Thrombophilic Gene Polymorphisms Research Articles

Thrombophilic gene polymorphisms and recurrent pregnancy loss: a systematic review and meta-analysis.

Recurrent pregnancy loss (RPL) is affecting 1-4% of women who conceive approximately, and no cause could be found in more than 50% of women suffering from RPL. Inherited thrombophilias have got increasing attention in women with unexplained RPL, so we aim to explore the relationship among these most common thrombophilic polymorphisms and RPL through a literature review and meta-analysis. Observational studies from PubMed, Embase, Cochrane, and Web of Science from 1997 to 7 April 2022 were searched. For each genetic variant, a fixed or random-effect model was used according to the heterogeneity test to calculate pooled ORs and 95% CIs for both dominant and recessive genetic models. Egger's line regression test was used to assess publication bias. The quality of the included articles was assessed by the Newcastle Ottawa scale. A total of 124 articles comprising 17,278 RPL patients and 16,021 controls were included. Results showed that hyperhomocysteinemia (MTHFR) C677T (dominant model: OR, 1.43; 95% CI, 1.25-1.64; recessive model: OR, 1.60; 95% CI, 1.36-1.87), MTHFR A1298C (dominant model: OR, 1.66; 95% CI, 1.26-2.18; recessive model: OR, 1.79; 95% CI, 1.42-2.26), PAI-1 4G/5G (dominant model: OR, 1.67; 95% CI, 1.36-2.06; recessive model: OR, 1.80; 95% CI, 1.39-2.32), angiotensin-converting enzyme I/D (OR, 1.23; 95% CI, 1.00-1.53), Factor XIII V34L (OR, 1.38; 95% CI, 1.02-1.87), and β-fibrinogen-455G/A (OR, 1.60; 95% CI, 1.02-2.51) were significantly associated with RPL. This study provides potentially useful clinical markers to evaluate the risk of RPL or to help unexplained RPL patients identify possible causes, which may allow for targeted treatment.

Study of common chromosomal abnormalities and Plasminogen activator Inhibitor(PAI-1) gene Polymorphism (5G/4G) and Prothrombin (F2)gene mutation(G20210A) in women with recurrent abortions in the North West of Iran

Background. Parental chromosomal abnormalities as well as changes in genes encoding thrombophilic factors are common causes of recurrent abortions. One of the causes of thrombophilia is Factor II (F2) gene mutation (G20210A) and plasminogen activator inhibitor gene (PAI-1) polymorphism (4G/5G). Therefore, the present study aimed to investigate the frequency of chromosomal abnormalities and the association of thrombophilic gene polymorphisms in patients with abortion in northwestern Iran. Methods. In the present case-control study, cytogenetic analysis of 60 couples with a history of recurrent abortions was performed by the standard 72-hour culture of lymphocytes and G-banding. The polymorphism (5G/4G) of PAI-1 gene and the mutation (G20210A) of F2 genes were evaluated using RFLP-PCR and ARMS-PCR molecular methods, respectively. The obtained data were analyzed using statistical software. Results. No significant abnormalities affecting abortion were observed in cytogenetic studies; in the molecular study, the frequency of the 4G allele in patients and control groups were 54.2% and 33.3%, respectively; the frequency of 5G allele in the patients and control groups were 45.8% and 66.8%, respectively. The frequency of 5G/5G and 4G/5G genotypes is 25.0% and 41.6% in the patient group, and 55.0% and 23.3% in the control group, respectively. Also, the frequency of 4G/4G genotype in patients and controls were 33.3% and 21.6%, respectively. Conclusion. The results of this study show that there is a significant relationship between the frequency of the 4G allele of the PAI-1 gene with susceptibility to recurrent abortions in northwestern women, while no was relationship between F2 gene mutation and recurrent abortions was observed.

Determining the association of thrombophilic gene polymorphisms with recurrent pregnancy loss in Iranian women

Objective Thrombophilia is known to be associated with poor pregnancy outcomes. In this study, three thrombophilic gene polymorphisms, including EPCR (Ser219Gly), F11 (rs4253417) and F7 (323 Ins10) were investigated in an Iranian population of women in order to determine the correlation between thrombophilia and recurrent pregnancy loss (RPL). Methods Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) were used to evaluate the frequency of three candidate thrombophilic risk factors for recurrent pregnancy loss. The frequencies of the polymorphisms were compared between the case (144 patients with a history of at least two miscarriages) and the control (150 healthy women with no abortion) group. Results Our results show that EPCR and FVII polymorphisms of the patient and control group have the same genotype frequency, and the difference is not statistically significant (p-value > .05). Regarding FXI polymorphism, TT genotype frequency was higher in the patient group than the control group (p-value < .05); however, CT heterozygote form was higher in the control group compared to the patient group (p-value < .05). Conclusion In FXI polymorphism, T allele is possibly an RPL risk factor and C allele has a protective role. Thus, wild type FXI could be related to RPL, but EPCR and FVII polymorphism have no such correlation.

