G20210A Prothrombin Gene Mutation Research Articles

Risk Factors, Clinical Manifestations, Anticoagulation Duration, and Outcomes in Carriers of Severe Inherited Thrombophilia

Severe Inherited thrombophilia comprises deficiencies of antithrombin (AT), protein C (PC), and protein S (PS), while gain-of-function (GoF) variants include homozygosity for factor V Leiden (FVL) or prothrombin gene G20210A mutation (PGM), or double-heterozygosity. Persons with AT, Protein C, or S deficiencies have a heightened risk of developing thrombosis from a young age. Several family members are usually affected, and thrombosis may occur in unusual locations.Homozygote or double heterozygous of GoF variants may not have a family history of thrombosis, and the first thrombotic event may present later in life. The optimal duration and type of anticoagulation and their long-term outcomes for persons with severe thrombophilia require further investigation. This study aimed to compare risk factors, clinical manifestations, type and duration of anticoagulation and clinical outcomes between persons with AT, protein C, and S deficiencies and homozygote or double heterozygous persons with GoF variants. Retrospective evaluation of electronic medical records of persons with severe inherited thrombophilia referred to the Center for Blood Disorders at Weill Cornell Medicine-New York Presbyterian Hospital between January 2009 and December 2022. Severe deficiencies of AT, PC and PS were defined as (AT ≤ 60%, PC ≤ 50% and PS ≤ 40%). Results needed to be confimed in second testing in one month interval. Statistical analysis was performed using descriptive statistics, and chi-square test and Fisher's exact test were applied to compare variables between persons with AC deficiencies and GoF variants. 795 persons with inherited thrombophilia were identified, of those 671 were excluded as they had mild thrombophilia. Of the remaining 124 persons, 17 were eliminated due to absence of confirmatory results. A total of 107 persons were analyzed. There were 47 (44%) persons with anticoagulant deficiencies (AT, PC, and PS) and 60 (56%) homozygotes for FVL, PGM or double heterozygote. Mean age (SD) was 48 (13.6) and 49 (12.2) for anticoagulation deficiency and GoF mutation, respectively (Table 1). Overall risk factors for thrombosis were similar in both groups. A positive family history of thrombosis in a first-degree family member was higher in the anticoagulant deficient group (68%) compared to the GoF mutation (42%) (p=0.008). In addition, persons with anticoagulant deficiency had higher rates of thrombosis before 40 years of age compared to the GoF mutation group, 68% and 26%, respectively (p=0.031). The most frequent anticoagulant prescribed was a DOAC in both groups, with 38% and 30% used for the anticoagulation deficient group and GoF mutation group, respectively. The duration of anticoagulation was similar in both groups with most patients remaining on anticoagulation for more than one year (79% anticoagulant deficient group, 65% GoF mutation group) (p=0.3). Patients with AC deficiency had more recurrent thrombotic events while on anticoagulation compared to GoF variants (17% vs 6.7%) (Table 2). Our results indicate that patients with severe inherited thrombophilia either due to anticoagulant deficiencies or GoF mutations are likely to remain on anticoagulation for long durations and may have recurrent thrombosis despite therapeutic anticoagulation.

