scholarly journals Frequency of Thrombophilia-Related Genetic Variations in Patients with Idiopathic Pulmonary Embolism in an Urban Emergency Department

2006 ◽  
Vol 52 (6) ◽  
pp. 1026-1032 ◽  
Author(s):  
Lori Kruse ◽  
Alice M Mitchell ◽  
Carlos A Camargo ◽  
Jackeline Hernandez ◽  
Jeffrey A Kline
Keyword(s):  
Risk Factors ◽  
Pulmonary Embolism ◽  
Methylenetetrahydrofolate Reductase ◽  
Factor V Leiden ◽  
Mthfr C677t ◽  
Prothrombin G20210a ◽  
Polymorphism Analysis ◽  
Sequence Variant ◽  
Factor V

Abstract Background: The frequency of the thrombophilic genetic variants factor V Leiden (FVL) G1691A, prothrombin G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T in acutely symptomatic ambulatory patients with idiopathic pulmonary embolism (PE) has not been measured. Methods: This prospective case–control study included patients presenting to urban emergency departments (EDs) with chest pain or shortness of breath. Cases were classified as idiopathic PE (49 patients with PE, but without overt risk factors for thrombosis). Control groups included (a) patients with nonidiopathic PE (152 patients with PE and risk factors); (b) patients in whom PE was excluded (91 patients who had PE ruled out with a structured protocol, including follow-up); and (c) patients in whom PE was not suspected (193 patients without a workup for PE, who were free of PE on follow-up). Blood DNA extracts were analyzed by PCR and restriction fragment length polymorphism analysis for the FVL, prothrombin, and MTHFR sequence variations. Results: Either the FVL or prothrombin variant was found in 10% (95% confidence interval, 3%–22%) of patients with idiopathic PE compared with 13% (8%–20%) of nonidiopathic PE, 2% (5%–14%) of PE excluded, and 9% (5%–14%) of PE not suspected patients. Patients with idiopathic PE tended to have a higher frequency of homozygous MTHFR sequence variants, but mean (SD) plasma homocysteine concentrations were not increased [15.6 (5.4) μmol/L vs 12.8 (4.6) μmol/L for homozygous, and wild-type, respectively; P = 0.40]. Conclusions: The frequency of either the FVL or prothrombin sequence variant was not increased in idiopathic PE patients compared with nonidiopathic PE patients or patients who had PE excluded. These data suggest that genotyping to detect idiopathic PE would have limited clinical utility in the urban ED setting.

Correlation of Genetic Polymorphisms Detected by Geneohm EPLEX™ Electrochemical Platform with Functional Study for Venous Thrombosis.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4054-4054
Author(s):  
Bo Xu ◽  
Steven Thompson ◽  
Carol Koenigberger ◽  
James Pettay ◽  
Arkadiy Silbergleit ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thrombosis ◽  
Genetic Polymorphisms ◽  
Factor V Leiden ◽  
Mthfr C677t ◽  
Plasma Homocysteine ◽  
Functional Study ◽  
Prothrombin G20210a ◽  
Factor V ◽  
History Of

