A Concept for Long-Term Anticoagulation Based On the Individual Risk of Lethal Pulmonary Embolism (PE) and Lethal Bleeding Using Oral Anticoagulants.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4174-4174
Author(s):  
Rainer B. Zotz ◽  
Christoph Sucker ◽  
Andrea Gerhardt
Keyword(s):  
Risk Factors ◽  
Oral Anticoagulation ◽  
Factor V Leiden ◽  
Bleeding Risk ◽  
Individual Risk ◽  
Factor V ◽  
Benefit Analysis ◽  
Initial Event ◽  
Risk Benefit Analysis

Abstract Abstract 4174 Objectives Indications for an indefinite oral anticoagulation are a matter of debate in patients with a first unprovoked proximal DVT. Methods An individual risk-benefit analysis is made using published prospective studies by determining the patient-specific lethal risk of bleeding under oral anticoagulation compared with the estimation of lethal PE-risk by type of initial thrombosis (spontaneous vs. secondarily caused, with or without PE). Results According to this risk-benefit analysis, long-term oral anticoagulation is indicated to prevent lethal PE in all patients with low risk of bleeding (1% per year, 0.1 % lethal bleeding per year) in the risk group with lethal PE > 0.2 % per year. This risk group includes patients with idiopathic proximal thrombosis and PE in the initial event (also without thrombophilic risk factors) and patients with an idiopathic initial event without PE, who have relevant thrombophilic risk factors with a relative risk ≥ 2, such as antithrombin deficiency, homozygous factor V Leiden or a combined heterozygous factor V Leiden and prothrombin G20210A mutation. In case of a higher bleeding tendency (0.3% lethal bleeding per year in a patient group with 1-2 bleeding risk factors like age >65 or diabetes) other risk-benefit estimations are present. Conclusions Our individual risk stratification is in contrast to current therapy recommendations, which generally consider long-term oral anticoagulation for patients with an idiopathic initial proximal DVT with a low bleeding risk, but do not specify these in individual cases. Disclosures: No relevant conflicts of interest to declare.

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.

scholarly journals Examination of in Factor V Leiden and Prothrombin II Thrombophilic Mutations in Czech Young Women Using ddPCR—Prevalence and Cost–Benefit Analysis

Healthcare ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1656
Author(s):  
Petra Riedlova ◽  
Dagmar Kramna ◽  
Silvie Ostrizkova ◽  
Hana Tomaskova ◽  
Vitezslav Jirik
Keyword(s):  
Risk Factors ◽  
Czech Republic ◽  
Young Women ◽  
Cost Benefit Analysis ◽  
Factor V Leiden ◽  
Cost Benefit ◽  
Factor V ◽  
Benefit Analysis ◽  
The Czech Republic ◽  
Factor Ii

Background: Thrombophilic mutations in genes for factor V Leiden and factor II prothrombin are among the most important risk factors for developing the thromboembolic disease (TED), along with the use of oral contraceptives (OCs) or smoking. Aim: This study aimed to investigate the occurrence of risk factors in young women using droplet digital PCR (ddPCR) and, based on the results of this investigation, to perform a cost–benefit analysis of ddPCR-based screening in young women starting to take OCs compared to the treatment costs of patients who develop preventable TED in the Czech Republic. Methods: In this cross-sectional study, female university students filled in a questionnaire and provided a blood sample for DNA isolation and ddPCR analysis of both aforementioned genetic risk factors. The results, along with data from literature and web search, were used for cost–benefit analysis valid for the Czech Republic. Results: Out of 148 participants, 30 (20%) were smokers and 49 (33%) took OCs. A mutation was confirmed in 6 women (4.1%) in the factor V gene and in 3 women (2%) in the factor II gene, respectively. A model calculation on a cohort of 50,000 women starting to use contraceptives in the Czech Republic every year showed that at maximum compliance, (i.e., non-use of OC and smoking cessation), screening could prevent 68 cases of TED over the course of the mean period of OC use (5.7 years). Economically, the costs of testing in this cohort (2.25 mil. USD) would be significantly lower than prevented treatment costs (16 mil. USD at maximum compliance); the cost–benefit break-even point would be at 14.1% compliance. Conclusion: The cost–benefit analysis based on our results indicates that screening for factor V Leiden and factor II prothrombin in young women before starting to use OCs would, in the conditions of the Czech Republic, likely be highly economically effective.

