O10 Epidemiology, risk factors and penetration of venous thrombosis (VT) in pregnancy among carriers of the factor V Leiden and the prothrombin gene G20210A mutations

SummaryWe have identified a novel heterozygous fibrinogen γ chain mutation, γN345S (Fibrinogen Saint-Germain II), in a subject with hypofibrinogenemia. There was no evidence by mass spectrometry of plasma fibrinogen containing the mutant chain. The hypofibrinogenemia was discovered in a 26-year-old man who experienced extensive deep venous thrombosis of the left leg associated with pulmonary embolism. Investigation of potential thromboembolic risk factors revealed heterozygosity of the factor V R506Q mutation (factor V Leiden) and heterozygosity of the prothrombin gene G20210A mutation. The hypofibrinogenemia may be contributory to the thrombophilic manifestations.

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Risk of venous thrombosis in pregnancy among carriers of the factor V Leiden and the prothrombin gene G20210A polymorphisms

Journal of Thrombosis and Haemostasis ◽

10.1111/j.1538-7836.2010.04038.x ◽

2010 ◽

Vol 8 (11) ◽

pp. 2443-2449 ◽

Cited By ~ 26

Author(s):

A. F. JACOBSEN ◽

A. DAHM ◽

A. BERGREM ◽

E. M. JACOBSEN ◽

P. M. SANDSET

Keyword(s):

Venous Thrombosis ◽

Factor V Leiden ◽

Factor V ◽

Prothrombin Gene ◽

In Pregnancy

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Retinal vein occlusion: A form of venous thrombosis or a complication of atherosclerosis?

Thrombosis and Haemostasis ◽

10.1160/th04-11-0768 ◽

2005 ◽

Vol 93 (06) ◽

pp. 1021-1026 ◽

Cited By ~ 136

Author(s):

Martin den Heijer ◽

Johannes Cruysberg ◽

Hub Wollersheim ◽

Sebastian Bredie ◽

Mirian Janssen

Keyword(s):

Risk Factors ◽

Venous Thrombosis ◽

Gene Mutation ◽

Factor V Leiden ◽

Anticardiolipin Antibodies ◽

Factor V ◽

Factor V Leiden Mutation ◽

Vein Occlusion ◽

Prothrombin Gene Mutation ◽

Prothrombin Gene

SummaryPrevious studies have shown an increased risk of retinal vein occlusion (RVO) in patients with hypertension, hypercholesterolemia and diabetes mellitus. Literature on the association between thrombophilic factors and RVO consists of small studies and case reports. The objective was to determine the relationship between thrombophilic risk factors and RVO. Thrombophilic risk factors analyzed were hyperhomocysteinemia, MTHFR gene mutation, factor V Leiden mutation, protein C and S deficiency, antithrombin deficiency, prothrombin gene mutation, anticardiolipin antibodies and lupus anticoagulant. For all currently known thrombophilic risk factors odds ratios for RVO were calculated as estimates of relative risk. The odds ratios were 8.9 (95% CI 5.7 –13.7) for hyperhomocysteinemia, 3.9 (95% CI 2.3 – 6.7) for anticardiolipin antibodies, 1.2 (95% CI 0.9 –1.6) for MTHFR, 1.5 (95% CI 1.0 – 2.2) for factor V Leiden mutation and 1.6 (95% CI 0.8 – 3.2) for prothrombin gene mutation. In conclusion, regarding thrombophilic risk factors and RVO there is only evidence for an association with hyperhomocysteinemia and anticardiolipin antibodies, factors that are known as risk factors for venous thrombosis as well as for arterial vascular disease. The minor effect of factor V Leiden mutation and the protrombin gene mutation (risk factors for venous thrombosis only) suggests that atherosclerosis might be an important factor in the development of CRVO.

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

Thrombosis and Haemostasis ◽

10.1055/s-0038-1642720 ◽

1995 ◽

Vol 74 (01) ◽

pp. 449-453 ◽

Cited By ~ 99

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

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THROMBOPHILIC RISK FACTORS IN PATIENTS WITH CRANIAL AND SPINAL DURAL ARTERIOVENOUS FISTULAE

Neurosurgery ◽

10.1227/01.neu.0000325730.77263.7e ◽

2008 ◽

Vol 63 (4) ◽

pp. 693-699 ◽

Cited By ~ 18

Author(s):

Rüediger Gerlach ◽

Martina Boehm-Weigert ◽

Joachim Berkefeld ◽

Judith Duis ◽

Andreas Raabe ◽

...