Genetic risk factors for venous thromboembolism among infertile men with Klinefelter syndrome

BackgroundKlinefelter syndrome (KS) is one of the commonest sex chromosome disorders. Affected males become infertile and highly susceptible to several health problems, including vascular thromboembolism (VTE). The risk of VTE may be exacerbated by an underlying genetically inherited thrombophilia. In this study, we aimed to investigate the genotype and allele frequencies of common gene polymorphisms related to hereditary thrombophilia in infertile males with KS compared to normal, fertile men. MethodsEighty-five infertile males with KS and 75 healthy control males were included in this case-control study. Genetic testing was done using an extended thrombophilia gene panel by Multiplex PCR reverse hybridization method. ResultsThere was an increased frequency of mutant alleles and heterozygous genotypes of FV Leiden, FV H 1299R, Pro G20210A, MTHFR C677T and PAI-1 4G/5G thrombophilic gene polymorphisms in KS patients compared to the control group. It was shown that 10.7% of KS patients had the A3 haplotype of the EPCR gene in comparison to 5.3% of control patients. The A3/A3 genotype was found only in KS patients (7.1%). Carriers of more than one mutant allele in KS patients exceeded the control (p < 0.001). ConclusionA high prevalence of thrombophilic gene polymorphisms and the coexistence of different mutant alleles were evident in infertile KS males. These data highlight the importance of conducting further studies to understand the role of hereditary thrombophilia in predicting venous thrombosis in patients with Klinefelter syndrome.

Combined presence of coagulation factor XIII V34L and plasminogen activator inhibitor 1 4G/5G gene polymorphisms significantly contribute to recurrent pregnancy loss in Serbian population.

Recurrent pregnancy loss (RPL) is a heterogeneous condition affecting up to 5% of women of reproductive age. Inherited thrombophilia have been postulated as one of the causes of RPL. Here we examined the prevalence of nine thrombophilic gene polymorphisms among women with history of recurrent miscarriages and fertile controls. The study included 70 women with history of at least three early pregnancy losses and 31 fertile controls with no miscarriages. We investigated mutations in genes responsible for clotting and fibrinolysis, including factor V (FV) Leiden, FV H1299R, factor II (FII) G20210A, methylene tetrahydrofolate reductase (MTHFR) C677T and A1298C, factor XIII (FXIII) V34L, plasminogen activator inhibitor-1 (PAI-1) 4G/5G and endothelial protein C receptor (EPCR) H1 and H3 haplotypes using reverse polymerase chain reaction ViennaLab cardiovascular disease StrippAssays. Our results showed no significant increase in prevalence of tested polymorphisms in women with RPL. However, relative risk for PRL among women heterozygous for FXIII V34L was 2.81 times increased (OR 2.81, 95% CI 1.15-6.87, P=0.023). Haplotype analysis showed that combined presence of high-risk genotypes for FXIII and PAI-1 significantly increases risk for RPL (OR 13.98, CI 95% 1.11-17.46, P=0.044). This is the first study in Serbian population that investigated prevalence of FVR2, A1298C, FXIII V34L and EPCR gene variants. Compound heterozygosity for FXIII V34L and PAI-1 4G is significant risk factor for recurrent miscarriage. Our results should be viewed in context of small case-control study, so further large prospective studies are need for confirmation of our findings.

