vitamin-b-12 and Thromboembolism

Cerebral venous thrombosis (CVT) is a rare disease, occurring in 0.5%-1% of all patients with strokes. Systemic and hereditary diseases and traumas are potential causes of CVT. We report a case of CVT and systemic thromboembolism complicated with hyperhomocysteinemia and iron-deficiency anemia caused by autoimmune gastritis. A 47-year-old female patient was admitted to the emergency department due to difficulty in movement, impaired consciousness, and urinary incontinence. Brain computed tomography (CT) and magnetic resonance imaging (MRI) showed bilateral thalamic edema associated with venous sinus thrombosis and embolic cerebral infarction in the deep white matter of the bilateral cerebral hemispheres. In addition, contrast enhanced whole-trunk CT scan showed deep femoral thrombosis and pulmonary artery embolism. She had no medical history of diseases or drug use that may cause thrombosis. Blood test results revealed iron-deficiency anemia and hyperhomocysteinemia, which were determined to be the cause of systemic thromboembolism. The patient tested positive for intrinsic factor antibodies. Moreover, the patient was diagnosed with autoimmune gastritis by gastrointestinal endoscopy. Therapies including anticoagulant and replacement with iron and vitamin B12 were administered. The patient was discharged from the hospital without neurological deficits. A favorable clinical course was achieved with anticoagulant administration and replacement therapy with iron and vitamin B12 for cerebral arteriovenous embolism that developed due to autoimmune gastritis.

Topics: Anemia, Iron-Deficiency; Anticoagulants; Embolism; Female; Gastritis; Humans; Hyperhomocysteinemia; Intracranial Thrombosis; Iron; Middle Aged; Thromboembolism; Venous Thrombosis; Vitamin B 12

The recreatinal use of nitrous oxide has become more common in recent years, especially in adolescents and young adults. It has been mainly associated with medical conditions like megaloblastic anemia and (myelo)neuropathy. We report on the thromboembolic complications, a less known side effect, associated with recreational inhalation of nitrous oxide. An extensive literature search was performed for publications reporting on the thromboembolic complications associated with recreational nitrous oxide abuse. Data about sex, age, location of thrombosis, laboratory findings, therapy and outcome were collected. A total of 13 case reports or case series were identified comprising a total of 14 patients. The reported thromboembolic side effects included deep venous thrombosis, pulmonary embolism, mesenterial-, portal and splenic vein thrombosis, cerebral sinus thrombosis, cortical vein thrombosis, stroke, acute myocardial infarction and peripheral artery thromboembolism. These side effects are possibly mediated by the interaction of nitrous oxide with vitamin B12, a cofactor of the methionine synthase complex, which eventually results in elevation of plasma levels of homocysteine. Despite being a known risk factor for cardiovascular disease, the exact pathophysiological mechanism remains unclear. Cessation of nitrous oxide inhalation is necessary to prevent recurrent thrombosis. Nitrous oxide abuse may thus result in a wide spectrum of thromboembolic complications. One should be aware of this etiology, especially in a young person with no obvious risk factors for cardiovascular disease. Spreading awareness is important to inform people about the potentially serious side effects associated with nitrous oxide inhalation.

Topics: Adolescent; Humans; Nitrous Oxide; Risk Factors; Thromboembolism; Thrombosis; Vitamin B 12; Young Adult

Venous thrombosis is considered as a multicausal disease. Hyperhomocysteinemia is considered as one of the risk factors for venous thrombosis. Because homocysteine levels are strongly influenced by the intake and concentrations of B vitamins, it is worthwhile to assess the role of these vitamins as a risk factor for venous thrombosis.

