Prothrombin Gene Research Articles

Whole-Exome Sequencing in Evaluation of Thrombophilia: Characterization of Novel Genetic Variants

Abstract Venous thromboembolism (VTE), defined as deep venous thrombosis and pulmonary embolism, is a cause of significant morbidity and mortality worldwide, with an overall incidence of about 10,000,000 cases per year. The majority of VTE is attributable to genetic factors, yet the five major heritable thrombophilias of factor V Leiden, prothrombin gene mutation, antithrombin deficiency, protein C deficiency, and protein S deficiency comprise only a minority of VTE cases, suggesting that further genetic factors must contribute to VTE risk. We performed whole-exome sequencing (WES) in 106 patients with VTE, focusing our analysis on a 55-gene extended thrombophilia panel comprising genes previously reported in next-generation sequencing studies to be associated with VTE. In our cohort, we identified a probable disease-causing genetic variant or variant of unknown significance (VUS) in approximately 60% of study patients. We then selected several novel VUS involving genes with known roles in hemostasis for further characterization to determine their biological and pathological significance in thrombophilia. Multiple sequence alignment analysis showed that several nonsynonymous variants produced amino acid substitutions in highly conserved regions of proteins relevant to hemostasis and thrombosis, including thrombomodulin (TM), heparin cofactor II, ADAMTS13, and von Willebrand factor (vWF). To evaluate the theoretical effects of selected VUS on thrombosis susceptibility, we visualized proteins using PyMol and performed in silico mutagenesis modeling to evaluate for structural alterations that can predict functional and physiological consequences. Our analyses showed that several variants caused conformational changes predicted to either result in a deleterious effect on enzymatic activity or prevent substrate binding to the active site. For example, variants in TM (P401L and V454A) are predicted to decrease thrombin binding and protein C activation, whereas a C668R variant in the spacer domain of ADAMTS13 is predicted to prevent binding to vWF, resulting in ultra-large vWF multimers. We plan to use these results in combination with clinical laboratory-based coagulation testing and family studies to determine pathogenicity of specific variants in thrombosis and thrombophilia. Overall, these findings indicate that WES is a potentially useful tool for inherited thrombophilia and can provide insight into the genetic factors contributing to VTE.

Evaluation of Factor V Leiden and prothrombin G20210A mutations in Sudanese women with severe preeclampsia

BackgroundPreeclampsia (PE) is a common pregnancy complication and one of the main causes of maternal and fetal morbidity and mortality, worldwide. While the pathogenesis of PE is unclear, it has been suggested that hypercoagulability due to Factor V Leiden (FVL) and prothrombin gene mutation (FII G20210A) play a role in its progression. PurposeThis study aimed to determine if there is an association between FVL and FII G20210A mutations and severe PE. Patients and methodsThis case-control study enrolled 50 women with severe PE and 50 healthy pregnant women as the control, at Khartoum North Teaching Hospital, in Khartoum State, Sudan, from January 2017 to June 2017. The presence of point mutations in FVL and FII G20210A were determined for each of the participants. Deoxyribonucleic acid (DNA) was extracted, and then an allele-specific polymerase chain reaction (PCR) was used to detect the point mutations in FVL and FII G20210A. ResultsThe results revealed a significant difference between the subjects in the severe PE group and the control group for the means of parity, gestational age/ week and hemoglobin concentration (P < 0.05). No statistically significant body mass index (BMI) differences were found between the groups (P > 0.05). Women with severe PE were found to have a significant difference in FVL (16%; P value = 0.0058; OR: 20.20; 95%CI: 1.132–360.5) and FII G20210A (14%; P value = 0.0125; OR: 17.41; 95%CI: 0.9659–314.0) in comparison to the women in the control group (0%). ConclusionOur findings intensely indicate that there is a statistically proven significant association between FVL, FII G20210A mutations and the development of severe preeclampsia in Sudanese pregnant women.

Neuron-generated thrombin induces a protective astrocyte response via protease activated receptors.

