Marburg I polymorphism of factor VII-activating protease and risk of recurrent venous thromboembolism

2006 ◽  
Vol 95 (01) ◽  
pp. 65-67 ◽  
Author(s):  
Talin Gulesserian ◽  
Gregor Hron ◽  
Georg Endler ◽  
Sabine Eichinger ◽  
Oswald Wagner ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Recurrence Risk ◽  
Factor Vii ◽  
Study Endpoint ◽  
Protease Gene ◽  
Confounding Factors ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Recurrent Venous Thromboembolism ◽  
Recurrent Vte

SummaryWhether a single nucleotide polymorphism (1601 G>A) in the factor VII-activating protease gene (FSAP Marburg I) is a risk factor for venous thromboembolism (VTE) is unclear. We investigated the relevance of the variant with respect to recurrent VTE. 854 patients with a first unprovoked VTE were followed for an average of 41 months after discontinuation of anticoagulation. Study endpoint was symptomatic recurrent VTE. VTE recurred in 7 of 41 patients (17%) with and in 106 of 813 patients (13%) without the variant. After3 years, the probability of recurrence was 20.0% (95% CI, 5.3% to 34.6%) among patients with and 12.2% (95% CI, 9.6% to 14.8%) among those without FSAP MarburgI (p = 0. 5). The relative recurrence risk among carriers of the variant was 1.3 (95% CI, 0.6 to 2.8; p = 0.5) before and 1.5 (95% CI, 0.7 to 3.3; p = 0. 3) after adjustment for potentially confounding factors. We conclude that FSAP Marburg I is, if at all, only a mild factor for recurrent VTE. Patients with FSAP Marburg I most probably will not benefit from extended anticoagulation.

Homozygosity in the Single Nucleotide Polymorphism Ser128Arg in the E-Selectin Gene Is Associated with Recurrent Venous Thromboembolism.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4086-4086
Author(s):  
Gregor Hron ◽  
Bernd Jilma ◽  
Claudia L. Marsik ◽  
Georg Endler ◽  
Sabine Eichinger ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Venous Thromboembolism ◽  
Cox Regression ◽  
Factor V Leiden ◽  
Hazard Ratio ◽  
Rank Test ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Recurrent Venous Thromboembolism ◽  
Recurrent Vte

Abstract Objective: The single nucleotide polymorphism (SNP) Ser128Arg in the E-selectin gene is over-represented in certain patient populations with atherosclerosis or restenosis. As this SNP enhances tissue factor triggered coagulation in humans during systemic inflammation, we hypothesized that it may also predispose for the development of recurrent venous thromboembolism (VTE). Methods and Results: Patients (n=585) after first VTE were prospectively followed up for recurrent, objectively documented, symptomatic VTE. Patients with secondary VTE, homozygous Factor V Leiden, natural inhibitor deficiencies, lupus anticoagulant, or long term anticoagulation were excluded. The S128R SNP was genotyped by mutagenically separated PCR. One-hundred and two patients (17.4%) were heterozygous and 11 were homozygous (1.9%) for the Ser128Arg mutation. Ninety patients (15.4%) suffered from recurrent VTE during follow-up. Homozygosity for the Ser128Arg SNP increased the cumulative likelihood particularly for early recurrent VTE (log rank test p<0.05) and was an independent predictor of recurrent VTE (hazard ratio: 4.1; 95% CI 1.5–11.4) in a multivariate Cox Regression model. In contrast, heterozygosity for the polymorphism was associated with an unaltered hazard ratio (HR: 1.1; 95% CI 0.6–1.9) for recurrent VTE. Conclusion: Homozygosity for the S128R E-selectin allele appears to increase the risk for recurrent VTE several-fold, and -if confirmed- may represent a novel risk factor for recurrent VTE. These results also expand our knowledge on the association of this SNP with thrombotic disorders.

scholarly journals Predicting the Risk of Recurrent Venous Thromboembolism: Current Challenges and Future Opportunities

2020 ◽  
Vol 9 (5) ◽  
pp. 1582 ◽  
Author(s):  
Hannah Stevens ◽  
Karlheinz Peter ◽  
Huyen Tran ◽  
James McFadyen
Keyword(s):  
Venous Thromboembolism ◽  
Prediction Models ◽  
Clinical Prediction ◽  
Bleeding Events ◽  
Clinical Prediction Models ◽  
Disease Pathogenesis ◽  
Recurrent Venous Thromboembolism ◽  
Novel Biomarkers ◽  
Recurrent Vte ◽  
Acute Venous Thromboembolism

