Haemostaseome-associated SNPs: has the thrombotic phenotype a greater influence than ethnicity?

2015 ◽  
Vol 113 (01) ◽  
pp. 66-76 ◽  
Author(s):  
Sylvie Labrouche ◽  
Christophe Hubert ◽  
Frédéric Bauduer ◽  
Geneviève Freyburger
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Genetic Markers ◽  
Factor V Leiden ◽  
Significant Snps ◽  
Low Risk ◽  
Coagulation System ◽  
Factor V ◽  
Wide Range ◽  
The Impact

SummaryThe Genetic Markers for Thrombosis (GMT) study compared the relative influence of ethnicity and thrombotic phenotype regarding the distribution of SNPs implicated in haemostasis pathophysiology (“haemostaseome”). We assessed 384 SNPs in three groups, each of 480 subjects: 1) general population of Aquitaine region (Southwestern France) used as control; 2) patients with venous thromboembolism from the same area; and 3) autochthonous Basques, a genetic isolate, who demonstrate unusual characteristics regarding the coagulation system. This study sought to evaluate i) the value of looking for a large number of genes in order to identify new genetic markers of thrombosis, ii) the value of investigating low risk factors and potential preferential associations, iii) the impact of ethnicity on the characterisation of markers for thrombosis. We did not detect any previously unrecognised SNP significantly associated with thrombosis risk or any preferential associations of low-risk factors in patients with thrombosis. The sum of ϰ2 values for our 110 significant SNPs demonstrated a smaller genetic distance between patients and controls (321 cumulated ϰ2 value) than between Basques and controls (1,570 cumulated ϰ2 value). Hence, our study confirms the genetic particularity of Basques especially regarding a significantly lower expression of the non-O blood group (p< 0.0004). This is mitigated by a higher prevalence of factor II Leiden (p< 0.02) while factor V Leiden prevalence does not differ. Numerous other differences covering a wide range of proteins of the haemostaseome may result in an overall different genetic risk for venous thromboembolism.

scholarly journals The Impact of Multiple Risk Factors for Venous Thromboembolism and Its Implications for Management

2019 ◽  
Vol 6 ◽  
pp. 2333794X1985916
Author(s):  
Anil P. George ◽  
Paul Kent
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Pediatric Patients ◽  
Assessment Tool ◽  
Factor V Leiden ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Multiple Risk Factors ◽  
Multiple Risk ◽  
The Impact

Venous thromboembolism (VTE) is a rare multifactorial disorder in childhood with an annual incidence of about 0.07 to 0.14 per 10 000 children. A 15-year-old female with a body mass index of 48 kg/m2 who endorsed oral contraceptive use presented with clinical findings consistent with deep venous thrombosis along with the presence of a pulmonary embolism. Further workup revealed that the patient was heterozygous for factor V Leiden and homozygous for prothrombin G20210A mutations. There are no current pediatric guidelines for the antithrombotic management of patients with multiple risk factors for VTE. Two such risk factors, obesity and the use of estrogen-containing hormone contraceptives, have been implicated in adult VTE cases but have not been clearly delineated in pediatric patients. The need for guidance regarding the VTE management of these patients has become more apparent given the increasing incidence of childhood obesity and the number of adolescents using oral contraceptives. Additionally, thrombophilia testing remains controversial though testing may be indicated in asymptomatic first-degree relatives and in families with antithrombin, protein C, or protein S deficiencies. Given the increased incidence of multiple risk factors for VTE, there is also a need to develop a comprehensive risk assessment tool for pediatric patients at high risk of VTE.

scholarly journals Thrombophilia in hepatocellular carcinoma

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Fayrouz O. Selim ◽  
Taghrid M. Abdalla ◽  
Thoraya A. M. Hosny
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Venous Thromboembolism ◽  
Protein C ◽  
Factor V Leiden ◽  
Coagulation System ◽  
Factor V ◽  
Lipoprotein A ◽  
Increased Risk ◽  
Fvl Mutation

Abstract Background Chronic liver disease and hepatocellular carcinoma (HCC) can cause a disturbance in the coagulation system. In this study, we aimed to assess the risk factors for venous thromboembolism either acquired or hereditary in patients with HCC. Results Serum levels of proteins C and S, AT activity, and lipoprotein (a) were significantly lower in both HCC and cirrhotic patients while homocysteine levels were significantly higher in HCC patients. The prevalence of activated protein C resistance (APCR) and factor V Leiden (FVL) mutation was higher in HCC patients but with no significant differences between the studied groups. With multivariate analysis, prothrombin time, Fbg, protein C and S deficiency, increased lipoprotein (a), hyperhomocysteinemia, APCR, and FVL mutation were independent risk factors for thromboembolic complications in HCC patients. Conclusions Thrombophilic abnormalities are prevalent in HCC patients, and they have a substantial increased risk of venous thromboembolism.