Astrocytes protect neurons during cerebral injury through several postulated mechanisms. Recent therapeutic attention has focused on enhancing or augmenting the neuroprotective actions of astrocytes but in some instances astrocytes can assume a neurotoxic phenotype. The signaling mechanisms that drive astrocytes toward a protective versus toxic phenotype are not fully known but cell-cell signaling via proteases acting on cell-specific receptors underlies critical mechanistic steps in neurodevelopment and disease. The protease activated receptor (PAR), resides in multiple brain cell types, and most PARs are found on astrocytes. We asked whether neuron-generated thrombin constituted an important astrocyte activation signal because our previous studies have shown that neurons contain prothrombin gene and transcribed protein. We used neuron and astrocyte mono-cell cultures exposed to oxygen-glucose deprivation and a model of middle cerebral artery occlusion. We found that ischemic neurons secrete thrombin into culture media, which leads to astrocyte activation; such astrocyte activation can be reproduced with low doses of thrombin. Media from prothrombin-deficient neurons failed to activate astrocytes and adding thrombin to such media restored activation. Astrocytes lacking PAR1 did not respond to neuron-generated thrombin. Induced astrocyte activation was antagonized dose-dependently with thrombin inhibitors or PAR1 antagonists. Ischemia-induced astrocyte activation in vivo was inhibited after neuronal prothrombin knockout, resulting in larger strokes. Restoring prothrombin to neurons with a lentiviral gene vector restored astrocyte activation and reduced stroke damage. We conclude that neuron-generated thrombin, released during ischemia, acts via PAR1 and may cause astrocyte activation and paracrine neuroprotection.

Genetic Testing for Thrombophilia-Related Genes: Observations of Testing Patterns for Factor V Leiden (G1691A) and Prothrombin Gene "Mutation" (G20210A).

Thrombophilia is a generic term that defines an increased propensity toward thrombosis and associated morbidity. Factor V Leiden (FVL; G1691A) and the prothrombin gene mutation (PGM; G20210A) comprise the most common genetic associations with thrombosis, and thus comprise the most commonly requested genetic thrombophilia investigations. This report describes an audit of local test findings that suggests growing futility in testing for FVL and PGM. Test requests for FVL and PGM were assessed for a recent period of 2.5 years (starting from 2016 to end of June 2018) from a large tertiary-level pathology provider. From a total of more than 10,000 thrombophilia-related test requests over the analysis period, 2,700 and 2,135 were, respectively, for FVL and PGM. The age ranges of patients varied across the full life span spectrum, but the peak investigation age range for the entire cohort was 30 to 39 years. Investigations were more often requested for females (> 70% of requests) than males, and the peak investigation age range for females (30-39 years) was earlier than males (50-59 years). However, proportionally more males than females were identified with FVL (15.4 vs. 6.6%) or PGM (10.4 vs. 4.3%), respectively. The age-related patterns of test ordering were also identified as closely aligned to birth patterns in females and thrombosis patterns in males. There has been a trend to annual reduction in detection of FVL mutation from a peak of more than 25% in 1996 to ∼10% in each year of the past decade, suggesting poorer patient selection. Of test-requesting indications, pregnancy/fetal morbidity was identified in 16.4% of all requests for females, and thromboembolism was identified in 21.4 and 18.0% of all requests for females and males, respectively. In terms of FVL identification, a heterozygous pattern was identified in 4.2% of women tested for pregnancy/fetal morbidity, but 11.7 and 15.1% of females and males, respectively, for thromboembolism. In comparison, the background rate of FVL detection in the general population in our geographical region is approximately 3 to 7%. Overall, better targeted patient selection for testing of FVL and PGM occurred in the male cohort based on higher relative capture of thrombophilia mutations than the female cohort. However, patient selection was not optimal in either the male or female cohorts, since the captured mutation rates were only marginally higher than the expected background population detection rate. Moreover, the decline in relative identification of FVL from overall test requests over time suggests deterioration of patient selection practices by referring physicians. Notably, tests requested in the setting of thromboembolism provided a higher likelihood of FVL detection than pregnancy/fetal morbidity. These data suggest some contemporary futility of genetic testing for FVL and PGM in the real world, and in particular, in females for indications around pregnancy/fetal morbidity, proposed to be related to poor patient selection in most instances.