Abstract Venous thrombosis (VT) is a multi-factorial disorder with both congenital and acquired risk factors. Mutations in several genes, such as factor V, prothrombin and methylene tetrahydrofolate reductase (MTHFR), are considered risk factors for thrombophilia. Since multiple mutations compound the risk for (VT), simultaneous discovery of mutations could directly alter patient management. In this study, we employed the GeneOhm ePlex™ platform to simultaneously detect genetic polymorphisms for six markers: factor V Leiden (FVL) and HR2A45374G, prothrombin G20210A, MTHFR C677T and A1298C, and plasminogen activator inhibitor 1 (4G/5G). Fifty-one patient samples were selected. Each sample was genotyped for all six markers on the GeneOhm ePlex™ electrochemical array and data from functional studies were analyzed and compared to the genotyping results. Among the 51 patients, 16 were tested for activated protein C resistance and the average values were 1.22, 1.76 and 2.64 for FVL homozygous, heterozygous and wild type normal patients, respectively. In addition, the average plasma homocysteine levels measured in 17 patients were 15.40, 6.42 and 11.93, 12.63 mmol/L for MTHFR C677T homozygous, heterozygous and MTHFR A1298C heterozygous and C677T/A1298C double heterozygous, respectively. Furthermore, 10 out of 11 patients with history of deep venous thrombosis (DVT) and/or pulmonary embolism (PE) displayed genetic abnormalities in FVL or prothrombin G20210A. The other patient with history of both DVT and PE showed homozygous in MTHFR C677T with high plasma homocysteine level (22.3 mmol/L) and heterozygous mutation in PAI-1. This study demonstrates the principle of multiplexed molecular diagnostics for the polymorphisms associated with thrombophilia and the utility of the GeneOhm ePlex platform. The study is being expanded to test a larger set of samples to establish the relationship between genetic polymorphism and corresponding clinical outcome for all six markers.

scholarly journals Evaluation of pai-1 polymorphisms in central and peripheral thromboembolies

2021 ◽  
Vol 38 (2) ◽  
pp. 167-171
Author(s):  
Özge Arıcı DÜZ ◽  
Oktay OLMUŞÇELİK ◽  
Ali İhsan GEMİCİ ◽  
Özlem SAATÇİ SANCAKTEPE
Keyword(s):  
Risk Factors ◽  
Methylenetetrahydrofolate Reductase ◽  
Vascular System ◽  
Factor V Leiden ◽  
Prothrombin G20210a ◽  
Genetic Mutations ◽  
Factor V ◽  
Significant Difference ◽  
Medium Risk ◽  
Pai 1

Thromboembolism is a clinical finding that occurs due to thrombus; formed in the vascular system and has various etiological factors. It can be classified as central and peripheral thromboembolism. Our objective in this study is to explore genetic risk factors in central and peripheral thromboembolism and reveal the differences. 342 thromboembolism patients were retrospectively included to the study between January 2016 and December 2019. Demographic characteristics, risk factors for thromboembolism and genetic mutations in central and peripheral thromboembolism groups were overviewed. The genetic mutations evaluated in patients were Factor V Leiden G1691A, Factor V HR1299R, Factor II (Prothrombin) G20210A, MTHFR (Methylenetetrahydrofolate reductase) C677T, MTHFR A1298C, PAI 4G/5G. Within the scope of the study, genetic analyzes of 106 patients were reached and included in the study. Seventy-two central thromboembolism (69.8%), 34 (31.2%) peripheral thromboembolisms were detected. Sixty-three of the central thromboembolisms were from arterial and nine were from venous origin. There was no significant difference between age, gender and risk factors of central thromboembolism and peripheral thromboembolism patients (p˃0.05), but smoking was more common in central thromboembolism patients (p: 0.041). 4G/5G polymorphism was observed more frequently in patients with central thromboembolism (p: 0.039). Thromboembolism is a multifactorial disease, PAI-1 4G/5G polymorphism is a medium risk factor for thromboembolism. We conclude that PAI-1 4G/5G polymorphism is more frequent in central thromboembolism than peripheral thromboembolism and its evaluation can give more information about the thromboembolic risk analyze.

scholarly journals Predisposition to Thrombophilia and Hypofibrinolysis in Pulmonary Embolism: Analysis of Inherited Factors

2013 ◽  
Vol 6 (2) ◽  
pp. 73-81
Author(s):  
Regina Komsa-Penkova ◽  
Pencho T. Tonchev ◽  
Katya S. Kovacheva ◽  
Galya B. Georgieva ◽  
Yavor Y. Ivanov ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pulmonary Embolism ◽  
Gene Mutation ◽  
Factor V Leiden ◽  
Mthfr C677t ◽  
Platelet Glycoprotein ◽  
Factor V ◽  
Prevention Policy ◽  
Prothrombin Gene Mutation ◽  
Prothrombin Gene

