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

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).

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Hereditary Thrombophilic Risk Factors and Venous Thromboembolism in Istanbul, Turkey: The Role in Different Clinical Manifestations of Venous Thromboembolism

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029607305620 ◽

2008 ◽

Vol 14 (2) ◽

pp. 168-173 ◽

Cited By ~ 12

Author(s):

Gulfer Okumus ◽

Esen Kiyan ◽

Orhan Arseven ◽

Levent Tabak ◽

Reyhan Diz-Kucukkaya ◽

...

Keyword(s):

Risk Factors ◽

Venous Thromboembolism ◽

Clinical Manifestations ◽

Factor V Leiden ◽

Protein S ◽

Prothrombin G20210a ◽

Factor V ◽

Vein Thrombosis ◽

Significant Difference ◽

Deep Vein

The aim of this study was to investigate the hereditary thrombophilic risk factors in patients with venous thromboembolism (VTE) and whether these risk factors play a different role in patients with isolated pulmonary embolism (PE) as compared with patients with deep vein thrombosis (DVT) and patients with PE + DVT. The protein C (PC), protein S, antithrombin activities, homocysteine levels, and factor V Leiden (FVL) G1691A and prothrombin G20210A mutations were evaluated in 191 patients with VTE and 191 controls. The prevalence of FVL and PC deficiency were higher in patients ( P = .003 and P = .02, respectively). There was no significant difference for the other risk factors. The combination of thrombophilic risk factors was significantly higher in patients with DVT + PE as compared with patients with isolated PE or DVT ( P = .04). In conclusion, the most important hereditary risk factors for VTE in this study were the FVL mutation and PC deficiency.

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Broadening the factor V Leiden paradox: pulmonary embolism and deep-vein thrombosis as 2 sides of the spectrum

Blood ◽

10.1182/blood-2012-02-407551 ◽

2012 ◽

Vol 120 (5) ◽

pp. 933-946 ◽

Cited By ~ 61

Author(s):

Kirsten van Langevelde ◽

Linda E. Flinterman ◽

Astrid van Hylckama Vlieg ◽

Frits R. Rosendaal ◽

Suzanne C. Cannegieter

Keyword(s):

Risk Factors ◽

Pulmonary Embolism ◽

Deep Vein Thrombosis ◽

Large Population ◽

Factor V Leiden ◽

Chronic Obstructive ◽

Factor V ◽

Vein Thrombosis ◽

Risk Estimates ◽

Deep Vein

AbstractRisk factors for deep-vein thrombosis have been shown not to be always the same as for pulmonary embolism. A well-known example is the factor V Leiden (FVL) paradox: the FVL mutation poses a clearly higher risk for deep-vein thrombosis (DVT) than for pulmonary embolism. We aimed to expand this paradox and therefore present risk estimates for several established risk factors for DVT and pulmonary embolism separately. When such separate risk estimates could not be retrieved from the literature, we calculated these risks in our own data, a large population-based case-control study on venous thrombosis (the MEGA study). Our results showed that the FVL paradox can be broadened (ie, the risk factors oral contraceptive use, pregnancy, puerperium, minor leg injuries, and obesity have an effect comparable with FVL). Furthermore, we found that pulmonary conditions, such as chronic obstructive pulmonary disease, pneumonia, and sickle cell disease, were risk factors with an opposite effect: a higher risk of pulmonary embolism, but little or no effect on DVT. These findings suggest that pulmonary embolism and DVT may not always have the same etiology, and encourage unraveling this phenomenon in further studies.

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Risk Factor Profiles in Patients with Different Clinical Manifestations of Venous Thromboembolism: A Focus on the Factor V Leiden Mutation

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650613 ◽

1996 ◽

Vol 76 (04) ◽

pp. 510-513 ◽

Cited By ~ 45

Author(s):

Bert Manten ◽

Rudi G J Westendorp ◽

Ted Koster ◽

Pieter H Reitsma ◽

Frits R Rosendaal

Keyword(s):

Pulmonary Embolism ◽

Deep Vein Thrombosis ◽

Venous Thromboembolism ◽

Clinical Manifestations ◽

Factor V Leiden ◽

Factor V ◽

Factor V Leiden Mutation ◽

Vein Thrombosis ◽

Increased Risk ◽

Deep Vein

Summary Background. Patients with venous thromboembolic disease may present with different clinical manifestations. Factor V Leiden mutation leading to resistance to activated protein C is associated with a sevenfold increased risk for presenting with deep-vein thrombosis. It is not yet established whether carriers of the mutation have a similarly increased risk for manifesting with pulmonary embolism. Methods. From an Anticoagulation Clinic monitoring coumarin therapy, a consecutive series of patients with a first thromboembolic event (objectively proven by current radiological methods) were enrolled. All patients were interviewed and blood was drawn for geno-typing. From the hospital charts and the personal interview, information was obtained on acquired risk factors and the signs and symptoms on hospital admission. Results. 45 patients presented with symptoms of pulmonary embolism only, 211 had only symptoms of deep-vein thrombosis whereas 23 had clinical features of both. In about half of the patients acquired risk factors for venous thromboembolism were present which did not differ between the three groups of patients. Recent surgery had been performed more often in patients presenting with pulmonary embolism than in other patients (33.3% vs. 18.5%, p <0,05). Factor V Leiden was present in 9% of the patients presenting with pulmonary embolism (relative risk: 3.3 95% Cl: 1.0-10.6) and 17% of the patients presenting with deep-vein thrombosis (relative risk: 6.9 95% Cl: 3.6-12.8). The prevalence of factor V Leiden was intermediate in patients with both clinical characteristics. Conclusion. These data suggest that patients with venous thromboembolism have different clinical presentation depending on the risk factor profile. Factor V Leiden may preferentially lead to manifest deep-vein thrombosis. Differences in structure of venous thrombi could underlie differences in embolic tendency.

