Pregnancy-associated risk for venous thromboembolism and pregnancy outcome in women homozygous for factor V Leiden

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.

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Incidence of Venous Thromboembolism in Families with Inherited Thrombophilia

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614442 ◽

1999 ◽

Vol 81 (02) ◽

pp. 198-202 ◽

Cited By ~ 210

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.

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

Thrombosis and Haemostasis ◽

10.1160/th04-11-0745 ◽

2005 ◽

Vol 93 (03) ◽

pp. 488-493 ◽

Cited By ~ 23

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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The Incidence of Venous Thromboembolism in Family Members of Patients with Factor V Leiden Mutation and Venous Thrombosis

Annals of Internal Medicine ◽

10.7326/0003-4819-128-1-199801010-00003 ◽

1998 ◽

Vol 128 (1) ◽

pp. 15 ◽

Cited By ~ 129

Author(s):

Saskia Middeldorp

Keyword(s):

Venous Thromboembolism ◽

Venous Thrombosis ◽

Family Members ◽

Factor V Leiden ◽

Factor V ◽

Factor V Leiden Mutation

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Combined Effect of Factor V Leiden and Prothrombin 20210A on the Risk of Venous Thromboembolism

Thrombosis and Haemostasis ◽

10.1055/s-0037-1616136 ◽

2001 ◽

Vol 86 (09) ◽

pp. 809-816 ◽

Cited By ~ 193

Author(s):

Frits Rosendaal ◽

Marco Cattaneo ◽

Maurizio Margaglione ◽

Valerio De Stefano ◽

Tony Cumming ◽

...

Keyword(s):

Venous Thromboembolism ◽

Odds Ratio ◽

Large Population ◽

Factor V Leiden ◽

Pooled Analysis ◽

Factor V ◽

Case Control Studies ◽

Vein Thrombosis ◽

G20210a Mutation ◽

Factor Ii

SummaryFactor V Leiden and factor II G20210A mutations are two frequent genetic risk factors involved in venous thromboembolism (VTE). The goal of this pooled analysis of 8 case-control studies, comprising a total of 2310 cases and 3204 controls, was to precisely estimate the risk of VTE in patients bearing both mutations (double heterozygotes). Odds ratios for VTE were 4.9 (95% CI; 4.1-5.9) for the factor V Leiden and 3.8 (3.0-4.9) for the factor II G20210A mutation. Fifty-one cases (2.2%) and none of the controls were double heterozygotes. The odds ratio for venous thrombosis in double heterozygotes was 20.0 (11.1-36.1). Twelve percent of patients heterozygous for factor V Leiden were also heterozygous for factor II G20210A and conversely 23% of patients heterozygous for factor II G20210A were also heterozygous for factor V Leiden. Furthermore, in this large population we analyzed the effect of oral contraceptive (OC) in women carrying one of these mutations. Odds ratio for VTE associated with OC was 2.29 (1.72-3.04). In factor V Leiden carriers using OC, the odds ratio for VTE was 10.25 (5.69-18.45). The odds ratio of the association of factor II mutation and OC use was 7.14 (3.39-15.04). Finally, we also confirmed that the frequency of factor V Leiden was lower in patients with pulmonary embolism than in patients with deep vein thrombosis without PE (odds ratio 0.69). Conversely, factor II G20210A mutation was equally balanced in both patient groups.

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High frequency of factor V Leiden in surgical patients with symptomatic venous thromboembolism despite prophylaxis

Thrombosis and Haemostasis ◽

10.1160/th06-11-0616 ◽

2007 ◽

Vol 97 (02) ◽

pp. 171-175 ◽

Cited By ~ 9

Author(s):

Mohamed Baba-Ahmed ◽

Grégoire Le Gal ◽

Francis Couturaud ◽

Karine Lacut ◽

Emmanuel Oger ◽

...

Keyword(s):

Venous Thromboembolism ◽

Close Association ◽

Factor V Leiden ◽

Plaster Cast ◽

Case Control ◽

Factor V ◽

Potential Significance ◽

Control Study ◽

Fvl Mutation

SummaryAmong candidate risk factors associated with postoperative venous thromboembolism (VTE), the role of factorV Leiden (FVL) mutation remains unclear. We performed a case-control study to assess the potential significance of FVL mutation in postoperative VTE cases despite prophylaxis. We used data from the ongoing case-control “EDITH” study. We extracted 133VTE cases and 144 controls who had undergone either surgery or had plaster cast in the previous three months. Prophylaxis adequacy with regard to the recommendations published by theAmerican College of Chest Physicians was retrospectively assessed. FVL mutation was present in 20VTE cases and four controls (OR 5.9, 95% CI 2–18). Prophylaxis was judged as adequate in 116 cases (88.5 %) and in 129 controls (87.2 %) (p = 0.66). The frequency of FVL mutation was not different in VTE cases occurring while on adequate prophylaxis and in VTE cases occurring after the end of adequate prophylaxis (p = 0.27). FVL mutation was closely associated with postoperative VTE in patients classified as having received an adequate prophylaxis (8.4; 95% CI, 2.4 to 29). This study shows a close association between the presence of factorV Leiden mutation in symptomaticVTE occurring after surgery despite prophylaxis.

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