The 20210 A Allele of the Prothrombin Gene Is a Common Risk Factor among Swedish Outpatients with Verified Deep Venous Thrombosis

1997 ◽  
Vol 78 (03) ◽  
pp. 0990-0992 ◽  
Author(s):  
Andreas Hillarp ◽  
Bengt Zӧller ◽  
Peter J Svensson ◽  
Bjӧrn Dahlbäck
Keyword(s):  
Risk Factor ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Odds Ratio ◽  
Untranslated Region ◽  
Control Group ◽  
Common Risk Factor ◽  
Apc Resistance ◽  
Healthy Control ◽  
Prothrombin Gene

SummaryA dimorphism in the 3’-untranslated region of the prothrombin gene (G to A transition at position 20210) has recently been reported to be associated with increases in plasma prothrombin levels and in the risk of venous thrombosis (1). We have examined the prothrombin dimorphism among 99 unselected outpatients with phlebography verified deep venous thrombosis, and in 282 healthy controls. The prevalence of the 20210 A allele was 7.1% (7/99) in the patient group, and 1.8% (5/282) in the healthy control group (p = 0.0095). The relative risk of venous thrombosis was calculated to be 4.2 (95% Cl, 1.3 to 13.6), and was still significant when adjustment was made for age, sex and the factor V:R506Q mutation causing APC resistance [odds ratio 3.8 (95% Cl, 1.1 13.2)]. As previously reported, 28% of the patients were carriers of the factor V:R506Q mutation. Thus, 34% (one patient carried both traits) of unselected patients with deep venous thrombosis were carriers of an inherited prothrombotic disorder. To sum up, our results confirm the 20210 A allele of the prothrombin gene to be an important risk factor for venous thrombosis.

Combined Factor V Leiden (R506Q) and prothrombin G20210A genotyping in young patients presenting with deep venous thrombosis

2006 ◽  
Vol 21 (1) ◽  
pp. 24-27 ◽  
Author(s):  
A Mansilha ◽  
F Araújo ◽  
M Severo ◽  
S M Sampaio ◽  
T Toledo ◽  
...  
Keyword(s):  
Risk Factor ◽  
Young People ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Young Patients ◽  
Factor V Leiden ◽  
First Episode ◽  
Control Group ◽  
Factor V ◽  
Factor V Leiden Mutation

Objective: To evaluate the association between the Factor V Leiden (FV R506Q) and prothrombin gene (FII G20210A) mutations and deep venous thrombosis (DVT) in young people. Methods: Blood samples were drawn from 199 subjects: 100 healthy controls and 99 unselected patients, with an objectively documented first episode of DVT under 40 years old. DNA analysis was performed using the polymerase chain reaction. Results: The mean age in the patient cohort was 27 years (range 16–40) and 68 (68.7%) were women. Patient prevalences were 20.6% and 10.1% for FV R506Q and FII G20210A, respectively. In the control group, carrier frequencies were 2% and 5%, respectively. We found an increased overall relative risk of DVT with statistical significance for FV R506Q carriers (OR: 12.8; 95% CI: 2.9–56.7; P < 0.001), but not for FII G20210A mutation (OR: 2.1; 95% CI: 0.7–6.5; P = 0.19). Conclusions: Our results suggest a possible increase in DVT risk for the young G20210A allele carriers, which can be more expressed in the presence of a circumstantial risk factor. There is extremely strong evidence that the Factor V Leiden mutation is an important risk factor in the development of a first episode of DVT in young people.

scholarly journals Fibrinogen γ′ increases the sensitivity to activated protein C in normal and factor V Leiden plasma

Blood ◽  
2014 ◽  
Vol 124 (9) ◽  
pp. 1531-1538 ◽  
Author(s):  
Farida Omarova ◽  
Shirley Uitte de Willige ◽  
Paolo Simioni ◽  
Robert A. S. Ariëns ◽  
Rogier M. Bertina ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thrombosis ◽  
Protein C ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Factor V ◽  
Common Risk Factor ◽  
Apc Resistance ◽  
Key Points

Key Points Fibrinogen, and particularly fibrinogen γ′, counteracts plasma APC resistance, the most common risk factor for venous thrombosis. The C-terminal peptide of the fibrinogen γ′ chain inhibits protein C activation, but still improves the response of plasma to APC.

