No evidence for an increased risk of venous thrombosis in patients with factor V Leiden by the homozygous 677 C to T mutation in the methylenetetrahydrofolate-reductase gene

Sarcoidosis is a multisystem granulomatous disease of unknown etiology and pathogenesis. It presents in patients younger than 40 years of age. The lungs are the most commonly affected organ. Till the present day, there is no single specific test that will accurately diagnose sarcoidosis; as a result, the diagnosis of sarcoidosis relies on a combination of clinical, radiologic, and histologic findings. Patients with sarcoidosis have been found to have an increased risk of pulmonary embolism compared to the normal population. MTHFR and factor V Leiden mutations have been reported to increase the risk of thrombosis in patients. We hereby present a case of a middle aged man with sarcoidosis who developed a right main pulmonary embolism and was found to be double heterozygous for methylenetetrahydrofolate reductase gene polymorphisms and factor V Leiden and homozygous for the D-allele of the angiotensin converting enzyme gene.

Download Full-text

Ethnic differences in the association of factor V Leiden mutation and the C677T methylenetetrahydrofolate reductase gene polymorphism with preeclampsia

European Journal of Obstetrics & Gynecology and Reproductive Biology ◽

10.1016/s0301-2115(03)00314-2 ◽

2004 ◽

Vol 112 (2) ◽

pp. 162-169 ◽

Cited By ~ 16

Author(s):

Damar Prasmusinto ◽

Snezana Skrablin ◽

Rolf Fimmers ◽

Katrin van der Ven

Keyword(s):

Gene Polymorphism ◽

Ethnic Differences ◽

Methylenetetrahydrofolate Reductase ◽

Factor V Leiden ◽

Factor V ◽

Factor V Leiden Mutation ◽

Reductase Gene ◽

Methylenetetrahydrofolate Reductase Gene Polymorphism ◽

Methylenetetrahydrofolate Reductase Gene

Download Full-text

PULMONARY EMBOLISM AND PREMATURE LABOR IN A PATIENT WITH BOTH FACTOR V LEIDEN MUTATION AND METHYLENETETRAHYDROFOLATE REDUCTASE GENE C677T MUTATION

Thrombosis Research ◽

10.1016/0049-3848(96)00133-8 ◽

1996 ◽

Vol 83 (3) ◽

pp. 243-251 ◽

Cited By ~ 6

Author(s):

Fangyu Peng ◽

Douglas Triplett ◽

Linda Barna ◽

Daryl Morrical

Keyword(s):

Pulmonary Embolism ◽

Methylenetetrahydrofolate Reductase ◽

Factor V Leiden ◽

Factor V ◽

Premature Labor ◽

Factor V Leiden Mutation ◽

Reductase Gene ◽

C677t Mutation ◽

Methylenetetrahydrofolate Reductase Gene

Download Full-text

Etiological factors in young patients with Retinal Vein Occlusion

Pakistan Journal of Medical Sciences ◽

10.12669/pjms.35.5.546 ◽

2019 ◽

Vol 35 (5) ◽

Author(s):

Serhad Nalcaci ◽

Cumali Degirmenci ◽

Cezmi Akkin ◽

Jale Mentes

Keyword(s):

Gene Mutation ◽

Methylenetetrahydrofolate Reductase ◽

Factor V Leiden ◽

Factor V ◽

Factor V Leiden Mutation ◽

Etiological Factors ◽

Reductase Gene ◽

Prothrombin Gene Mutation ◽

Prothrombin Gene ◽

Methylenetetrahydrofolate Reductase Gene

Objective: To present the etiological factors of patients with Retinal Vein Occlusion (RVO) under the age of 50 years. Methods: The study was conducted at Ege University Medicine Faculty Department of Ophthalmology. The clinical records of patients with RVO under the age of 50 seen between January 2014 and March 2018 were analyzed retrospectively. Forty patients comprised the study. Detailed ophthalmologic examination was performed. Past medical history, drug use, thrombophilic features, hyperviscosity syndromes and pathologies that may cause vasculitis were noted. Results: Forty patients, 22 (55%) male and 18 (45%) female, were included. Mean age was 41.6 ± 10.01 years. Mean intraocular pressure and best-corrected visual acuity were 16.8 ± 5.47mmHg and 0.76 ± 0.64 logMAR, respectively. Hyperhomocystenemia (15 patients, 37.5%), Behçet’s disease (three patients, 7.5%), diabetes and/or hypertension (16 patients, 40%), methylenetetrahydrofolate reductase gene mutation (11 patients, 27.5%), prothrombin gene mutation (four patients, 10%) and factor V Leiden mutation (five patients, 12.5%) were present among the patients as etiological factor. Multiple etiological factors were detected in 11 (27.5%) patients. Factor V Leiden mutation and methylenetetrahydrofolate reductase gene mutation were detected in one patient (2.5%) with Behçet’s disease. Four patients with diabetes and/or hypertension also had hyperhomocystenemia and one of them had additionally prothrombin gene mutation. Two patients with methylenetetrahydrofolate reductase gene mutation also had a factor V Leiden mutation and one of them had additionally a prothrombin gene mutation. Three patients with methylenetetrahydrofolate reductase gene mutation also had hyperhomocystenemia and one patient with prothrombin gene mutation also had methylenetetrahydrofolate reductase gene mutation. Conclusions: Etiological factors that might result in RVO in young individuals should be investigated in detail. Targeted therapies may help to prevent development of new RVOs and potential vascular problems in other organs. doi: https://doi.org/10.12669/pjms.35.5.546 How to cite this:Nalcaci S, Degirmenci C, Akkin C, Mentes J. Etiological factors in young patients with Retinal Vein Occlusion. Pak J Med Sci. 2019;35(5):---------. doi: https://doi.org/10.12669/pjms.35.5.546 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download Full-text