Clinical and laboratory manifestations of the prothrombin gene mutation in women of reproductive age.

Research objectiveTo research the association of prothrombin (factor II) activity given the prothrombin G20210A mutation carriage with its clinical manifestations as thrombotic complications.Materials and methodsA prospective clinical cohort study of 290 women of reproductive age was conducted. Two cohort groups were identified: the study group of 140 patients with prothrombin mutation G20210A genotype and the control group of 150 women with G20210G genotype.ResultsThe prothrombin G20210A mutation carriage is associated with the risk of thrombotic complications compared to the wild G20210G type (RR =17.1; p<0.0001) and is characterized by thrombosis localized both in the venous (66.7%) and arterial (33.3%) vascular pools. The threshold value of prothrombin activity (174.8%) for G20210A genotype was calculated, making it possible to conclusively predict the risk of thrombotic events with the accuracy of 90.4%.ConclusionThe phenotypic manifestation of the prothrombin G20210A mutation in the form of venous and arterial thromboses in women of reproductive age is associated with a super-threshold increase in prothrombin (factor II) activity, which makes it possible to stratify the patients into the group of high risk of thromboses.

A Study on the Role of Thrombophilic Genetic Disorders as a Risk Factor for Thrombotic Complications in Patients with Myeloproliferative Disorders

Summary Myeloproliferative neoplasms (MPN) are haematological diseases, characterized by clonal hematopoiesis. Hemostasis abnormalities are among the most critical and frequent complications, affecting the quality of life and a possible reason for death. Thrombotic complications are common and multifactorial. Our aim was to study some genetic thrombophilia factors – Factor V Leiden (FVL), G20210A mutation in prothrombin gene (PR G20210A) and PLA2 allele polymorphism of glycoprotein IIIa gene (GPIIIa gene), and their frequency and association with thrombotic risk in both Philadelphia-positive and Philadelphia-negative MPN – chronic myelogenous leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary and secondary myelofibrosis (MF). In our patient population, PLA2 allele polymorphism of GPIIIa gene proved to be the most common and significantly associated with thrombotic complications – 26.85% of our patients were carriers, and 24.14% of them reported thrombotic complications.

Prothrombin gene mutations do not causerecurrent pregnancy loss in the Indianpopulation

Prothrombin gene mutations do not causerecurrent pregnancy loss in the Indianpopulation

Model for calculating the risk of venous thrombosis

Aim. To develop a model for calculating the risk of venous thrombosis, taking into account the presence of known risk factors, comorbidity and congenital thrombophilia. Material and methods . During the study (2015 to 2017), 79 patients with venous thrombosis were examined (36 men and 43 women, mean age — 56,76±15,570). The control group consisted of 83 patients and healthy volunteers without thrombosis at the moment and in history (35 men and 48 women, average age — 43,95±18,136). All individuals included in the study were analyzed for the presence of G1691A mutations in the factor V gene, G20210A in the prothrombin gene, C677T polymorphism in the 5,10-methylenetetrahydrofolate reductase gene, and polymorphism in the SERPINE1 gene of plasminogen activator inhibitor. Real-time polymerase chain reaction was used to identify mutations. To create a risk calculation model, a linear regression analysis was performed. Results. We have developed a model for calculating the risk of venous thrombosis. The resulting formula showed high prognostic accuracy (the area under the ROC curve is 95,9%). For patients who do not have data on the presence of these mutations, a short version of the risk calculation model was developed (the area under the ROC curve is 94,6%). Conclusion. We have developed a risk calculation model taking into account the presence of known risk factors, congenital thrombophilia and comorbidities. Thromboprophylaxis is necessary in &gt;0,45 individual risk, which corresponds to a high risk of developing venous thrombosis. Patients who have not previously been diagnosed with thrombophilia and are in the middle risk group for venous thrombosis, according to a short version of the model, must be screened for congenital thrombophilia to clarify the risk.

