The Risk of Fetal Loss in Family Members of Probands with Factor V Leiden Mutation

1999 ◽  
Vol 82 (10) ◽  
pp. 1237-1239 ◽  
Author(s):  
Daniela Tormene ◽  
Paolo Simioni ◽  
Sonia Luni ◽  
Barbara Innella ◽  
Paola Sabbion ◽  
...  
Keyword(s):  
Relative Risk ◽  
Family Members ◽  
Fetal Loss ◽  
Factor V Leiden ◽  
First Trimester ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
First Trimester Of Pregnancy ◽  
Late Miscarriage ◽  
Normal Genotype

SummaryIn order to investigate the risk of fetal loss in carriers of factor V Leiden who are family members of probands with this mutation, we performed a retrospective cohort study including 109 women who had been pregnant at least once and were family members of 61 probands with venous thromboembolism and a single identified factor V Leiden mutation. The rate of pregnancies ending in unexplained fetal loss, early miscarriage, late miscarriage or stillbirth in women with the factor V Leiden was compared with that of women with normal genotype. In the 65 women who were carriers of factor V Leiden 31 of the 191 pregnancies (16.2% per pregnancy ) resulted in unexplained fetal loss, as compared to 13 of the 121 pregnancies (10.7% per pregnancy) in the 44 non-carriers (relative risk, 1.5; 95% CI, 0.8-3.2). After the first trimester of pregnancy, 25 pregnancies (13.1% per pregnancy) among carriers of factor V Leiden ended in fetal loss, as compared to 7 (5.8% per pregnancy) among females with normal genotype (relative risk, 2.3; 95% CI, 1.01 to 5.1). We conclude that carriers of factor V Leiden who are family members of probands with this mutation have a statistically significant and clinically important risk of late miscarriage or stillbirth. Studies addressing the benefit-to-risk ratio of adopting routinary thromboprophylactic measures following the first trimester of pregnancy in these women are strongly indicated.

The Outcome of Pregnancy in Patients with Thrombophilia after Anticoagulation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4164-4164
Author(s):  
Qingqi Jiang ◽  
Judith Andersen
Keyword(s):  
Unfractionated Heparin ◽  
Fetal Loss ◽  
Factor V Leiden ◽  
Protein S ◽  
Severe Bleeding ◽  
Factor V ◽  
Protein C Deficiency ◽  
Factor V Leiden Mutation ◽  
G20210a Mutation ◽  
History Of

Abstract Background: Both inherited and acquired thrombophilia predispose pregnant women to venous thromboembolism and recurrent fetal loss. The safety profile and tolerability of low molecular heparin (LWMH) has allowed us to evaluate effects of anticoagulation in the outcome of pregnancy in patients with thrombophilia. Methods: 20 patients with thrombophilia received either tinzaparin or enoxaparin combined with aspirin before and during pregnancy and the outcome of pregnancy was monitored for a period of 2 years. The median age of the patients was 28 years (25–49); 75% were Caucasians, 20% were aferican-american, 5% were others. The inherited and acquired thrombophilias include Factor V leiden mutation, prothrombin mutation in G20210A, mutation in methylenetetrahydrofolate (MTHFR), protein S deficiency, protein C deficiency, hyperhomocyteinemia, antiphospholipid syndrome, sticky platelet syndrome, etc. The majority of patients had more than 2 thrombophilia factors and had history of miscarriage. 15 of 20 patients (75%) received tinzaparin and 4 of 20 (20%) patients received enxoparin subcutaneously before they were conceived. Only one patient received unfractionated heparin. The LWMH was continued during pregnancy until 34 to 36 weeks gestation when it was changed to unfractionated heparin in order to prevent large amount of bleeding from upcoming delivery. All of the patients also received aspirin prior, during, and after the pregnancy. There were 21 live births including one triplet and one twins. Only two patients were complicated with miscarriage. There was no episode of severe bleeding or thromboembolism during pregnancy or postpartum. Conclusion: LWMH and aspirin has been effective in the prevention of fetal loss in women with thrombophilia disorders.