Acute venous thromboembolism (VTE) is a commonly diagnosed condition and requires treatment with anticoagulation to reduce the risk of embolisation as well as recurrent venous thrombotic events. In many cases, cessation of anticoagulation is associated with an unacceptably high risk of recurrent VTE, precipitating the use of indefinite anticoagulation. In contrast, however, continuing anticoagulation is associated with increased major bleeding events. As a consequence, it is essential to accurately predict the subgroup of patients who have the highest probability of experiencing recurrent VTE, so that treatment can be appropriately tailored to each individual. To this end, the development of clinical prediction models has aided in calculating the risk of recurrent thrombotic events; however, there are several limitations with regards to routine use for all patients with acute VTE. More recently, focus has shifted towards the utility of novel biomarkers in the understanding of disease pathogenesis as well as their application in predicting recurrent VTE. Below, we review the current strategies used to predict the development of recurrent VTE, with emphasis on the application of several promising novel biomarkers in this field.

Two doses of rivaroxaban versus aspirin for prevention of recurrent venous thromboembolism

2015 ◽  
Vol 114 (09) ◽  
pp. 645-650 ◽  
Author(s):  
Rupert Bauersachs ◽  
Jan Beyer-Westendorf ◽  
Henri Bounameaux ◽  
Timothy Brighton ◽  
Alexander Cohen ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Anticoagulant Therapy ◽  
Low Dose ◽  
Double Blind ◽  
Once Daily ◽  
Safety Outcome ◽  
Dose Aspirin ◽  
Recurrent Venous Thromboembolism ◽  
Low Dose Aspirin ◽  
Recurrent Vte

SummaryPatients with unprovoked venous thromboembolism (VTE) are at high risk for recurrence. Although rivaroxaban is effective for extended VTE treatment at a dose of 20 mg once daily, use of the 10 mg dose may further improve its benefit-to-risk ratio. Low-dose aspirin also reduces rates of recurrent VTE, but has not been compared with anticoagulant therapy. The EINSTEIN CHOICE study is a multicentre, randomised, double-blind, active-controlled, event-driven study comparing the efficacy and safety of two once daily doses of rivaroxaban (20 and 10 mg) with aspirin (100 mg daily) for the prevention of recurrent VTE in patients who completed 6–12 months of anticoagulant therapy for their index acute VTE event. All treatments will be given for 12 months. The primary efficacy objective is to determine whether both doses of rivaroxaban are superior to aspirin for the prevention of symptomatic recurrent VTE, while the principal safety outcome is the incidence of major bleeding. The trial is anticipated to enrol 2,850 patients from 230 sites in 31 countries over a period of 27 months. In conclusion, the EINSTEIN CHOICE study will provide new insights into the optimal antithrombotic strategy for extended VTE treatment by comparing two doses of rivaroxaban with aspirin (clinicaltrials.gov NCT02064439).

Anticoagulation after venous thromboembolism

2013 ◽  
Vol 33 (03) ◽  
pp. 211-217 ◽  
Author(s):  
S. Eichinger
Keyword(s):  
Venous Thromboembolism ◽  
Prediction Models ◽  
Oral Anticoagulants ◽  
Bleeding Risk ◽  
Patient Characteristics ◽  
Recurrence Risk ◽  
Recurrence Rates ◽  
Clinical Patient ◽  
Recurrent Venous Thromboembolism

SummaryDeciding on the optimal duration of anticoagulation is based on the risk of recurrent venous thromboembolism (VTE) and of bleeding during anticoagulation. The duration of anticoagulation should be at least three months since shorter courses double the recurrence rates.At three months anticoagulation can be stopped in patients with a VTE provoked by a transient risk factor, as the recurrence risk is expected to be lower than the bleeding risk during anticoagulation. Patients with unprovoked VTE are at higher risk of recurrence and prolonged anticoagulation is currently recommended.However, attempts are made to stratify these patients according to their recurrence risk and to identify those with a low recurrence risk who would not benefit from extended anticoagulation. Novel approaches to optimize the management of patients with unprovoked VTE are the use of prediction models which link clinical patient characteristics with laboratory testing to discriminate between patients with a low risk (who may discontinue anticoagulation) and those with high risk (in whom long term anticoagulation is justified). Moreover, new antithrombotic concepts including new oral anticoagulants or aspirin both of which potentially confer a lower bleeding risk and are more convenient for the patients have been explored for extended thromboprophylaxis.