Keyword(s):

Risk Factors ◽

Protein C ◽

Factor V Leiden ◽

Factor V ◽

Arteriovenous Fistulae ◽

Factor V Leiden Mutation ◽

Exact Test ◽

G20210a Mutation ◽

Cardiolipin Antibodies ◽

Prothrombin Gene

ABSTRACT OBJECTIVE Numerous studies have reported the technical aspects and results of surgical and/or endovascular treatment of cranial dural arteriovenous fistulae (cDAVF) and spinal dural arteriovenous fistulae (sDAVF). Only a few of them have addressed the question of thrombophilic conditions, which may be relevant as pathogenetic factors or can increase the risk for venous thromboembolic events. Therefore, the objective of this study is to compare thrombophilic risk factors in patients with cDAVF and sDAVF with no history of trauma. METHODS A total of 43 patients (25 with cDAVF and 18 with sDAVF) were included in this study. Blood samples were analyzed for G20210A mutation of the prothrombin gene and factor V Leiden mutation. In all patients, prothrombin time, international normalized ratio, fibrinogen, antithrombin, protein C and S activity, von Willebrand factor antigen, ristocetin cofactor activity, D-dimer, coagulation factor VIII activity, and tissue factor pathway inhibitor were determined. Screening was performed for the occurrence of lupus antiphospholipid and cardiolipin antibodies. RESULTS The prevalence of G20210A mutation of the prothrombin gene was significantly higher in patients with cDAVF (n = 6) compared with patients with sDAVF (n = 0; P < 0.05, Fisher's exact test). A factor V Leiden mutation was found in 3 patients with sDAVF and in 1 patient with cDAVF (P = 0.29, Fisher's exact test). No significant difference was found for other parameters, except for fibrinogen, but decreased protein C activity was more frequent in patients with cDAVF compared with patients with sDAVF (4 versus 1). Decreased protein S activity was encountered in 3 patients (2 with sDAVF and 1 with cDAVF). Cardiolipin antibodies were found in 2 patients with cDAVF but in none with sDAVF, whereas only 1 patient with sDAVF had lupus antiphospholipid antibodies. CONCLUSION In both groups of patients with dural arteriovenous fistulae, genetic thrombophilic abnormalities occurred in a higher percentage than in the general population. The differences of the genetic abnormalities may be involved in different pathophysiological mechanism(s) in the development of these distinct neurovascular entities.

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

Thrombosis and Haemostasis ◽

10.1055/s-0037-1613052 ◽

2002 ◽

Vol 87 (04) ◽

pp. 580-585 ◽

Cited By ~ 59

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.

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Risk of Pregnancy-related Venous Thrombosis in Carriers of Severe Inherited Thrombophilia

Thrombosis and Haemostasis ◽

10.1055/s-0037-1616134 ◽

2001 ◽

Vol 86 (09) ◽

pp. 800-803 ◽

Cited By ~ 64

Author(s):

Cristina Legnani ◽

Paolo Bucciarelli ◽

Elvira Grandone ◽

Valerio De Stefano ◽

Pier Mannuccio Mannucci ◽

...

Keyword(s):

Venous Thrombosis ◽

Gene Mutations ◽

Factor V Leiden ◽

Study Cohort ◽

Factor V ◽

Thrombotic Risk ◽

Increased Risk ◽

Prothrombin Gene ◽

Heterozygous Carriers ◽

Anticoagulant Prophylaxis

SummaryHomozygous carriers of factor V Leiden have an approximately 80-fold increased risk of venous thrombosis. Also double heterozygous carriers of both the factor V Leiden and the prothrombin gene mutations are at high thrombotic risk. The magnitude of the risk of venous thrombosis in pregnant women with the two severe thrombophilic conditions has not been estimated so far. We performed a multicenter retrospective family study in women with homozygous factor V Leiden, double heterozygous factor V Leiden and the prothrombin gene mutation, and women with normal coagulation. Only relatives of index patients with thrombosis formed the study cohort. Fifteen homozygous and 39 double heterozygous women were compared to 182 women with normal coagulation. Venous thrombosis occurred in 3 of 19, 2 of 50 and 1 of 221 pregnancies, respectively. One thrombotic episode occurred in the third trimester, the remaining 5 in the postpartum. The prevalence of venous thrombosis was 15.8% (95% CI 3.4-39.6) for homozygotes, 4.0% (95% CI 0.5-13.7) for double heterozygotes and 0.5% for women with normal coagulation. The relative risk of pregnancy-related venous thrombosis was 41.3 (95% CI 4.1-419.7) for homozygous and 9.2 (95% CI 0.8-103.2) for double heterozygous carriers. In conclusion, homozygous carriers of factor V Leiden and, to a lesser extent, double heterozygous carriers of factor V Leiden and of the prothrombin mutation have an increased risk of venous thrombosis during pregnancy, particularly high during the postpartum period. On the basis of these findings we recommend that these women receive anticoagulant prophylaxis at least in the postpartum, that should perhaps be extended to the whole pregnancy in homozygous carriers.