The association between adverse pregnancy outcomes and maternal factor V Leiden genotype: a meta-analysis

2004 ◽  
Vol 91 (04) ◽  
pp. 700-711 ◽  
Author(s):  
John Attia ◽  
Tracy Dudding
Keyword(s):  
Pregnancy Outcomes ◽  
Odds Ratio ◽  
Fetal Loss ◽  
Factor V Leiden ◽  
Adverse Pregnancy Outcomes ◽  
Factor V ◽  
Third Trimester ◽  
Factor V Leiden Mutation ◽  
Increased Risk ◽  
Adverse Pregnancy

SummaryThe conclusions of studies to date which evaluate a possible association between factor V Leiden and adverse pregnancy outcome have been conflicting. This study was undertaken to further investigate this association. Our objective was to evaluate the association between adverse pregnancy outcomes and maternal factor V Leiden genotype by meta-analysis. Inclusion criteria were: (a) cohort or case control design; (b) outcomes clearly defined as one of the following: first or second/ third trimester miscarriage or intrauterine death, preeclampsia, fetal growth retardation, or placental abruption; (c) both the case and control mothers tested for the factor V Leiden mutation; (d) sufficient data for calculation of an odds ratio. Both fixed and random effect models were used to pool results and heterogeneity and publication bias were checked. For first trimester fetal loss, the pooled odds ratio was heterogeneous (p=0.06) and no dose-response curve could be found. For second/third trimester fetal loss, there was a consistent and graded increase in risk: the odds ratio was 2.4 (95% CI 1.1-5.2) for isolated (non-recurrent) third trimester fetal loss, rising to 10.7 (95% CI 4.0-28.5) for those with 2 or more second/third trimester fetal losses. FactorV Leiden is associated with a 2.9 fold (95% CI 2.0-4.3) increased risk of severe preeclampsia, and a 4.8 fold (95% CI 2.4-9.4) increased risk of fetal growth retardation. These results support factor V Leiden testing for women with recurrent fetal loss in the second/third trimester. Women with only 1 event may also warrant testing if the fetal loss occurred in the third trimester. Conversely, in those women known to have the factor V Leiden mutation, monitoring for adverse pregnancy outcomes is warranted; whether this means increased vigilance or anti-coagulant prophylaxis is still contentious.

Factor V Leiden and Fatal Pulmonary Embolism

1998 ◽  
Vol 79 (03) ◽  
pp. 511-516 ◽  
Author(s):  
Rogier Bertina ◽  
Zandra Holmes ◽  
Caroline Spaargaren ◽  
Joannes van Krieken ◽  
Bert Manten ◽  
...  
Keyword(s):  
Relative Risk ◽  
The Netherlands ◽  
Confidence Interval ◽  
Cause Of Death ◽  
Factor V Leiden ◽  
Severe Illness ◽  
Factor V ◽  
Pulmonary Emboli ◽  
Factor V Leiden Mutation ◽  
Number Of Patients

SummaryTo investigate whether the factor V Leiden mutation increases the risk of fatal pulmonary emboli, we determined the presence of the factor V Leiden mutation in pathology material from two series of autopsies of patients from the Leiden University Hospital, The Netherlands. The first series consisted of consecutive autopsies in which pulmonary emboli were mentioned in the autopsy report; most patients of this series had major underlying disease. The second series consisted of autopsies in patients younger than age 70 in which pulmonary emboli were the sole cause of death and no major acquired risk factor for venous thrombosis was present. Extraction of DNA was done on newly prepared tissue from archival paraffin blocks. In the first series, the presence of factor V Leiden was determined in 44 patients, 1 of whom carried the mutation (2.3 percent; 95% confidence interval 0.06 to 12.0 percent). This prevalence is not different from the general population prevalence in The Netherlands. In the second series, factor V Leiden could be determined in 30 patients of whom 3 carried the mutation (10 percent; 95% confidence interval 2.1 to 26.5 percent), which would lead to a threefold relative risk. A large number of patients with diverse psychiatric diagnoses was present in the second series (eleven). We conclude that in the presence of severe illness, the factor V Leiden mutation plays no additional role in the development of pulmonary emboli. The relative risk of the very rare fatal pulmonary embolus that is the sole cause of death might also be less than the relative risk for deep-vein thrombosis in carriers of the factor V Leiden mutation.

Venous Thrombotic Risk in Family Members of Unselected Individuals with Factor V Leiden

2000 ◽  
Vol 83 (06) ◽  
pp. 817-821 ◽  
Author(s):  
R. P. M. Lensen ◽  
R. M. Bertina ◽  
H. de Ronde ◽  
J. P. Vandenbroucke ◽  
F. R. Rosendaal
Keyword(s):  
Risk Factors ◽  
Positive Family History ◽  
Family Members ◽  
Factor V Leiden ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Thrombotic Risk ◽  
Asymptomatic Carriers ◽  
Kaplan Meier ◽  
Increased Risk