Topics: Homocysteine; Humans; Hyperhomocysteinemia; Risk Factors; Thromboembolism; Venous Thrombosis; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B 6; Vitamin B 6 Deficiency; Vitamin B Deficiency

Homocysteine is a sulfur-containing amino acid intermediate involved in two metabolic pathways, in the remethylation to methionine and in the transsulfuration to cysteine. Severe hyperhomocysteinemia (> 100 mumol/l) is found in congenital homocystinuria. Moderate (15-30 mumol/l) or intermediate (> 30-100 mumol/l) hyperhomocysteinemia is caused by defects in genes encoding for enzymes of homocysteine metabolism or by inadequate intake of those vitamins that are involved in homocysteine metabolism (folic acid, cobalmin, and vitamin B6). Today, hyperhomocysteinemia should be considered an important risk factor for atherosclerotic vascular and venous thromboembolic diseases. Homocysteine-plasma levels above the 95th percentile were found to be associated with a 2 to 3-fold elevated relative risk for deep-vein thrombosis and pulmonary embolism. Moreover, mild hyperhomocysteinemia has been shown to be associated with a 2 to 4-fold increased relative risk for coronary artery disease, cerebrovascular disease, and peripheral arterial occlusive disease. Several mechanisms have been proposed by which hyperhomocysteinemia contributes to atherogenesis and thrombogenesis. Several studies have shown that hyperhomocysteinemia can be corrected by supplementation of folic acid, cobalamin and vitamin B6. Clinical trials are urgently needed which investigate the preventive effect of supplementation of these vitamins on thrombotic diseases.

Topics: Arteriosclerosis; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Pyridoxine; Risk Factors; Thromboembolism; Vitamin B 12

An elevated level of total homocysteine (tHcy) in blood, denoted hyperhomocysteinemia, is emerging as a prevalent and strong risk factor for atherosclerotic vascular disease in the coronary, cerebral, and peripheral vessels, and for arterial and venous thromboembolism. The basis for these conclusions is data from about 80 clinical and epidemiological studies including more than 10,000 patients. Elevated tHcy confers a graded risk with no threshold, is independent of but may enhance the effect of the conventional risk factors, and seems to be a particularly strong predictor of cardiovascular mortality. Hyperhomocysteinemia is attributed to commonly occurring genetic and acquired factors including deficiencies of folate and vitamin B12. Supplementation with B-vitamins, in particular with folic acid, is an efficient, safe, and inexpensive means to reduce an elevated tHcy level. Studies are now in progress to establish whether such therapy will reduce cardiovascular risk.

Topics: Arteriosclerosis; Cardiovascular Diseases; Coronary Artery Disease; Female; Folic Acid; Folic Acid Deficiency; Forecasting; Homocysteine; Humans; Intracranial Arteriosclerosis; Male; Peripheral Vascular Diseases; Prevalence; Risk Factors; Safety; Thromboembolism; Vitamin B 12; Vitamin B 12 Deficiency

Acute promyelocytic leukemia (APL) is characterized by proliferation of morphologically abnormal promyelocytes and a severe bleeding diathesis. The abnormal promyelocyte is characterized by abundant, large granules, many of which are spindle-shaped. Electron microscopic appearance of the granules closely resembles that of Auer rods. The granules appear to possess tissue thromboplastin activity by both immunologic and clotting assays. Coagulation studies in APL are generally consistent with disseminated intravascular coagulation. Prolongation of the prothrombin time and elevation of fibrinogen degradation products are the tests that are most commonly abnormal. Although occasional reports indicate a favorable response of the coagulopathy to drugs that inhibit fibrinolysis, the use of prophylactic heparin appears to be the treatment of choice. The response rate of APL to chemotherapy regimens that contain an anthracycline is comparable to that of acute myelogenous leukemia. The recent description of the 15;17 chromosomal translocation which may be pathognomonic for APL is only the second example of a chromosomal marker of human neoplasia. Marked elevation of serum vitamin B12 and B12 binding proteins appears to be another characteristic feature of APL. An in vitro cell line of APL cells has been demonstrated to have the capacity to differentiate to functional polymorphonuclear leukocytes, but the cause for the maturation arrest is unknown.

