Association of factor V gene polymorphisms (Leiden; Cambridge; Hong Kong and HR2 haplotype) with recurrent idiopathic pregnancy loss in Tunisia

2006 ◽  
Vol 95 (04) ◽  
pp. 612-617 ◽  
Author(s):  
Walid Zammiti ◽  
Nabil Mtiraoui ◽  
Eric Mercier ◽  
Nesrine Abboud ◽  
Sarra Saidi ◽  
...  
Keyword(s):  
Hong Kong ◽  
Pregnancy Loss ◽  
Fetal Loss ◽  
Factor V Leiden ◽  
Factor V ◽  
Inherited Thrombophilia ◽  
Factor V Gene ◽  
Fv Leiden ◽  
Clinical Risks ◽  
Control Study

SummaryInherited thrombophilia has been shown to be linked with fetal loss. We performed a case-control study on the association between thrombosis-related polymorphisms in the factor V (FV) gene (Leiden, Cambridge, Hong Kong; HR2 haplotype) and idiopathic recurrent pregnancy loss (RPL) in Tunisian women. A total of 348 women with RPL, and 203 control women were studied, corresponding to 1,250 pregnancy losses and 1,200 successful pregnancies. FV Leiden was seen in 19.4% of patients (4.3% in the homozygous state) and in 5.5% of controls. The prevalence of the FV HR2 haplotype was similar in patients and controls, but with 7 homozygous patients for 1 control. FV Cambridge and Hong Kong were absent from both patients and controls. The study of all pregnancy losses evidenced that the frequency of the factor V Leiden polymorphism was zero in women who had miscarried before7 weeks of gestation, and then sharply increased to a plateau. After categorization of pregnancy losses (before8 weeks of gestation; weeks 8 and 9; weeks 10 to 12; from the 13th week of gestation onwards), heterozygous and homozygous factor V Leiden polymorphisms, and homozygous FV HR2 haplotype, were associated with significant and independent risks of pregnancy loss during weeks 8 and 9, which increased during weeks 10 to 12, then culminated after week 12. In Tunisian women with idiopathic RPL, factor V Leiden polymorphism and homozygous FV HR2 haplotype are not a risk factor for very early pregnancy loss, before 8 weeks of gestation, but are thereafter associated with significant clinical risks, which gradually increase from the 8th week onwards.

Role of Inherited Bleeding Disorders in Women with Pregnancy Loss

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4657-4657
Author(s):  
Manuela Krause ◽  
Daniele Pillitteri ◽  
Ann-Kathrin Pilgrimm ◽  
Thomas Scholz ◽  
Rainer Schwerdtfeger ◽  
...  
Keyword(s):  
Pregnancy Loss ◽  
Conflicts Of Interest ◽  
Fetal Loss ◽  
Factor V Leiden ◽  
Mthfr C677t ◽  
Von Willebrand Disease ◽  
Factor V ◽  
Bleeding Disorders ◽  
Increased Risk ◽  
Fv Leiden

Abstract Abstract 4657 Introduction: Pregnancy is a hypercoagulable state, and thromboembolism is the leading cause of antepartum and postpartum maternal mortality. Women with thrombophilic mutations (factor V leiden, prothrombin, and MTHFR) and inherited bleeding disorders, such as deficiency of factor XIII and fibrinogen, have been shown to be at increased risk of pregnancy loss. However, the risk of miscarriage in women with other inherited bleeding disorders has been discussed controversially. Due to the lack of data, it cannot be determined if the risk of miscarriage is increased in women with von Willebrand disease (vWD). The aim of our study was to clarify the association between inherited bleeding disorders and pregnancy loss. Patients and Methods: Subjects Concerning this investigation we included 91 female patients with two [n=46] or more [n=45] miscarriages occurring prior to 28 weeks of gestation and/or stillbirth without apparent reason. The median age of the examined group at the time of first fetal loss was 29 years, ranging from 17 to 41 years. Methods At first we compiled a detailed clinical history of bleedings of all patients. Subsequently, we performed various tests to gather information regarding coagulation abnormalities and thrombophilic defects. Therefore a molecular and functional assessment of the following data was performed: Coagulation factors, vWF:Ag, vWF:RCo, phospholipid antibodies, hyperhomocysteinaemia (HHCY), protein S (PS), protein C (PC), antithrombin (AT) and FV-Leiden mutation (G1691A), FII mutation (G20210A) and MTHFR C677T. Results: In our investigated population consisting of 91 women we registered 299 pregnancies of which 240 resulted in fetal loss, 232 prior to week 28 of pregnancy and 8 stillbirths. Seven out of 91 patients (8%) were carriers of inherited coagulation disorders; vWD: n=2 (2%), FVII deficiency: n=3 (3%), thrombocytopathy: n=2 (2%). In our study collective there was no increased rate of patients with vWD. None of the patients showed a FXIII- or fibrinogen deficiency. However, 17 patients (19%) have a bleeding diathesis. In 55 patients (60%) we could detect the following thrombophilic defects: FV-Leiden (G1691A): n=10, MTHFR C677T: n=42, PS: n=1, PC: n=1, APS: n=1. Conclusion: The incidence of vWD patients in our miscarriage collective is the same as the overall incidence of vWD patients in the general population. Therefore vWD is not associated with an increased risk of fetal loss. Disclosures: No relevant conflicts of interest to declare.