PS1579 AN EPIDEMIOLOGIC STUDY OF PREGNANCY RELATED VENOUS THROMBO‐EMBOLISM IN SOUTH AFRICA: ARE HIV INFECTED WOMEN A NEW HIGH‐RISK GROUP?

Background:Venous thrombo‐embolism (VTE) is an important cause of preventable morbidity and mortality in pregnancy. While much consideration has been given to inherited thrombophilias and a past history of VTE, epidemiologic studies to date have not examined the significance of human immunodeficiency virus (HIV) as a potential risk factor for pregnancy and postpartum related VTE. In South Africa this is of particular concern, considering that approximately one‐third of women attending antenatal clinics are HIV infected.Aims:A study was therefore performed at a single academic centre to investigate the clinical spectrum, incidence and risk factors for VTE in pregnancy and the puerperium in a population of Black South African women in order to guide evidence‐based thromboprophylaxis.Methods:A case control study of first time VTE during pregnancy or within 42 days postpartum was conducted between January and December 2018. A control group (n = 295) matched for population affinity and gestation were recruited. The medical records were reviewed for 30 baseline antepartum and/or postpartum risk factors for VTE. Statistical comparisons were performed using Fisher's exact test with calculation of odds ratios (OR) and 95% confidence intervals (CI). The study was approved by the Human Research Ethics Committee of the University of the Witwatersrand (M181018).Results:59 patients with the diagnosis of VTE in pregnancy or the puerperium were identified during the study period (34 with deep vein thrombosis, 23 with pulmonary embolus and two with both). The total number of deliveries during the study period was 8 361, giving an incidence of 4.4 per 1000 deliveries. In the multivariate analysis, HIV infection was associated with a four‐fold increased risk for VTE among pregnant and postpartum women (95% CI, 1.97‐ 6.63, P &lt; 0.001). In addition, medical co‐morbidities, in particular peripartum cardiomyopathy, (OR, 11.04, 95% CI, 3.90–31.25), pre‐eclampsia with foetal growth restriction (OR, 6.88, 95% CI, 1.91–24.79), preterm delivery (OR, 7.60, 95% CI, 2.80–20.62), caesarean delivery in labour (OR, 3.17, 95% CI, 1.13–8.87), postpartum haemorrhage (OR, 22.60, 95% CI, 5.75–88.84) and prolonged hospital admission (OR, 7.78, 95% CI, 2.38–25.45) were independent risk factors for VTE. In 41 women thrombophilia screening was performed. Protein S deficiency was confirmed in five patients (three of which were HIV infected with virologic suppression) and the prothrombin gene mutation (not the classic G20210A mutation) was confirmed in a single patient.Summary/Conclusion:This study demonstrated that the incidence of VTE complicating pregnancy in Black South Africans is higher than the reported prevalence in White and Asian population groups. The findings of this study support many of the existing guideline recommendations and may provide valuable information to local obstetricians for identifying high‐risk pregnant and postpartum women requiring thromboprophylaxis. In addition, HIV emerged as a significant risk factor for VTE in this study population.

DIFFERENTIATED APPROACH TO RISK ASSESSMENT OF DEVELOPING PLACENTA-ASSOCIATED COMPLICATIONS IN PREGNANT WOMAN WITH PREECLAMPSIA

Preeclampsia remains the main cause of maternal and perinatal morbidity and mortality. It was shown that the developments of complications from the mother and fetus side or their absence in women with preeclampsia have different pathophysiological mechanisms. It is necessary to distinguish two types of hypertensive disorders during pregnancy: the first one is severe preeclampsia, which has an early onset and is accompanied by complications that threaten the life of the mother and child. Second – it is a mild pre-eclampsia, that specificfor the late stages of pregnancy and occurs without significant associated complications. It has been shown that the markers of the propensity to develop obstetric and perinatal complications in pregnant women with preeclampsia are the following gene polymorphisms: 1691 GA in gene factor V Leiden – increases the risk in 2.9 times (95 % CI 1.94–4.33), 20210 GA in prothrombin gene – 2.36 times (95 % CI 1.54–3.6), 20210 AA in prothrombin gene – 3.12 times (95 % CI 2.4–4.0). Pregnancy on the background of these gene polymorphisms is associated with severe pre-eclampsia, early onset and development of life-threatening maternal and fetal complications.