Influence Of Antithrombin Deficiency On Symptomatic Recurrent Venous Thromboembolism (VTE) In Children: A Multicenter Cohort Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3619-3619
Author(s):  
Gili Kenet ◽  
Verena Limperger ◽  
Neil A Goldenberg ◽  
Christine Heller ◽  
Susanne Holzhauer ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Venous Thromboembolism ◽  
Pediatric Patients ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Antithrombin Deficiency ◽  
Increased Risk ◽  
Recurrent Venous Thromboembolism ◽  
At Deficiency ◽  
Recurrent Vte

Abstract Objective To determine the importance of antithrombin [AT] deficiency as risk factor or predictor for fatal/non-fatal recurrent venous thromboembolism (VTE) in children. Methods In the present cohort of 874 consecutively enrolled pediatric patients with VTE aged newborn to <18 years the rate of VTE recurrence and the time to recurrence in relation to AT-deficiency [confirmed by underlying gene mutations; type 1 deficiency n=17; type 2 deficiency n=3], age and sex was determined. Twenty of 874 patients [2.4%] suffered from AT-deficiency. From the same cohort 150 VTE children carrying the heterozygous F5 G1691A mutation [F5: 17.7%] served as controls. Patients were prospectively followed for a median of 84 months. Data were pooled across participating sites to increase power and to enhance the generalisability of the data. Incidence rates were given as events per 1000 person-years. Results Of the 170 children enrolled 26 [AT n=9; F5 n=17] had recurrent VTE at a median of 15 months [95%CI: 12-36] following VTE onset: two of nine [AT] and two of 17 [F5] children suffered recurrent VTE while on anticoagulation with warfarin. The overall incidence rate of recurrence was 61.5 in patients with AT-deficiency compared to 23.5 for pediatric F5 carriers [p=0.02]. The recurrent-free survival probability is shown in the figure [logrank p-value: p=0.001]. When comparing AT patients and F5 children multivariate analysis [Cox regression] adjusted for age, sex and duration of anticoagulation treatment showed that AT deficiency [HR/95%CI: 4.1/1.8-9.4] significantly influenced the hazard for recurrent VTE. Conclusions Based on multivariate analysis, the presence of AT deficiency was associated with an increased risk of VTE recurrence. AT-deficiency in pediatric patients should be identified at VTE onset and the possible influence of intensified treatment protocols on recurrence should be studied in future prospective international studies. Condensed abstract To determine the relative importance of antithrombin deficiency or factor V (FV) mutations as risk factors for fatal/non-fatal recurrence in pediatric thromboembolism (VTE). Antithrombin deficiency influenced the hazard for recurrent VTE. Disclosures: No relevant conflicts of interest to declare.

Risk of recurrent venous thromboembolism after a first oestrogen-associated episode

2010 ◽  
Vol 104 (09) ◽  
pp. 498-503 ◽  
Author(s):  
Grégoire Le Gal ◽  
Michael Kovacs ◽  
Marc Carrier ◽  
Kimberley Do ◽  
Susan Kahn ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Oral Contraceptives ◽  
Hormone Replacement ◽  
Anticoagulant Treatment ◽  
Exogenous Oestrogen ◽  
Recurrent Venous Thromboembolism ◽  
Recurrent Vte ◽  
Post Menopausal ◽  
Age Range

SummaryThe use of exogenous oestrogen in women with otherwise unprovoked venous thromboembolism (VTE) could be considered sufficient explanation to classify VTE as provoked if the risk of recurrent VTE after 3–6 months of anticoagulant treatment is similar to the risk of recurrent VTE observed after a surgery or prolonged immobilisation. Our objective was to assess the risk of recurrent VTE in women after a first unprovoked episode on oestrogen. The REVERSE study is a cohort study of patients with a first unprovoked VTE treated with anticoagulant treatment for 5–7 months. The risk of recurrent VTE during follow-up was compared between women users and non users of oestrogen at the time of index VTE. Among the 646 patients included, 314 were women, of them 67 were current users of oestrogen at the time of their VTE: 49 were on oral contraceptives and 18 on post-menopausal hormone replacement therapy (HRT). No significant association was found between oestrogen exposure, either oral contraceptives or HRT, and a lower risk of recurrent VTE after adjustment for age, or analysis restricted to women in the same age range as oestrogen contraceptives and HRT users, respectively. The risk of recurrent VTE is low in women after a first otherwise unprovoked oestrogen-associated VTE. However, this risk is not significantly lower than in women whose VTE was not related to oestrogen use.