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The Risk for Venous Thrombosis in Patients with Increased Body Mass Index and Interactions with Other Genetic and Acquired Risk Factors: The MEGA Study

Blood ◽

10.1182/blood.v118.21.1234.1234 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1234-1234

Author(s):

Daniel D. Ribeiro ◽

Willem M. Lijfering ◽

Frits R. Rosendaal ◽

Suzanne C. Cannegieter

Keyword(s):

Risk Factors ◽

Venous Thrombosis ◽

Blood Group ◽

Reference Group ◽

Factor V Leiden ◽

Factor V ◽

Odds Ratios ◽

Thrombosis Risk ◽

Increased Risk ◽

High Bmi

Abstract Abstract 1234 Background: Obesity (prevalence of 20–25% in Western populations), blood group non-O (present in 50% of Western populations) and factor V Leiden (present in 5% of Caucasian populations) are frequent prothrombotic risk factors and may therefore have a considerable impact on the overall incidence of venous thrombosis. We previously reported that the increased risk of venous thrombosis in individuals with a high BMI is mediated by factor VIII induced APC-resistance, and that the combination of blood group non-O with a high BMI or factor V Leiden leads to higher venous thrombosis risks than expected when these prothrombotic factors are analyzed separately (ASH Annual Meeting Abstracts. 2009;114:453). However, small numbers did not enable us to sufficiently study the risk of venous thrombosis for the combination of a high BMI with factor V Leiden and blood group non-O, or to study these effects in subgroups. Objectives: To investigate whether the presence of factor V Leiden with blood group non-O can modify the risk for venous thrombosis in individuals with different body mass index strata in a larger population based study than previously reported. To evaluate the presence of gene-environment interactions in specific subgroups. Methods: MEGA study: 4956 consecutive patients aged 18–70 years with a first episode of venous thrombosis, and 6297 age- and sex-matched controls were included. Information about BMI, blood group and factor V Leiden was available in 4062 patients and 4659 controls. Odds ratios for venous thrombosis and their 95% confidence intervals (95% CIs) were calculated for BMI tertiles with logistic regression and adjusted for age and sex (matching factors). An interaction analysis among the BMI tertiles, factor V Leiden and blood group non-O was performed. Subgroup analyses involved stratification by venous thrombosis place (i.e. deep vein thrombosis or pulmonary embolism), sex, and presence or absence of acquired venous thrombosis risk factors. Results: A progressive increase in BMI was associated with an increased risk for venous thrombosis, odds ratios 1.1 (95% CI, 0.9–1.3) for those with a BMI in the median tertile, and 1.9- (95% CI, 1.6–2.3) for those in the upper tertile, as compared to individuals in the first BMI tertile, blood group O, and no factor V Leiden (i.e. the reference group). The addition of factor V Leiden and blood group non O in the model increased the risk in all BMI tertiles; odds ratios for venous thrombosis were 3.8 (95% CI, 3.2–4.6) in the third BMI tertile of individuals with blood group non-O, and 5.4 (95% CI, 3.5–8.5) in the third BMI tertile of individuals with factor V Leiden, respectively. When both factor V Leiden and blood group non-O were present, odds ratios for venous thrombosis were 9.1 (95% CI, 5.9–14.0) in the first BMI tertile, 9.4 (95% CI, 6.6–13.5) in the second BMI tertile, and 12.5 (95% CI, 8.9–17.6) in the BMI third BMI tertile as compared to the reference group. Subgroup analyses revealed similar joint interactions of BMI with blood group non-O and factor V Leiden on venous thrombosis risk. Disclosures: No relevant conflicts of interest to declare.

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