Intérêt des variants génétiques dans la prédiction du risque de thrombose associée au cancer

Venous thromboembolism (VTE) is a major public health problem in cancer patients and there is a clear need to precisely define the risk of VTE and to administer thromboprophylaxis specifically to the group of high-risk patients who have a favourable risk-benefit ratio. Current risk assessment models (RAM) for identifying high-risk cancer patients, who could benefit from primary thromboprophylaxis, are based solely on clinical and laboratory parameters. Khorana score (KS) is the best validated RAM and recommended by the main clinical guidelines. All current RAM, including KS, have low positive predictive value and limited clinical applicability. Our group was the first to determine that VTE, a multifactorial and complex disease, has a large genetic component with 60% heritability. We showed that the combination of genetic and clinical factors of thrombotic risk improves the predictive capacity of RAM of VTE in the general population. In this way, we have been pioneers in the development of a predictive tool to determine thromboembolic risk in general population, which is already being used in clinical practice. From these results and aware of the importance of the genetic base in the risk of VTE in general population, we wonder what role this genetic base already known could have in the increased risk of VTE in cancer patients. In cancer patients none of the current RAM to estimate the risk of VTE has taken into account the genetic factors of thrombotic risk, although some prothrombotic mutations such as Factor V Leiden and the G20210A mutation in the prothrombin gene have been associated with an increased risk of VTE in cancer patients (Vienna CATS study and the Tromso cohort). The first data of our project indicate that a risk score including clinical and genetic data of the cancer patients at 6 months of clinical follow-up significantly improves KS in the identification of cancer patients undergoing out-of-hospital chemotherapy at high risk of suffering thromboembolic events. At this point in the study, the KS applied to our patients had a very low predictive capacity, in terms of discrimination, (AUC) of 0.58 (95% CI 0.51–0.65). However, the score developed from our study significantly increased the predictive capacity of thrombosis risk with the incorporation of genetic and clinical risk factors for thrombosis (AUC 0.73, 95% CI 0.67–0.79, P With these results, we can conclude that our score has a better predictive capacity than the KS to identify cancer patients treated with chemotherapy at high risk of thrombosis, potentially, reducing the morbidity and mortality associated with this pathology. Therefore, our results have a direct applicability that may change the clinical practice.

ТРОМБОФІЛІЯ ЯК КЛЮЧОВА ЛАНКА ПАТОГЕНЕЗУ УСКЛАДНЕНЬ В АКУШЕРСТВІ ТА ГІНЕКОЛОГІЇ

The analysis of gemostasiologikal researches on hidden got and genetic forms of trombophilia at women with the burdened anamnesis of syndrome of loss of a fetus. For certain established (p&lt;0,05), that got thrombophilia, conditioned by the AFS at patients with FLS average - 28,6 % cases. The genetic mutation FVLeiden more frequent took place at patients with late abortions (14,3 %), the mutation of prothrombin gene G20210A met for certain rarer in all groups of reproduction losses - 4,8 %. The most widespread appeared the mutation МTHFR C677T - (45,2 %). Factor of potential action of the AFA is genetic thrombophilia: AFS and MTHFR C677T at FLS in 17,4 %, AFS and FV Leiden at FLS at 9,6 %. Patogenetically grounded hidden got end genetic thrombophilia, syndrome of loss of fetus, thromboprophylaxis at these obstetric complications of LMWH - by сleхanе, begun with a fertile cycle and on the stage of invasion of throphoblasta, in absolute most cases (92 – 96 %) considerably improves the end of pregnancy.