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D-Dimer as a Risk Factor for Deep Vein Thrombosis: The Leiden Thrombophilia Study

Thrombosis and Haemostasis ◽

10.1055/s-0037-1612942 ◽

2002 ◽

Vol 87 (01) ◽

pp. 47-51 ◽

Cited By ~ 46

Author(s):

Astrid Andreescu ◽

Frits Rosendaal ◽

Mary Cushman

Keyword(s):

Risk Factors ◽

Deep Vein Thrombosis ◽

Odds Ratio ◽

Factor V Leiden ◽

Factor V ◽

Vein Thrombosis ◽

Unknown Risk ◽

Deep Vein ◽

D Dimer ◽

Prothrombin 20210A

SummaryWe studied the association of D-dimer with the risk of deep vein thrombosis (DVT). D-dimer was measured in 474 patients more than 6 months after diagnosis of a first DVT and in 474 age-and sexmatched controls. For D-dimer above the 70th percentile (130.5 ng/ml), the odds ratio (OR) for DVT was 2.2 (95% CI, 1.6-2.9). The association was unchanged with adjustment for other risk factors. Excluding participants with Factor V Leiden, prothrombin 20210A, or factors VIIIc or IX above the 90th percentile, the OR was 1.6 (95% CI, 1.1-2.3). The risks of DVT with the joint presence of high D-dimer and either factor V Leiden or prothrombin 20210A were increased 12.4-fold (95% CI 5.6-27.7) and 7.2-fold (95% CI 2.1-25.1), respectively. Higher Ddimer concentration was associated with the risk of DVT, and was supra-additive to the risks associated with factor V Leiden and the prothrombin 20210A variant. Persistence of this association in the absence of other hemostatic risk factors for DVT suggests that high D-dimer may be related to other, as yet unknown, risk factors for venous thrombosis. Confirmation of these findings is desirable.

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Prevalence of factor V Leiden and FV HR2 haplotypes as risk factors for deep vein thrombosis: a study from north India

Journal of Thrombosis and Haemostasis ◽

10.1111/j.1538-7836.2003.tb03483.x ◽

2003 ◽

Vol 1 ◽

pp. P0337-P0337

Author(s):

R. Das ◽

G. Garewal ◽

J. Ahluwalia ◽

S. Varma

Keyword(s):

Risk Factors ◽

Deep Vein Thrombosis ◽

Factor V Leiden ◽

North India ◽

Factor V ◽

Vein Thrombosis ◽

Deep Vein

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Is the Prevalence of the Factor V Leiden Mutation in Patients with Pulmonary Embolism and Deep Vein Thrombosis Really Different?

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614474 ◽

1999 ◽

Vol 81 (03) ◽

pp. 345-348 ◽

Cited By ~ 22

Author(s):

Rosa Karemaker ◽

Philomeen Kuijer ◽

Martin Prins ◽

Harry Büller ◽

Franktien Turkstra

Keyword(s):

Pulmonary Embolism ◽

Deep Vein Thrombosis ◽

Venous Thromboembolism ◽

Odds Ratio ◽

Factor V Leiden ◽

Factor V ◽

Factor V Leiden Mutation ◽

Vein Thrombosis ◽

Common Odds Ratio ◽

Deep Vein

Summary Introduction. Previous investigations have suggested a lower prevalence of the factor V Leiden mutation in patients with pulmonary embolism, as compared to patients with deep leg vein thrombosis. Methods. We studied unselected patients with pulmonary embolism, in whom we also assessed the presence of deep vein thrombosis by ultra-sonography. We assessed the prevalence of heterozygosity for the factor V Leiden mutation and compared the outcome of patients with a normal ultrasound (primary pulmonary embolism) to those with an abnormal ultrasound (combined form of venous thromboembolism). Furthermore, we performed a literature search to identify all articles regarding the prevalence of heterozygous factor V Leiden mutation in patients with primary deep vein thrombosis, primary pulmonary embolism and a combined form of venous thromboembolism. We calculated a (common) odds ratio for these 3 manifestations of venous thromboembolism, including the current findings. Results. In 92 patients with proven pulmonary embolism, 25 (27%) had also an abnormal ultrasound. In these patients, the prevalence of the factor V Leiden mutation was 24% (95% CI 9%-45%), whereas the mutation was present in 5 of 67 patients with primary pulmonary embolism (7%; 95% CI 2%-16%). The literature analysis indicated the common odds ratio for the presence of heterozygous factor V Leiden mutation in patients with primary deep vein thrombosis, primary pulmonary embolism and the combined form of venous thromboembolism to be 7.9 (95% CI 5-12), 3.5 (95% CI 2-6) and 6.8 (95% CI 3-14), respectively. Conclusion. In patients with primary pulmonary embolism the prevalence of the factor V Leiden mutation appears to be half of that reported in patients with primary deep vein thrombosis. The mechanism remains unclear.

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