Topics: Blood Coagulation Disorders; Bone Marrow; Cell Line; Chromosome Banding; Daunorubicin; Fibrinogen; Fibrinolysis; Hemorrhage; Heparin; Humans; Leukemia, Myeloid, Acute; Prognosis; Prothrombin Time; Thromboembolism; Vitamin B 12

Topics: Age Factors; Animals; Blood Coagulation; Cerebrovascular Disorders; Chemical and Drug Induced Liver Injury; Contraceptives, Oral; Contraceptives, Oral, Hormonal; Coronary Disease; Folic Acid; Humans; Hypertension; Metabolism; Myocardial Infarction; Neoplasms; Progestins; Skin; Smoking; Teratogens; Thromboembolism; Time Factors; Vitamin B 12

Elevated total homocysteine levels are associated with a higher risk for venous thromboembolism. Whether decreasing homocysteine levels with vitamin therapy reduces the risk for venous thromboembolism is not known.. To determine whether decreasing homocysteine levels alters the risk for symptomatic venous thromboembolism.. Secondary analysis of data from the randomized, placebo-controlled Heart Outcomes Prevention Evaluation 2 (HOPE-2) trial.. 145 clinical centers in 13 countries.. 5522 persons 55 years of age or older with known cardiovascular disease or diabetes mellitus and at least 1 other risk factor for vascular disease.. A daily supplement of 2.5 mg of folic acid, 50 mg of vitamin B(6), and 1 mg of vitamin B(12) or matching placebo for 5 years.. Prospectively diagnosed and confirmed symptomatic deep venous thrombosis or pulmonary embolism.. The geometric mean homocysteine level decreased by 2.2 micromol/L in the vitamin therapy group and increased by 0.80 micromol/L in the placebo group. Venous thromboembolism occurred in 88 participants during a mean follow-up of 5 years. The incidence rate of venous thromboembolism was the same in the vitamin therapy group and the placebo group (0.35 per 100 person-years; hazard ratio, 1.01 [95% CI, 0.66 to 1.53]). Vitamin therapy did not reduce the risk for deep venous thrombosis (hazard ratio, 1.04 [CI, 0.63 to 1.72]), pulmonary embolism (hazard ratio, 1.14 [CI, 0.57 to 2.28]), or unprovoked venous thromboembolism (hazard ratio, 1.21 [CI, 0.66 to 2.23]).. The proportion of patients with a previous episode of venous thromboembolism at enrollment was not known, and venous thromboembolism events were not centrally adjudicated.. Decreasing homocysteine levels with folic acid and vitamins B6 and B12 did not reduce the risk for symptomatic venous thromboembolism.

Topics: Aged; Female; Folic Acid; Humans; Hyperhomocysteinemia; Incidence; Male; Middle Aged; Prospective Studies; Pulmonary Embolism; Risk Factors; Thromboembolism; Venous Thrombosis; Vitamin B 12; Vitamin B 6

To compare the levels of total homocysteine (tHcy), folate, vitamin B6 and B12, in women not using oral contraceptives (OC) vs. those using OC.. 219 healthy women were enrolled in the study; 159 of them had not been using OC for at least 12 months prior to their enrollment, while 60 were on regular OC treatment.. The median levels of vitamin B6 and B12 were significantly lower in OC users than in non-users (24.2 vs. 32.9 nmol/l, p=0.029; 278 vs. 429 ng/ml, p<0.001). There were no statistically significant differences in the levels of tHcy (fasting and post-methionine loading) and folate.. In our cross-sectional study, OC use was associated with low vitamin B6 and B12 levels. Since low vitamin B6 levels are independently associated with heightened risks for arterial and venous thromboembolism (TE), they could partly account for the increased TE risk of OC users.

Topics: Adult; Contraceptives, Oral; Female; Folic Acid; Homocysteine; Humans; Middle Aged; Risk Assessment; Thromboembolism; Vitamin B 12; Vitamin B 6

Topics: Adult; Aged; Choline; Clinical Trials as Topic; Drug Synergism; Female; Folic Acid; Heparin; Humans; Joint Diseases; Lipid Metabolism; Male; Middle Aged; Niacinamide; Thromboembolism; Vitamin B 12