Thrombophilic gene polymorphisms are associated with deep venous thrombosis in a cohort of Egyptian patients

Background There is several evidence suggesting, that inherited thrombophilia increases the susceptibility to venous thromboembolism (VTE). Aim is to detect prothrombotic genes polymorphisms possible association with the risk of occurrence of venous thrombosis. Methods A group of eleven gene polymorphisms related to the risk of thromboembolic events were studied; including Factor V Leiden(FVL) 1691G>A, Methylene tetrahydrofolate reductase gene (MTHFR) C677>T and others. Genotyping was done using PCR, and identification of corresponding bands using the StripAssay in 493 patients with clinical symptoms of deep venous thrombosis (DVT). Five hundred age and sex matched healthy individuals were included as a control group. Results Genotyping of DVT patients showed significantly higher prevalence of FVL 1691G>A, MTHFR C677>T, MTHFR 1298A>C, Prothrombin 20210G>A, PAI 4G, FVIII V34L, B Fibrinogen 455G>A, HPA-1, ACE and APO E e4 gene polymorphisms (p Conclusion Individuals carrying thrombophilic genes polymorphisms are at a greater risk for venous thrombosis.

Prevalence of Thrombophilia in Palestine and the Association of Thrombophilic Gene Polymorphisms with Recurrent Pregnancy Loss

Prevalence of Thrombophilia in Palestine and the Association of Thrombophilic Gene Polymorphisms with Recurrent Pregnancy Loss

Association between Thrombophilic Gene Polymor-phisms and Recurrent Pregnancy Loss in Iranian Women

Background: Recurrent pregnancy loss (RPL) is a common problem among couples, and acquired thrombophilia is the well-known etiology of RPL. The aim of this study was to establish the association between inherited thrombophilic gene polymorphisms and RPL. Methods: This case-control study was conducted on 50 women with unexplained RPL and 50 parous women with no history of miscarriage (age range: 17–48 years). The data were collected during 2013–2015 in Sarem Hospital, Tehran, Iran. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for glycoprotein IIIa (PLA1/PLA2), KDR (Q472H), and β-fibrinogen (-455G/A); tetra-primer amplification refractory mutation system (ARMS)-PCR for glycoprotein Ia (807c/t) and vascular endothelial growth factor (VEGF) (2578c/a), and ins/del PCR for angiotensin I-converting enzyme (ACE) (intron 16 I/D). The association between the frequency of the genotypes and RPL was determined by Chi-square and Fisher’s exact tests. Results: The results of the present study revealed a significant relationship between glycoprotein Ia (807C/T), VEGF (2578C/A), and ACE (intron 16 I/D) polymorphisms and RPL (P=0.00, 0.02, and 0.00, respectively). In contrast, no relationship was observed between β-fibrinogen (-455G/A), KDR (Q472H), and glycoprotein IIIa (PLA1/PLA2) polymorphisms and increased risk of RPL (P>0.05). Conclusion: This study demonstrated that glycoprotein Ia (807C/T), VEGF (2578C/A), and ACE (intron 16 I/D) polymorphisms may be a risk factor for the women with a history of RPL.

Thrombophilic gene polymorphisms and recurrent pregnancy loss in Greek women.

Recurrent pregnancy loss (RPL) is a multifactorial disorder. The aim of this study was the detection of various genetic polymorphisms and their correlation to RPL, in Greek women. The impact of 12 thrombophilic polymorphisms was evaluated, among 48 Greek women with a history of RPL, vs 27 healthy parous women. Multiplex PCR and in situ hybridization on nitrocellulose films were performed, to investigate 12 genetic polymorphisms previously reported as risk factors for RPL. Heterozygous FV Leiden, homozygous PAI-1 4G/4G, heterozygous MTHFR C677T, homozygous MTHFR A1298C, as much as the combined thrombophilic genotypes MTHFR 677T + ACE Ι/D, MTHFR 677T/1298C + ACE D/D, ACE I/D + b-fibrinogen -455G/A, FV HR2 + b-fibrinogen -455G/A showed a correlation as risk factors for RPL, whereas the rest of the investigated polymorphisms and their combinations did not render statistically significant differences between the two groups in study. The results of this study, as well as those of similar studies, concerning the detection of genetic, environmental, and physiological factors underlying RPL, will prove of critical significance in the investigation and treatment of thrombophilic predisposition, in cases of RPL.

Study of thrombophilic gene polymorphisms in Egyptian patients with deep venous thrombosis using in situ hybridization technique.