Risk assessment of venous thromboembolism in inflammatory bowel disease by inherited risk in a population-based incident cohort.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease of the digestive tract with increasing prevalence globally. Although venous thromboembolism (VTE) is a major complication in IBD patients, it is often underappreciated with limited tools for risk stratification. To estimate the proportion of VTE among IBD patients and assess genetic risk factors (monogenic and polygenic) for VTE. Incident VTE was followed for 8465 IBD patients in the UK Biobank (UKB). The associations of VTE with F5 factor V leiden (FVL) mutation, F2 G20210A prothrombin gene mutation (PGM), and polygenic score (PGS003332) were tested using Cox hazards regression analysis, adjusting for age at IBD diagnosis, gender, and genetic background (top 10 principal components). The performance of genetic risk factors for discriminating VTE diagnosis was estimated using the area under the receiver operating characteristic curve (AUC). The overall proportion of incident VTE was 4.70% in IBD patients and was similar for CD (4.46%), UC (4.49%), and unclassified (6.42%), and comparable to that of cancer patients (4.66%) who are well-known at increased risk for VTE. Mutation carriers of F5/F2 had a significantly increased risk for VTE compared to non-mutation carriers, hazard ratio (HR) was 1.94, 95% confidence interval (CI): 1.42-2.65. In contrast, patients with the top PGS decile had a considerably higher risk for VTE compared to those with intermediate scores (middle 8 deciles), HR was 2.06 (95%CI: 1.57-2.71). The AUC for differentiating VTE diagnosis was 0.64 (95%CI: 0.61-0.67), 0.68 (95%CI: 0.66-0.71), and 0.69 (95%CI: 0.66-0.71), respectively, for F5/F2 mutation carriers, PGS, and combined. Similar to cancer patients, VTE complications are common in IBD patients. PGS provides more informative risk information than F5/F2 mutations (FVL and PGM) for personalized thromboprophylaxis.

Evaluation of acquired and hereditary risk factors for the development of thromboembolism in patients with systemic lupus erythematosus.

Although the contribution of antiphospholipid antibodies (aPL) to thrombolembolism in systemic lupus erythematosus (SLE) is well known, there is not enough data on the contribution of various hereditary thrombophilic factors. In this study, we aimed to determine acquired and hereditary thrombophilic factors in adult patients with SLE. A total of 93 SLE patients (87 women and 6 men) were included. Data on clinical, demographic and laboratory characteristics, and disease activity scores (SLEDAI) of the patients were evaluated. The patients were analyzed with a screen, including lupus anticoagulant, anticardiolipin antibodies (aCL), antithrombin III, protein C, protein S, and homocysteine levels; factor V Leiden ( FVL ), methylenetetrahydrofolate reductase ( MTHFR ) and prothrombin G20210A gene mutations. A total of 23 thromboembolic events were reported in 17 (18.3%) of the patients. The frequency of pregnancy complications and SLEDAI scores were significantly higher in SLE patients who had a thromboembolism event ( P < 0.05). Thromboembolism was detected in 12 (32.4%) of 37 patients with positive aPL antibody and 5 (8.9%) of 56 patients with negative aPL antibody ( P = 0.006). In addition, thromboembolism developed in 11 (32.3%) of 34 lupus anticoagulant-positive patients and 6 (10.1%) of 59 lupus anticoagulant-negative patients ( P = 0.012). Moreover, protein C levels were significantly lower in patients who developed thromboembolism ( P < 0.05). Patients with and without thromboembolism were similar in terms of genetic thrombophilia factors ( MTHFR A1298C, MTHFR C677T, FVL and Prothrombin G20210A ) ( P > 0.05). In conclusion, in the current study, some acquired (aPL, lupus anticoagulant and cCL IGG) and hereditary (protein C deficiency) thrombophilic factors were shown to be associated with the development of thrombosis in SLE patients. However, the effect of other hereditary factors on the development of thromboembolism could not be demonstrated. According to the data of this study, genetic screening seems inappropriate in terms of the risk of thromboembolism in patients with SLE.

Association of single nucleotide polymorphisms (4G/5G) of plasminogen activator inhibitor-1 and the risk factors for placenta-related obstetric complications.

