Allele 4G of gene PAI-1 associated with prothrombin mutation G20210A increases the risk for venous thrombosis

2003 ◽  
Vol 90 (12) ◽  
pp. 1061-1064 ◽  
Author(s):  
Doris Barcellona ◽  
Lara Fenu ◽  
Cristiana Cauli ◽  
Giulia Pisu ◽  
Francesco Marongiu
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Odds Ratio ◽  
Final Conclusion ◽  
Thrombotic Risk ◽  
G20210a Mutation ◽  
Increased Risk ◽  
Prothrombin Mutation ◽  
Pai 1

SummarySeveral studies have tried to clarify the role of polymorphism 4G/5G of the PAI-1 gene in venous thromboembolism without reaching any final conclusion. It has been demonstrated that this polymorphism may induce an increased risk for venous thromboembolism (VTE) in patients with thrombophilic defects. We studied the association of prothrombin mutation G20210A with 4G/5G polymorphism in 402 VTE patients and 466 healthy controls. Patients affected by prothrombin mutation G20210A, with or without the concomitant presence of allele 4G, had a 3.7 thrombotic risk (C.I. 95% 2.3–6.0; p<0.0001). Moreover, genotype 4G/4G is a mild risk factor for VTE, irrespectively of whether the prothrombin mutation was present.Logistic regression analysis showed that patients carrying the G20210A prothrombin mutation with allele 4G gave an odds ratio for VTE of 6.1 (C.I. 95% 3.2 – 11.4; p<0.001). The risk increased up to 13.0 (C.I. 95% 3.0 – 60.4; p<0.001) when we considered the association of the prothrombin mutation with genotype 4G/4G. The G20210A mutation without allele 4G (5G/5G) was not a risk factor for VTE. In conclusion, we believe that patients affected by VTE with concomitant presence of the G20210A prothrombin mutation could be tested for genotype 4G/4G to better define their thrombotic risk.

The VITA Project: Prothrombin G20210A Mutation and Venous Thromboembolism in the General Population

1999 ◽  
Vol 82 (11) ◽  
pp. 1395-1398 ◽  
Author(s):  
Alberto Tosetto ◽  
Edoardo Missiaglia ◽  
Maurizio Frezzato ◽  
Francesco Rodeghiero
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
General Population ◽  
Odds Ratio ◽  
Genetic Variant ◽  
Population Based ◽  
Prothrombin G20210a ◽  
Cross Sectional ◽  
G20210a Mutation ◽  
Increased Risk

SummaryRecently a new identified genetic variant in the 3’-untranslated region of the prothrombin gene (G20210A allele) associated with increased plasma prothrombin levels has been linked to an increased risk of venous thromboembolism (VTE). Most of our knowledge on the G20210A allele as a risk factor for VTE derives from a population-based case-control study and from studies on selected series of VTE patients. To determine the importance of the G20210A allele as a causative risk factor for VTE in the general population, we analyzed the cross-sectional data of the Vicenza Thrombophilia and Atherosclerosis (VITA) Project. One hundred sixteen cases of VTE, ascertained in a random fashion within the general population aged 18-65, were age and sex-matched with 232 healthy subjects. Heterozygosity for the G20210A allele was present in 4.3% of VTE cases and in 3.4% of controls, indicating a marginal increase of VTE risk in carriers of the allele (odds ratio: 1.26; 95% CI 0.4-3.9). However, the VTE risk was substantially higher in subjects with idiopathic VTE before age 45 or with recurrent, idiopathic VTE (odds ratio: 2.8; 95% CI 0.6-13.8) or in subjects with a family history of VTE (odds ratio: 7.6; 95% CI 1.8-32.8). Accordingly, our results suggest that the G20210A allele associates with VTE only in selected cases, and that screening for this genetic variant is not warranted for all patients with VTE.

Is APC Resistance a Risk Factor for Venous Thromboembolism in Patients over 70 Years?