Up to 70% of thrombotic patients with no identifiable risk factors were termed idiopathic. Now, molecular diagnostics combined with existing laboratory techniques allow accurate classification of at least half of patients with inherited thrombotic disorders. However, the previously studied genetic variants explain only a fraction of all thromboembolic events, so the aim of the present study was to expand the genetic prevalence determination to include also more extensive thrombophilic gene polymorphisms in patients with DVT compared to healthy subjects in Egyptian population. This study was conducted on 75 patients with DVT and 45 age and sex matched healthy subjects as control group. The diagnosis of DVT was based on patient’s history, clinical findings, D-dimer test, and confirmed by Doppler ultrasonography. Both groups were assessed for thrombophilic gene polymorphisms using multiplex polymerase chain reaction and reverse-hybridization technique through CVD strip assay. It was found that FV Leiden G1691A (P=0.001), Factor V H1299R (P=0.02), MTHFR A1298C (P=0.02), β-fibrinogen−455 G/A (P=0.01), PAI-1 4G/5G (P=0.03) and ACE (P=0.03) polymorphisms were all significantly associated with an increased risk of DVT. Our data are of extreme importance in clinical practice for introducing the extended CVD panel into routine molecular diagnostic tests to allow management of thrombotic patients and screening, thromboprophylaxis and genetic counselling for high-risk individuals.

The thrombophilic gene polymorphisms and recurrent pregnancy loss dilemma: From Minsk/Belarus and Canakkale – Sivas/Turkish populations

The thrombophilic gene polymorphisms and recurrent pregnancy loss dilemma: From Minsk/Belarus and Canakkale – Sivas/Turkish populations

Association of Hemostatic Gene Polymorphisms With Early-Onset Ischemic Heart Disease in Egyptian Patients.

The association between hereditary thrombophilia and venous thrombosis is well established but controversial data exist with respect to arterial thrombosis. We performed a pilot study on 31 patients with acute myocardial infarction (AMI), 21 patients with unstable angina (UA), and 20 healthy volunteers to investigate the role of various hemostatic gene polymorphisms in young Egyptian patients, who survived their first ischemic heart disease (IHD). Thrombophilic gene polymorphisms were tested using multiplex polymerase chain reaction and reverse-hybridization technique. We showed an increased risk of AMI with factor V (FV) Leiden and prothrombin G20210A heterozygosity. The increased risks of UA was associated with GA and A allele of fibrinogen β-455G→A polymorphism. Conversely, factor XIII (FXIII) Val34Leu GT and T allele were protective in the UA group. Nevertheless, the prevalence of FV H1299R, plasminogen activator inhibitor 1 4G/5G, glycoprotein IIIa C1565T, 5,10-methylenetetrahydrofolate reductase C677T, and A1298C mutations did not differ between patients with IHD and controls. The data have clinical implications regarding screening and thromboprophylaxis in high-risk individuals younger than 40 years.

Genetic susceptibility to deep venous thromboembolism: the roles of inherited thrombophilia polymorphisms.

Recently much attention has been paid to the possibly considerable role of the thrombophilic gene polymorphisms in the pathogenesis of deep venous thromboembolism (DVT). However, the reported results are controversial. Hence, this study aimed to disclose the association between factor VII (FVII) 10976G/A, angiotensin-converting enzyme (ACE; intron 16 I/D), glycoprotein Ia (GPIa) 807C/T, tissue-type plasminogen activator (t-PA; intron 8 D/I) and tissue-factor pathway inhibitor 536C/T polymorphisms and DVT. We investigated these gene polymorphisms in 693 study participants including 193 patients who showed clinical symptoms of DVT and 500 healthy individuals without both personal and family histories of thromboembolic disorders. Genotyping was performed using the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) technique. Comparison of genotypes distribution revealed that the FVII 10976G/A polymorphism was significantly related with DVT (P < 0.05), whereas there was no association between the ACE (intron 16 I/D), GPIa807C/T, t-PA (intron 8 D/I) and tissue-factor pathway inhibitor 536C/T gene polymorphisms and DVT (P > 0.05). In addition, the prevalence of homozygote genotype and mutant allele for FVII 10976G/A polymorphism was significantly higher in cases compared with controls (P < 0.05). Taken together, our data provide evidence to support the hypothesis that FVII 10976G/A polymorphism may be associated with a predisposition to DVT.