To investigate serum levels of homocysteine (Hcys) and the risk that altered levels carry for thrombosis development in ulcerative colitis (UC) patients.. 55 UC patients and 45 healthy adults were included. Hcys, vitamin B12 and folic acid levels were measured in both groups. Clinical history and thromboembolic events were investigated.. The average Hcys level in the UC patients was 13.3 +/- 1.93 micromol/L (range 4.60-87) and was higher than the average Hcys level of the control group which was 11.2 +/- 3.58 micromol/L (range 4.00-20.8) (P < 0.001). Vitamin B12 and folic acid average values were also lower in the UC group (P < 0.001). When multivariate regression analysis was performed, it was seen that folic acid deficiency was the only risk factor for hyperhomocysteinemia. Frequencies of thromboembolic complications were not statistically significantly different in UC and control groups. When those with and without a thrombosis history in the UC group were compared according to Hcys levels, it was seen that there were no statistically significant differences. A negative linear relationship was found between folic acid levels and Hcys.. We could not find any correlations between Hcys levels and history of prior thromboembolic events.

Topics: Adult; Aged; Biomarkers; Case-Control Studies; Chi-Square Distribution; Colitis, Ulcerative; Female; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Hyperhomocysteinemia; Linear Models; Male; Middle Aged; Risk Assessment; Risk Factors; Thromboembolism; Up-Regulation; Vitamin B 12; Young Adult

Topics: Aged; Female; Folic Acid; Humans; Hyperhomocysteinemia; Incidence; Male; Middle Aged; Prospective Studies; Pulmonary Embolism; Risk Factors; Thromboembolism; Venous Thrombosis; Vitamin B 12; Vitamin B 6

Topics: Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Risk Factors; Thromboembolism; Vitamin B 12; Vitamin B 6

Hyperhomocysteinaemia is a well-known risk factor for venous thromboembolic disease (VTD). However, it is not clear whether homocysteine (Hc) itself or a related metabolite or a cofactor is primarily responsible for VTD. We carried out a case-control study to investigate whether vitamin concentrations that are involved in the Hc metabolism are associated or not with an elevated risk of VTD.. Case-control study.. We measured serum vitamin B12, folate, creatinine and albumin concentrations and plasma Hc concentrations in 101 consecutive patients with VTD, diagnosed by image tests and 101 control subjects, matched for age and sex.. Serum vitamin B12 concentrations were significantly lower in VTD patients than in the control subjects. There were no differences in plasma Hc or serum folate concentrations between the groups. Among the male subgroup aged more than 70 years, serum vitamin B12 concentrations were significantly lower (240.88 +/- 103.07 vs. 421.20 +/- 314.31 pmol L(-1); P = 0.03) and plasma Hc concentrations were significantly higher (13.1 +/- 4.18 vs. 10.56 +/- 3.06 micromol L(-1); P =0.04) in VTD patients than in the control group. On multivariate analysis, in patients aged more than 70 years, serum vitamin B12 concentrations were independently associated with VTD. Compared with the highest quartile of vitamin B12 (>512.6 pmol L(-1)) the odds ratio (OR) for VTD in the lowest quartile (<230.9 pmol L(-1)) was 3.8 (95% CI 1.44-10.18; P = 0.01). In the VTD group, lowest vitamin B12 concentrations (percentile 10 <152.8 pmol L(-1)) were associated with the factor V Leiden mutation (OR = 6.07, 95% CI 0.93-38.55; P = 0.04).. Measuring vitamin B12 concentrations in elderly males may help in identifying people at risk of venous thromboembolism in our population.

Topics: Age Factors; Aged; Biomarkers; Case-Control Studies; Creatinine; Female; Folic Acid; Homocysteine; Humans; Logistic Models; Male; Risk Assessment; Thromboembolism; Venous Thrombosis; Vitamin B 12; Vitamin B Deficiency