Placenta-related obstetric complications (PROCs) such as miscarriage, fetal growth restriction, preeclampsia, and preterm birth are the major causes of maternal and fetal morbidity and mortality. The objective of this study was to search the relevance of plasminogen activator inhibitor-1 (PAI-1) polymorphisms and co-morbidities and the risk factors for PROCs such as miscarriage, fetal growth restriction, preeclampsia, and preterm birth. This retrospective study analyzed the PAI-1 genotype in a cohort of 268 multiparous women with poor obstetric history. Poor obstetric history was defined as the presence of at least one of the PROCs and/or poor gestational outcomes at the previous pregnancy/pregnancies. 5G allele frequency was higher than the 4G allele frequency in the cohort (0.767 vs. 0.233). The frequencies of having at least one risk factor are relatively similar among the different PAI-1 genotypes (P > 0.05). However, the presence of MTHFR polymorphisms (homozygous and compound heterozygous forms of C677T and A1298G) and hereditary thrombophilia (Factor V Leiden and prothrombin G20210A gene mutations, and FXIII deficiency) were found to be associated with PAI 4G/4G (P = 0.048) and 5G/5G (P = 0.022) genotypes, respectively. Significant differences were not observed in other risk factors and co-morbidities such as autoimmune disorders, chronic inflammatory diseases, history of venous thromboembolism, carbohydrate metabolism disorders, hyperlipidemia, cardiovascular and cerebrovascular diseases depending on PAI-1 genotypes (P > 0.05). MTHFR polymorphisms were found to be associated with PAI 4G/4G genotype, while 5G/5G genotype was observed more frequently in hereditary thrombophilia cases.

A Comprehensive Review of Risk Factors for Venous Thromboembolism: From Epidemiology to Pathophysiology

Venous thromboembolism (VTE) is the third most common cause of death worldwide. The incidence of VTE varies according to different countries, ranging from 1-2 per 1000 person-years in Western Countries, while it is lower in Eastern Countries (<1 per 1000 person-years). Many risk factors have been identified in patients developing VTE, but the relative contribution of each risk factor to thrombotic risk, as well as pathogenetic mechanisms, have not been fully described. Herewith, we provide a comprehensive review of the most common risk factors for VTE, including male sex, diabetes, obesity, smoking, Factor V Leiden, Prothrombin G20210A Gene Mutation, Plasminogen Activator Inhibitor-1, oral contraceptives and hormonal replacement, long-haul flight, residual venous thrombosis, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, trauma and fractures, pregnancy, immobilization, antiphospholipid syndrome, surgery and cancer. Regarding the latter, the incidence of VTE seems highest in pancreatic, liver and non-small cells lung cancer (>70 per 1000 person-years) and lowest in breast, melanoma and prostate cancer (<20 per 1000 person-years). In this comprehensive review, we summarized the prevalence of different risk factors for VTE and the potential molecular mechanisms/pathogenetic mediators leading to VTE.

The risk of major bleeding in patients with factor V Leiden or prothrombin G20210A gene mutation while on extended anticoagulant treatment for venous thromboembolism

BackgroundThrombophilia predisposes to venous thromboembolism (VTE) because of acquired or hereditary factors. Among them, it has been suggested that gene mutations of the factor V Leiden (FVL) or prothrombin G20210A mutation (PGM) might reduce the risk of bleeding, but little data exist for patients treated using anticoagulants. ObjectivesTo assess whether thrombophilia is protective against bleeding. MethodsThis multicentre, multinational, prospective cohort study evaluated adults receiving long-term anticoagulants after a VTE event. We analyzed the incidence of major bleeding as the primary outcome, according to the genotype for FVL and PGM (wild-type and heterozygous/homozygous carriers). ResultsOf 2260 patients with genotype testing, during a median follow-up of 3 years, 106 patients experienced a major bleeding event (17 intracranial and 7 fatal). Among 439 carriers of FVL, 19 experienced major bleeding and there were no differences between any mutation vs wild-type (hazard ratio [HR], 0.89 [0.53-1.49]; p = .66). The comparison of major bleeding events between the 158 patients with any-PGM mutation (heterozygous or homozygous) vs wild-type also showed a nonstatistically significant difference with HR of 0.53 (0.19-1.43), p = .21. However, multivariate analysis demonstrated that major bleeds or clinically relevant nonmajor bleeding were statistically less likely for patients with either FVL and/or PGM compared with patients with both wild-type factor V and prothrombin genes (HR, 0.73; 95% CI = 0.55-0.97; p = .03). ConclusionThis study demonstrates that thrombophilia, defined as the presence of either FVL or the prothrombin G20210A mutation, is related with a lower rate of major/clinically relevant nonmajor bleeding while on anticoagulants in the extended treatment for VTE.