Cytogenetic Analysis and Thrombophilia-Associated Gene Mutations of Couples with Recurrent Miscarriage

Introduction: Three or more pregnancy losses before 20 weeks of gestation are usually defined as recurrent miscarriage. Parental chromosomal translocations, thrombophilic gene polymorphisms, autoimmune factors, uterine, endocrine factors associated with recurrent miscarrige (RM). Factor V Leiden, prothrombin gene mutation G20210A, protein S/Protein C/antithrombin deficiency and MTHFR mutations responsible for hereditary thrombophilia and has been included to keep a very common practice of RM pathogenesis. This study aimed to determine the incidence of these factors believed to be the effects of RM. Materials and methods: All patients were took a full genetic analysis; full genetic examination and pedigree drawing was done to exclude known nonchromosomal causes of the anomaly. Cytogenetic analysis was done for 635 patients. The study included peripheral lymphocyte culture by a standard method using Leishmann-banding technique, centromerebanding (C-banding), and nucleolar organizing region staining was done when needed. Pyrosequencing was used to genotype the 392 individual. Results: Male/female in patients with an inherited thrombophilia tested four types of changes, including; MTHFR C677T/1298, FV Leiden G1691A and prothrombin G20210A. Among them, 152 men and woman did not carry any mutation.

Comparison of the thrombophilic gene polymorphisms and recurrent pregnancy loss: Results on combined gene effect of FVLeiden, FVR2, FXIII, MTHFR(A1298C and C677T), PAI-1 4G/5G and ACE I/D genes in RPL Women from Misk/Belarus and Canakkale - Sivas/Turkey

Comparison of the thrombophilic gene polymorphisms and recurrent pregnancy loss: Results on combined gene effect of FVLeiden, FVR2, FXIII, MTHFR(A1298C and C677T), PAI-1 4G/5G and ACE I/D genes in RPL Women from Misk/Belarus and Canakkale - Sivas/Turkey

Polymorphisms in thrombophilic genes are associated with deep venous thromboembolism in an Iranian population

It has been revealed that the inherited thrombophilia increases the risk of thrombosis in the venous system. To study the association of factor V G1691A, factor V HR2 (4070A/G), prothrombin G20210A, and PAI-1 (−675 I/D, 5G/4G) polymorphisms with deep venous thromboembolism (DVT), these polymorphisms were investigated.A total of 193 patients who presented clinical symptoms of deep venous thromboembolism including 103 men and 90 women, and 500 healthy individuals without both personal and family histories of thromboembolic disorders including 275 men and 225 women were recruited into the study. Genotyping was carried out using the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) technique.Our results showed that the genotype distribution for FV (G1691A and A4070G) and PAI-1 4G/5G polymorphisms in DVT patients were significantly higher than healthy control (P<0.05). Also, the mutant allele frequencies for all studied polymorphisms differed significantly between the case and control groups (P<0.05).We concluded that the prevalence of FV (G1691A and A4070G) and PAI-1 4G/5G polymorphisms increased the risk of DVT occurrence in subjects. These findings provide additional evidence to support the hypothesis that thrombophilic gene polymorphisms are involved in vascular thromboembolism.

Prevalence of thrombophilic gene polymorphisms in an azari population of iran.

There is several evidence suggests that thrombophilic gene polymorphisms may influence susceptibility to thromboembolic events. The prevalence of these polymorphisms is different in various races and ethnics. Accordingly, we studied the prevalence of Factor V (G1691A and A4070G), prothrombin G20210A and PAI-1 4G/5G in healthy northwest population of Iran. In this prospective study, 500 healthy individuals, who had no history of both personal and family history of thromboembolic disorders, were selected as a sample of healthy population in northwestern Iran. Genotyping of these polymorphisms was performed using the amplification refractory mutation system-polymerase chain reaction method. No significant differences were detected between the expected and observed frequencies of FV G1691A and A4070G, prothrombin G20210A polymorphisms (P>0.05), while the expected frequency of 4G allele was significantly more than observed frequency in the studied population (P<0.01). These findings were compared with other reports from various populations. In conclusion, the allele frequency for FV G1691A and PAI-1 4G/5G polymorphisms showed relative consistency compared to those of previous studies, while the incidence pattern of FV A4070G polymorphism in Northwestern population of Iran showed conflicting results regarding other studied population. The prothrombin G20210A polymorphism was observed at a higher frequency than other studied populations.