The influence of thrombophilia on the long-term survival of patients with a history of venous thromboembolism

2013 ◽  
Vol 109 (01) ◽  
pp. 79-84 ◽  
Author(s):  
Sylvia Reitter-Pfoertner ◽  
Thomas Waldhoer ◽  
Michaela Mayerhofer ◽  
Ernst Eigenbauer ◽  
Cihan Ay ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Multivariable Analysis ◽  
Factor V Leiden ◽  
Arterial Disease ◽  
Factor V ◽  
Term Survival ◽  
Long Term Survival ◽  
History Of

SummaryData on the long-term survival following venous thromboembolism (VTE) are rare,and the influence of thrombophilia has not been evaluated thus far. Our aim was to assess thrombophilia-parameters as predictors for long-term survival of patients with VTE. Overall, 1,905 outpatients (99 with antithrombin-, protein C or protein S deficiency, 517 with factor V Leiden, 381 with elevated factor VIII and 160 with elevated homocysteine levels, of these 202 had a combination and 961 had none of these risk factors) were included in the study between September 1, 1994 and December 31, 2007. Retrospective survival analysis showed that a total of 78 patients (4.1%) had died during the analysis period, among those four of definite or possible pulmonary embolism and four of bleeding. In multivariable analysis including age and sex an association with increased mortality was found for hyperhomocysteinemia (hazard ratio 2.0 [1.1.-3.5]) whereas this was not the case for all other investigated parameters. We conclude that the classical hereditary thrombophilia risk factors did not have an impact on the long-term survival of patients with a history of VTE. Thus our study supports the current concept that thrombophilia should not be a determinant for decision on long term anticoagulation. However, hyperhomocysteinaemia, known as a risk factor for recurrent VTE and arterial disease, might impact survival.

Incidence of Venous Thromboembolism in Families with Inherited Thrombophilia

1999 ◽  
Vol 81 (02) ◽  
pp. 198-202 ◽  
Author(s):  
Paolo Simioni ◽  
Bernd-Jan Sanson ◽  
Daniela Tormene ◽  
Philip Friederich ◽  
Bruno Girolami ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Oral Contraceptive ◽  
Contraceptive Use ◽  
Post Partum ◽  
Family Members ◽  
Factor V Leiden ◽  
Factor V ◽  
Relative Risks ◽  
Oral Contraceptive Use

SummaryThe risk of spontaneous or risk-period related venous thromboembolism in family members of symptomatic carriers of antithrombin (AT), protein C (PC) or protein S (PS) defects, as well as of the Factor V Leiden mutation is still undefined. We performed a retrospective cohort study in family members (n = 793) of unselected patients with a documented venous thromboembolism and one of these deficiencies to make an estimate of this risk. The annual incidences of total and spontaneous venous thromboembolic events in carriers of AT, PC or PS defects (n = 181) were 1.01% and 0.40%, respectively, as compared to 0.10% and 0.04% in non-carriers, respectively (relative risks both 10.6). In carriers of Factor V Leiden (n = 224), the annual incidences of total and spontaneous venous thromboembolism were 0.28% and 0.11%, respectively, as compared to 0.09% and 0.04% in non-carriers, respectively (relative risks 2.8 and 2.5). Additional risk factors (immobilisation, surgery and trauma; oral contraceptive use; and pregnancy/ post-partum) increased the risk of thrombosis in carriers of AT, PC and PS defects as compared to non-carriers (relative risks 8.3, 6.4 and 8.2, respectively). Oral contraceptive use and pregnancy/ post-partum period increased the risk of thrombosis in carriers of Factor V Leiden to 3.3-fold and 4.2-fold, respectively, whereas other risk factors had only a minor effect.These data lend some support to the practice of screening family members of symptomatic carriers of a AT, PC and PS deficiency. For family members of symptomatic carriers of Factor V Leiden, screening does not seem to be justified except for women in fertile age.