MMP-3-1612 polymorphism - a risk factor for deep venous thrombosis formation

VASA ◽  
2016 ◽  
Vol 45 (3) ◽  
pp. 233-239
Author(s):  
La-Mei Yu ◽  
Nai-Xuan Li ◽  
Yu-Guo Sheng
Keyword(s):  
Risk Factor ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Allele Frequency ◽  
Rat Model ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Control Groups ◽  
And Control

Abstract. Background: We investigated the association of the 5A/6A polymorphism in the promoter region at -1612 of the matrix metalloproteinase-3 gene (MMP-3-1612) and deep venous thrombosis (DVT). Patients, materials and methods: The distribution of the MMP-3 (-1612 5A/6A) polymorphism in the case and control groups was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Serum MMP-3 level of two groups was detected using enzyme-linked immunosorbent assay (ELISA). HepG2 cells containing MMP-3-1612 recombinant plasmid were cultured in vitro and the MMP-3 level was defined by luminescence intensity of luciferase. A DVT rat model was built. Serum MMP-3 level in the rats’ wounded vein at different time points was detected by ELISA and recorded for investigation of the association between MMP-3 and DVT. Statistical data analysis was conducted with SPSS18.0. Results: On the basis of the observation of MMP-3-1612 genotype frequency and allele frequency in the case and control groups, we identified significantly higher MMP-3-1612 5A allele frequency and higher serum MMP-3 level in the case group than in the control group (both P < 0.05). According to in vitro luciferase measurements, the 5A allele had higher transcriptional activity than the 6A allele. As observed in the rat model, serum MMP-3 level increased with time passing and thrombosis formation after modelling. Conclusions: The MMP-3-1612 5A/6A polymorphism may effect serum MMP-3 level and over-expression of serum MMP-3 level may be a risk factor for DVT formation.

The Risk of Venous Thrombosis Related to Increase in Body Mass Index Is Mediated by Factor VIII Induced APC-Resistance.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 453-453 ◽  
Author(s):  
Willem M Lijfering ◽  
Sverre C Christiansen ◽  
Inger-Anne Naess ◽  
Jens Hammerstrøm ◽  
Astrid van Hylckama Vlieg ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Blood Group ◽  
Odds Ratio ◽  
Reference Group ◽  
Control Group ◽  
Odds Ratios ◽  
Apc Resistance ◽  
Increased Risk ◽  
Fv Leiden ◽  
High Bmi

