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.

Coexistence of three genetic risk factors in a Spanish thrombophilic family: Factor V Leiden, prothrombin 20210 and a new type I antithrombin deficiency

2007 ◽  
Vol 97 (01) ◽  
pp. 153-155 ◽  
Author(s):  
Adriana Ordóñez ◽  
Carmen de Cos ◽  
Antonia Miñano ◽  
David Hernández-Espinosa ◽  
Juan Muñoz ◽  
...  
Keyword(s):  
Risk Factors ◽  
Genetic Risk ◽  
Factor V Leiden ◽  
Genetic Risk Factors ◽  
Type I ◽  
Factor V ◽  
Antithrombin Deficiency ◽  
Family Factor ◽  
New Type

Third Generation Oral Contraceptives and Heritable Thrombophilia as Risk Factors of Non-fatal Venous Thromboembolism

1998 ◽  
Vol 79 (01) ◽  
pp. 28-31 ◽  
Author(s):  
Birthe Søgaard Andersen ◽  
Jørn Olsen ◽  
Gunnar Lauge Nielsen ◽  
Flemming Hald Steffensen ◽  
Henrik Toft Sørensen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Oral Contraceptives ◽  
Factor V Leiden ◽  
Factor V ◽  
Third Generation ◽  
Confounding By Indication ◽  
Antithrombin Deficiency ◽  
Factor V Leiden Mutation ◽  
Increased Risk

SummaryThird generation oral contraceptives (OCs) are apparently stronger risk factors for venous thromboembolism (VTE) than other OCs, however, the increased risk may be due to confounding by indication related to differences in prescription behaviour.We estimated the risk of VTE associated with use of OCs with and without the presence of Factor V Leiden mutation, protein C-, protein S- or antithrombin deficiency.Sixty-seven cases with VTE were compared with 134 controls. The risk of VTE in the presence of thrombophilia was of the same magnitude for third generation OC users as for users of other OCs; OR: 52.5 (95% CI: 3.7-738.1) and OR: 63.3 (95% CI: 6.2-648.4), respectively.It is unlikely that confounding by indication entirely explains the risk of VTE associated with third generation OCs since the combined effect exceeds what could be explained if this source of error was the only determinant of the association.

scholarly journals Frequency and association of 1691 (G>A) FVL, 20210 (G>A) PT and 677 (C>T) MTHFR with deep vein thrombosis in the population of Bosnia and Herzegovina

2016 ◽  
Vol 19 (1) ◽  
pp. 43-50 ◽  
Author(s):  
A Jusić-Karić ◽  
R Terzić ◽  
Z Jerkić ◽  
A Avdić ◽  
M Pođanin
Keyword(s):  
Risk Factors ◽  
Deep Vein Thrombosis ◽  
Venous Thromboembolism ◽  
Genetic Risk ◽  
Factor V Leiden ◽  
Control Group ◽  
Published Data ◽  
Factor V ◽  
Vein Thrombosis ◽  
Deep Vein

AbstractThe 1691 (G>A) factor V Leiden (FVL) and 20210 (G>A) prothrombin (PT) mutations are the two most common genetic risk factors in venous thromboembolism. The 677 (C>T) methylene tetrahydrofolate reductase (MTHFR) mutation is the most frequently mentioned as an independent genetic risk factor for venous thromboembolism. As there are limited published data on the prevalence of the 1691, 20210 and 677 mutations in our population, the aim of this study was to determine the frequencies and association of these deep vein thrombosis mutations in the Bosnian population.This study included 111 thromboembolic patients and 207 healthy subjects with absence of known risk factors for venous thromboembolism. Genotyping of the 1691, 20210 and 677 mutations was done by polymerase chain reaction (PCR), followed by restriction digestion with MnlI, HindIII and HinfI enzymes.Out of the 111 patients, 18.0% were heterozygous and 2.70% were homozygous for the 1691 mutation. Among 207 healthy controls, 3.86%, were heterozygous for the 1691 mutation. This study confirmed the association of the 1691 mutation with deep vein thrombosis in the Bosnian population odds ratio (OR) [95% confidence interval (CI)] = 6.0 (2.62-14.14); p = 0.0001). The 20210 mutation was detected in 2.70% of patients and it was totally absent in the control group. Allele and genotype frequency of 677 did not differ significantly between the cases and controls (χ2 = 1.03; p = 0.309).

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.

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.

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.

Basal high-sensitivity-C-reactive protein levels in patients with spontaneous venous thromboembolism

2005 ◽  
Vol 93 (03) ◽  
pp. 488-493 ◽  
Author(s):  
Rainer Vormittag ◽  
Thomas Vukovich ◽  
Verena Schönauer ◽  
Stephan Lehr ◽  
Erich Minar ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Statistical Significance ◽  
Factor V Leiden ◽  
High Sensitivity ◽  
Prothrombin G20210a ◽  
Factor V ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Hs Crp

SummaryThe role of C-reactive protein (CRP) in venous thromboembolism (VTE) is still under discussion because of controversial results in the literature. Conflicting data may have partly been due to bias by exogenous factors altering CRP levels. We investigated CRP concentrations in patients with spontaneous VTE applying a study design that allowed the measurement of basal high sensitivity (hs)-CRP levels. Patients with a history of deep vein thrombosis (DVT, n=117) and pulmonary embolism (PE, n=97) were compared to healthy individuals (n=104). Hs-CRP levels (mg/dl) were significantly higher in patients (n=214, median/interquartile range: 0.171/0.082–0.366) than in controls (0.099/0.053–0.245, p=0.001). The unadjusted odds ratio (OR) for VTE per 1 mg/dl increase of CRP was 2.8 [95% confidence interval (CI): 1.1–6.8, p=0.03]. This association remained significant after adjustment for factor V Leiden, prothrombin G20210A and factor VIII activity above 230% (OR = 2.9, 95% CI [1.1–7.5]), but became remarkably attenuated and lost its statistical significance after adjustment for BMI alone (OR = 1.7 [0.7–4.0]). CRP was also not independently associated with VTE in subgroups of patients (those with DVT without symptomatic PE, those with PE and patients without established risk factor) in multiple regression analysis. In summary, we observed significantly higher basal hs-CRP levels in patients with spontaneous VTE compared to healthy controls. This association was independent of hereditary and laboratory risk factors for VTE, but lost its significance after adjustment for BMI. Increased basal CRP levels do not appear to represent an independent risk factor for VTE.

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