Hyperhomocysteinemia has been recently described in patients with inflammatory bowel disease (IBD), that could be related to the increased risk for thrombosis that exists in this disease. The aim of this study was the assessment of hyperhomocysteinemia in patients with IBD and its relation among vitamin B12 and folate levels, and methylenetetrahydrofolate reductase (MTHFR) 677C-->T and 1298A-->C mutations.. Fifty two consecutive patients with IBD were studied (29 women and 23 men); age: mean (standard deviation 41.7 [11.9] years) and 186 controls with no difference in age and gender. Hyperhomocysteinemia was considered as homocysteine levels higher than mean plus two standard deviations of the control group (> or = 13 micromol/l).. patients had an elevated prevalence of hyperhomocysteinemia (17.3 vs. 3.7%; p = 0.002) and lower folate (7.6 [4.1] vs. 8.9 [3.7] ng/ml; p = 0.01) and B12 vitamin levels (499 [287] vs. 603 [231] pg/ml; p = 0.003). Homocysteinemia was higher (14.3 [5.8] vs. 9.1 [3.9] micromol/l; p = 0.006) in 6 patients (11.5%) that had suffered thromboembolism. Frequency of MTHFR 677C-->T (13.5 vs. 11.3%; p = 0.66) and 1298A-->C (7.8 vs. 7.0%; p = 0.76) mutations was not increased in patients. Odds ratio (OR) for IBD in hyperhomocysteinemic patient was 5.51, 95% confidence interval (CI), 1.81-16.76; p = 0.002). Hyperhomocysteinemia was negatively associated with feminine gender (OR 0.08, 95% CI 0.01-0.49; p = 0.006) and folate levels (OR 0.04, 95%CI: 0.007-0.20; p < 0.001).. hyperhomocysteinemia is associated with IBD and low folate levels, and could be involved in development of thromboembolism. MTHFR 677C-->T and 1298A-->C mutations are not related with the disease.

Topics: Adult; Confidence Intervals; Data Interpretation, Statistical; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Inflammatory Bowel Diseases; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Mutation; Odds Ratio; Prevalence; Sex Factors; Thromboembolism; Vitamin B 12

Topics: Chronic Disease; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Methylenetetrahydrofolate Reductase (NADPH2); Polymorphism, Genetic; Thromboembolism; Vitamin B 12; Vitamin B 6

Thromboembolic disease is a major cause of morbidity and mortality in many countries. Our previous study found that Chinese subjects carried the same polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene as described in Western studies. The aim of the present study was to determine the influence of MTHFR polymorphism, B vitamins and other factors on plasma homocysteine (Hcy) levels and risk of thromboembolic disease in Chinese.. One hundred and six subjects were enrolled into the study. They were categorized into 4 groups: healthy individuals (n = 42); those with diabetes mellitus (n = 20); those with deep vein thrombosis (DVT) (n = 11); and those with coronary artery disease (CAD) (n = 33). Plasma levels of folic acid, vitamins B6 and B12, Hcy, and fasting blood sugar were measured; total cholesterol, triglycerides, complete blood count, and 677 C-->T mutation in MTHFR were determined.. Plasma Hcy was lowest in the healthy subjects, higher in diabetics, followed by patients with DVT, and highest in patients with CAD (p < 0.001, ANOVA). MTHFR C677T polymorphism was the common factor affecting plasma logHcy levels in all 4 groups of subjects. Triglycerides affected plasma logHcy in the CAD patients. For the 4 groups as a whole, MTHFR polymorphism, triglycerides, and vitamin B12 were the most significant factors influencing plasma Hcy.. We suggest that high plasma Hcy is an important risk factor for CAD. Other factors including MTHFR polymorphism, vitamin B12, triglycerides, total cholesterol, and gender might affect Hcy levels in different diseases and conditions.

Topics: Adult; Aged; Aged, 80 and over; Coronary Disease; Female; Folic Acid; Homocysteine; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Mutation; Polymorphism, Genetic; Risk Factors; Thromboembolism; Vitamin B 12; Vitamin B 6