Acute scrotum caused by an extraspermatic venous thrombosis associated with G20210A prothrombin gene mutation in a pediatric patient: A case report

Thrombosis of an extraspermatic blood vessel has been reported to be an unusual cause of acute scrotum. We describe the case of a 7-year-old boy who presented with an acute painful left scrotal swelling. Imaging demonstrated a heterogeneous left scrotal mass, which was surgically resected. The anatomopathologic study revealed a thrombosed vascular structure. Three months later, another extraspermatic venous thrombosis occurred and was also resected. A complete thrombophilia study was done. A G20210A prothrombin gene heterozygous mutation was identified as the cause of the thrombotic event. A venous thrombosis should be considered as a possible cause of acute scrotum in European Caucasian patients, due to its increased prevalence. We reviewed the G20210A prothrombin gene mutation, which is associated with thrombosis.

The risk factors of portal vein thrombosis in patients with liver cirrhosis.

This study was designed to identify and assess risk factors for portal vein thrombosis (PVT) in patients with cirrhosis. A total of 98 cirrhosis patients with PVT were identified and 101 cirrhosis patients without PVT were chosen as the control group in this retrospective study. Several variables were measured and the two groups PVT and non-PVT were compared statistically. PVT was identified in 98 patients (10%). Significant differences in hematocrit, international normalized ratio, albumin, bilirubin and glucose were determined between the groups (P<0.05). Out of the thrombophilic risk factors in the patients with PVT factor V Leiden was identified in 8.8%, prothrombin gene 6.6% and methylenetetrahydrofolate reductase 2.2%. There was no difference in survival time between groups (P>0.05).

Abstract TP419: PFO Stroke With Thrombophilia Has Higher Risk of Recurrent Stroke and Responds to PFO Closure

Background: Hypercoagulability due to thrombophilia may increase the risk of paradoxic embolism. However, previous randomized controlled trials that evaluated the efficacy of PFO closure or medical therapy on the risk of recurrent stroke and/or transient ischemic attack (TIA) events, have excluded these potentially high-risk thrombophilia patients. In this study, we want to investigate the effect of PFO management on the risks of recurrent stroke and/or TIA among patients with thrombophilia. Methods: Patients with a PFO attributable ischemic stroke or TIA are prospectively recruited. Hypercoagulable tests for protein C, protein S, antithrombin III, homocysteine levels, IgG and IgM anticardiolipin antibodies, factor V Leiden and prothrombin gene variant were obtained. The primary outcome was occurrence of stroke and/or TIA after index event. Results: Thrombophilia is diagnosed in 120 PFO stroke patients who subsequently underwent PFO closure (n= 76) vs medical therapy (n= 44) ( Table 1 ). The mean duration of follow-up was 45 months in the closure group and 40 months in the medical-therapy group. The primary end point occurred in 5 patients (6.6%) in the closure group and in 14 (31.8%) in the medical therapy group (hazard ratio for medical therapy vs. closure, 5.797; 95% confidence interval [CI], 2.094 to 16.051; P = 0.001) ( Figure 1 ) with recurrent rate of 18.2% vs. 5.3% for TIA (P = 0.023) and 13.6% vs. 1.3% for stroke (P = 0.018) respectively. Conclusions: PFO stroke patients with hypercoagulable state had higher rate of recurrent stroke than those patients in clinical trials. Among patients who had cryptogenic embolism with thrombophilia, closure of a PFO was associated with a lower rate of recurrent stroke and/or TIA than medical therapy.

Factor-V Leiden G1691A and prothrombin G20210A polymorphisms in Sudanese women with preeclampsia, a case -control study