Summary Pulmonary embolism (PE) is a relatively common cardiovascular emergency, though its exact incidence is difficult to assess. Accurate diagnosis is critical because of the high 30-day mortality in patients in whom the diagnosis is missed on admission. Doubt for PE is often raised by the presence of risk factors for venous thromboembolism (VTE), which are categorized into inherited and acquired. Among these, the importance of inherited/genetic thrombophilic factors is increasingly recognized. The most frequent markers of inherited thrombophilia are Factor V Leiden (FVL) and G2021OA prothrombin gene mutation. Among the inherited factors causal to thrombophilia, the C677T variant in methylentetrahydrofolate reductase (MTHFR) gene as well as factors like P1A1/P1A2 polymorphism in platelet glycoprotein Ilb/IIIa (P1A2) and hypofibrinolytic polymorphism 4G/4G in PAI-1 gene are discussed with controversial results. In our study, thrombophilic and hypofibrinolytic genetic variants were identified in 54.2% of 115 patients with PE. The most common significant genetic defects were FVL- 16.5% in patients versus 6.2% in controls (OR=3.102; p=0.05), G20210A PT 5.7% versus 2.1% (OR=2.983; p>0.05). P1A2 was found in 27.3% patients versus 19.9% in controls (OR= 1.523, p>0.05) and PAM 27.8% versus 22.6% (OR =1.501 p>0.05). MTHFR C677T carriage was inverse: 6.7% in patients versus 13.4% in controls. (OR=0.461 p=0.05). Of all the patients studied, 15.65% had a history of recurrent embolic incidents. The risk of recurrence was higher for the carriers of FVL and G20210A prothrombin gene mutation. The association between carriage of thrombophilic genetic factor and the early onset of the first embolic episode was found in the patients with PE. The awareness of risk factors and risk stratification is a critical issue in treatment and prevention policy. Preventive measures should be taken in particular medical conditions.

Prothrombotic Genotypes Are not Associated with Pre-eclampsia and Gestational Hypertension: Results from a Large Population-based Study and Systematic Review

2002 ◽  
Vol 87 (05) ◽  
pp. 779-785 ◽  
Author(s):  
E. R. Morrison ◽  
D. M. Campbell ◽  
N. E. Haites ◽  
B. J. Wilson ◽  
M. S. Watson ◽  
...  
Keyword(s):  
Systematic Review ◽  
Methylenetetrahydrofolate Reductase ◽  
Gestational Hypertension ◽  
Severe Disease ◽  
Large Population ◽  
Factor V Leiden ◽  
Mthfr C677t ◽  
Population Based ◽  
Prothrombin G20210a ◽  
Factor V

SummaryDNA samples collected as part of a large population-based casecontrol study were genotyped to examine the associations of five prothrombotic gene polymorphisms with pre-eclampsia (PE) and gestational hypertension (GH). The polymorphisms studied were: G1691A in Factor V (Factor V Leiden; FVL), prothrombin G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T, plasminogen activator inhibitor-1 4G/5G and the platelet collagen receptor α2β1 C807T. A group of 404 women who developed PE were retrospectively compared with 303 women with GH and 164 control women. The frequency of genotypes did not differ significantly between cases of PE or GH and controls for any of the five polymorphisms studied. We conclude that these prothrombotic genotypes are not associated with the development of PE or GH in our population. The systematic review supports our conclusion, for all but cases of severe disease, which appear to be associated with FVL and, to a lesser extent, MTHFR C677T. There is little value in antenatal screening for prothrombotic polymorphisms to predict the development of pre-eclampsia or gestational hypertension.

scholarly journals The Role of Factor V Leiden, Prothrombin G20210A, and MTHFR C677T Mutations in Neonatal Cerebral Sinovenous Thrombosis