2002 ◽  
Vol 88 (10) ◽  
pp. 587-591 ◽  
Author(s):  
Karine Lacut ◽  
Grégoire Le Gal ◽  
Patrick Van Dreden ◽  
Luc Bressollette ◽  
Pierre-Yves Scarabin ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Odds Ratio ◽  
Dna Analysis ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Factor V ◽  
Apc Resistance ◽  
Increased Risk ◽  
History Of

SummaryActivated protein C (APC) resistance is the most common risk factor for venous thromboembolism (VTE). Previous studies mostly analysed patients under 70 years and reported a four-to sevenfold increased risk. This case-control study included consecutive patients referred for a clinical suspicion VTE to our medical unit: 621 patients with a well-documented diagnosis (cases) and 406 patients for which the diagnosis was ruled out and who had no personal history of VTE (controls). APC resistance related to factor V Leiden was defined by either a positive DNA analysis or a positive STA® Staclot APC-R assay. Under 70 years, APC resistance was associated with a threefold increased risk of VTE (odds ratio 3.2, 95% CI, 1.7 to 6.0), whereas in patients over 70 years, it appeared to be no longer a strong risk factor (odds ratio 0.8, 95% CI, 0.4 to 1.7). Age appeared as an effectmeasure modifier with a significant interaction (p = 0.005). Our data suggest that APC resistance is not a risk factor for VTE in elderly.

The Homozygous Leu Variant of the Factor XIII Val34Leu Polymorphism as a Risk Factor for the Manifestation of Thrombotic Microangiopathies

2007 ◽  
Vol 15 (2) ◽  
pp. 197-200 ◽  
Author(s):  
Christoph Sucker ◽  
Firuseh Farokhzad ◽  
Christine Kurschat ◽  
Bernd Grabensee ◽  
Rudiger E. Scharf ◽  
...  
Keyword(s):  
Risk Factor ◽  
Odds Ratio ◽  
Factor Xiii ◽  
Genetic Variant ◽  
Thrombotic Microangiopathies ◽  
Thrombocytopenic Purpura ◽  
Thrombotic Risk ◽  
Thrombotic Risk Factor ◽  
Uremic Syndrome

The 34 Leu (100T) variant of the factor XIII Val34Leu (G100T-) polymorphism slows down fibrinolysis and has been proposed as a thrombotic risk factor. In this pilot study, we enrolled 40 patients (mean age ± SD = 38 ± 11 years) and 728 controls to assess the role of this genetic variant for the manifestation of thrombotic microangiopathies. From the genotype prevalences, an increased manifestation risk for carriers of the TT genotype (homozygous Leu variant) of the factor XIII Val34Leu (G100T-) polymorphism was calculated (odds ratio [OR] = 2.44; 95% confidence interval [CI] = 0.8-7.6; P = .11). This association was statistically significant for patients with thrombotic thrombocytopenic purpura—hemolytic-uremic syndrome (TTP-HUS) (OR = 6.6; 95% CI = 1.7-25.9; P = .006). Our data suggest a role of the homozygous Leu variant of the factor XIII Val34Leu polymorphism in the manifestation of thrombotic microangiopathies. Decreased fibrinolysis in the presence of this genetic variant provides a plausible explanation for this association.

Impaired fibrinolysis in retinal vein occlusion: a role for genetic determinants of PAI-1 levels

2004 ◽  
Vol 92 (07) ◽  
pp. 54-60 ◽  
Author(s):  
Rossella Marcucci ◽  
Cinzia Fatini ◽  
Francesca Gensini ◽  
Elena Sticchi ◽  
Andrea Sodi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Risk Factor ◽  
Retinal Vein Occlusion ◽  
Smoking Habit ◽  
Activity Levels ◽  
Vein Occlusion ◽  
Increased Risk ◽  
Pai 1