Abstract Abstract 453 Background: The reason why a high BMI predisposes to venous thrombosis is not clarified. People with overweight or obesity tend to be more immobile which may lead to clot formation through stasis. It is also possible that these subjects acquire a prothrombotic state. Factor (F) VIII can be released by adipose tissue through inflammatory cytokines, which consequently might induce APC-resistance. This APC-resistance could be aggravated in case FV Leiden is also present. In addition, presence of high levels of FVIII in non-O blood group subjects could worsen this further. Objective: To determine whether an association exists between BMI and APC-resistance, and whether the combination of both high BMI and APC-resistance increased the risk of venous thrombosis in the Leiden Trombophilia Study (LETS). Whether increasing FVIII levels induced APC-resistance was also studied. In a pooled analysis of LETS and a Norwegian case-cohort study (TROL), we verified if FV Leiden modified the risk of increasing BMI on the occurence of venous thrombosis and whether these risks were further increased by blood group non-O. Methods: Linear regression was used to determine the relation between increasing APC-resistance and BMI, increasing FVIII levels and BMI, increasing APC-resistance and FVIII levels, and between increasing APC-resistance and BMI adjusted for FVIII levels. Cut-off points needed to create tertile categories of APC-resistance were derived from the control-group of the LETS and the TROL population separately. Logistic regression was used to calculate odds ratios and their 95% confidence intervals, adjusted for age and sex. To make the TROL and LETS population more similar for the current analysis, we restricted the analysis in the TROL subjects to those who were younger than 70 and to those who had a DVT only (n=183 cases and n=696 controls). Results: APC-resistance increased linearly with increasing BMI. A same phenomenon was observed for FVIII, i.e. an increase of BMI led to higher FVIII levels. Increased APC-resistance was in its turn associated with an increase of FVIII levels. FVIII explained part of the relation between APC and BMI, as the slope of the regression line of APC-resistance on BMI levels decreased after adjustment for FVIII. To examine the effect of increasing BMI, independent of existing APC-resistance, on the risk of venous thrombosis, we restricted the analysis to subjects from the LETS in whom APC-resistance was not related to other factors such as FV Leiden or oral contraceptive use. In these subjects (n=237 cases and n=369 controls), the risk of venous thrombosis increased 1.4-fold for those with a BMI in the median tertile (odds ratio 1.4; 95% CI, 0.9-2.3) and 2.5-fold for those in the upper tertile (odds ratio 2.5; 95% CI, 1.6-3.9), as compared to subjects in the lowest tertile. Adjustment for APC-resistance or FVIII led to a slight decrease in these relative risk estimates. Non-FV Leiden-carriers with blood group O were only at risk of venous thrombosis when they had a BMI in the upper tertile compared to non-FV Leiden-carriers with blood group O and a BMI in the lowest tertile; (adjusted odds ratio 1.9). This risk was modestly increased when non FV Leiden carriers with non-O blood group were compared with this reference group, with adjusted odds ratios of 1.5, 2.4 and 3.4, respectively, within the BMI tertiles. This risk was strongly increased when FV Leiden carriers with blood group O were compared to the reference group, with adjusted odds ratios of 3.0, 8.3 and 9.7, respectively, within the BMI tertiles. Risk of FV Leiden carriers with non-O blood group showed the highest risk of venous thrombosis compared to the reference group, no longer in a dose-response way, with adjusted odds ratios of 40.6, 23.3 and 25.2, respectively, within the BMI tertiles. Conclusion: The increased risk of venous thrombosis in subjects with high BMI is mediated by FVIII induced APC-resistance. Subjects with FV Leiden and increasing BMI had a higher risk of venous thrombosis compared to non-carriers, and this risks was more than 20 fold increased in carriers of blood group non-O and FV Leiden. Future studies are needed to show if these risks can be downgraded by weight loss. Disclosures: No relevant conflicts of interest to declare.

Prevalence of the Prothrombin Gene Variant (nt20210A) in Venous Thrombosis and Arterial Disease

1997 ◽  
Vol 78 (06) ◽  
pp. 1430-1433 ◽  
Author(s):  
Valder R Arruda ◽  
Joyce M Annichino-Bizzacchi ◽  
Marilda S Gonçalves ◽  
Fernando F Costa
Keyword(s):  
Risk Factor ◽  
Venous Thrombosis ◽  
Genetic Risk ◽  
Arterial Disease ◽  
Control Group ◽  
Gene Variant ◽  
Disease Group ◽  
High Prevalence ◽  
Amazonian Indians ◽  
Prothrombin Gene

SummaryThe prothrombin gene variant resulting form a G→A transition at position 20210 has been described as a common genetic risk factor for venous thrombosis. However, the risk for developing arterial disease is unknown. In this investigation, we studied 116 patients with venous thrombosis and 71 with arterial disease, all of whom were compared with 295 controls. Additionally, we also investigated the distribution of the prothrombin alleles among African descendents and Amazonian Indians from Brazil. The prevalence of 0.7% for 20210A allele in the control group increased to 4.3% (P = 0.021) among patients with venous thrombosis. There was also a high prevalence of the mutated allele in a selected arterial disease group (5.7%) without hyperlipoproteinemia, hypertension, and diabetes mellitus when compared to the controls (P = 0.013). Heterozygotes for the allele 20210A were common among individuals of African descent (2%) and rare among Indians. These data support the hypothesis that the prothrombin variant is a risk factor for venous thrombosis and suggest that it may also be a risk factor for arterial disease.

