vitamin-b-12 and Venous-Thromboembolism

Hyperhomocysteinemia, considered "the cholesterol of nineties", is an established risk factor for cardiovascular diseases and premature atherosclerosis. Hyperhomocysteinemia is due to genetic and acquired factors (unhealthy lifestyle with poor diet in folate and vitamin B, elderly, renal impairment, thyroid diseases, malignancies). More recently, hyperhomocysteinemia was associated with venous thrombosis. Several studies found a correlation with a usual site of thrombosis (central retinal vein, mesenterical level, cerebral veins, Budd-Chiari syndrome). Other studies showed the association between hyperhomocysteinemia and recurrent venous thrombosis. This condition is of high interest because homocysteine may represent a potentially reversible cause of thrombophilia. Although methylenetetrahydrofolate reductase (MTHFR) C677T genotype and deficits of folic acid, vitamin B12 lead to hyperhomocysteinemia, in cases with a thrombotic event the correlations between homocysteine level and folic acid as well as between homocysteinemia and vitamin B12 were found to be weak and no significant correlation between homocysteinemia and MTHFR was identified. Recently, some authors reported an independent association between low levels of folic acid or vitamin B12 and venous thrombosis. Regarding the MTHFR genotype, the risk for venous thrombosis is increased only in patients with factor V Leiden. A recent meta-analysis of 24 retrospective and 3 prospective studies published in electronic literature showed that a 5 micromol/L higher homocysteine level was associated with a 27% (95% CI: 1-59) higher risk of venous thrombosis in prospective studies and a 60% (95% CI: 10-134) higher risk in retrospective studies. A meta-analysis of the short-term trials of therapy with folic acid showed a reduction of 25% of homocysteinemia and a further reduction of 7% when vitamin B12 was associated. This situation may be associated with a 10% to 20% decreased risk of venous thrombosis. Further trials are required to estimate if this is worthwhile from the clinical point of view. In medical practice the measurement of homocysteinemia may be indicated in unexplained idiopathic venous thrombosis, or recurrent episodes or venous thrombosis occurred at an early age or at an uncommon site.

Topics: Folic Acid; Folic Acid Deficiency; Humans; Hyperhomocysteinemia; Risk Factors; Venous Thromboembolism; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins

A 27-year-old man presented with altered mental status and unilateral right lower limb swelling. Brain imaging and cerebrospinal fluid analysis were unremarkable. He reported history of nitrous oxide misuse after he recovered from his delirium. The diagnosis of drug induced psychosis was made. The right lower limb swelling was found to be due to extensive deep vein thrombosis. In another case, a 21-year-old woman presented with headache, vomiting and dipoplia. Brain imaging showed extensive cerebral venous sinus thrombosis. She also misused nitrous oxide. Both cases had low-normal vitamin B12 and elevated methylmalonic acid, consistent with nitrous oxide misuse. The woman was found to have elevated homocysteine because of functional vitamin B12 deficiency. Homocysteine was not measured in the man. Raised homocysteine is associated with increased thrombosis risk. Fourteen cases of nitrous oxide misuse associated arterial and venous thrombosis have been reported. These two cases highlighted the importance of inquiring about recreational drug use in young patients who presented with apparently unprovoked venous thromboembolism.

Topics: Adult; Female; Humans; Male; Nitrous Oxide; Substance-Related Disorders; Venous Thromboembolism; Venous Thrombosis; Vitamin B 12; Vitamin B 12 Deficiency; Young Adult

Both venous thromboembolism (VTE) and high plasma vitamin B12 levels (cobalamin, Cbl) are markers of occult cancer and aggressive cancer with a poor prognosis. In this population-based cohort study, we assessed VTE risk among cancer patients with high plasma Cbl levels.. We used Danish health registries to identify a Cb1 cohort of 25,310 cancer patients with a plasma Cbl measurement prior to cancer diagnosis. The cohort was subdivided according to Cbl levels (pmol/L): 200-600 (population reference range), 601-800 and >800. All VTE events were considered provoked and categorised as either cancer-associated if no other provoking factors were present before VTE or provoked by other risk factors (surgery, trauma, or pregnancy). We calculated cumulative incidence proportions and adjusted hazard ratios computed from Cox regression analysis (reference: plasma Cbl of 200-600pmol/L) for the risk of VTE before and after the cancer diagnosis date (index date).. The risk of cancer-associated VTE 30days after index date increased with higher Cbl levels. The cumulative incidence (95% CI) by Cbl levels was: 200-600pmol/L: 0.24 (0.18-0.31); 601-800pmol/L: 0.63 (0.34-1.09); >800pmol/L: 0.86 (0.49-1.40). Adjusted hazard ratios (95% CI) were: 601-800 vs. 200-600: 2.55 (1.32-4.92); >800 vs. 200-600: 2.36 (1.19-4.71). We found similar results for VTE provoked by other risk factors and for VTE occurring before index date, but scarcity of events produced uncertain risk estimates.. We demonstrated an association between high plasma Cbl levels and risk of VTE in cancer patients. Any clinical implications warrant further study.