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 The HR2 Haplotype of Factor V Is not Associated with the Risk of Myocardial Infarction

2000 ◽  
Vol 84 (11) ◽  
pp. 815-818 ◽  
Author(s):  
Carine Doggen ◽  
Marieke de Visser ◽  
Hans Vos ◽  
Rogier Bertina ◽  
Volkert Cats ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Factor V Leiden ◽  
Myocardial Infarctions ◽  
Control Group ◽  
Factor V ◽  
Increased Risk ◽  
Factor V Gene ◽  
Heterozygous Carriers ◽  
First Myocardial Infarction ◽  
Control Study

SummaryThe HR2 haplotype of the factor V gene, which contains the histidine to arginine substitution at position 1299, has been reported to be associated with reduced factor V levels. Because high factor V levels have been found to be associated with an increased risk of myocardial infarction, we examined how the presence of the R2 allele affected the risk of myocardial infarction in the case-control “Study of Myocardial Infarctions Leiden”.Among 560 men with a first myocardial infarction before the age of 70 years, 9.5% were heterozygous carriers of the R2 allele. The control group consisted of 646 men, in which 9.9% were heterozygous and 0.2% homozygous carriers of the R2 allele. The risk of myocardial infarction in the presence of the R2 allele was not increased (odds ratio, 0.9; 95% confidence interval 0.6 to 1.4). Exclusion of factor V Leiden carriers did not change this result. The risk was 4.4-fold increased for smokers who carried the R2 allele compared to non-smoking noncarriers. No synergy was found between metabolic risk factors and the presence of the R2 allele.We conclude that the risk of myocardial infarction for men in the presence of the R2 allele of the His1299Arg polymorphism is neither increased nor decreased.

scholarly journals Molecular Analysis of Factor V Leiden, Factor V Hong Kong, Factor II G20210A, Methylenetetrahydrofolate Reductase C677T, and A1298C Mutations Related to Turkish Thrombosis Patients

2007 ◽  
Vol 13 (4) ◽  
pp. 435-438 ◽  
Author(s):  
Bilgen Dölek ◽  
Serpil Eraslan ◽  
Sevim Eroğlu ◽  
Belgin Eroglu Kesim ◽  
Turgut Ulutin ◽  
...  
Keyword(s):  
Hong Kong ◽  
Methylenetetrahydrofolate Reductase ◽  
Factor V Leiden ◽  
Mthfr C677t ◽  
Enzyme Analysis ◽  
Restriction Enzyme Analysis ◽  
Factor V ◽  
Conformation Analysis ◽  
Factor Ii ◽  
Fv Leiden

Inherited gene disorders related to the hemostatic system have been documented as risk factors for thrombosis. The roles of factor V Hong Kong (FV Hong Kong), factor V Leiden (FV Leiden), factor II G20210A (FII G20210A), methylenetetrahydrofolate reductase (MTHFR) C677T, and MTHFR A1298C mutations in Turkish patients with thrombosis (270 patients) compared with healthy controls (114 subjects) were evaluated. Polymerase chain reaction—based restriction enzyme analysis was carried out to screen these mutations, and single-strand conformation analysis was established to identify variations using the primers selected for restriction enzyme analysis studies. As a result, a significant relationship was determined among FV Leiden, FII G20210A, and thrombosis. The FV Hong Kong mutation was observed in only 2 patients with pulmonary vein thrombosis who are FV Leiden/FV Hong Kong compound heterozygous for FV gene. MTHFR C677T and A1298C were equally distributed in the patient group compared with the control group. All named mutations were also identified with single-strand conformation analysis, but a new variant/polymorphism during studies was not found. Because some inherited abnormalities are associated with thromboembolic disorders, determining the mutations and gene-to-gene interactions in patients with thrombosis history has a great impact on diagnosis and treatment of these diseases.