Prevalence of 20210 A Allele of the Prothrombin Gene in Venous Thromboembolism Patients

1998 ◽  
Vol 80 (07) ◽  
pp. 49-51 ◽  
Author(s):  
Bernard Mercier ◽  
Emmanuel Oger ◽  
Eric Chenu ◽  
Jean-François Abgrall ◽  
Claude Férec ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Odds Ratio ◽  
Factor V Leiden ◽  
Clinical Suspicion ◽  
Control Group ◽  
Factor V ◽  
Factor V Gene ◽  
Prothrombin Gene ◽  
Allele Variation

SummaryBackground. The 20210 A allele variation in the 3’ -untranslated region of the prothrombin gene was recently identified as a risk factor as regards deep venous thrombosis. Aim. To assess the frequency of the variation in unselected patients with a proven venous thromboembolism (VTE). Methods. The presence of the prothrombin variation was determined in all consecutive patients referred from July 1994 to August 1997 for a clinical suspicion of VTE, and in whom the diagnosis was confirmed. A control group consisted of bone marrow volunteer donors. Results. Of the 366 patients included, 17 (4.6%) were carriers of the 20210 A allele (95% CI, 2.4% to 6.7%). The mutation was present in 1.0% of the 400 controls. Odds ratio for having VTE in the presence of the 20210 A allele was 4.8 (95% CI, 1.5 to 19.8). Forty-six (12.5%) patients had the mutation of the factor V gene and five (1.4%) patients shared both mutations. After excluding the carriers of the factor V mutation, odds ratio for having VTE in the presence of the 20210 A allele was 3.7 (95% CI, 1.1 to 13.6). Mean age at admission as well as mean age of the first VTE episode were both significantly higher in patients free from the two mutations studied, as compared to carriers of the 20210 A allele (p = 0.04 and 0.01, respectively). Conclusion. Our findings in a large series of patients (1) confirm the 20210 A allele prothrombin gene as a risk factor for VTE. (2) suggest that its association with the factor V Leiden is not uncommon.

Factor XIII Val34Leu Is a Genetic Factor Involved in the Aetiology of Venous Thrombosis

1999 ◽  
Vol 81 (05) ◽  
pp. 676-679 ◽  
Author(s):  
P. H. Reitsma ◽  
D. Lourenço ◽  
F. H. Maffei ◽  
V. Morelli ◽  
M. H. Tavella ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Risk Factor ◽  
Venous Thrombosis ◽  
Plasma Levels ◽  
Odds Ratio ◽  
Untranslated Region ◽  
Factor Xiii ◽  
Genetic Factor ◽  
Protective Factor ◽  
Homozygous State

SummaryA mutation in the factor XIII gene (FXIII Val34Leu) gene was recently reported to confer protection against myocardial infarction, but its relationship with venous thrombosis is unknown. In addition, a mutation in the 5’-untranslated region of the FXII gene (46 C→T) was identified which is associated with low plasma levels of the protein. Its prevalence in patients with venous thrombosis is also unknown. We investigated the frequency of the FXIII Val34Leu and FXII 46 C→T mutations in 189 patients with deep venous thrombosis and in 187 age-, gender- and race-matched controls. FXIII Val34Leu was detected in 38.6% of the patients and in 41.2% of the controls. Interestingly, homozygosity for the FXIII mutation was found in 1.6% of the patients and in 9.6% of the controls, yielding an odds ratio (OR) for venous thrombosis of 0.16 (95% CI: 0.05-0.5). The OR for hetero-zygotes was 1.1 (95% CI: 0.7-1.7). The FXII 46 C→T mutation was detected in 46.0% of the patients and in 48.6% of the controls. The OR for heterozygotes was 0.9 (95% CI: 0.6-1.4) and for homozygotes the OR was 0.8 (95% CI: 0.3-1.9). Our data indicate that the FXII 46 C→T mutation is unlikely to be a major risk factor for venous thrombotic disease. In contrast, the homozygous state for FXIII Val34Leu is a strong protective factor against venous thrombosis, which emerges as a novel genetic factor involved in the aetiology of thrombophilia.

