Association of inherited thrombophilia with embryonic and postembryonic recurrent pregnancy loss (original) (raw)
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The impact of hereditary thrombophilias in recurrent pregnancy loss
Genetika
Introduction: Recurrent pregnancy loss (RPL) is defined as two or more consecutive pregnancy loss which occurs before the 20th weeks of pregnancies for the last menstrual period. Hereditary cause of thrombophilic gene mutations and polymorphism may play an essential role in RPLs. Material and Method: 291 women with a history of two or more consecutive abortions as a study group and 61 women without the history of miscarriages as a control group were included in a study. In this study we analysed the effects of Factor II Prothrombin mutation ,FV Leiden mutation, MTHFR C677T, MTHFT A1298C, PAI-1, ?-fibrinogen, Factor XIIIA (V34L) and Glycoprotein IIIa (L33P) polymorphisms on RPL by using pyrosequencing. Chi-square and multiple regression analysis were used for statistical analysis. Results: FII prothrombin mutation, FV Leiden mutation, MTHFR C677T, MTHFR A1298C, PAI1 and Beta fibrinogen were found statistically significant in the chi-square test. Heterozygous FV G1691A (OR:8.092, CI: ...
Egyptian Journal of Medical Human Genetics, 2020
Background: Recurrent pregnancy loss (RPL) is a common disorder that affects around 3 to 5% of pregnant women. It has different causes, and in about 50%, it is of unknown etiology. Thrombophilia might increase the risk of RPL by adversely affecting the normal placental vascular function. Our study aimed to determine the frequency of factor V Leiden (FVL) and prothrombin G20210A gene mutations in Algerian women with RPL and to correlate their presence with the occurrence of such health's problem. A total of 80 women with previous fetal losses and 100 age-matched women with no history of fetal loss were recorded. Participants were tested for activated protein C resistance (APCR), protein C (PC), protein S (PS), and antithrombin (AT) deficiencies. The screening of FVL and prothrombin G20210A mutations was also done using a duplex polymerase chain reaction. Results: APCR was detected in 6.25% of cases and was absent in controls (p = 0.011). PC and PS deficiencies were documented in 7.5% of patients. FVL was detected in 8.33% of patients and was absent in controls (p = 0.047). Prothrombin G20210A mutation was found in 8.33% of patients compared to 11.11% of controls (p = 0.631). A significant association of FVL mutation with the abortion which occurred in the second trimester was found (p = 0.001). Conclusion: There is a significant association between FVL mutation and RPL especially the loss occurring during the second trimester. No correlation was found regarding prothrombin G20210A mutation.
Annals of Hematology, 2007
Factor V Leiden (FV-Leiden) and prothrombin gene mutations (FII G20210A) are well-established independent risk factors for thrombosis. In the recent years, many studies have suggested that these mutations are associated with an increased risk of recurrent pregnancy loss (RPL). We aimed to investigate the prevalence of these molecular defects in subjects with a history of early RPL. One hundred and fourteen women with three or more consecutive unexplained first-trimester miscarriages were compared to 185 parous women with uncomplicated pregnancies from the same ethnic origin. The presence of FV-Leiden and FII G20210A mutations was assessed by polymerase chain reaction analysis. Overall, 11 out of the 114 women with early RPL (9.6%) had either FV-Leiden or FII G20210A mutation, as compared with 16 out of the 185 women with normal pregnancies (8.6%; p = 0.756). The prevalence of FV-Leiden mutation was 7.9% (9/114) in patient group, compared with 7% (13/185) in control group (p = 0.780). One hundred and two patients were primary and 12 were secondary aborters. All FV-Leiden positive cases were primary aborters (8.8%; 9/102, p = 0.584). Concerning the FII G20210A, two out of 114 (1.7%) were first-trimester RPL (primary aborters) and three out of 185 (1.6%) controls were carriers of the FII G20210A mutation (1.7 vs 1.6%, p = 0.931). The results obtained from patients with first-trimester RPL and the control group have no statistical significant differences in the prevalence of FV-Leiden and FII G20210A mutations. These results suggest that mutations have no role in etiology of first-trimester recurrent abortions.
The association between hereditary thrombophilias and pregnancy loss
Haematologica, 2005
The correlation between hereditary thrombophilia and fetal loss is supported by several observations. In murine models, the protein C system has been shown to be essential for the maintenance of pregnancy, as it indirectly acts as a growth factor for trophoblast cells and protects them from apoptosis. In humans, it has been shown that the placenta replaces the yolk sac as an essential source of blood supply to the embryo during the 8th and 9th weeks of gestation. Furthermore, meta-analysis of epidemiological data demonstrates a correlation between thrombophilic polymorphisms such as factor V Leiden and prothrombin 20210G-->A and isolated or recurrent fetal losses. Finally, therapeutic non-controlled trials indicate the benefits and safety of low-molecular weight heparins as secondary prophylaxis. However, it is still necessary to further clarify the association between thrombophilia and fetal loss, especially during a first pregnancy, with regard to the type of pregnancy loss and...
Hereditary thrombophilic risk factors for recurrent pregnancy loss
This review summarizes current knowledge about the role of hereditary hypercoagulation factors predisposing to thrombophilia-associated recurrent fetal loss. Thrombophilias are a major cause of adverse pregnancy outcome, playing a role in the etiology of up to 40% of cases worldwide. Hereditary thrombophilic predispositions to recurrent pregnancy wastage include genetic lesions in blood coagulation factors II and V as well as natural anticoagulants antithrombin, protein C, and protein S. Furthermore, methylenetetrahydrofolate reduc-tase gene variants conferring higher thrombophilia risk in combination with these mutations and the newly described annexin A5 gene M2 promoter allele are associated with repeated fetal loss. The review gives a concise description of the molecular defects arising from the genetic changes, of the role these factors play in the timing and definition of fetal loss, and risk estimates from available studies and meta-analysis. This knowledge is instrumental for a more precise assessment of individual risks for repeated fetal loss and should guide therapeutic strategies, where relevant. Since the average childbearing age increases in Western societies, the importance of a timely diagnosis of fetal loss predisposition is increasing.