scholarly journals Clinical Utilization and Cost of Thrombophilia Testing in Patients with Venous Thromboembolism

TH Open ◽  
2020 ◽  
Vol 04 (03) ◽  
pp. e153-e162
Author(s):  
Manila Gaddh ◽  
En Cheng ◽  
Maha A.T. Elsebaie ◽  
Imre Bodó
Keyword(s):  
Venous Thromboembolism ◽  
Patient Management ◽  
Clinical Decision Making ◽  
Factor V Leiden ◽  
Direct Costs ◽  
Cost Of Care ◽  
Factor V ◽  
Test Results ◽  
Thrombophilia Testing ◽  
The Impact

Abstract Introduction Testing for inherited and acquired thrombophilias adds to the cost of care of patients with venous thromboembolism (VTE), though results may not influence patient management. Methods This is a single-center, retrospective study conducted at Emory University Hospitals from January to December 2015 to (1) determine the pattern of thrombophilia testing in patients with VTE, (2) study the impact of results of thrombophilia testing on clinical decision-making, and (3) determine the direct costs of thrombophilia testing in patients with VTE. Results Of the 266 eligible patients, 189 (71%) underwent testing; 51 (26.9%) tested positive and the results impacted management in 32 (16.9%) of tested patients. Patient undergoing testing were more likely to be younger than 40 years (30.9 vs. 18.2%), have had prior pregnancy loss (9.0 vs. 0%), or known family history of hypercoagulability (24.9 vs. 10.4%), and were less likely to have had provoked VTE (37 vs. 79.2%). The most common thrombophilias tested were antiphospholipid syndrome (60.1%), factor V Leiden (59.7%), and prothrombin gene mutation (57.5%). Direct costs of thrombophilia testing were $2,364.32 per patient, $12,331.55 to diagnose 1 positive, and $19,653.41 per patient-management affected. Conclusion We noted significant variability in selection of patients and panel of tests, sparse utilization of test results in patient management, but high cost associated with thrombophilia testing in patients with VTE. With guidelines advocating selective use of thrombophilia testing and attention to potential impact of test results in patient management, we propose the need for measures at institutional levels to improve test-ordering practices.

Factor V Leiden (G1691A) and Prothrombin Gene G20210A Mutations as Potential Risk Factors for Venous Thromboembolism after Total Hip or Total Knee Replacement Surgery

2002 ◽  
Vol 87 (04) ◽  
pp. 580-585 ◽  
Author(s):  
G. Larson ◽  
T. L. Lindahl ◽  
C. Andersson ◽  
L. Frison ◽  
D. Gustafsson ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Factor V Leiden ◽  
Composite Endpoint ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
G20210a Mutation ◽  
Symptomatic Pulmonary Embolism ◽  
Increased Risk ◽  
Prothrombin Gene

SummaryPatients (n = 1600) from 12 European countries, scheduled for elective orthopaedic hip or knee surgery, were screened for Factor V Leiden and prothrombin gene G20210A mutations, found in 5.5% and 2.9% of the populations, respectively. All patients underwent prophylactic treatment with one of four doses of melagatran and ximelagatran or dalteparin, starting pre-operatively. Bilateral ascending venography was performed on study day 8-11. The patients were subsequently treated according to local routines and followed for 4-6 weeks postoperatively. The composite endpoint of screened deep vein thrombosis (DVT) and symptomatic pulmonary embolism (PE) during prophylaxis did not differ significantly between patients with or without these mutations. Symptomatic venous thromboembolism (VTE) during prophylaxis and follow-up (1.9%) was significantly over-represented among patients with the prothrombin gene G20210A mutation (p = 0.0002). A tendency towards increased risk of VTE was found with the Factor V Leiden mutation (p = 0.09). PE were few, but significantly over-represented in both the Factor V Leiden and prothrombin gene G20210A mutated patients (p = 0.03 and p = 0.05, respectively). However, since 90% of the patients with these genetic risk factors will not suffer a VTE event, a general pre-operative genotyping is, in our opinion, of questionable value.