BackgroundPreeclampsia can lead to adverse maternal and perinatal outcomes. There are few studies on the association of preeclampsia with thrombophilia in Africa including Sudan.MethodsA case –controls study was conducted at Saad Abualila Hospital in Khartoum, Sudan during the period of February through November 2017. The cases were women with preeclampsia and healthy pregnant women were the controls (180 women in each arm of the study). Genotyping for Factor-V Leiden 1691G/A and Prothrombin gene variation 20210G/A was done by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP).ResultsThere was no significant difference in the age, parity, body mass index (BMI) and the other characteristics between the cases and the controls. Genotypes distribution of Factor V Leiden 1691G/A and prothrombin gene 20210G/A in controls was in accordance with the Hardy–Weinberg equilibrium (P > 0.05). The factor V Leiden-variation was present in 9.6% of the cases compared with 0.6% of the controls, P < 0.001 (OR = 18.60, 95% CI = 2.38–136.1). Only 4 patients with severe preeclampsia had homozygous variation A/A and it was not detected in the controls. Prothrombin G20210A variations not detected neither in the cases nor in the controls group.ConclusionsHigh prevalence of Factor V Leiden 1691G/A variation in preeclamptic patients compared to controls suggest an involvement of this variation in predisposing to preeclampsia in this setting.

Genetic correlation between Prothrombin G20210A polymorphism and retinal vein occlusion risk.

The aim of this study was to perform an updated meta-analysis to quantitatively investigate the association between G20210A polymorphism of Prothrombin gene and the risk of retinal vein occlusion (RVO), based on the available publications with inconsistent results. We utilized the Stata software to perform the heterogeneity test, association test, Begg's and Egger's tests, and sensitivity analysis. We searched three on-line databases (PubMed, Embase, and WOS) and obtained a total of 422 articles. Based on our selection criteria, 24 case-control studies were finally enrolled in this overall meta-analysis; a subgroup analysis by the factors ethnicity, control source, and RVO type was done. Through the association test of overall meta-analysis, we did not observe a significant difference between RVO cases and controls under the A vs G (allele) (z=1.49, P=0.137), A vs G (carrier) (z=1.42, P =0.155), GA vs GG (z=1.50, P=0.135), and GA+AA vs GG (z=1.50, P=0.135). Furthermore, we observed similar negative results in the association test of subgroup analysis (all P>0.05). Heterogeneity, Begg's, and Egger's tests excluded the presence of high heterogeneity and publication bias. Statistically stable results were observed in the sensitivity analyses. Based on integrated analysis of the current evidence, Prothrombin gene G20210A polymorphism is likely unrelated to the risk of RVO.

Homozygous prothrombin gene mutation and ischemic cerebrovascular disease: A case report and review of literature

This report describes a 32-year-old Saudi nonsmoker man who presented to the emergency department with a history of left-sided hemiparesis and no risk factors for cerebral stroke being reported, except type II diabetes mellitus. Magnetic resonance imaging (MRI) showed an ischemic stroke involving the right putamen and the posterior limb of the right internal capsule. During the hospitalization, he developed new weakness bilaterally, and repeat MRI showed infarctions involving both basal ganglia with a new acute infarct in the left putamen. The patient had normal laboratory hematological investigations; however, he was found to be homozygous for the G20210A mutation in the 3'-untranslated region of the prothrombin gene. In the absence of multiple risk factors that are usually related with cerebral stroke, the association between homozygous prothrombin gene mutation and cerebral stroke was suggested.

Plu]na tromboembolija i uloga faktora V Leiden u njenom nastanku - pregled literature

Pulmonary embolism (PE) and deep vein thrombosis (DVT) are associated with considerable morbidity and mortality, and for as much as twenty-five percent of PE patients the primary clinical appearance is unexpected death. Diagnosis of PE is based on clinical suspicious at first, but sometimes its diagnostics can be extremely difficult. Newly increased interest in an inherited thrombophilic states has been provoked by the discovery of several common inherited abnormalities, i.e. the prothrombin (PT) gene G20210A, Factor V Leiden (FVL) mutation (Arg506Gln), hyperhomocystenemia and homocysteiuria, Wein-Penzing defect, Sticky Platelet Syndrome (SPS), Quebec platelet disorder (QPD) and Sickle Cell Disease (SCD). PE incidence rates increase in recent years. The only explanation at this moment is increased awareness of PE, especially after any kind of surgery, immobile state or unexplained shorthness of breath.

Phenotypic Manifestations of Prothrombin Gene Mutation, Genotype, in Women of Reproductive Age

Phenotypic Manifestations of Prothrombin Gene Mutation, Genotype, in Women of Reproductive Age