Outcomes during and after Pregnancy in Patients with Primary Hypercoagulable States.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 887-887
Author(s):  
Aysha Khalid ◽  
Alice J. Cohen
Keyword(s):  
Gene Mutation ◽  
Fetal Loss ◽  
Factor V Leiden ◽  
Retrospective Chart Review ◽  
First Trimester ◽  
Therapeutic Interventions ◽  
Hypercoagulable State ◽  
Factor V ◽  
Increased Risk ◽  
Adverse Pregnancy

Abstract Pregnant women with primary hypercoagulable states have an increased risk of recurrent fetal loss, fetal growth retardation, preclampsia, and placental abruption, as well as thromboembolism in both the antepartum and postpartum periods. Conditions that have been associated with adverse pregnancy outcomes include inherited gene mutation disorders such as Factor V Leiden G1691A (FVL); prothrombin gene mutation G20210A (PGM); hyperhomocysteinemia with C677T mutation (MTHFR); deficiencies of protein S (PS), protein C (PC), antithrombin III (ATIII); and anticardiolipin antibodies/lupus anticoagulants (LA). Screening by obstetricians for these disorders has led to an increase in diagnosis yet there are no established guidelines and therapeutic interventions are variable. A retrospective chart review was conducted on 59 women and 197 pregnancies (1–12 per pt) in whom primary hypercoagulable state was diagnosed: FVL (n=7), PGM (n=11), MTHFR (n=3), ATIII (n=2), PC (n=1), PS (n=8), LA (n=10), and those with more than one thrombophilic risk (TR) (n=12) or lupus (n=2). Of the 197 pregnancies, only 106 (54%) were carried to term in 50 pts (85%). Of the remaining 91 pregnancies, there were 16 terminations, 5 ectopic pregnancies and 4 preterm live births. 66 fetal losses occurred: 45 in the first trimester (26 with single TR/19 with >1 TR), 19 in the 2nd–3rd trimester (14 with single TR/5 with > 1 TR) and 2 unknown. See Table for risk of fetal loss by class of hypercoagulable state. Venous thromboembolism occurred in 8/106 (8%) of term pregnancies, including 5 postpartum. Of women with previous fetal losses, management with anticoagulation (A/C) subsequently was utilized in 20 pregnancies: 9 low molecular weight heparin (LMWH), 6 LMWH+aspirin (ASA), 3 heparin (H), 1 ASA, and 1 H+ASA. 18/20(90%) of these pregnancies resulted in live term births; 1 loss due to intracranial hemorrhage at 27 weeks in a patient on L+ASA. Compared to 146 pregnancies untreated with A/C, successful completion of pregnancy was significantly greater on A/C, 90% vs. 58% (p=0.006). Conclusions: Fetal losses secondary to TR occurred in both the first and late trimesters in high proportion of pregnancies in women with hypercoagulable states. Outcomes may be improved with the use of A/C therapy. Table - Risk of Fetal Loss by Class of Hypercoagulable State LA PGM MTHFR PS FVL ATIII FVL/other Trimester1 9/38 (24%) 7/44 (16%) 3/9 (33%) 3/27 (11%) 1/27 (4%) 2/5 (40%) 17/42 (40%) Trimester 2–3 5/38 (13%) 1/36 (3%) 0% 5/16 (31%) 2/27 (7%) 1/5 (20%) 4/44 (9%)

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.

Maternal thrombophilias are not associated with early pregnancy loss

2004 ◽  
Vol 91 (02) ◽  
pp. 290-295 ◽  
Author(s):  
Michael Paidas ◽  
Edmund Funai ◽  
Edward Kuczynski ◽  
Charles Lockwood ◽  
Henry Roqué
Keyword(s):  
Protein C ◽  
Activated Protein C ◽  
Fetal Loss ◽  
Factor V Leiden ◽  
Anticardiolipin Antibodies ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Increased Risk ◽  
Pregnancy Wastage ◽  
Adverse Pregnancy

