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.

Factor V Leiden Is Associated with Repeated and Recurrent Unexplained Fetal Losses

1997 ◽  
Vol 77 (05) ◽  
pp. 0822-0824 ◽  
Author(s):  
Elvira Grandone ◽  
Maurizio Margaglione ◽  
Donatella Colaizzo ◽  
Marina d'Addedda ◽  
Giuseppe Cappucci ◽  
...  
Keyword(s):  
Protein C ◽  
Strong Association ◽  
Activated Protein C ◽  
Fetal Loss ◽  
Factor V Leiden ◽  
Factor V ◽  
Significant Difference ◽  
History Of ◽  
Fv Leiden ◽  
Caucasian Women

SummaryActivated protein C resistance (APCR) is responsible for most cases of familial thrombosis. The factor V missense mutation Arg506>Gln (FV Leiden) has been recognized as the commonest cause of this condition. Recently, it has been suggested that APCR is associated with second trimester fetal loss. We investigated the distribution of FV Leiden in a sample (n = 43) of Caucasian women with a history of two or more unexplained fetal losses. A group (n = 118) of parous women with uneventful pregnancies from the same ethnical background served as control. We found the mutation in 7 cases (16.28%) and 5 controls (4.24%; p = 0.011). A statistically significant difference between women with only early fetal loss vs those with late events (p = 0.04) was observed. Our data demonstrate a strong association between FV Leiden and fetal loss. Furthermore, they indicate that late events are more common in these patients.

scholarly journals High risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance) [see comments]

Blood ◽  
1995 ◽  
Vol 85 (6) ◽  
pp. 1504-1508 ◽  
Author(s):  
FR Rosendaal ◽  
T Koster ◽  
JP Vandenbroucke ◽  
PH Reitsma
Keyword(s):  
Venous Thrombosis ◽  
Protein C ◽  
Absolute Risk ◽  
Thrombotic Event ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Coagulation Factor ◽  
Factor V ◽  
Increased Risk ◽  
The Absolute

Resistance to activated protein C (APC) is a common inherited risk factor for venous thrombosis, which is associated with a mutation in coagulation factor V (factor V Leiden). We investigated the risk of venous thrombosis in individuals homozygous for this abnormality. We determined the factor V Leiden genotype in 471 consecutive patients aged less than 70 years with a first objectively confirmed deep-vein thrombosis and in 474 healthy controls. We found 85 heterozygous and seven homozygous individuals among the cases with thrombosis and 14 heterozygous individuals among the control subjects. The expected number of homozygous individuals among the controls was calculated from Hardy-Weinberg equilibrium and estimated at 0.107 (allele frequency, 1.5%). Whereas the relative risk was increased sevenfold for heterozygous individuals, it was increased 80-fold for homozygous individuals. These patients experienced their thrombosis at a much younger age (31 v 44 years). The homozygous individuals were predominantly women, most likely due to the effect of oral contraceptives. Because of the increased risk of thrombosis with age, the absolute risk becomes most pronounced in older patients, both for heterozygous and homozygous individuals. For the homozygous individuals, the absolute risk may become several percentage points per year. This implies that most individuals homozygous for factor V Leiden will experience at least one thrombotic event in their lifetime.

A Reduced Sensitivity for Activated Protein C in the Absence of Factor V Leiden Increases the Risk of Venous Thrombosis

Blood ◽  
1999 ◽  
Vol 93 (4) ◽  
pp. 1271-1276 ◽  
Author(s):  
Marieke C.H. de Visser ◽  
Frits R. Rosendaal ◽  
Rogier M. Bertina
Keyword(s):  
Risk Factor ◽  
Confidence Interval ◽  
Venous Thrombosis ◽  
Protein C ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Apc Resistance ◽  
Increased Risk