A unique case of Lemierre&amp;apos;s Syndrome and cerebral vein thrombosis in a carrier of prothrombin gene G20210A mutation

Introduction: We describe here a case of a woman admitted to our Internal Medicine Unit for multifocal pneumonia. During the stay, she presented a few neurological symptoms: headache, nausea, emesis, photophobia, and gait disturbance. Methodology: Chest computed tomography (CT) detected multiple areas interpreted as septic emboli. Moreover, a left internal jugular thrombosis (LIJT) was incidentally reported. A CT-angiography showed the LIJT extension to cerebral sinuses. Ear, nose, and throat consultation revealed a left medium otitis. Anticoagulation with Fondaparinux was associated to antibiotic therapy with improvement in neurological symptoms that totally remitted over the next 2 weeks. Results: These findings confirmed the diagnosis of a Lemierre&amp;apos;s Syndrome with thrombosis extension to cerebral sinuses. The genetic thrombophilic panel showed a heterozygosis for prothrombin gene G20210A mutation and the patient was discharged with Rivaroxaban for home continuation of anticoagulant therapy for at least 6 months. Conclusion: The prevalence of inherited thrombophilias in Lemierre&amp;apos;s Syndrome is unknown and to our knowledge, this article is the first to identify a prothrombin gene G20210A mutation in a patient with Lemierre&amp;apos;s Syndrome with thrombosis extension into the cerebral venous system. Exploring patients with Lemierre&amp;apos;s Syndrome for underlying thrombophilia could clarify whether this promotes retrograde jugular vein thrombosis extension.

Risk Factors of Venous Thromboembolism in Sudanese Pregnant Women.

Venous thromboembolism (VTE) is one of the major causes of pregnancy-related mortality and morbidity. This study aimed to determine the frequency of factor V Leiden (FVL) and prothrombin G20210A polymorphisms and measure the plasma levels of protein C (PC), protein S (PS) and antithrombin (AT) in pregnant women with VTE and healthy pregnant women. This prospective case-control study determined the frequencies of FVL G1691A and prothrombin G20210A polymorphisms and measured the plasma levels of PC, PS and AT in 198 pregnant women with VTE and 198 healthy pregnant women. Allele-specific polymerase chain reaction (ASPCR) was used to detect the FVL G1691A polymorphisms and prothrombin G20210A gene mutations. The FVL G1691A polymorphism and prothrombin G20210A gene mutations were detected only in pregnant women with VTE, with frequencies of 4.0 and 0.5%, respectively. The highest frequency of FVL G1691A polymorphism was observed in patients with deep vein thrombosis (DVT) and positively associated with contraceptive use and termination. Pregnant women with VTE had significantly lower levels of PC, PS and AT than those of controls. In conclusion, among the VTE cases, FVL G1691A polymorphism and PC, PS and AT deficiencies were the most common findings in patients presenting with DVT. Antithrombin deficiency was more common than PC and PS deficiencies. Contraceptive use, high body mass index (BMI) and termination correlated strongly with FVL G1691A polymorphism and PC and PS deficiencies in patients with VTE.

Hereditary thrombophilia and adverse pregnancy outcomes

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.

Factor V Leiden G1691A and Prothrombin Gene G20210A Mutations on Pregnancy Outcome.

Factor V Leiden (FVL) G1619A mutation and prothrombin gene (PTG) G20210A are the most common inherited thrombophilias. They have been associated with various obstetric complications such as venous thromboembolism, recurrent pregnancy loss, preeclampsia, abruptio placentae, and small for gestational age fetus. The prevalence of these two mutations is 3-15% in Caucasians and is assumed to be far less common in other ethnic populations. However, there have been several controversies regarding advising routine screening of these thrombophilias because of a widely variable strength of association between different ethnic groups, as well as contradictory conclusions by different studies in regards to the association. In this study, the literature was analyzed thoroughly for the effect of FVL G1619A and PTG G20210A mutations on various obstetric outcomes. A review of multiple case-control and prospective studies suggests that despite the availability of robust data on this subject the results remain inconclusive and insubstantial. Further superior quality research, preferably prospective studies, is warranted to conclusively establish this relationship and to enable practitioners to follow a definitive protocol in the screening of various populations for these mutations to achieve an improved pregnancy outcome.

