Vitamin B12 deficiency, hyperhomocysteinemia and thrombosis: a case and control study

Abstract

This study aimed at assessing the relationship between thrombosis, hyperhomocysteinemia and vitamin B12 deficiency using a case-control study carried out in 326 patients with thrombosis (case group) and 351 patients from the same hospital (control group). Apart from the classic risk factors, a number of hematological variables were evaluated, including serum vitamin B12 (B12), red cell folate (RCF), and serum homocysteine (Hcy). An evaluation of serum methylmalonic acid (MMA) and a clinical study were carried out to investigate B12 pathology. Results of univariate analysis demonstrated decreased B12 levels in thrombosis (Student's t test, p < 0.0001). Vitamin B12 below 200 pmol/l (LB200) or below 150 pmol/l (LB150), and red cell folate below 600 nmol/l were found in 17.2, 8.6, and 2.2% of cases with thromboembolism, respectively. An increase in Hcy was detected in 86 cases with thrombosis (26.3%). An abnormality in vitamin B12 and/or renal function was found in 80% of cases with hyperHcy and thrombosis. The MMA increase demonstrated that vitamin B12 deficiency was present in these patients with low levels of vitamin B12 in serum, and the MMA levels were in concordance with Hcy levels. The clinical study revealed B12 malabsorption in most cases with LB200. Multivariate analysis showed that serum vitamin B12 (RR 0.998, CI 0.997-0.999) was moderately related to thromboembolism. The results indicated that vitamin B12 deficiency was common among patients with hyperhomocysteinemia and thrombosis. Moreover, HyperHcy was caused by vitamin B12 deficiency and/or chronic renal failure in most patients with thrombosis. As the main cause of vitamin B12 deficiency was vitamin malabsorption, parenteral vitamin B12 with or without folic acid should be administered for the treatment of this condition. However, it remains to be demonstrated whether this treatment approach prevents recurrent thromboses in patients with vitamin B12 deficiency and thrombosis, as suggested by some case reports.

B12 deficiency in chronic kidney disease: early recognition matters

“…7 As expected, patients with thrombosis showed a significantly increased proportion of hyperhomocysteinaemia and low B12 levels. 7 Another interesting element of our case presentation is the slightly increased haematocrit, detected in a nonsmoker with chronic kidney disease and without evidence of hypoxia. Due to persistently increased haematocrit during and after his hospitalisation, further testing was performed.…”

Genomic and Metabolic Responses to Methionine-Restricted and Methionine-Restricted, Cysteine-Supplemented Diets in Fischer 344 Rat Inguinal Adipose Tissue, Liver and Quadriceps Muscle

“…Metabolomic analysis showed that, compared to CF rats, MR rats had significantly lower levels of 5MeTHF and pyridoxal (vitamin B6). These are important co-factors in the conversion of homocysteine to methionine and cystathionine, and deficiencies of these two molecules are well documented to increase plasma homocysteine levels [56,57,58]. Because supplementation of the MR diet with cysteine restored homocysteine to control levels and increased levels of 5MeTHF and vitamin B6 but not of CBS protein in the liver, it could be argued that the changes in the bioavailability of these co-factors are contributing significantly to the hyperhomocysteinemic phenotype of MR rats as proposed by Gürdöl [59].…”

DTI Correlates of Cognition in Conventional MRI of Normal-Appearing Brain in Patients with Clinical Features of Subacute Combined Degeneration and Biochemically Proven Vitamin B12 Deficiency

“…The diagnosis of vitamin B 12 deficiency was based on low serum vitamin B 12 levels (Ͻ200 pg/mL). 17 The serum homocysteine level was measured by an enzymatic method. 18 Routine hematologic examinations that included hemoglobin levels and red cell mean corpuscular volume were also performed.…”