Gene-Gene and Gene-Environment Interactions Determine Risk of Thrombosis in Families With Inherited Antithrombin Deficiency

Blood ◽  
1999 ◽  
Vol 94 (8) ◽  
pp. 2590-2594 ◽  
Author(s):  
H.H. van Boven ◽  
J.P. Vandenbroucke ◽  
E. Briët ◽  
F.R. Rosendaal
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Venous Thromboembolism ◽  
Genetic Risk ◽  
Factor V Leiden ◽  
Genetic Defects ◽  
Factor V ◽  
Antithrombin Deficiency ◽  
Gene Environment ◽  
Genetic And Environmental Factors

To analyze inherited antithrombin deficiency as a risk factor for venous thromboembolism in various conditions with regard to the presence or absence of additional genetic or acquired risk factors, we compared 48 antithrombin-deficient individuals with 44 nondeficient individuals of 14 selected families with inherited antithrombin deficiency. The incidence of venous thromboembolism for antithrombin deficient individuals was 20 times higher than among nondeficient individuals (1.1% v 0.05% per year). At the age of 50 years, greater than 50% of antithrombin-deficient individuals had experienced thrombosis compared with 5% of nondeficient individuals. Additional genetic risk factors, Factor V Leiden and PT20210A, were found in more than half of these selected families. The effect of exposure to 2 genetic defects was a 5-fold increased incidence (4.6% per year; 95% confidence interval [CI], 1.9% to 11.1%). Acquired risk factors were often present, determining the onset of thrombosis. The incidence among those with exposure to antithrombin deficiency and an acquired risk factor was increased 20-fold (20.3% per year; 95% CI, 12.0% to 34.3%). In conclusion, in these thrombophilia families, the genetic and environmental factors interact to bring about venous thrombosis. Inherited antithrombin deficiency proves to be a prominent risk factor for venous thromboembolism. The increased risks among those with exposure to acquired risk factors should be considered and adequate prophylactic anticoagulant therapy in high-risk situations seems indicated in selected families with inherited antithrombin deficiency.

Risk Determinants of Nonarteritic Ischemic Optic Neuropathy (NAION)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5349-5349 ◽  
Author(s):  
Rainer B. Zotz ◽  
Clara Finger ◽  
Andrea Gerhardt ◽  
Rudiger E. Scharf
Keyword(s):  
Risk Factors ◽  
Significant Risk ◽  
Factor V Leiden ◽  
Ischemic Optic Neuropathy ◽  
Factor V ◽  
Healthy Controls ◽  
Factor V Leiden Mutation ◽  
Wide Range ◽  
Risk Determinants ◽  
Pai 1

Abstract Background: The aim of our present study was to examine the risk factors for atherosclerosis as well as thrombophilic risk factors for their role in patients with NAION in comparison to healthy controls. Methods: Prospective case-control-design with 109 Patients and 109 age-and sex-matched healthy controls. Results: Elevated levels of fibrinogen, FVIII:C, FIX:C, FXI:C, plasminogen activity, von Willebrand antigen (vWF:Ag) and activity, triglycerides, elevated erythrocyte sedimentation rate and decreased levels of high density lipoprotein (HDL) proved to be significant risk factors associated with NAION (OR 1.9 to 5.4; p&lt;0.05). The combination of these risk determinants further increased the risk in a multiplicative or supra-multiplicative way (up to OR 16.5; p&lt;0.0001). None of the examined genetic risk factors (factor V Leiden mutation, Prothrombin mutation, platelet polymorphisms KOZAK and VNTR of glycoprotein 1bα, Hpa-1 polymorphism of GPIIb-IIIa, C807T polymorphism of GPIa/IIa, 4G/5G polymorphism of PAI-1 and C667T mutation of MTHFR gene) was significantly associated with the disease. However, when the HPA-1b allele, GPIa807T allele or the PAI-1 polymorphism were combined with increased levels of fibrinogen or vWF:Ag, a significant interaction with a supra-multiplicative increase in risk could be demonstrated. Conclusions: In this first comprehensive analysis of a wide range of risk determinants of atherosclerosis and thrombophilia in NAION patients, several risk factors could be identified and quantified. Risk factors of arterial thrombosis appear to interact with risk factors of inflammatory atherosclerosis triggering NAION.