Prevalence of Factor V Leiden G1691A and Prothrombin G20210A Gene Mutation Among Pregnant Women: Experience from a Multi-Center Study in Nigeria.

IntroductionInherited thrombophilia and venous thromboembolism (VTE) have been closely linked to adverse pregnancy outcomes such as preeclampsia/eclampsia contributing to increased maternal and perinatal morbidity and mortality. There is, however, little genetic data from Africa including Nigeria that explores the prevalence of common VTE genetic risk markers such as factor V Leiden mutation (FVL G1691A) and prothrombin gene mutation (F2 G20210A) among pregnant women in Nigeria.PurposeTo determine the prevalence and distribution of FVL G1691A and F2 G20210A in pregnant women in Lagos, Nigeria.Patients and MethodsThis hospital-based cross-sectional pilot study was conducted among pregnant women between 1 July 2019 and 31 August 2020. The genotype of interest was determined through amplification by polymerase chain reaction using G1691A of FV and prothrombin A20210G specific primers. Descriptive data were presented using Stata version 15 (Stata Corp) statistical software.ResultsOf the 400 recruited participants, 397 and 389 samples were successfully processed for FVL G1691A and F2 G20210A mutations, respectively. Three participants had FVL heterozygous mutation; thus, the prevalence of heterozygous mutation of FVL among the study participants was 0.76%, 95% CI: 0.002–0.023%, n=3/397. There was no F2 G20210A mutation detected among the study participants.ConclusionThis study indicates that screening for factor V Leiden mutation and prothrombin gene mutation in pregnancy might not be of any clinical significance among Nigerian women. However, carrying out a genome-wide associated study is recommended to determine the true impact of these two common inherited thrombophilias in this population.

Association of Factor V Leiden G1691A and Prothrombin gene G20210A mutations with adverse pregnancy outcomes.

To determine the association of Factor V Leiden / prothrombin gene mutation in Pakistani women with adverse pregnancy outcomes. 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. 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. The prevalence of Factor V Leiden / prothrombin gene mutation in women with recurrent pregnancy loss was found to be very low.

Inherited and acquired thrombophilia in women of Indian ethnicity with recurrent pregnancy loss: An observational study from North India.

The spectrum of thrombophilia in women with recurrent pregnancy loss (RPL) is different in Indian ethnicity as reported by few studies. We aimed to study the prevalence of thrombophilia in RPL patients referred to hematology department of a tertiary centre. This is an observational study of 112 RPL patients with no apparent cause after extensive workup for non-hematological causes. The investigations performed were routine coagulogram, APLA workup, plasma homocysteine, MTHFRC677T polymorphisms, Protein C, free Protein S, Anti-thrombin III levels, test for Activated Protein C resistance (APC-R) ,Factor V Leiden and Prothrombin gene G20210A mutation. Of 112 patients, at least one thrombophilia was identified in 70.5% and combined thrombophilia in 12.5% patients. Hyperhomocysteinemia (30.4%) and APLA (25.9%) were the commonest thrombophilia whereas anticoagulant defects were seen in 12.5% of the population. Protein C deficiency (5.35%) was the commonest anticoagulant defect followed by APCR (3.6%). Mutational analysis revealed MTHFRC677T polymorphism in 20.5% whereas Factor V Leiden heterozygous in 1.8% patients. None of the patients had homozygous Factor V Leiden or Prothrombin gene G20210A mutation. Hyperhomocysteinemia, MTHFRC677T and Protein C deficiency were more associated with early pregnancy losses whereas Protein S deficiency, Factor V Leiden and APLA caused both early and late losses. Patients with greater number of losses were positive for homozygous MTHFRC677T, factor V Leiden and APLA. The approach to investigating Indian women with RPL should be based on the prevalence of thrombophilia which is unique to Indian ethnicity.

Association of G20210A Prothrombin Gene Mutation and Cerebral Ischemic Stroke in Young Patients.