Prevalence of Activated Protein C Resistance Due To Factor V Leiden Mutation among South Asians (India and Pakistan) with Venous Thromboembolism.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4043-4043
Author(s):  
Sirisha Perumandla ◽  
Yelena Patsiornik ◽  
Neetha Mahajan ◽  
Anju Ohri
Keyword(s):  
Protein C ◽  
Chart Review ◽  
South Asians ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Factor V ◽  
Inherited Thrombophilia ◽  
Apc Resistance ◽  
Fv Leiden ◽  
Work Up

Abstract Objective: To study the prevalence of Activated Protein C (APC) resistance due to Factor V Leiden (FV Leiden) mutation among the first generation immigrants from India and Pakistan with venous thromboembolism (VTE). Introduction: APC resistance due to the substitution of Arginine 506 by Glutamine in coagulation Factor V is caused by G1691A mutation in exon 10 of Factor V gene. This is the commonest cause of inherited thrombophilia in Caucasians, but the frequency of this mutation is low in non-Caucasians. Among subjects in the Physician Health Study, the frequency of FV Leiden was found to be 5.27% in Caucasian Americans vs. 0.45% in Asian Americans. Another study found no mutation in 191 Asian Americans tested. In non-Caucasians with VTE, it is generally considered not cost effective to screen for this mutation. However Asians are a heterogeneous group and the Leiden gene frequency varies among different ethnic populations. While the frequency of FV Leiden gene has been documented to be low in China, Korea, Japan, Thailand, Indonesia etc, the frequency in India and Pakistan is not well studied. Two studies found a carrier frequency of 2% (Rees et al) and 4.2 % (Gou et al) among the general population from India and Pakistan. This is similar to the frequency found in Middle Eastern and European population. We did not come across any study of FV Leiden gene frequency in patients with VTE from India and Pakistan. Patients and Methods: A retrospective chart review of patients of Indian or Pakistani origin seen at Coney Island Hospital, from July 1996 to June 2003, who had a work up for inherited thrombophilia after an episode of VTE. During the chart review age, sex, first or recurrent episode and any predisposing factors such as immobilization, malignancy, hormonal therapy, surgery, pregnancy, and the presence of SLE or MPD were noted. Thrombophilia work up included functional assays for Protein C, S and Antithrombin III, Lupus anticoagulant, ACA and Homocysteine levels. APC resistance was measured by a clotting assay using Factor V depleted plasma and all patients who were borderline or resistant were tested for the presence of FV Leiden mutation by PCR. Results: A total of 18 patients were studied. All had an episode of VTE documented by a Doppler ultrasonography or a Ventilation Perfusion lung scan or a CT angiogram. 3 out of 18 patients (16.6%) had APC resistance. All the three patients were confirmed to be heterozygous for FV Leiden mutation. Two were male and one was a female with a median age of 36 yrs (27, 36 and 57 yrs). The female patient had a recurrent episode, first one occurred during pregnancy, but the second episode had no precipitating events. One male patient had trauma to the leg and was immobilized at the time of the VTE, another male patient was a cab driver by occupation. None of the patients had any other concurrent inherited thrombophilic state. Conclusions: The prevalence of the FV Leiden mutation is significantly high among South Asians with VTE in our study. If the findings are confirmed by a larger study, screening for this mutation for thrombophilia would be relevant in patients of South Asian origin and screening recommendations for family members would be identical to Caucasian population. The high prevalance as in Caucasians suggests a founder effect and possible spread of the mutation by the migration of Neolithic farmers from the Middle East towards Europe and India, ten thousand years ago. This has been confirmed by haplotype analysis.

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.

scholarly journals Is Factor V Leiden a Risk Factor for Fetal Loss?

1999 ◽  
Vol 42 (3) ◽  
pp. 93-96 ◽  
Author(s):  
Petr Dulíček ◽  
Ladislav Chrobák ◽  
Ivo Kalousek ◽  
Lenka Pešavová ◽  
Miroslav Pecka ◽  
...  
Keyword(s):  
Risk Factor ◽  
Pregnancy Loss ◽  
Fetal Loss ◽  
Factor V Leiden ◽  
Control Group ◽  
Factor V ◽  
Group Factor ◽  
Successful Pregnancy ◽  
Prospective Group ◽  
Increased Risk