Fetal gene defects precipitate platelet-mediated pregnancy failure in factor V Leiden mothers
Journal of Experimental Medicine, 2007
Recurrent pregnancy loss, defi ned as two or more spontaneous abortions, aff ects %5ف of all women of reproductive age. Epidemiological studies suggest that inherited and acquired thrombophilia of the mother, such as that caused by the Leiden polymorphism in blood coagulation factor V, contributes to the pathogenesis of fetal loss, as well as other adverse pregnancy outcomes (1-3). These studies also demonstrate a high study-to-study variability of association strength, suggesting the existence of as yet uncharacterized risk modifi ers. The pathogenesis of thrombophilia-associated fetal loss remains to be established. Evaluation of placental pathologies has not revealed a clear correlation between the prothrombotic status of the mother and the presence of villous infarcts, blood clots, or fi brin deposits in the placenta (4, 5), raising the question of whether thrombotic processes are indeed causative in thrombophilia-associated fetal loss or constitute an epiphenomenon. On the other hand, clinical trials suggest that heparin anticoagulation may indeed mitigate pregnancy failure in prothrombotic women (6-9). In view of the uncertain etiology of thrombophilia-associated pregnancy failure and the lack of established criteria for a more precise risk stratifi cation enabling identifi cation of truly at-risk pregnancies, the prophylactic anticoagulation of asymptomatic women and the risk-to-benefi t balance of anticoagulation therapy during pregnancy are subjects of intense debate (10-12).
Risk of early recurrent fetal loss and levels of thrombin-activatable fibrinolysis inhibitor
Thrombosis Research, 2012
Introduction: Though thrombin-activatable fibrinolysis inhibitor (TAFI) may contribute to hypercoagulability during pregnancy, limited data are available on the role of TAFI in women with recurrent fetal loss. Material/Methods: We performed a case-control study aimed at evaluating any possible association between TAFI levels and early recurrent fetal loss (≥ 3, or 2 with at least one normal fetal karyotype, before the 10th week of gestation). 140 women with early recurrent fetal loss and 140 age-matched healthy controls with at least one normal pregnancy were included. The number of miscarriages was 2.59 and occurred at gestational age 6.89 weeks. TAFI levels were determined by a chromogenic assay measuring total potential activatable TAFI. Results: TAFI levels were significantly lower in early recurrent fetal loss women (12.2 ± 2.3 μg/ml vs 13.2± 2.6 μg/ml in healthy controls, p = 0.001). ORs of early recurrent fetal loss (crude and adjusted for possible confounding variables) were calculated after stratification of TAFI levels into quartiles. 25/140 (17.8%) early recurrent fetal loss women had TAFI levels above 14.0 μg/ml (4th quartile) vs 44/140 (31.3%) in healthy women (p= 0.014). Crude and adjusted ORs of early recurrent fetal loss in women with TAFI levels in the 4th quartile vs those in the reference category (1st quartile= below 11.0 μg/ml) were 0.42 (95%CI: 0.22-0.82) and 0.39 (95%CI: 0.19-0.80), respectively. Conclusions: Our study provides evidence that high TAFI levels are associated with reduced risk of early recurrent fetal loss. Further studies are needed to better understand the actual role of TAFI in recurrent fetal loss.
Inherited thrombophilia and pregnancy loss. Study of an Argentinian cohort
Medicina Clínica (English Edition), 2019
Background and objectives: Thrombophilia might increase the risk of suffering from obstetric complications by adversely affecting the normal placental vascular function. Our aim was to study the distributions of five thrombosis-associated genetic variants: factor V Leiden, prothrombin G20210A, −675 4G/5G PAI-1, 10034C/T gamma fibrinogen and 7872C/T factor XI and the frequencies of the deficiencies of protein C, S and antithrombin in Argentinian patients with recurrent pregnancy loss (RPL) and, therefore, to analyse their association with the risk and timing of RPL and the risk of suffering other vascular obstetric pathologies. Patients and methods: We performed a case-control study that included 247 patients with idiopathic RPL (cases), 107 fertile controls and 224 subjects from general population (reference group). Cases were stratified according to the gestational time of the losses (early RPL, n = 89; late losses, n = 158; foetal losses, n = 107) and according to the type of vascular obstetric pathologies. Results: No differences were found in the distribution of the genetic variants among RPL group vs. control/reference group (p > .05). Similarly, no differences were observed in their distributions when analysing RPL patients stratified according to gestational times or vascular obstetric pathologies (p > .05), except for the factor V Leiden carriage in patients with foetal growth retardation vs. controls (11.8%, 4/34 vs. 1.9%, 2/107; p = .04) (OR = 7.11 [1.24-40.93], p = .03). Conclusions: Factor V Leiden might have a significant impact on certain obstetric pathologies such as foetal growth retardation. The genetic variants, 10034C/T gamma fibrinogen and 7872C/T factor XI, associated with thromboembolic disease, would not have an impact on PRE.
Hereditary thrombophilia and fetal loss: a prospective follow-up study
Journal of Thrombosis and Haemostasis, 2004
To cite this article: Vossen CY, Preston FE, Conard J, Fontcuberta J, Makris M, van der Meer FJM, Pabinger I, Palareti G, Scharrer I, Souto JC, Svensson P, Walker ID, Rosendaal FR. Hereditary thrombophilia and fetal loss: a prospective follow-up study. J Thromb Haemost 2004; 2: 592-6.