Ischemic stroke is an acute episode of neurological dysfunction resulting from the focal brain and spinal cord infarction. Many etiologies have been reported and vary significantly with the age of the patients. This study aims to show the association of G20210A prothrombin gene mutation and cerebral ischemic stroke in young patients. The prothrombin gene mutation is the second most common inherited thrombophilia after the factor V mutation. In this single missense mutation, guanine is substituted by adenine base pair in the nucleotide position 20210 of the 3'-untranslated region of the prothrombin gene, resulting in abnormal thrombin production predisposing to both arterial or venous thrombosis. Forty-seven relevant articles were selected after a thorough screening process using a regular keyword ‘G20210A Prothrombin’ and/or ‘Ischemic Stroke’ mostly from the PubMed database. We included the studies that are published in the last 22 years with patients age ≤57 years. This review article depicts the association of G20210A prothrombin gene mutation with ischemic stroke in young patients irrespective of ethnicity and zygosity status of their genotype. However, more multicenter prospective studies are needed to better understand the application of prothrombin gene mutation in predicting the associated risk of ischemic stroke in young patients and its importance in deciding the patients' treatment or prognosis.

Direct Oral Anticoagulants in Select Patients With Hypercoagulable Disorders.

To summarize the literature assessing the safety and efficacy of direct oral anticoagulants (DOACs) for the acute treatment and secondary prevention of venous thromboembolism (VTE) in select patients with hypercoagulable disorders. An electronic PubMed literature search was conducted from January 2010 to July 2020 using the following keywords: DOAC, rivaroxaban, apixaban, dabigatran, edoxaban, thrombophilia, cancer, antiphospholipid syndrome, protein C deficiency, protein S deficiency, antithrombin deficiency, factor V Leiden, prothrombin G20210A gene mutation, congenital thrombophilia, hypercoagulable, hereditary thrombophilia, acquired thrombophilia. Articles were included if they reported clinical outcomes associated with cancer-associated VTE, antiphospholipid syndrome (APS), and other hereditary thrombophilias. The safety and efficacy of using a DOAC is highly dependent on the type of hypercoagulable disease state. Current trials support the use of edoxaban, rivaroxaban, and apixaban for the treatment of cancer-associated thrombosis (CAT), with apixaban being preferred because of lower bleeding rates compared with standard of care. The use of DOACs, especially rivaroxaban, have been associated with worse outcomes in patients with APS, whereas data on DOAC use in hereditary thrombophilia remains scarce and limited to low-risk patients. This review evaluates the literature assessing the safety and efficacy of DOACs in patients with various hypercoagulable disorders. The current body of evidence supports the use of select DOACs for the treatment of CAT. In contrast, DOAC use in patients with APS and hereditary thrombophilia should be avoided at this time.

May the morphological findings in the first-trimester abortion materials be indicative of inherited thrombophilia?

İnherited thrombophilia is associated with severe pregnancy complications including recurrent spontaneous abortion. In the light of this strong association, the impact of thrombophilic mutations on the placenta and their morphological reflections has aroused attention of both clinicians and pathologists. In the present study, we aimed to show the association between placental abnormalities with thrombophilia by examining the morphological findings in a wide range of first-trimester chorionic villi. We performed a histological examination on the abortion specimens obtained from 129 patients with recurrent pregnancy losses that were evaluated with respect to inherited thrombophilia based on the presence of Factor V Leiden (G1691A), Prothrombin G20210A and methylenetetrahydrofolate reductase (MTHFR) C677T gene mutations detected by genetic analysis. Abortion materials either with and without thrombophilia were evaluated in terms of the morphological parameters such as hydropic change, vascularity, fibrosis, fibrinoid degeneration, Hofbauer macrophage, syncytiotrophoblast knotting, villitis, calcification, villous contour and villous size, hemorrhage, thrombus, proliferation of trophoblasts, villous stromal or villous vascular karyorrhexis. No statistically significant difference was found between the patient groups with and without thrombophilia in terms of morphological findings except vascularity of chorionic villi. The avascular chorionic villi (<3 vessels per villus) were found in 62.9% and 16.9% obtained from the women with and without thrombophilic mutation, respectively. This difference was statistically significant (P < 0.001). As a conclusion, it could be stated that the analysis of morphological findings in the abortion specimen is not a time-wasting process. Particularly, data related with vascularity of chorionic villi would be precious and beneficial. We suggest that highlighting the presence of avascular villi in the pathology report as a parameter would be guiding for clinicians regarding the impact of the thrombophilic gene mutations.