SummaryThe factor V Leiden mutation (FVL) leads to a seven-fold increased risk of venous thromboembolism (VTE). In thrombophilic families, 25% of carriers have experienced thrombosis before the age of 40 years. Aim of our study was to assess the association of FVL with VTE in first-degree family members of unselected symptomatic and asymptomatic carriers of FVL.We tested 197 relatives of consecutive thrombosis patients with FVL and 36 relatives of asymptomatic carriers on the presence of FVL and the occurrence of VTE.The incidence of VTE in relatives with FVL of symptomatic carriers was 0.34%/year. This was similar to the incidence in relatives with FVL of asymptomatic carriers. Kaplan Meier analysis in relatives of symptomatic propositi showed that at the age of 58 years, thrombosisfree survival was reduced to 75% in carriers and 93% in non-carriers (P < 0.05). Carriers of FVL had a three times higher thrombotic risk than non-carriers. In combination with environmental risk factors, FVL clearly adds to the risk of VTE. The thrombotic incidence rate in these unselected relatives with FVL, however, is considerably lower than was seen in carriers of thrombophilic families (1.7%/year). Therefore, special care should be paid to individuals with a positive family history of venous thrombosis while exposed to these risk factors.

The IVS1-401 T-Allele of the Estrogen Receptor (ER)-α Is an Independent Predictor of Late Fetal Loss.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4023-4023
Author(s):  
Andrea Gerhardt ◽  
Rudiger E. Scharf ◽  
Barbara Mikat-Drozdzynski ◽  
Jan S. Kruessel ◽  
Hans G. Bender ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Subgroup Analysis ◽  
Odds Ratio ◽  
Fetal Loss ◽  
Factor V Leiden ◽  
First Trimester ◽  
Factor V ◽  
Fetal Malformation ◽  
History Of ◽  
Normal Women

Abstract Estrogens are involved in the regulation of placental function and fetal development through their interaction with estrogen receptor a (ER-α). Sequence variants in the gene encoding for ER-a could disturb estrogen-dependent mechanisms in pregnancy maintenance, probably leading to fetal loss. We determined the IVS1-401C/T polymorphism of the human ER-α, the G1691A mutation of the factor V gene (factor V Leiden), the G20210A mutation of the prothrombin gene, and the C677T polymorphism of the methylenetetrahydrofolate-reductase (MTHFR) gene in 104 women with fetal loss and 277 normal women. Inclusion criteria for the women with fetal loss&lt;were either recurrent early fetal loss (three or more consecutive fetal losses at &lt; 12 weeks gestation and no late fetal loss) or at least one late fetal loss (≥ 12 weeks gestation). Only women with post-embryonic loss after ultrasonic disappearance of fetal pulse from the intrauterine fetal pole were included in the study. Documented first trimester preclinical and blighted ovum abortions as well as fetal losses that were the result of documented fetal malformation or the result of an infectious complication were excluded. The women enrolled with recurrent fetal loss had no previous history of venous or arterial thromboembolic disease, diabetes mellitus, chronic hypertension, thyroid dysfunction, systemic lupus erythematosus, intrauterine growth retardation, pregnancy-induced hypertension, or preeclampsia. They all had a detailed investigation which was negative for potential causes of fetal demise including fasting glucose, basal FSH, LH and estradiol levels on day 3 of a natural cycle, TSH and prolactin levels and antinuclear factor. In addition, transvaginal scanning was performed in all patients included to verify ovarian morphology. Women with three or more first trimester or one or more second or third trimester pregnancy losses underwent a hypersalpingography and/or hysteroscopy to confirm uterine cavity normalcy, and both partners were also investigated for chromosomal aberrations. The 277 normal women had at least one previous pregnancy and no previous fetal loss or late pregnancy complications, and no history of previous arterial or venous thromboembolism In a subgroup analysis of women with recurrent early fetal loss (n=34), the prevalence of the genetic markers did not differ significantly between women with early fetal loss and normal women. In contrast, in the subgroup analysis of women with at least one late miscarriage (n=70), the prevalences of the ER-α IVS1-401 T-allele (TT vs. CC, odds ratio 2.85, p=0.018, TT+CT vs. CC, odds ratio 2.28, p=0.043) and of heterozygous factor V Leiden (odds ratio 3.2, p=0.002) were significantly higher among women with late fetal loss than among normal women. Carriers of both risk determinants have an at least additive increase in risk for late abortions (odds ratio 7.0, p=0.0004). The fraction of all late abortions that would be attributable to the genetic variants (population attributable risk) was 13.9 percent for factor V Leiden and 49.2 percent for the ER-α IVS1-401 T-allele. Women with the IVS1-401 T-allele of the ER-α and/or factor V Leiden are at increased risk of late fetal loss.

Sign in / Sign up

Export Citation Format

Share Document