A successful pregnancy is dependent on the development of adequate placental circulation. The abnormalities of placental vasculature may result in a number of gestational pathologies, including fetal loss. The aim of our study was to determine whether women with f V Leiden are at an increased risk of pregnancy loss. For this purpose we assessed three groups of women. In a prospective group we examined 30 females with spontaneous abortions for f V Leiden. In a retrospective group we assessed the frequency of abortions in 80 women (l72 pregnancies) with f V Leiden (72 heterozygous, 8 homozygous) from 57 unrelated families. In a control group we evaluated the frequency of abortions in 45 women without f V Leiden. Factor V Leiden was found in 3% of women in the 1st group. Fetal loss occurred in 10% of women in the 2nd group and in 9% in the 3rd group. Factor V Leiden was not found to be a risk factor for fetal loss in our study group.

scholarly journals FV Leiden Mutation and Deep Venous Thrombosis in Vojvodina: A Case-Control Study

2011 ◽  
Vol 30 (1) ◽  
pp. 51-54
Author(s):  
Iva Salatić ◽  
Katarina Kiralj ◽  
Gorana Mitić ◽  
Igor Veselinović ◽  
Dušan Vapa
Keyword(s):  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Case Control Study ◽  
Factor V Leiden ◽  
Case Control ◽  
Factor V ◽  
Increased Risk ◽  
Fv Leiden ◽  
Heterozygous Carriers ◽  
Control Study

FV Leiden Mutation and Deep Venous Thrombosis in Vojvodina: A Case-Control StudyBetween September 2007 and February 2010, the occurrence of symptomatic deep venous thrombosis (DVT) was investigated in a cohort of 79 consecutive patients. A case-control study inclu ded 71 healthy controls matched with cases for sex and age. The prevalence of factor V G1691A mutation genotype was analyzed. Eighteen cases (22.79%; 95% confidence interval (CI) 13.53% to 32.03%) and four controls (5.63%; 95% CI 0.27% to 10.99%) were heterozygous carriers of FV Leiden (p= 0.025). The odds ratio for DVT was 4.94 (95% CI 1.58 to 15.42) and the relative risk 4.04 (95% CI 1.44-11.38) compared with FV 1691G carriers. Four cases were homozygous carriers of FV Leiden, giving a prevalence of 5.06% (95% CI 0.23 to 9.89%) and no controls, therefore OR and RR calculation was based on the prevalence of homozygotes in the general Caucasian population. The OR for DVT was 47.28 (95% CI 0.04 - 52167.3) and the RR 45.57 (95% CI 0.04 to 49540.77; p=0.025) compared with FV 1691 G carriers. Our study confirms that factor V Leiden carriers in Vojvodina, as in similar studies previously carried out in other populations, have an increased risk of developing DVT. The evaluated risk of DVT in heterozygous carriers of the mutation is four- to five-fold higher, whereas for homozygous carriers it is 45- to 48-fold higher than in non-carriers. These results confirm that patients with DVT and their relatives should undergo screening for FV Leiden mutation.

Prevalence of Factor V Leiden Mutation in Non-European Populations

1997 ◽  
Vol 77 (02) ◽  
pp. 329-331 ◽  
Author(s):  
Guglielmina Pepe ◽  
Olga Rickards ◽  
Olga Camacho Vanegas ◽  
Tamara Brunelli ◽  
Anna Maria Gori ◽  
...  
Keyword(s):  
Factor V Leiden ◽  
Indirect Evidence ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
The World ◽  
Fv Leiden ◽  
Sub Saharan ◽  
Low Prevalence ◽  
European Populations ◽  
Apparently Healthy

SummaryA difference in the prevalence of venous thromboembolism (TE) in major human groups has been described and an uneven distribution of FV Leiden mutation over the world has recently been reported.We investigated FV Leiden mutation in 584 apparently healthy sub#jects mostly from populations different from those previously investi#gated: 170 Europeans (Spanish, Italians), 101 sub-saharan Africans (Fon, Bariba, Berba, Dendi), 115 Asians (Indonesians, Chinese, Tharus), 57 Amerindians (Cayapa), 84 Afroamericans (Rio Cayapa, Viche), and 57 Ethiopians (Amhara, Oromo).The mutation was detected in only 1/115 Asian (Tharu) and in 5/170 Europeans (4 Italians, 1 Spanish).These data confirm that in non-Europeans the prevalence of FV mutation is at least 7 times lower than in Europeans and provide indirect evidence of a low prevalence not only of the FV Leiden gene but also of other genes leading to more severe thrombophilia. Finally, findings from the literature together with those pertaining to this study clearly show a marked heterogeneity among Europeans.

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