We have assessed the relationship between homocysteine, its thiol metabolites, specific folate coenzymes, and vitamin B12 according to the two main functionally relevant genotype-genotype categories that maintain the balance between homocysteine transsulphuration to cysteine, and homocysteine remethylation via folate dependent methionine biosynthesis, namely 2756A-->G-MS/66A-->G-MSR and 677C-->T-MTHFR/1298A-->C-MTHFR. We examined 152 individuals who were being treated for either thromboembolic (TE) or non-thromboembolic (non-TE) events. Chi2 test for linear trend in odds ratio provides reasonable evidence for an altered risk of thromboembolism within the range of compound MS/MSR genotypes encountered (wt/wt-->recessive/recessive) (p< or =0.05), but not within the same range of MTHFR/MTHFR genotypes. Logistic regression analysis of the risk for a TE event gave OR=0.49 (95% CI, 0.26-0.92; p=0.026) for 2756A-->G-MS, OR=1.08 (95% CI, 0.65-1.78) for 66A-->G-MSR, OR=1.19 (95% CI, 0.69-2.06) for 677C-->T-MTHFR and OR=0.98 (95% CI, 0.52-1.85) for 1298A-->C-MTHFR. When genotypes were examined individually, one-way ANOVA showed only 677C-->T-MTHFR (p=0.005 [TE]) and 2756A-->G-MS (p=0.005 [non-TE] and p=0.0006 [all subjects]) influence homocysteine. One-way ANOVA also showed that MTHFR/MTHFR compound genotype significantly influences TE homocysteine distribution (p=0.044), but no other variable. In MS/MSR, homocysteine distribution is not significantly affected in TE subjects, but approaches significance in non-TE individuals (p=0.062). However, the increased power obtained when all subjects are analysed demonstrates a significant influence of MS/MSR upon homocysteine distribution (p=0.008). Other significant influences of MS/MSR were on total cellular 5-methyl-H4folate in non-TE subjects (p=0.042) and vitamin B12 in TE subjects (p=0.018). Given the central role of vitamin B12 in MS/MSR activity, 5-methyl-H4folate and homocysteine were also looked at by vitamin B12 quartile, independent of genotype: Vitamin B12 quartile significantly affected homocysteine distribution in TE (p=0.013) but not non-TE individuals, with no effect on 5-methyl-H4folate distributions. Similarly, the prevalence of clinical phenotypes (p=0.013) and of 'high risk' 2756A-->G-MS wildtypes (p=0.039) was associated with the disposition of homocysteine/B12 in TE but not non-TE subjects. Overall, results indicate compound MS/MSR genotype is associated with risk for a TE event. This may be related t

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Aged; Alleles; Data Interpretation, Statistical; Ferredoxin-NADP Reductase; Folic Acid; Folic Acid Deficiency; Genetic Predisposition to Disease; Genotype; Homocysteine; Humans; Nutritional Status; Point Mutation; Polymorphism, Single Nucleotide; Prevalence; Reverse Transcriptase Polymerase Chain Reaction; Thromboembolism; Vitamin B 12; Vitamin B 12 Deficiency

Thromboembolism is a significant cause of morbidity and mortality in patients with inflammatory bowel disease (IBD). Plasma total homocysteine (tHcy) is a risk factor for vascular disease and has been implicated as a mediator of thromboembolic events in adults with IBD. The authors studied the link between tHcy and IBD in children, in whom associations may be clearer, and investigated associations with plasma von Willebrand factor antigen, a marker of vascular damage.. This cross-sectional study included 43 patients with IBD (27 Crohn disease, 9 ulcerative colitis, and 7 indeterminate colitis) and 46 control subjects from a pediatric gastroenterology clinic. Plasma tHcy, plasma 5-methyl tetrahydrofolate, red cell folate, plasma vitamin B12, plasma von Willebrand factor antigen, and methylene tetrahydrofolate reductase (MTHFR) genotype (for the C677T mutation) were measured.. Plasma tHcy concentrations were higher in children with IBD than in control subjects, when corrected for age (P < 0.05), and plasma tHcy was negatively correlated with plasma 5 methyl tetrahydrofolate (P < 0.0005). Plasma 5 methyl tetrahydrofolate and age were the main predictors of plasma tHcy. Neither MTHFR genotype nor von Willebrand factor showed any association with any other measure, and there were no differences between children with IBD and control subjects.. Elevated plasma tHcy is a consequence of IBD in children, probably mediated by poor folate status associated with diet or the pathophysiology of the disease.