SummaryWe investigated the association between inherited and acquired maternal thrombophilias and adverse pregnancy events. A cohort of 491 patients with a history of adverse pregnancy outcomes was evaluated for activated protein C resistance, factor V Leiden and prothrombin G20210A mutations, hyperhomocysteinemia, deficiencies of antithrombin, protein C and S and both anticardiolipin antibodies and lupus anticoagulants. The study had an 80% power to detect a 15% difference in the prevalence of thrombophilia for 1st trimester loss. In our high-risk cohort the presence of 1 maternal thrombophilia or more than one thrombophilia were found to be protective of recurrent losses at < 10 weeks (1 thrombophilia: OR: 0.55, 95% CI: 0.33–0.92; >1 thrombophilia: OR: 0.48, 95%CI:0.29–0.78). In contrast, the presence of maternal thrombophilia(s) was modestly associated with an increased risk of losses ≥ 10 weeks (1 thrombophilia: OR:1.76, 95%CI: 1.05–2.94, >1 thrombophilia: OR:1.66, 95%CI:1.03–2.68). Women who experienced only euploid losses were not more likely to have an identified thrombophilia than women who experienced only aneuploid losses (OR 1.03; 0.38–2.75). The presence of maternal thrombophilia was associated with an increased risk of fetal loss after 14 weeks, fetal growth restriction, abruption and preeclampsia. There was a significant “dose-dependent” increase in the risk of abruption (OR:3.60, 95%CI: 1.43–9.09) and preeclampsia (OR:3.21, 95%CI:1.20–8.58). In conclusion, these data indicate maternal thrombophilias are not associated with pregnancy wastage prior to 10 weeks of gestation.

scholarly journals Hereditary thrombophilia and adverse pregnancy outcomes

2021 ◽  
Vol 64 (3) ◽  
pp. 68-77
Author(s):  
Valentin Friptu ◽  
◽  
Diana Mitryuk ◽  
Olga Popusoi ◽  
◽  
...  
Keyword(s):  
Gene Mutation ◽  
Pregnancy Outcomes ◽  
Intrauterine Growth Restriction ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Fetal Loss ◽  
Factor V Leiden ◽  
Factor V ◽  
Intrauterine Growth ◽  
Adverse Pregnancy

Background: Multiple studies have found a relatively increased risk of placenta-mediated pregnancy complications in women with congenital thrombophilia, especially early recurrent pregnancy loss, fetal loss, early-onset preeclampsia, intrauterine growth restriction, and premature abruption of normally positioned placenta. However, the extent of the association and the absolute risk are very modest, but they significantly increase in pregnant women with severe obstetric complications. Conclusions: There is convincing evidence that deficiency of natural anticoagulants (antithrombin, protein C, protein S) is a risk factor for late fetal loss. Factor V Leiden G1691A gene mutation and prothrombin G20210A gene mutation are associated with a double risk for early and unexplained recurrent pregnancy loss and for non-recurrent late fetal loss. The association of congenital thrombophilia with preeclampsia is much more uncertain, being probably limited factor V Leiden G1691A gene mutation and more severe cases of preeclampsia. Fewer data are available on intrauterine growth restriction (IUGR) and premature abruption of the normally positioned placenta. There is insufficient evidence to suggest an association of other forms of congenital thrombophilia with adverse pregnancy outcomes. In addition, genetic and epidemiological research suggests that placenta-mediated pregnancy complications are of polygenic multifactorial etiology, with a risk determined by the interaction of multiple genetic variants and other risk factors.

55 UNEXPLAINED SPORADIC FIRST-TRIMESTER MISCARRIAGE: FACTOR V LEIDEN GENE MUTATION.

2007 ◽  
Vol 55 (2) ◽  
pp. S357.4-S357
Author(s):  
J. Munjal ◽  
L. Rovner ◽  
S. Gogineni ◽  
T. Tracy ◽  
P. Wang ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Factor V Leiden ◽  
First Trimester ◽  
Factor V

UNEXPLAINED SPORADIC FIRST-TRIMESTER MISCARRIAGE: FACTOR V LEIDEN GENE MUTATION.

2007 ◽  
Vol 55 (2) ◽  
pp. S357
Author(s):  
J. Munjal ◽  
L. Rovner ◽  
S. Gogineni ◽  
T. Tracy ◽  
P. Wang ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Factor V Leiden ◽  
First Trimester ◽  
Factor V

Is Factor V Leiden Associated with an Increased Risk for Fetal Loss?