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.

scholarly journals Not Using a Tourniquet May Reduce the Incidence of Asymptomatic Deep Venous Thrombosis After ACL Reconstruction: An Observational Study

2021 ◽  
Vol 9 (12) ◽  
pp. 232596712110566
Author(s):  
Masaki Nagashima ◽  
Kenichiro Takeshima ◽  
Nobuto Origuchi ◽  
Ryo Sasaki ◽  
Yoshifumi Okada ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Odds Ratio ◽  
Cruciate Ligament ◽  
Control Group ◽  
Level Of Evidence ◽  
Surgical Field ◽  
The Mean ◽  
Anterior Cruciate ◽  
Without Tourniquet

Background: Deep venous thrombosis (DVT) and pulmonary embolism are serious potential complications after anterior cruciate ligament reconstruction (ACLR). Little is known about the influence of tourniquet use on the incidence of DVT after ACLR. Purpose: To compare the incidence of DVT after ACLR with and without the use of a tourniquet. Study Design: Cohort study; Level of evidence, 3. Methods: Between November 2018 and May 2020, a total of 60 consecutive ACLRs in 60 patients, including 7 revision surgeries, were performed without tourniquet use at our hospital and were enrolled in this study (T– group). In addition, 55 consecutive ACLRs in 55 patients, including 10 revision surgeries, were performed with tourniquet use between April 2017 and September 2018 and were enrolled as the control group (T+ group). DVT was diagnosed using ultrasonography of both legs performed preoperatively and at postoperative week 1. The incidence of postoperative DVT was compared between the T– and T+ groups. Logistic regression analysis was performed to evaluate the effect of older age (≥40 vs <40 years) and tourniquet use on the occurrence of DVT. Results: No DVTs were detected preoperatively. The incidence of postoperative DVT was significantly lower in the T– group compared with the T+ group (1 patient [1.7%] vs 9 patients [16.4%]; P = .005). All patients with DVT were asymptomatic. Although the mean operative time was not significantly different (80.8 minutes in the T+ group vs 78.5 minutes in the T– group; P = .461), the mean blood loss from the drain was significantly lower in the T– group than in the T+ group (149.9 vs 201.9 mL; P < .001). Age ≥40 years and tourniquet use were significantly related to the occurrence of DVT (odds ratio, 8.3 [95% CI, 1.9-36.8]; P = .005; and odds ratio, 8.8 [95% CI, 1.0-75.3]; P = .047, respectively). Conclusion: ACLRs performed without tourniquet resulted in a significantly lower incidence of DVT after ACLR and significantly less bleeding from drains. If adequate visibility of the surgical field is obtained, ACLR without tourniquet use may reduce the incidence of DVT.

scholarly journals Evaluating the Use of a Negative D-Dimer and Modified Low Wells Score in Excluding above Knee Deep Venous Thrombosis in an Outpatient Population, Assessing Need for Diagnostic Ultrasound

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Maryam Rahiminejad ◽  
Anshul Rastogi ◽  
Shirish Prabhudesai ◽  
David Mcclinton ◽  
Peter MacCallum ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Lower Limb ◽  
Clinical Risk Factor ◽  
Diagnostic Pathway ◽  
Clinical Diagnostic ◽  
Retrospective Audit ◽  
Wells Score ◽  
D Dimer

Aims. Colour doppler ultrasonography (CDUS) is widely used in the diagnosis of deep venous thrombosis (DVT); however, the number of scans positive for above knee DVT is low. The present study evaluates the reliability of the D-dimer test combined with a clinical probability score (Wells score) in ruling out an above knee DVT and identifying patients who do not need a CDUS. Materials and Method. This study is a retrospective audit and reaudit of a total of 816 outpatients presenting with suspected lower limb DVT from March 2009 to March 2010 and from September 2011 to February 2012. Following the initial audit, a revised clinical diagnostic pathway was implemented. Results. In our initial audit, seven patients (4.9%) with a negative D-dimer and a low Wells score had a DVT. On review, all seven had a risk factor identified that was not included in the Wells score. No patient with negative D-dimer and low Wells score with no extra clinical risk factor had a DVT on CDUS (negative predictive value 100%). A reaudit confirmed adherence to our revised clinical diagnostic pathway. Conclusions. A negative D-dimer together with a low Wells score and no risk factors effectively excludes a lower limb DVT and an ultrasound is unnecessary in these patients.

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