scholarly journals Do Genetic Contributors to Warfarin Responsiveness or Common Thrombophilias Influence the Risk of Major Bleeding in Patients on Extended Duration Vitamin K Antagonist (VKA) for Venous Thromboembolic Disease?

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 272-272
Author(s):  
Philip S Wells ◽  
Michael J. Kovacs ◽  
David Anderson ◽  
Susan R. Kahn ◽  
Clive Kearon ◽  
...  
Keyword(s):  
Risk Ratio ◽  
Major Bleeding ◽  
Research Funding ◽  
Factor V Leiden ◽  
Bleeding Risk ◽  
Factor V ◽  
Incidence Risk ◽  
Extended Duration ◽  
Incidence Risk Ratio

Abstract Background: Recent studies have indicated that genetic factors such as polymorphisms in the CYP2C9 and the VKORC1 genes play an important role in vitamin K antagonist (VKA) response and perhaps bleeding. There are also data to suggest, especially for factor V Leiden, that thrombophilia may confer a decreased risk of bleeding (which could explain its persistence and high prevalence in the population). The influence of major genetic factors on risk of bleeding have not previously been evaluated in large prospective cohort studies of patients with VTE on extended (treatment after the first 3 to 6 months) VKA therapy. Aims: We sought to determine the effect of genetic variants that influence warfarin metabolism and thrombophilias on the rates of major bleeding during extended VKA therapy in patients with VTE disease. Methods: The Bleeding Risk study is a multicentre, multinational prospective cohort study of patients on extended VKA for unprovoked VTE, or provoked VTE with prior VTE. Patients were enrolled after at least 3 months of VKA. All major bleeding events during long term VKA were captured and adjudicated. A blood sample was taken from each patient at their first study visit and analysed in a central lab to identify the following genetic variant types: CYP2C9*2 (C/T), CYP2C9*3 (T/G), 1639G-A (G/A), Factor V Leiden (G/A: FVL), CYP4F2 (G/A), and Prothrombin gene 20210 variant (PGV). Rates of major bleeding were then evaluated for patients with each genetic variant in isolation and in combination. Results: 2290 of the 2514 patients enrolled at 12 sites have contributed over 7000 years of observation and were included in this analysis. The mean patient age was 60.2±14.7 years, 64% were male, 92% Caucasian, average BMI was 31.3, and 9% of patients were on antiplatelet agents. Patients were followed for a mean of 2.8 years (range, 0.1 to 6.8 years. 121 patients (4.8%) experienced at least one episode of major bleeding. The annual rate of bleeding was 1.7 per 100 patient-years of observation. The CYP2C9*2 variant heterozygous/homozygous versus wildtype (476 patients vs 1584) was protective against bleeding (Incidence risk ratio 0.5, p =0.01), CYP2C9*3 variant heterozygous/homozygous versus wildtype (215 patients vs 1845) was associated with major bleeding (Incidence risk ratio 2.0, p =0.01), VKORC1 and CYP4F2 had no association with major bleeding, and CYP2C9*3 variant heterozygous/homozygous in combination with wildtype CYP2C9*2 (186 patients) was associated with major bleeding (Incidence risk ratio 3.24, p =0.02). Both FVL (19% of patients) and PGV (8% of patients) had no effect on major bleeding, with p values > 0.35 for comparison of the wildtype to heterozygous/homozygous. Conclusion: This is the largest study we are aware of to determine if warfarin metabolic genotype variants and common thrombophilias influence major bleeding risk in patients followed long-term with extended duration VKA therapy for VTE. The thrombophilias do not influence bleeding risk but those with CYP2C9*3 hetero/homozygous inheritance had double the risk and CYP2C9*2 hetero/homozygous inheritance half the risk. There appears to be an interaction between the CYP2C9*2 and *3 genotypes. Disclosures Wells: BMS/Pfizer: Research Funding; Bayer Healthcare: Other: Speaker Fees and Advisory Board; Janssen Pharmaceuticals: Consultancy; Itreas: Other: Served on a Writing Committee. Kovacs:LEO Pharma: Honoraria; Bayer: Honoraria, Research Funding; Daiichi Sankyo Pharma: Research Funding; Pfizer: Honoraria, Research Funding. Anderson:Bayer Healthcare: Research Funding. Rodger:Canadian Agency for Drugs and Technologies in Health: Consultancy; Boehringer Ingelheim: Research Funding.