2001 ◽  
pp. 217-221
Author(s):  
P. Dulíček ◽  
L. Chrobák ◽  
I. Kalousek ◽  
L. Pešavová ◽  
M. Pecka ◽  
...  
Keyword(s):  
Fetal Loss ◽  
Factor V Leiden ◽  
Factor V ◽  
Increased Risk

Association of factor V Leiden G1691A and prothrombin gene G20210A mutations with adverse pregnancy outcomes

2021 ◽  
pp. 1-15
Author(s):  
Sidra Asad Ali ◽  
Bushra Moiz ◽  
Lumaan Sheikh
Keyword(s):  
Gene Mutation ◽  
Pregnancy Outcomes ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Factor V Leiden ◽  
Control Group ◽  
Factor V ◽  
Prothrombin Gene Mutation ◽  
Prothrombin Gene ◽  
Adverse Pregnancy

Abstract Objective: To determine the association of Factor V Leiden / prothrombin gene mutation in Pakistani women with adverse pregnancy outcomes. Method: The prospective study was conducted at the Aga Khan University Hospital, Karachi, from January 1 to December 31, 2016, and comprised females ?40 years having history of two or more foetal losses with no apparent aetiology. Restriction fragment length polymorphism- Polymerase chain reaction was performed using MnlI and HindIII restriction enzymes for factor V Leiden G1691A and prothrombin gene mutation G20210A. Females with two or more consecutive normal pregnancies were enrolled as the control group. Data was analysed using SPSS 19. Results: Of the 172 participants with a mean age of 29.3±5.9 years (range: 19-38 years). 86(50%) each were healthy controls and those with recurrent pregnancy loss. There were 238 livebirths among the controls compared to 13 in the other group. Factor V Leiden G1691A was identified in 2(2.3%) women, and prothrombin gene mutation G20210A in 1(1.2%) woman in the patient group, while no mutation was identified in the control group. Conclusion: The prevalence of Factor V Leiden / prothrombin gene mutation in women with recurrent pregnancy loss was found to be very low. Continuous....

Prevalence of Thrombophilia in Women with Spontaneous Pregnancy Loss.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1048-1048
Author(s):  
Maria Teresa De Sancho ◽  
Lamar Richardson ◽  
Jacob H. Rand
Keyword(s):  
Gene Mutation ◽  
Antiphospholipid Antibodies ◽  
Homocysteine Level ◽  
Factor V Leiden ◽  
Protein S ◽  
First Trimester ◽  
Factor V ◽  
Prothrombin Gene Mutation ◽  
Prothrombin Gene ◽  
Thrombophilic Condition

Abstract We retrospectively analyzed the records of 145 female patients ages 18 to 50 who were referred to the Thrombosis and Hemostasis Section of the Hematology-Oncology Division at Mt. Sinai Hospital from January 2000 to June 2004 for evaluation of thrombophilia as the etiology of pregnancy loss (PL). Recurrent Pregnancy Loss (RPL) was defined as 2 or more PL in the first trimester of gestation. Women with one or more PL in the second and/or third trimester of gestation or stillbirth, or a combination of above were also analyzed. The following thrombophilic conditions were evaluated: factor V Leiden, prothrombin gene mutation (G20210), antiphospholipid (APL) antibodies and lupus anticoagulant (LAC), homocysteine and functional levels of protein C, S and antithrombin. Of the 145 patients, 20 were excluded from analysis for the following reasons: isolated 1 first trimester PL (15 patients), no verification of antiphospholipid antibodies (4 patients) and insuficient data (1 patient). Of the evaluable patients, 75 (60%) had 2 or more first trimester PL, 14 (11.2%) patients had 1 or more second trimester PL, 2 (1.6%) patients had 1 or more third trimester PL and 24 (19.2%) patients had PL in different trimesters. 70 of the 125 patients (56%) were found to have a thrombophilic condition: 25 had antiphospholipid antibodies, 21 had factor V Leiden (20 heterozygous and 1 homozygous), 16 had prothrombin gene mutation (all heterozygous), 5 had protein S deficiency, 2 had homocysteine level, and 1 had protein C deficiency. We did not identify any patient with antithrombin deficiency. Of the 75 patients with first trimester PL, 36 (48%) were found to have a thrombophilic condition: 18 (50%) had antiphospholipid antibodies, 9 (25) had factor V Leiden (1 homozygous and 8 heterozygous) (17%), 5 (13.8) had heterozygous prothrombin gene mutation (8%), 3 (8.3%) had increased homocysteine level and 3 had a low protein S level (8.3%). In summary, we found a thrombophilic condition associated with PL in 56% in this patient population. The majority of patients had recurrent first trimester PL. The most prevalent thrombophilic disorder was the presence of antiphospholipid antibodies, followed by factor V Leiden, prothrombin gene mutation and protein S deficiency and the least common was increased homocysteine level. These results suggest that testing for thrombophilia may be warranted in women with recurrent PL.

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.

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