças Vasculares Periféricas/etiologia , Tromboembolia/etiologia , Trombofilia/complicações , Tromboembolia Venosa/etiologia , Adulto , Estudos de Coortes , Doença da Artéria Coronariana/enzimologia , Doença da Artéria Coronariana/epidemiologia , Fator IX/metabolismo , Fator VIII/metabolismo , Fator XI/metabolismo , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Doenças Vasculares Periféricas/enzimologia , Doenças Vasculares Periféricas/epidemiologia , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Tromboembolia/enzimologia , Tromboembolia/epidemiologia , Trombofilia/enzimologia , Trombofilia/epidemiologia , Regulação para Cima , Tromboembolia Venosa/enzimologia , Tromboembolia Venosa/epidemiologiaAssuntos
Proteínas de Transporte/sangue , Perda do Embrião/sangue , Perda do Embrião/etiologia , Morte Fetal/sangue , Morte Fetal/etiologia , Complicações Hematológicas na Gravidez/sangue , Trombofilia/sangue , Trombofilia/complicações , Adolescente , Adulto , Estudos de Coortes , Perda do Embrião/genética , Feminino , Morte Fetal/genética , Humanos , Pessoa de Meia-Idade , Gravidez , Complicações Hematológicas na Gravidez/genética , Estudos Retrospectivos , Fatores de Risco , Trombofilia/genética , Tromboembolia Venosa/sangue , Tromboembolia Venosa/complicações , Tromboembolia Venosa/genética , Adulto JovemRESUMO
OBJECTIVE: To estimate whether parental thrombophilic defects after fetal death, either acquired or inherited, were more prevalent than in the normal population and to estimate associations between these thrombophilic defects and different fetal death causes. METHODS: In a multicenter, prospective cohort study of 750 fetal deaths, we tested couples for antithrombin, protein C, total and free protein S, and von Willebrand factor (vWF) plasma levels. Mothers' values were compared with reference values in gestational age-matched healthy pregnant women, and fathers were compared with healthy men. Prevalence of factor V Leiden, prothrombin G20210A mutation, and lupus anticoagulant were compared with the normal population. A panel classified death cause. RESULTS: More women with fetal death had decreased antithrombin (16.8%, P<.001) and protein C (4.0%, P=.03) and increased vWF (15.5%, P<.001) plasma levels than healthy pregnant women (2.5%). However, compared with normal ranges in the nonpregnant population, we only observed more women with increased vWF (12.4%, P<.001). More fathers had decreased free protein S (6.3%, P<.001) and elevated vWF (12.1%, P<.001) than healthy men (2.5%). Prevalence of inherited thrombophilias was not higher in couples with fetal death than in the population. Neither inherited nor acquired maternal or paternal thrombophilic defects were associated with the main cause of death. Of placental causes, abruption and infarction were associated with acquired maternal defects. CONCLUSION: Except for vWF and paternal free protein S, acquired and inherited thrombophilic defects were not more prevalent after fetal death. Routine thrombophilia testing after fetal death is not advised. LEVEL OF EVIDENCE: II.
Assuntos
Morte Fetal/etiologia , Trombofilia/complicações , Feminino , Humanos , Pais , Gravidez , Prevalência , Estudos Prospectivos , Proteína S/análise , Trombofilia/sangue , Fator de von Willebrand/análiseRESUMO
Hereditary thrombophilia is associated with an increased risk of fetal loss. Assuming that fetal loss is due to placental thrombosis, anticoagulant treatment might improve pregnancy outcome. In an observational family cohort study, we prospectively assessed the effects of anticoagulant drugs on fetal loss rates in women with hereditary deficiencies of antithrombin, protein C or protein S. The cohort contained 376 women (50 probands and 326 deficient or non-deficient relatives). Probands were consecutive deficient patients with venous tromboembolism. Thromboprophylaxis during pregnancy was recommended in deficient women, irrespective of prior venous thromboembolism, and in non-deficient women with prior venous thromboembolism. Outcome of first pregnancy was analysed in 55 eligible women. Of 37 deficient women, 26 (70%) received thromboprophylaxis during pregnancy, compared with three of 18 (17%) non-deficient women. Fetal loss rates were 0% in deficient women with thromboprophylaxis versus 45% in deficient women without (P = 0.001) and 7% in non-deficient women without thromboprophylaxis (P = 0.37). The adjusted relative risk of fetal loss in women who received thromboprophylaxis versus women who did not was 0.07 (95% confidence interval 0.001-0.7; P = 0.02). Our data suggest that anticoagulant treatment during pregnancy reduces the high fetal loss rate in women with hereditary deficiencies of antithrombin, protein C or protein S.
Assuntos
Anticoagulantes/uso terapêutico , Transtornos Herdados da Coagulação Sanguínea/tratamento farmacológico , Morte Fetal/prevenção & controle , Complicações Hematológicas na Gravidez/tratamento farmacológico , Trombofilia/tratamento farmacológico , Adolescente , Adulto , Antitrombinas/deficiência , Feminino , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Pessoa de Meia-Idade , Gravidez , Cuidado Pré-Natal/métodos , Estudos Prospectivos , Deficiência de Proteína C/tratamento farmacológico , Deficiência de Proteína S/tratamento farmacológico , Tromboembolia/prevenção & controle , Resultado do Tratamento , Trombose Venosa/prevenção & controleRESUMO
Pregnancy is associated with an increased risk of venous thromboembolism, which probably varies according to the presence of single or multiple thrombophilic defects. This retrospective family cohort study assessed the risk of venous thromboembolism during pregnancy and puerperium, and the contribution of concomitant thrombophilic defects in families with hereditary antithrombin, protein C or protein S deficiencies. Probands were excluded. Of 222 female relatives, 101 were deficient and 121 non-deficient. Annual incidences of venous thromboembolism were 1.76% in deficient women versus 0.19% in non-deficient women [adjusted relative risk (RR) 11.9; 95% confidence interval (CI), 3.9-36.2]. Other single and multiple thrombophilic defects increased the risk in deficient women from 1.55% to 2.14% and 2.92%, and in non-deficient women from 0.16% to 0.09% and 0.54% respectively. Deficient women were at lower risk (1.37%; 0.80-2.19) than deficient women that had never been pregnant (2.96%; 1.53-5.18); RR 0.5 (0.2-0.99). This difference was due to the predominance of events related to oral contraceptives in deficient women that had never been pregnant (75%), while 71% of events in deficient women that had had at least one pregnancy were pregnancy-related. In conclusion, women with hereditary deficiencies of antithrombin, protein C or protein S are at high risk of pregnancy-related venous thromboembolism. This risk is increased by multiple additional thrombophilic defects.