Resistance to Activated Protein C and Factor V Leiden as Risk Factors for Venous Thrombosis

1995 ◽  
Vol 74 (01) ◽  
pp. 449-453 ◽  
Author(s):  
Rogier M Bertina ◽  
Pieter H Reitsma ◽  
Frits R Rosendaal ◽  
Jan P Vandenbroucke
Keyword(s):  
Risk Factors ◽  
Venous Thrombosis ◽  
Protein C ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Factor V

Influence of single nucleotide polymorphisms on thrombin generation in factor V Leiden heterozygotes

2014 ◽  
Vol 111 (03) ◽  
pp. 438-446 ◽  
Author(s):  
Olivier Segers ◽  
Paolo Simioni ◽  
Daniela Tormene ◽  
Elisabetta Castoldi
Keyword(s):  
Thrombin Generation ◽  
Factor V Leiden ◽  
Individual Variability ◽  
Intermediate Phenotype ◽  
Individual Risk ◽  
Factor V ◽  
Nucleotide Polymorphisms ◽  
Factor X ◽  
Large Variability ◽  
Fv Leiden

SummaryCarriership of the factor V (FV) Leiden mutation increases the risk of venous thromboembolism (VTE) ~4-fold, but the individual risk of each FV Leiden carrier depends on several co-inherited risk and protective factors. Under the hypothesis that thrombin generation might serve as an intermediate phenotype to identify genetic modulators of VTE risk, we enrolled 188 FV Leiden heterozygotes (11 with VTE) and determined the following parameters: thrombin generation in the absence and presence of activated protein C (APC); plasma levels of prothrombin, factor X, antithrombin, protein S and tissue factor pathway inhibitor; and the genotypes of 24 SNPs located in the genes encoding these coagulation factors and inhibitors. Multiple regression analysis was subsequently applied to identify the (genetic) determinants of thrombin generation. The endogenous thrombin potential (ETP) showed a striking inter-individual variability among different FV Leiden carriers and, especially when measured in the presence of APC, correlated with VTE risk. Several SNPs in the F2 (rs1799963, rs3136516), F10 (rs693335), SERPINC1 (rs2227589), PROS1 (Heerlen polymorphism) and TFPI (rs5940) genes significantly affected the ETPAPC and/or the ETP+APC in FV Leiden carriers. Most of these SNPs have shown an association with VTE risk in conventional epidemiological studies, suggesting that the genetic dissection of thrombin generation leads to the detection of clinically relevant SNPs. In conclusion, we have identified several SNPs that modulate thrombin generation in FV Leiden heterozygotes. These SNPs may help explain the large variability in VTE risk observed among different FV Leiden carriers.

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.