Topics: Adolescent; Aging; Child; Child, Preschool; Colitis, Ulcerative; Crohn Disease; Cross-Sectional Studies; Female; Folic Acid; Genotype; Homocysteine; Humans; Hyperhomocysteinemia; Inflammatory Bowel Diseases; Male; Methylenetetrahydrofolate Reductase (NADPH2); Reproducibility of Results; Risk Factors; Sensitivity and Specificity; Tetrahydrofolates; Thromboembolism; Vitamin B 12; von Willebrand Factor

Although hyperhomocysteinemia is an established risk factor for venous thromboembolism there is no consensus for routine determination of circulating homocysteine in the UK, either at the beginning or end of oral anticoagulation therapy. The purpose of this study was to evaluate the prevalence of hyperhomocysteinemia and its relationship to folate and vitamin B12 status in subjects with venous thromboembolism 4 weeks after discontinuation of warfarin therapy. In 78 consecutively recruited patients, plasma homocysteine was significantly higher (p < 0.001) and red cell folate significantly lower (p = 0.03) than in controls. Plasma vitamin B12 was similar in both groups. Strikingly, 38.5% of patients had hyperhomocysteinemia (> 15 micromol/l). Retrospective analysis revealed a significant positive association between plasma total homocysteine and duration of warfarin therapy (p < 0.001) but a negative, though non-significant (p = 0.06), trend with warfarin dose. The results do not suggest any direct interaction between warfarin and plasma homocysteine but raise the possibility of reduced intake of a common food source of folate and vitamin K. One possibility is the shortage of green-leafy vegetables since patients are often advised to limit their intake of this major source of vitamin K. On the basis of this study we suggest that homocysteine screening should be carried out at the time that patients begin warfarin therapy.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Female; Folic Acid; Genotype; Homocysteine; Humans; Hyperhomocysteinemia; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Retrospective Studies; Substance Withdrawal Syndrome; Thromboembolism; Vitamin B 12; Warfarin

Vitamin B12 dependent methionine synthase (MS) regulates de novo production of methionine from homocysteine (Hcy). Since moderate elevations in Hcy are considered vasculotoxic, we examined a common variant (A2756G-MS) of the gene coding for this enzyme as a risk for thromboembolism.. We investigated A2756G-MS and folate/thiol status in 51 individuals who had experienced a thromboembolic event (TE) and 95 subjects being treated for non-thromboembolic (NTE) vascular problems.. The prevalence of the mutant G allele was lower in TE subjects than in controls, indicating a protective role for this base substitution (OR 0.39; 95%CI 0.20-0.78; p=0.010). Consistent with an advantage conferred by this allele, heterozygotes had generally lower levels of Hcy and glutathione (GSH), and higher levels of B-vitamins than wildtypes. The OR for the wildtype having an increased risk for TE was 2.32 (95%CI 1.06-5.08). Additionally, as might be predicted, TE-wildtypes had elevated GSH levels compared to corresponding NTE-wildtypes (p=0.004) - a likely response to oxidative stress. NTE subjects showed a dramatic reduction in Hcy between wildtype and heterozygote (p=0.017), and again between recessive and heterozygote genotypes (p=0.002). The same pattern, although not significant, occurred in TE subjects. The similarity in Hcy between clinical groups for each genotype raises questions on the etiological role of Hcy in TE. The functional relationship between enzyme variant and its B12-cofactor may be of more interest, since the polymorphic site occurs near the B12-binding domain, and our results indicate wildtype-TE subjects have a much lower level of vitamin B12 than heterozygote-TE subjects (p=0.0019). This effect is attenuated in NTE subjects.. . A2756G-MS may protect against a thromboembolic event. The role of Hcy remains unclear.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Aged; Genetic Predisposition to Disease; Glutathione; Homocysteine; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Prevalence; Sulfhydryl Compounds; Thromboembolism; Vitamin B 12

Topics: Behcet Syndrome; Folic Acid; Genetic Predisposition to Disease; Genotype; Homocysteine; Humans; Methylenetetrahydrofolate Reductase (NADPH2); Oxidoreductases Acting on CH-NH Group Donors; Risk Factors; Thromboembolism; Vitamin B 12; Vitamin B 6