Association of common genetic variations and idiopathic venous thromboembolism

2010 ◽  
Vol 103 (06) ◽  
pp. 1161-1169 ◽  
Author(s):  
Aurélien Delluc ◽  
Lénaïck Gourhant ◽  
Karine Lacut ◽  
Bernard Mercier ◽  
Marie-Pierre Audrezet ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Factor V Leiden ◽  
Coagulation Cascade ◽  
Factor V ◽  
Cascade Process ◽  
Nucleotide Polymorphisms ◽  
Factor Xi ◽  
Bonferroni Adjustment ◽  
Adrenergic Systems

SummaryVenous thromboembolism (VTE) is a multifactorial disease, caused by interacting environmental and genetic risk factors. Gene-centric geno-typing strategy is one of the approaches to explore unexplained associations between risk factors and VTE. It was the objective of this study to evaluate, using a gene-centric genotyping strategy, polymorphisms in genes involved in the following pathways: coagulation cascade process, renin-angiotensin or adrenergic systems, lipid metabolism, platelet aggregation. Allele frequency was compared between 677 cases with idiopathic VTE and their matched controls. After Bonferroni adjustment, four single nucleotide polymorphisms (SNPs) were significantly associated with VTE: Factor XI rs925451 polymorphism, factor XI rs2289252 polymorphism, factor II rs1799963 (G20210A) polymorphism and factor V Leiden rs6025. An additive mode of inheritance fitted best both factor XI polymorphisms. In this hospital-based case-control study, two polymorphisms located on the factor XI gene were significantly associated with VTE. Other newly investigated polymorphisms with potentially false negatives may warrant further analyses.

scholarly journals Evaluation of Direct Oral Anticoagulants in the Treatment of Venous Thromboembolism for Inherited Thrombophilia Disorders

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5007-5007 ◽  
Author(s):  
Ali McBride ◽  
Reem Diri ◽  
Ravitharan Krishnadasan ◽  
Pavani Chalasani ◽  
Ivo Abraham ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Protein C ◽  
Factor V Leiden ◽  
Secondary Prophylaxis ◽  
Factor V ◽  
Inherited Thrombophilia ◽  
Dvt Prophylaxis ◽  
Prothrombin Gene ◽  
Baseline Characteristics

Abstract Background Venous thromboembolism can be classified according to the presence of either environmental or genetic risk factors. Risk factors for thrombosis can include activated protein C resistance, and heritable including deficiencies of antithrombin, protein C or protein S. Factor V Leiden deficiency and prothrombin gene mutations are some of the more common thrombophilias, with a slight increased risk for venous thromboembolism (VTE). Current guidelines suggest the use of low-molecular weight heparins for secondary prophylaxis in patients with VTE. However, there is a lack of data on the use of Direct Oral Anticoagulant (DOACs) in patients with inherited thrombophilia. We evaluated our use of rivaroxaban in patients with thrombophilia disorders treated for secondary DVT prophylaxis. Method We performed a retrospective evaluation of patients in our institution with inherited thrombophilia with an active VTE diagnosis who received DOACs for secondary prophylaxis from November 2013 until April 2016. Data collected included patient demographics, inherited thrombophilia mutation, previous history of VTE, prior treatments, and efficacy and safety of anticoagulation with DOACs. Results We had 13 patients with inherited thrombophilia mutation and 4 patients diagnosed with concomitant cancer (non-Hodgkin lymphoma, melanoma, and 2 with breast cancer) (Table 1). Out of 13 patients 3 failed warfarin, and one failed fondaparinux prior to switching to a DOAC. Mutation with heterozygous Factor V Leiden deficiency was reported in 7 patients, while mutations with Protein C and/or S deficiency were found in 4 patients. One patient had both Factor V Leiden and Protein C deficiency mutations. The prothrombin gene mutation was identified in one patient. The median of length of therapy was 2 years with 8/13 still on rivaroxaban in April 2016. The shortest treatment duration was 41 days for a patient who failed rivaroxaban with a second clot and was switched to apixaban without subsequent treatment failure. Two patients experienced 4 non-major episodes of gastrointestinal bleeding, nose bleeding and dark stool. One patient developed rash with noted bruising during their rivaroxaban therapy. Conclusion: This is the first report on outcomes for secondary DVT prophylaxis with DOACs in patients with underlying thrombophilia mutations. Safety and efficacy of DOACs for secondary VTE prophylaxis yielded favorable results; however, future prospective studies in the setting of thrombophilia are warranted. Table 1 Summary of baseline characteristics and outcomes. Table 1. Summary of baseline characteristics and outcomes. Disclosures McBride: Sanofi: Research Funding.

Sign in / Sign up

Export Citation Format

Share Document