SummaryFew and contrasting data are available on the presence of a thrombophilic state in patients with retinal vein occlusion (RVO), and we have previously demonstrated a role of elevated PAI-1 activity as a risk factor for this condition. The present study was undertaken to investigate whether PAI 4G/5G and ACE I/D polymorphisms are independent risk factors for RVO and whether they account for elevated PAI-1 activity levels. We studied 112 RVO patients (52 males and 60 females; range 18–83 years; median age 60 years) and 112 healthy subjects (52 males and 60 females; range 20–84 years; median age 57 years). PAI-1 activity was determined by a chromogenic assay and ACE I/D and PAI-1 4G/5G polymorphisms by polymerase chain reaction (PCR) and restriction length fragment polymorphism (RLFP) methods. Elevated PAI-1 activity (above 95th percentile of the controls) was significantly associated with RVO at multivariate analysis after adjustment for age, sex, traditional cardiovascular risk factors and haemostasis-related risk factors (OR = 4.93, 95% CI 1.70–14.30; p = 0.003).The homozygosity for ACE DD was found to be an independent risk factor for RVO at multivariate analysis (OR = 1.98, 95% CI 1.013.83; p = 0.049), whereas no significant association between homozygosity for PAI-1 4G4G and risk of RVO was observed. Subjects carrying both ACE DD genotype and PAI-1 4G4G genotype showed an increased risk for RVO at multivariate analysis (OR = 4.82, 95% CI 1.89–12.29; p = 0.001). In 45/112 patients without the established risk factors for RVO (hypertension, hypercholesterolemia and diabetes) or characteristics known to be associated to increased PAI-1 activity (overweight, hypertriglyceridemia, and smoking habit) the contemporary presence of ACE DD and PAI-1 4G4G genotype was significantly associated with a risk for RVO (OR = 8.26, 95% CI 1.1857.92; p = 0.034). In conclusion, in our study: 1-indicates that ACE DD genotype is a risk factor for RVO in the whole group of patients, and in the subgroup of patients without the established risk factors for RVO or characteristics influencing the PAI-1 activity, when associated to PAI-1 4G4G genotype, and 2-confirms the role of hypofibrinolysis, documented by high levels of PAI-1 activity, in the occurrence of patients with RVO.

scholarly journals Effect of aspirin on short-term outcomes in hospitalized patients with COVID-19

2021 ◽  
pp. 1358863X2110127
Author(s):  
Aditya Sahai ◽  
Rohan Bhandari ◽  
Matthew Godwin ◽  
Thomas McIntyre ◽  
Mina K Chung ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Venous Thromboembolism ◽  
Cerebrovascular Accident ◽  
Antiplatelet Agents ◽  
Hospitalized Patients ◽  
Short Term ◽  
Thrombotic Risk ◽  
Increased Risk ◽  
Inflammatory Drugs

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is an ongoing viral pandemic marked by increased risk of thrombotic events. However, the role of platelets in the elevated observed thrombotic risk in COVID-19 and utility of antiplatelet agents in attenuating thrombosis is unknown. We aimed to determine if the antiplatelet effect of aspirin may mitigate risk of myocardial infarction, cerebrovascular accident, and venous thromboembolism in COVID-19. We evaluated 22,072 symptomatic patients tested for COVID-19. Propensity-matched analyses were performed to determine if treatment with aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) affected thrombotic outcomes in COVID-19. Neither aspirin nor NSAIDs affected mortality in COVID-19. Thus, aspirin does not appear to prevent thrombosis and death in COVID-19. The mechanisms of thrombosis in COVID-19, therefore, appear distinct and the role of platelets as direct mediators of SARS-CoV-2-mediated thrombosis warrants further investigation.

scholarly journals SARS-CoV-2 Receptors are Expressed on Human Platelets and the Effect of Aspirin on Clinical Outcomes in COVID-19 Patients

2020 ◽  
Author(s):  
Aditya Sahai ◽  
Rohan Bhandari ◽  
Milka Koupenova ◽  
Jane Freedman ◽  
Mathew Godwin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Venous Thromboembolism ◽  
Confocal Microscopy ◽  
Cell Surface ◽  
Cerebrovascular Accident ◽  
Human Platelets ◽  
Thrombotic Risk ◽  
Increased Risk ◽  
Inflammatory Drugs