Abstract Activated protein C (APC) resistance caused by the factor V Leiden mutation is associated with an increased risk of venous thrombosis. We investigated whether a reduced response to APC, not due to the factor V point mutation, is also a risk factor for venous thrombosis. For this analysis, we used the Leiden Thrombophilia Study (LETS), a case-control study for venous thrombosis including 474 patients with a first deep-vein thrombosis and 474 age- and sex-matched controls. All carriers of the factor V Leiden mutation were excluded. A dose-response relationship was observed between the sensitivity for APC and the risk of thrombosis: the lower the normalized APC sensitivity ratio, the higher the associated risk. The risk for the lowest quartile of normalized APC-SR (&lt;0.92), which included 16.5% of the healthy controls, compared with the highest quartile (normalized APC-SR &gt; 1.05) was greater than fourfold increased (OR = 4.4; 95% confidence interval, 2.9 to 6.6). We adjusted for VIII:C levels, which appeared to affect our APC resistance test. The adjusted (age, sex, FVIII:C) odds ratio for the lowest quartile was 2.5 (95% confidence interval, 1.5 to 4.2). So, after adjustment for factor VIII levels, a reduced response to APC remained a risk factor. Our results show that a reduced sensitivity for APC, not caused by the factor V Leiden mutation, is a risk factor for venous thrombosis.

Oral Contraceptive-Associated Thromboembolism. A Retrospective Analysis of Thrombophilic Work-out and Long Term Follow up in 57 Cases

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5348-5348
Author(s):  
Emmanouil Papadakis ◽  
Smaragda Efremidou ◽  
Haris Kartsios ◽  
Margarita Mpraimi ◽  
Kiriaki Kokoviadou ◽  
...  
Keyword(s):  
Family History ◽  
Protein C ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Apc Resistance ◽  
Increased Risk ◽  
Fv Leiden

Abstract Introduction: The increased risk of venous thrombosis in women taking oral contraceptives (OCs) has been recognized since the early 1960s. Coexistence of hereditary risk factors appears to have an additive effect. Women under OCs that carry the factor V Leiden mutation have a 35-fold increased risk of thromboembolic events compared to women without the mutation who are not on OCs. Evaluation of family and personal history is the mainstay of prophylaxis prior to OC administration, but often family thrombophilia or thromboembolic (TE) events are not reported prior to OCs prescription. Patients-Methods: Fifty-seven women with a median age of 28 (21–48) years, which suffered OC-associated TE, were studied. The median period of OC therapy prior to TE event was 2 months (0.5–60). Fifty-five of them experienced VTE while 2 suffered stroke. Leg thrombosis was the most common clinical finding [37/55 (67,2%) patients] Apart from personal and family history, Thrombophilia investigation included measurement of : serum Homocysteine, Antithrombin, Protein C and S, Lipoprotein (a), Activated Protein C (APC) resistance, antiphospholipid antibodies and lupus anticoagulant. In addition the presence of FV Leiden, FII 20210 GA mutations and MTHFR 677 CT polymorphism were determined. Results: A high prevalence of the factor V Leiden mutation was detected in the study group; 50% had APC-resistance test positive, 26 (45%) patients were found to be heterozygous and 3 (5,2%) homozygous for the FV Leiden mutation. Lp(a) elevation was observed in 19,3% and Homocysteine elevation in 15,8% of patients. In 9 women (15,8%) both family history and thrombophilic profile were negative. Serious VTE events (2 abdominal and 6 CNS thromboses) were observed only in the Leiden subgroup. During the follow up period ranging from months to 18 years, 3 women (6,25%) experienced a miscarriage and 14 suffered additional VTE events (25%) and they are currently on permanent anticoagulation. Conclusions : Universal thrombophilia screening of women prior to prescription of OCs is not advisable as it does not appear to be cost effective. However, screening certain subgroups, such as women with a known personal or family history, may be of great value. If a full thrombophilic profile can’t be performed, a mere activated protein C resistance test, that reflects the presence of the factor V Leiden mutation, may provide an easy and cheap way of identifying and consulting properly women at higher risk for VTE prior to OC use. Women with OC-associated VTE and thrombophilia carry a substantial recurrence risk that persists for years.