Polymorphisms in the protein C gene as risk factor for venous thrombosis

Thrombosis and Haemostasis ◽

10.1160/th08-08-0502 ◽

2009 ◽

Vol 101 (01) ◽

pp. 62-67 ◽

Cited By ~ 25

Author(s):

Carine Doggen ◽

Hans Vos ◽

Pieter Reitsma ◽

Frits Rosendaal ◽

Elisabeth Pomp

Keyword(s):

Oral Contraceptive ◽

Venous Thrombosis ◽

Protein C ◽

Contraceptive Use ◽

Factor V Leiden ◽

Factor V ◽

Thrombotic Risk ◽

Control Subjects ◽

Oral Contraceptive Use ◽

Increased Risk

SummaryProtein C is an important inhibitor of blood coagulation. We investigated the effect of two polymorphisms within the promoter region of the protein C gene (C/T at position 2405 and A/G at position 2418) on risk of venous thrombosis and on plasma protein C levels. In addition the combined effect of the two polymorphisms with factor V Leiden and oral contraceptive use was investigated. Previous studies on these polymorphisms were small and were not able to investigate synergistic effects. In the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA study), protein C levels were determined in 2,043 patients with venous thrombosis and 2,857 control subjects, and the two polymorphisms in 4,285 patients and 4,863 control subjects. The CC/GG genotype was associated with the lowest protein C levels. Compared to carriers of the TT/AA genotype – a genotype associated with higher protein C levels – the risk of venous thrombosis in CC/GG carriers was 1.3-fold increased (95% confidence interval 1.09–1.48). The combination of factor V Leiden with the CC/GG genotype led to a 4.7-fold increased risk, compared to non-carriers with the TT/AA genotype. Oral contraceptive use together with the CC/ GG genotype resulted in a 5.2-fold increased risk. In conclusion, the CC/GG genotype is associated with lower levels of protein C and an elevated risk of venous thrombosis compared to the TT/AA genotype. There is no clear synergistic effect of the CC/ GG genotype with factor V Leiden or oral contraceptive use on thrombotic risk.

Download Full-text

High risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance) [see comments]

Blood ◽

10.1182/blood.v85.6.1504.bloodjournal8561504 ◽

1995 ◽

Vol 85 (6) ◽

pp. 1504-1508 ◽

Cited By ~ 648

Author(s):

FR Rosendaal ◽

T Koster ◽

JP Vandenbroucke ◽

PH Reitsma

Keyword(s):

Venous Thrombosis ◽

Protein C ◽

Absolute Risk ◽

Thrombotic Event ◽

Activated Protein C ◽

Factor V Leiden ◽

Coagulation Factor ◽

Factor V ◽

Increased Risk ◽

The Absolute

Resistance to activated protein C (APC) is a common inherited risk factor for venous thrombosis, which is associated with a mutation in coagulation factor V (factor V Leiden). We investigated the risk of venous thrombosis in individuals homozygous for this abnormality. We determined the factor V Leiden genotype in 471 consecutive patients aged less than 70 years with a first objectively confirmed deep-vein thrombosis and in 474 healthy controls. We found 85 heterozygous and seven homozygous individuals among the cases with thrombosis and 14 heterozygous individuals among the control subjects. The expected number of homozygous individuals among the controls was calculated from Hardy-Weinberg equilibrium and estimated at 0.107 (allele frequency, 1.5%). Whereas the relative risk was increased sevenfold for heterozygous individuals, it was increased 80-fold for homozygous individuals. These patients experienced their thrombosis at a much younger age (31 v 44 years). The homozygous individuals were predominantly women, most likely due to the effect of oral contraceptives. Because of the increased risk of thrombosis with age, the absolute risk becomes most pronounced in older patients, both for heterozygous and homozygous individuals. For the homozygous individuals, the absolute risk may become several percentage points per year. This implies that most individuals homozygous for factor V Leiden will experience at least one thrombotic event in their lifetime.

Download Full-text

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.

Download Full-text