Abstract Coronavirus disease-2019 (COVID-19) caused by SARS-CoV-2 is an ongoing viral pandemic marked by increased risk of thrombotic events. However, the role of platelets in the elevated observed thrombotic risk in COVID-19 and utility of anti-platelet agents in attenuating thrombosis is unknown. We aimed to determine if human platelets express the known SARS-CoV-2 receptor-protease axis on their cell surface and assess whether the anti-platelet effect of aspirin may mitigate risk of myocardial infarction (MI), cerebrovascular accident (CVA), and venous thromboembolism (VTE) in COVID-19. Expression of ACE2 and TMPRSS2 on human platelets were detected by immunoblotting and confirmed by confocal microscopy. We evaluated 22,072 symptomatic patients tested for COVID-19. Propensity-matched analyses were performed to determine if treatment with aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) affected thrombotic outcomes in COVID-19. Neither aspirin nor NSAIDs affected mortality in COVID-19. However, both aspirin and NSAID therapies were associated with increased risk of the combined thrombotic endpoint of (MI), (CVA), and (VTE). Thus, while platelets clearly express ACE2-TMPRSS2 receptor-protease axis for SARS-CoV-2 infection, aspirin does not prevent thrombosis and death in COVID-19. The mechanisms of thrombosis in COVID-19, therefore, appears distinct and the role of platelets as direct mediators of SARS-CoV-2-mediated thrombosis warrants further investigation.

scholarly journals Type and Location of Venous Thromboembolism in Carriers of Factor V Leiden or Prothrombin G20210A Mutation Versus Patients With No Mutation

2008 ◽  
Vol 16 (1) ◽  
pp. 66-70 ◽  
Author(s):  
Mirjana Kovac ◽  
Gorana Mitic ◽  
Zeljko Mikovic ◽  
Nebojsa Antonijevic ◽  
Valentina Djordjevic ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Venous Thromboembolism ◽  
Clinical Manifestations ◽  
Factor V Leiden ◽  
Transverse Sinus ◽  
Prothrombin G20210a ◽  
Factor V ◽  
G20210a Mutation ◽  
Increased Risk

Factor V Leiden (FVLeiden) and prothrombin G20210A are the most common genetic causes of thrombophilia and established risk factors for different clinical manifestations of venous thromboembolism (VTE). This study investigated whether the clinical manifestation of VTE, the extension of deep vein thrombosis (DVT) and the presence of transient risk factors at the time of the first VTE, differed among patients with mutations (97 with FVLeiden; 33 with prothrombin G20210A) and in 109 patients without thrombophilia. Isolated pulmonary embolism (PE) was less prevalent in patients with FVLeiden (6%) and no thrombophilia (6%) than in those with prothrombin G20210A (15%). No difference was found in the incidence of distal DVT. Regarding the extension of proximal DVT, the lowest incidence for isolated popliteal vein and the highest for iliofemoral vein were observed in patients with prothrombin G20210A. No difference was observed between groups of patients with or without thrombophilia by unprovoked VTE. The pregnancy/puerperium was the most prevalent risk factor in carriers of prothrombin G20210A. Among FVLeiden carriers, the most prevalent risk factor was surgery, and in patients without thrombophilia, it was trauma ( P < .05). Thrombosis of the upper limb was more frequent in a group without thrombophilia than in patients with mutations ( P < .01). Transverse sinus venous thrombosis was present only in patients with prothrombin G20210A. Carriers of prothrombin G20210A have an increased risk of developing isolated PE and more severe clinical manifestations than those with FVLeiden or without thrombophilia.

The deletion polymorphism in the angiotensin-converting enzyme gene is a moderate risk factor for venous thromboembolism

2003 ◽  
Vol 89 (05) ◽  
pp. 847-852 ◽  
Author(s):  
Andreas Czwalinna ◽  
Cornelia Wermes ◽  
Roswith Eisert ◽  
Inge Scharrer ◽  
Arnold Ganser ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Venous Thromboembolism ◽  
Independent Risk Factor ◽  
Blood Donors ◽  
Angiotensin Converting Enzyme Gene ◽  
Deletion Polymorphism ◽  
Moderate Risk ◽  
G20210a Mutation

SummaryACE displays potent vasoconstrictive effects, attenuation of fibrinolysis, and platelet activation and aggregation, thus possibly promoting venous thromboembolism (VTE). The ACE gene contains an insertion (I) or deletion (D) polymorphism accounting for 50% of the variation in serum ACE concentration. To evaluate the role of the I/D polymorphism in VTE, its prevalence was determined in 931 patients with VTE and 432 blood donors. The prevalence of the DD genotype was 27.6% in patients and 21.3% in controls (OR 1.4; p <0.02). In multivariate analysis there was a trend of the DD genotype to be an independent risk factor (OR 1.4; p = 0.08). No differences in DD genotype prevalence according to exogenous risk factors were found. Coinheritance of FV G1691A, PT G20210A mutation, and PS deficiency with the DD genotype increased the relative risk of VTE. Thus, the ACE DD genotype is a moderate risk factor of hereditary thrombophilia. Exogenous risk factors did not alter the manifestation of VTE among carriers of the DD genotype, whereas coinheritance of the DD genotype with the aforementioned defects increased the risk for VTE considerably.