Inherited thrombophilia and recurrent pregnancy loss: a single-center case-control study in North-Western Algeria

BackgroundRecurrent 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.ResultsAPCR 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).ConclusionThere 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.

Association of Prothrombin G20210A Mutation with Unexplained Recurrent Pregnancy Loss

Purpose: To assess the relationship of Prothrombin G20210A gene mutations as a risk factor for idiopathic repeated pregnancy loss. The focus has been on Prothrombin G20210 Amutation that may predispose women to microthrombosis during the stages of embryo implantation and placentation. Method: A total of 70 women with recurrent pregnancy loss, mean age 31.1±4.2 years, were involved in the study. As a control group, 70 women [mean age 32.2±3.3y ears with at least two live-born child and no history of abortion were included. We used real-time polymerase chain reaction (PCR) to determine the frequencies of Prothrombin G20210 Agenotype. Results: The frequency of heterozygotes for F2 was significantly higher in women with repeated pregnancy loss compared to women without abortion (p = 0.0001). Conclusion: In summary we found an association of prothrombin G20210A mutation with recurrent pregnancy loss .we recommend for prothrombin G20210A screening in cases with repeated pregnancy loss so they can start anticoagulant therapy more earlier

Venous Cerebral Infarction Caused by Intake of Hormonal Contraceptives in Adolescents with Congenital Thrombophilia

In recent years, an increase in dysmenorrhea among adolescents has been observed worldwide. Oral contraceptives are used in gynaecological practice to correct this condition. However, the prescription of drugs belonging to this group often misses the risk of developing vascular complications, such as cerebral venous thrombosis and cerebral venous infarction. Due to the growing percentage of patients with congenital genetic mutations, it is relevant and reasonable to consider the risk factors and clinical signs of venous infarction in adolescents. First, it is necessary to exclude congenital thrombophilia, factor V Leiden and prothrombin G20210A gene mutations, and deficiency of proteins C, S and antithrombin. Of particular notice are the young patients and adolescents with complaints of a first-time, intense, poorly treatable headache (or headache in anamnesis), changes in the eye fundus (edematous, hyperemic optic disks; dilated, plethoric veins in the fundus of the eye). In such cases, a thorough medical history is extremely important, including, in particular, detection of an infectious process, traumatic brain injury, venous thrombosis of any localization; the use of drugs (especially hormonal ones) that can provoke the development of a hypercoagulable state; and investigation of the family history. These measures will help to prevent development of a cerebral venous circulation disorder (venous infarction).

Embolie pulmonaire et agénésie de veine cave inférieure : une association inhabituelle

Inferior vena cava agenesis is a rare congenital anomaly, generally associated with thrombophilic conditions, and a predisposing factor for deep venous thrombosis (DVT), rarely complicated by pulmonary embolism, in a young population with atypical clinical features and frequent absence of risk factors. We report the case of a 30-year-old woman who developed a right iliac DVT, initially presenting as a low back pain and complicated by a pulmonary embolism, 8 months after a sleeve gastrectomy. Chest CT angiography revealed abnormalities that led to the diagnosis of inferior vena cava agenesis. Thrombophilic screening showed a heterozygous prothrombin gene mutation G20210A and hyperhomocysteinemia. The patient was treated with rivaroxaban with good results after 2 years of follow-up. In young patients without risk factors developing a deep venous thrombosis, an inferior vena cava anomaly should be considered. Although no therapeutic consensus has been currently established, inferior vena cava agenesis seems to be associated with a high prevalence of thrombophilic disorders. Screening could be useful, particularly in patients with a thrombotic family history.