2019 ◽  
Vol 25 ◽  
pp. 107602961983435 ◽  
Author(s):  
Maria Garrido-Barbero ◽  
Juan Arnaez ◽  
Begoña Loureiro ◽  
Gemma Arca ◽  
Thais Agut ◽  
...  
Keyword(s):  
Methylenetetrahydrofolate Reductase ◽  
Clinical Symptoms ◽  
Newborn Infants ◽  
Factor V Leiden ◽  
Mthfr C677t ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Case Control Studies ◽  
Cerebral Sinovenous Thrombosis ◽  
Sinovenous Thrombosis

Little is known about the pathogenesis of cerebral sinovenous thrombosis (CSVT) in the neonate. Although thrombophilia has been described as increasing the risk of CSVT in adults, it remains controversial in pediatric patients, and prospective case–control studies regarding neonatal CSVT are lacking. From 2008 to 2017, all 26 consecutive newborn infants ≥35 weeks of gestation diagnosed with neonatal CSVT, and their mothers, were tested for factor V Leiden (FV) G1691A, FII G20210A, and methylenetetrahydrofolate reductase C677T (MTHFR C677T) mutations. Eighty-five mother–infant pairs were recruited as controls. All infants except 1 with CSVT were suspected due to clinical symptoms, mainly seizures (22/25). Magnetic resonance imaging was performed in 24/26 infants. Heterozygous FV G1691A, FII G20210A, and homozygous MTHFR C677T mutations were present in 1/26, 3/26, and 3/20 infants with CSVT, respectively. FII (odds ratio: 10.96; 95% confidence interval [CI]: 1.09-110.35) and male sex (3.93; 95% CI: 1.43-10.76) were associated with CSVT. When FII G20210A analysis was adjusted for sex, the OR for FII G20210A was 6.70 (95% CI: 0.65-69.22). No differences were found for FV G1691A or homozygous MTHFR mutations between neonates with CSVT and their mothers, compared to controls.

Association of increased C-Reactive Protein and hypocomplementemia with risk factors for thrombosis in women who have susceptibility for poor gestational outcome; importance of preconceptional counseling

2021 ◽  
pp. 1-6
Author(s):  
Mehmet Sinan Beksac ◽  
Hanife Guler Donmez
Keyword(s):  
Risk Factors ◽  
Inflammatory Diseases ◽  
Factor V Leiden ◽  
Care Program ◽  
Prothrombin G20210a ◽  
Study Group ◽  
Factor V ◽  
C Reactive Protein ◽  
Mthfr Polymorphisms ◽  
Reactive Protein

This study aimed to investigate the association of increased C-Reactive Protein (CRP) and hypocomplementemia with risk factors for thrombosis such as Factor V Leiden (FVLP) and Prothrombin G20210A polymorphisms (PP), increased Activated Protein C Resistance (APCR) and decreased anti-thrombin III (ATIII) activity in women who have metabolic (MTHFR polymorphisms) and immunological risk factors (autoimmune antibody positivity, autoimmune disorders, and chronic inflammatory diseases). All patients (n= 197) were evaluated in terms of risk factors for thrombosis including FVLP, PP, increased APCR, and decreased ATIII activity as well as CRP and complement (C) 3 and C4 levels within a framework of preconceptional care program. Patients with high CRP levels together with hypocomplementemia were included to the study group (n= 13), while women with normal levels of CRP, C3, and C4 were accepted as controls (n= 184). Decreased ATIII activity was found to be statistically more frequent in the study group compared to controls (p= 0.036). There were no significant differences between the study and control groups in terms of the presence of FVLP, PP and increased APCR (p= 0.386, p= 0.462, p= 0.625, respectively). Decreased ATIII activity should be the concern of preconceptional and antenatal care programs in risky patients with increased CRP levels and hypocomplementemia in order to prevent placental inflammation related gestational complications.

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