Neonatal aortic arch thrombosis: analysis of thrombophilic risk factors and prognosis

2013 ◽  
Vol 24 (1) ◽  
pp. 33-39 ◽  
Author(s):  
Ivonne Wieland ◽  
Thomas Jack ◽  
Kathrin Seidemann ◽  
Martin Boehne ◽  
Florian Schmidt ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Aortic Arch ◽  
Case Reports ◽  
Statistical Significance ◽  
Rare Event ◽  
Factor V Leiden ◽  
High Rate ◽  
Factor V ◽  
Factor V Leiden Mutation

AbstractArterial thrombosis in neonates and children is a rare event and is often associated with external risk factors such as asphyxia or sepsis. We report our experiences with two neonates with spontaneous aortic arch thrombosis mimicking aortic coarctation. Despite single case reports until now, no data exist for the underlying thrombophilic risk factors and prognosis of this rare event. Both patients were carriers of a heterozygous factor V Leiden mutation, which has been reported once before as a risk factor for aortic arch thrombosis. One of our patients was operated upon successfully and is alive. The second patient suffered a large infarction of the right medial cerebral artery and had a thrombotic occlusion of the inferior caval vein. The patient obtained palliative care and died at the age of 6 days. In the literature, we identified 19 patients with neonatal aortic arch thrombosis. Of the 19 patients, 11 (58%) died. Including the two reported patients, the mortality rate of patients with multiple thromboses was 80% (8/10) compared with 18% (2/11) for patients with isolated aortic arch thrombosis; this difference reached statistical significance (p = 0.009). The analysis of thrombophilic disorders revealed that factor V Leiden mutation and protein C deficiency seem to be the most common risk factors for aortic arch thrombosis.Conclusion:Neonatal aortic arch thrombosis is a very rare but life-threatening event, with a high rate of mortality, especially if additional thrombotic complications are present. Factor V Leiden mutation seems to be one important risk factor in the pathogenesis of this fatal disease.

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.

Homozygous and double heterozygous Factor V Leiden and Factor II G20210A genotypes predispose infants to thromboembolism but are not associated with an increase of foetal loss

2003 ◽  
Vol 90 (10) ◽  
pp. 628-635 ◽  
Author(s):  
Patrick Hundsdoerfer ◽  
Barbara Vetter ◽  
Brigitte Stöver ◽  
Christian Bassir ◽  
Tristess Scholz ◽  
...  
Keyword(s):  
Factor V Leiden ◽  
Individual Risk ◽  
Factor V ◽  
Thromboembolic Events ◽  
Foetal Loss ◽  
Asymptomatic Children ◽  
Factor Ii ◽  
The Individual ◽  
The Impact

SummaryProspective and controlled data about the individual risk profile in asymptomatic children with homozygous or double heterozygous risk genotypes for Factor V Leiden (FVL) and factor II (FII) G20210A are currently unavailable. The systematic and prospective observational study presented here was designed to determine the impact of the homozygous and double heterozygous FVL and FII G20210A genotypes on the prenatal and postnatal risk profiles of affected children. Risk infants and heterozygous controls were identified by screening of 85,304 neonates. Follow-up included the comparison of prenatal and postnatal development, ultrasonography of brain and kidneys, and a panel of independent determinants of thrombophilia. The numbers of identified or expected FVL homozygotes and double heterozygotes did not differ significantly (FVL: 116 ver-sus 91, p=0.08; FVL/FII: 94 versus 76, p=0.17), indicating the absence of a prenatal disadvantage. A prenatal advantage was suggested in FII homozygotes, whose identified number far exceeded the expected (19 versus 4, p=0.002). Clinical and/or imaging abnormalities indicated spontaneous thromboembolic events in 4 of 129 risk infants (3%) but in none of the 178 controls (p=0.02). Physical and neurological development was normal in both groups during the first 2 years of life. The risk genotypes appear to confer a significant predisposition for spontaneous thromboembolic events in infancy without impeding development within the first two years of life. Foetal risk genotypes do not cause an increased foetal loss rate. Moreover, homozygous FII G20210A appears to be associated with a prenatal advantage.

Sign in / Sign up

Export Citation Format

Share Document