Prevalence of thrombophilic gene polymorphisms (FVL G1691A and MTHFR C677T) in patients with myocardial infarction

BackgroundInherited thrombophilia may be caused by mutations, polymorphisms in a variety of genes mainly involved in haemostatic pathways.Aim of the study, was to find the prevalence of thrombophilic gene factor V Leiden (FVL) and methylene tetrahydrofolate reductase (MTHFR) gene polymorphism in patients with myocardial infarction (MI), aiming at early diagnostic methods and guiding preventive procedures. Subjects and methodsThis study was carried on 30 patients who survived their first MI as compared to 15 healthy volunteers. Patients and controls were subjected to history, physical examination. Factor VL G1691A and MTHFR C677T genotypes were determined by RT PCR. ResultsThe prevalence of heterozygous FVL GA genotype was significantly higher among MI patients as compared to the control group. The prevalence of mutant homozygous AA was significantly higher in MI patients as compared to control. The low risk cases had a higher frequency of GA genotype as compared to high risk cases.As regards MTHFR C677T gene polymorphism, the prevalence of heterozygous MTHFR C677T CT genotype showed significant increase in MI patients compared with the control group. The prevalence of mutant homozygous TT genotype was significantly higher in MI patients as compared to the control group. The low risk cases had a higher frequency of heterozygous MTHFR C677T CT genotype than high risk cases. To concludeThe prevalence of heterozygous (FVL G1691A) and MTHFR C677T gene polymorphisms was significantly increased in MI patients compared with the control group and these gene polymorphisms are probably risk factors for myocardial infarction among Egyptian cases especially if integrated with other environmental and genetic risk factors. We recommended screening high risk patients for this polymorphism and the use of specific thromboprophylaxis to prevent recurrent thrombotic disease.

PLA2 polymorphism of platelet glycoprotein IIb/IIIa but not Factor V Leiden and prothrombin G20210A polymorphisms is associated with venous thromboembolism and more recurrent events in central Iran

Inherited thrombophilic gene polymorphisms have been linked to the pathogenesis of venous thromboembolism (VTE). As there are very limited data of these polymorphisms in the Iranian population, we aimed to investigate the correlation between them and VTE in central Iran. Seventy-two unrelated VTE patients and 306 healthy control individuals were recruited for the study. Genotyping from venous blood with EDTA for the factor V Leiden (FVL), prothrombin (FII) G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T and PLA2 polymorphism of platelet glycoprotein IIb/IIIa were undertaken by PCR-restriction fragment length polymorphism (PCR-RFLP). A total of 57 investigated polymorphisms with a mean of 0.79 per individual and 151 with a mean of 0.49 were found in patients and controls, respectively (P<0.001). FVL and FII G20210A were found, respectively, in 5.6 and 1.4% of the patients compared with 2.3 and 1% of the controls (P=NS). PLA2 polymorphism of GPIIb/IIIa was seen in 27.8 and 10.1% in patients and controls, respectively [odds ratio (OR), 3.4; 95% confidence interval (CI), 1.08-6.44, P<0.001]. Approximately 15.3% of VTE patients compared with 5.9% of controls had coinheritance of more than one genetic risk factor (P=0.007) and more recurrent events occurred in such patients. Patients with PLA2 polymorphism had more recurrent events than the other patients (P=0.02). Patients with more than one genetic risk factor and recurrent events were younger. The prevalence of these polymorphisms is different from some previously published data in other populations, but is consistent with some others. Higher prevalence of PLA2 polymorphism of GPIIa/IIIb in VTE patients is indicative of the impact of this polymorphism in the pathogenesis of VTE in this population. Because of the impact of coinheritance on the recurrence and the age of occurrence, such patients may need to be managed differently.

Risikoschwangerschaften und deren Therapie

SummaryRecurrent abortions are a common problem. A therapy with low-molecular-weight heparin is usual in deep vein thrombosis with thrombophilia, in woman with recurrent abortions or other risks, like EPH-gestosis or HELLP-Syndrom. Patients, method: The efficacy of a mono-therapy with LMWH (3000–16 000 daily) in women with risk pregnancies has been examined prospectively. The dates of 676 pregnant women have been analysed and compared to the current literature about live birth rates without therapy and tot he results of other, similar studies. The live birth rate has been the target variable. Results: We obtained main a live birth rate of 98.6%.There has been no record of serious adverse effects. We obtained a live birth rate of 95.8% if NMH therapy starts early, and a live birth rate of 100% if NMH therapy starts between week 20 and 25. For the live birth rate the existence of thrombophilic gene polymorphisms is irrelevant. Conclusion: The high live birth weight is depended on early starting the therapy with NMH. For the late risk it is favourable to start the therapy with heparin between week 20 and 25 week of pregnancy.