Resistance to Activated Protein C, Factor V Leiden and the Prothrombin G20210A Variant in Patients with Colorectal Cancer

2002 ◽  
Vol 32 (1) ◽  
pp. 2-7 ◽  
Author(s):  
Gregorios A. Paspatis ◽  
Aikaterini Sfyridaki ◽  
Nikolaos Papanikolaou ◽  
Kostantinos Triantafyllou ◽  
Aikaterini Livadiotaki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Protein C ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Prothrombin G20210a ◽  
Factor V

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.

scholarly journals Portal Thrombosis in Cirrhosis: Role of Thrombophilic Disorders

2020 ◽  
Vol 9 (9) ◽  
pp. 2822
Author(s):  
José Ignacio Fortea ◽  
Inés García Carrera ◽  
Ángela Puente ◽  
Antonio Cuadrado ◽  
Patricia Huelin ◽  
...  
Keyword(s):  
Portal Vein ◽  
Protein C ◽  
Mutational Analysis ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Jak2 V617f ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Vein Thrombosis

In patients with liver cirrhosis the contribution of inherited and acquired prothrombotic disorders in the development of non-malignant portal vein thrombosis (PVT) is inconclusive. The purpose of this retrospective study was to examine the prevalence of thrombophilia in this setting at our center from January 2012 to November 2019. Tests included gene mutational analysis for Factor V Leiden, prothrombin G20210A, JAK2 (V617F), Calreticulin (CARL), in addition to activated protein C resistance, antithrombin III, protein C and S levels, and antiphospholipid antibodies. We included 77 patients, six of whom (7.8%) had a thrombophilic disorder: antiphospholipid syndrome in four patients, prothrombin gene mutation in one and factor V Leiden mutation in one. This latter patient had also been diagnosed with polycythemia vera years before PVT development. Complete thrombosis of the main portal vein and re-thrombosis after stopping anticoagulation were more frequent in patients with thrombophilia, but the rates of recanalization under anticoagulant therapy were similar among groups. No other difference was accounted between groups. The low prevalence of acquired and inherited thrombophilia found in patients with cirrhosis and PVT support testing for these disorders on an individual basis and avoiding universal screening to reduce costs and unwarranted testing.

The HR2 Haplotype of Factor V: Effects on Factor V Levels, Normalized Activated Protein C Sensitivity Ratios and the Risk of Venous Thrombosis

2000 ◽  
Vol 83 (04) ◽  
pp. 577-582 ◽  
Author(s):  
Joan Guasch ◽  
Pieter Kamphuisen ◽  
Hans Vos ◽  
Frits Rosendaal ◽  
Rogier Bertina ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Protein C ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Compound Heterozygous ◽  
Factor V ◽  
Vein Thrombosis ◽  
Increased Risk ◽  
V Antigen ◽  
Deep Vein

SummaryWe studied the HR2 haplotype of the factor V gene in a case-control study for venous thrombosis including 474 patients with a first deep-vein thrombosis and 474 age- and sex-matched healthy controls (Leiden Thrombophilia Study, LETS). We investigated both the original His1299Arg (A4070G) polymorphism and the Met385Thr (T1328C) polymorphism. This latter polymorphism, located in exon 8 (heavy chain), is always present in the HR2 haplotype, but also occurs on its own in a His1299 (wt) background. The HR2 haplotype was not associated with an increased risk of venous thrombosis (OR = 1.2, 95% confidence interval: 0.8-2.0). We did not find an association between the HR2 haplotype and a reduced sensitivity for activated protein C (APC) in non-carriers of factor V Leiden (FVL). However, in compound heterozygous FVL/HR2 carriers the sensitivity for APC was reduced. The HR2 haplotype was also associated with reduced factor V antigen levels in both patients and controls. Sequence analysis of the promoter region of factor V in HR2 homozygotes did not reveal any sequence variations that could explain the reduced FV levels. Our results show that the HR2 haplotype is not associated with an increased risk of venous thrombosis or with a reduced sensitivity for APC in non-FVL carriers. However, the HR2 haplotype is associated with a reduced sensitivity for APC in carriers of FVL and with reduced factor V antigen levels.

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