Scoring Systems for Estimating the Risk of Recurrent Venous Thromboembolism

2017 ◽  
Vol 43 (05) ◽  
pp. 493-499 ◽  
Author(s):  
Ilaria Nichele ◽  
Alberto Tosetto
Keyword(s):  
Venous Thromboembolism ◽  
Absolute Risk ◽  
Scoring Systems ◽  
Recurrence Risk ◽  
First Episode ◽  
Prediction Rules ◽  
Advantages And Disadvantages ◽  
Recurrent Venous Thromboembolism ◽  
Treat All ◽  
Optimal Therapeutic Strategy

AbstractThe risk of recurrence after suspension of anticoagulant treatment in patients with a first episode of unprovoked venous thromboembolism (VTE) is highly variable from patient to patient. Not all patients are candidates for life-long anticoagulant therapy, essentially because there remain concerns for such an option regarding hemorrhagic complications and clinical monitoring. Thus, the “treat all” approach may be inadequate for some patients at low risk of relapse. Proper assessment of the recurrence risk may be helpful to decide the optimal therapeutic strategy in such patients. In recent years, attempts have been made to develop and validate clinical prediction rules to estimate the absolute risk of VTE recurrence in individual patients. This article highlights the advantages and disadvantages of such options, presenting three different prediction rules that have been published so far.

Influence of thrombophilia on risk of recurrent venous thromboembolism while on warfarin: results from a randomized trial

Blood ◽  
2008 ◽  
Vol 112 (12) ◽  
pp. 4432-4436 ◽  
Author(s):  
Clive Kearon ◽  
Jim A. Julian ◽  
Michael J. Kovacs ◽  
David R. Anderson ◽  
Philip Wells ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Warfarin Therapy ◽  
Factor V Leiden ◽  
International Normalized Ratio ◽  
Antiphospholipid Antibody ◽  
Factor V ◽  
Antithrombin Deficiency ◽  
Recurrent Venous Thromboembolism ◽  
Prothrombin Gene Mutation ◽  
Recurrent Vte

Abstract We sought to determine whether thrombophilic defects increase recurrent venous thromboembolism (VTE) during warfarin therapy. Six hundred sixty-one patients with unprovoked VTE who were randomized to extended low-intensity (international normalized ratio [INR], 1.5-1.9) or conventional-intensity (INR, 2.0-3.0) anticoagulant therapy were tested for thrombophilia and followed for a mean of 2.3 years. One or more thrombophilic defects were present in 42% of patients. The overall rate of recurrent VTE was 0.9% per patient-year. Recurrent VTE was not increased in the presence of factor V Leiden (hazard ratio [HR], 0.7; 95% CI, 0.2-2.6); the 20210G>A prothrombin gene mutation (HR, 0); antithrombin deficiency (HR, 0); elevated factor VIII (HR, 0.7; 95% CI, 0.1-5.4); elevated factor XI (HR, 0.7; 95% CI, 0.1-5.0), or elevated homocysteine (HR, 0.7; 95% CI, 0.1-5.3), but showed a trend to an increase with an antiphospholipid antibody (HR, 2.9; 95% CI, 0.8-10.5). Compared with patients with no thrombophilic defects, the rate of recurrence was not increased in the presence of one (HR, 0.7; 95% CI, 0.2-2.3) or more than one (HR, 0.7; 95% CI, 0.2-3.4) defect. We conclude that single or multiple thrombophilic defects are not associated with a higher risk of recurrent VTE during warfarin therapy.

Non-OO blood type influences the risk of recurrent venous thromboembolism

2013 ◽  
Vol 110 (12) ◽  
pp. 1172-1179 ◽  
Author(s):  
Esteban Gándara ◽  
Michael J. Kovacs ◽  
Susan R. Kahn ◽  
Philip S. Wells ◽  
David A. Anderson ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Anticoagulant Therapy ◽  
Oral Anticoagulation ◽  
Blood Type ◽  
Increased Risk ◽  
Recurrent Venous Thromboembolism ◽  
Abo Blood Type ◽  
Recurrent Vte

SummaryThe role of ABO blood type as a risk factor for recurrent venous thromboembolism (VTE) in patients with a first unprovoked VTE who complete oral anticoagulation therapy is unknown. The aim of this study was to determine if non-OO blood type is a risk factor for recurrent VTE in patients with a first unprovoked VTE who completed 5–7 months of anticoagulant therapy. In an ongoing cohort study of patients with unprovoked VTE who discontinued oral anticoagulation after 5–7 months of therapy, six single nucleotide polymorphisms sites were tested to determine ABO blood type using banked DNA. The main outcome was objectively proven recurrent VTE. Mean follow-up for the cohort was 4.19 years (SD 2.16). During 1,553 patient-years of follow-up, 101 events occurred in 380 non-OO patients (6.5 events per 100 patient years; 95% CI 5.3–7.7) compared to 14 events during 560 patient years of follow-up in 129 OO patients (2.5 per 100 patient years; 95% CI 1.2–3.7), the adjusted hazard ratio was 1.98 (1.2–3.8). In conclusion, non-OO blood type is associated with a statistically significant and clinically relevant increased risk of recurrent VTE following discontinuation of anticoagulant therapy for a first episode of unprovoked VTE.

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