Topics: Aged; Cohort Studies; Female; Humans; Neoplasms; Risk Factors; Venous Thromboembolism; Vitamin B 12

Hyperhomocysteinemia has been suspected of favoring thrombosis. Several case-control studies and even a meta-analysis have confirmed a link between venous thrombosis and hyperhomocysteinemia. Homocysteine is due to genetic and acquired factors (poor diet in folate and vitamin B12, older age, renal impairment, thyroid diseases, and malignancies) induced by the intake and the concentrations of vitamin B9 or B12 in the majority of cases.. We report the cases of four Moroccan patients who presented with acute vein thrombosis of different sites: a 34-year-old man, a 60-year-old man, a 58-year-old man, and a 47-year-old woman. All patients had a low level of cobalamin with marked hyperhomocysteinemia with normal serum and red cell folic acid. Venous thrombosis revealed pernicious anemia in all patients. Their low levels of cobalamin, atrophic gastritis, and positive results for gastric parietal cell antibodies confirmed the diagnosis of pernicious anemia. There was no evidence of immobilization, recent surgery, malignancy, antiphospholipid antibody, myeloproliferative disorder, or hormone replacement therapy. No deficiencies in protein C and protein S were detected; they had normal antithrombin III function and factor V Leiden; no prothrombin gene mutations were detected. Treatment included orally administered anticoagulation therapy and cobalamin supplementation. The outcome was favorable in all cases.. These reports demonstrate that pernicious anemia, on its own, can lead to hyperhomocysteinemia that is significant enough to lead to thrombosis. Understanding the molecular pathogenesis of the development of thrombosis in patients with hyperhomocysteinemia related to Biermer disease would help us to identify patients at risk and to treat them accordingly. The literature concerning the relationship between homocysteine and venous thrombosis is briefly reviewed.

Topics: Adult; Anemia, Pernicious; Antibodies; Anticoagulants; Female; Folic Acid; Humans; Hyperhomocysteinemia; Male; Middle Aged; Parietal Cells, Gastric; Treatment Outcome; Venous Thromboembolism; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins

Topics: Adult; Anticoagulants; Blood Coagulation; Gastrectomy; Humans; Hyperhomocysteinemia; Male; Obesity, Morbid; Recurrence; Thrombophilia; Treatment Outcome; Venous Thromboembolism; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins

Topics: Female; Humans; Male; Orthopedic Procedures; Venous Thromboembolism; Vitamin B 12

Elevated vitamin B12 serum levels are associated with systemic inflammation and mortality. Since venous thromboembolism (VTE) is associated with systemic inflammation and mortality as well, we have hypothesized that it is also associated with elevated vitamin B12 serum levels in elderly patients following major orthopedic surgery of the lower limb.. This is a retrospective study. Medical charts of consecutive elderly (≥65 years) patients admitted for rehabilitation following major orthopedic surgery of the lower limb during 2007-2009 were reviewed. The study group included symptomatic VTE patients. The control group included patients in whom VTE was excluded. Demographics, co-morbidities, VTE risk factors, vitamin B12 serum levels, and 1-year mortality were studied.. The cohort included 197 elderly patients (median age: 82 years): 140 (71.1%) women and 57 (28.9%) men. Overall, 20 (10.2%) patients had VTE (study group) and in 177 (89.8%) patients VTE was excluded (control group). Vitamin B12 serum levels were higher in the study group compared with the control group (median: 634 vs. 409 pg/dL, p=0.024). The incidence of elevated vitamin B12 serum levels (≥500 pg/dL) was higher in the study group compared with the control group (odds ratio 3.1, p=0.031). Elevated vitamin B12 serum levels were associated with VTE (odds ratio 5.3, p=0.011) and with 1-year mortality (odds ratio 6.6, p=0.015) independent of demographics, co-morbidities, and VTE risk factors.. Symptomatic VTE is associated with elevated vitamin B12 serum levels in elderly patients following major orthopedic surgery of the lower limb.

Topics: Aged; Aged, 80 and over; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Case-Control Studies; Comorbidity; Female; Hemiarthroplasty; Hip Fractures; Humans; Male; Odds Ratio; Orthopedic Procedures; Orthopedics; Postoperative Complications; Retrospective Studies; Venous Thromboembolism; Vitamin B 12