Factor V Leiden and Prothrombin Gene G20210A Mutation in Children with Venous Thromboembolism

2002 ◽  
Vol 87 (06) ◽  
pp. 972-977 ◽  
Author(s):  
Mirta Hepner ◽  
Gabriela Sciuccati ◽  
Graciela Pieroni ◽  
Aurora Feliú-Torres ◽  
Claudia Mardaraz ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Odds Ratio ◽  
Factor V Leiden ◽  
Paediatric Population ◽  
Control Group ◽  
Factor V ◽  
G20210a Mutation ◽  
Prothrombin Gene ◽  
Haematological Analysis

SummaryTo determine whether factor V Leiden (FVL) and/or prothrombin gene G20210A mutation (PT20210A) are risk factors for venous thromboembolism (VTE) in Argentinean children. One hundred and thirty consecutive children with VTE were prospectively assisted at a single centre. Blood samples were available from 110 of them for detailed haematological analysis. The prevalence of both mutations was compared with a control group. The odds ratio for VTE was significantly increased in patients with FVL (OR 3.64; 95% CI: 1.14-11.6, p <0.029) whereas odds ratio for VTE was not significantly increased in patients with PT20210A (OR 1.06; 95% CI: 0.24-4.73, p = 0.938). Combined disorders were found in 5 of the 10 children with the aforementioned mutations. In 21 children (19%) without these mutations other inherited and acquired disorders were detected. Our data show that FVL is a risk factor for VTE whereas PT20210A does not seem to be a risk factor in our paediatric population.

Combined Effect of Factor V Leiden and Prothrombin 20210A on the Risk of Venous Thromboembolism

2001 ◽  
Vol 86 (09) ◽  
pp. 809-816 ◽  
Author(s):  
Frits Rosendaal ◽  
Marco Cattaneo ◽  
Maurizio Margaglione ◽  
Valerio De Stefano ◽  
Tony Cumming ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Odds Ratio ◽  
Large Population ◽  
Factor V Leiden ◽  
Pooled Analysis ◽  
Factor V ◽  
Case Control Studies ◽  
Vein Thrombosis ◽  
G20210a Mutation ◽  
Factor Ii

SummaryFactor V Leiden and factor II G20210A mutations are two frequent genetic risk factors involved in venous thromboembolism (VTE). The goal of this pooled analysis of 8 case-control studies, comprising a total of 2310 cases and 3204 controls, was to precisely estimate the risk of VTE in patients bearing both mutations (double heterozygotes). Odds ratios for VTE were 4.9 (95% CI; 4.1-5.9) for the factor V Leiden and 3.8 (3.0-4.9) for the factor II G20210A mutation. Fifty-one cases (2.2%) and none of the controls were double heterozygotes. The odds ratio for venous thrombosis in double heterozygotes was 20.0 (11.1-36.1). Twelve percent of patients heterozygous for factor V Leiden were also heterozygous for factor II G20210A and conversely 23% of patients heterozygous for factor II G20210A were also heterozygous for factor V Leiden. Furthermore, in this large population we analyzed the effect of oral contraceptive (OC) in women carrying one of these mutations. Odds ratio for VTE associated with OC was 2.29 (1.72-3.04). In factor V Leiden carriers using OC, the odds ratio for VTE was 10.25 (5.69-18.45). The odds ratio of the association of factor II mutation and OC use was 7.14 (3.39-15.04). Finally, we also confirmed that the frequency of factor V Leiden was lower in patients with pulmonary embolism than in patients with deep vein thrombosis without PE (odds ratio 0.69). Conversely, factor II G20210A mutation was equally balanced in both patient groups.

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