Thromboembolic diseases remain a major cause of morbidity and mortality in most countries. The present study was thus conducted to determine the influences of age, sex, the methylenetetrahydrofolate reductase (MTHFR) gene mutation and the B vitamins on the plasma homocysteine (Hcy) levels in the Chinese. Our previous study found that Chinese carry the same mutation of the methylenetetrahydrofolate reductase (MTHFR) gene described in Western populations, with a 677CAET substitution being another possible cause of thrombosis.. The study population comprised 445 consecutively enrolled Chinese subjects of different ages and sex. Overall 69 subjects were found to have homozygous 677CAET mutation of the MTHFR gene, and were classified as Group I; 164 subjects were found to have heterozygous mutation and classified as Group II; 212 had no such mutation and were classified as Group III.. The mean plasma Hcy did not differ significantly between these 3 groups. When each group was divided again by gender, we found that both age and plasma Hcy levels were significantly higher in the males than in the females. In addition to Hcy levels, we also measured plasma vitamin B(12) and folate levels in 258 randomized subjects. Univariate and multivariate analysis showed MTHFR mutation could affect Hcy level, and univariate and multivariate analysis showed that age, MTHFR mutation and vitamin B(12) could affect the log(Hcy) levels.. We demonstrate that some Chinese carry the 677CAET mutation of the methylenetetrahydrofolate reductase gene. This could affect their homocysteine levels and thus be a risk factor for thromboembolic disease.

Topics: Age Factors; Aged; China; Female; Folic Acid; Genetic Predisposition to Disease; Homocysteine; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Mutation; Oxidoreductases Acting on CH-NH Group Donors; Sex Factors; Thromboembolism; Vitamin B 12

The risk for thrombotic events is increased in inflammatory bowel disease. The factors responsible for such a risk are poorly defined. Recently, an elevated homocysteine level is emerging as a risk factor for thrombosis. The aim of this study was to determine the levels of homocysteine in a well-characterized population of patients with Crohn's disease and to compare it to controls.. The levels of homocysteine were determined in 105 well-characterized patients with Crohn's disease and 106 controls. The levels of folate and B12, which are involved in the metabolism of homocysteine were determined as well. Patients were treated with steroid preparations only.. Homocysteine levels were significantly elevated in the patient population. Elevated levels were correlated with both low B12 and folate levels, but folate deficiency turned out to be a more important factor. Low B12 levels were in correlation with the involvement of the terminal ileum. No correlation was found between homocysteine levels and either disease activity or involvement of the terminal ileum.. Homocysteine levels are increased in patients with Crohn's disease and this finding is inversely correlated with folate levels. Supplementation of folate to patients with Crohn's disease may be warranted.

Topics: Adult; Aged; Anti-Inflammatory Agents; Budesonide; Case-Control Studies; Crohn Disease; Female; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Male; Middle Aged; Prednisone; Risk Factors; Thromboembolism; Time Factors; Vitamin B 12

Severe hyperhomocysteinemia due to inborn errors of methionine metabolism results in precocious development of arteriosclerosis and predisposition to venous and arterial thromboembolism. Although the findings of several studies have indicated that mild hyperhomocysteinemia is common in occlusive arterial disease, no similar studies have been made on venous thromboembolism. In this study of subjects under 50 years of age, we found no significant differences in the plasma homocysteine concentrations, either in the fasting state or after methionine loading, between 42 patients with venous thromboembolism and 42 healthy controls. Nonetheless, male patients manifested a tendency toward higher homocysteine concentrations than male controls; 6 patients (14%) versus 2 controls (5%) responded abnormally to methionine loading which might indicate heterozygosity for cystathionine synthase deficiency. Thus, further studies on plasma homocysteine in venous thromboembolism are warranted.

Topics: Adult; Creatinine; Cystathionine beta-Synthase; Fasting; Female; Folic Acid; Genetic Carrier Screening; Genotype; Homocysteine; Homocystinuria; Humans; Male; Methionine; Thromboembolism; Vitamin B 12