International Journal of Hematology

, Volume 93, Issue 4, pp 458–464 | Cite as

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

  • Angel F. RemachaEmail author
  • Joan Carles Souto
  • José Luis Piñana
  • María Pilar Sardà
  • Josep Maria Queraltó
  • Joan Martí-Fabregas
  • Xavier García-Moll
  • Cristina Férnandez
  • Alvaro Rodriguez
  • Jorge Cuesta
Original Article


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.


Vitamin B12 Homocysteine Thrombosis Methylmalonic acid 


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Copyright information

© The Japanese Society of Hematology 2011

Authors and Affiliations

  • Angel F. Remacha
    • 1
    Email author
  • Joan Carles Souto
    • 2
  • José Luis Piñana
    • 2
  • María Pilar Sardà
    • 2
  • Josep Maria Queraltó
    • 3
  • Joan Martí-Fabregas
    • 4
  • Xavier García-Moll
    • 5
  • Cristina Férnandez
    • 1
  • Alvaro Rodriguez
    • 1
  • Jorge Cuesta
    • 1
  1. 1.Department of HematologyComplejo Hospitalario Toledo, Hospital Virgen de la SaludToledoSpain
  2. 2.Department of HematologyHospital de Sant PauBarcelonaSpain
  3. 3.Department of BiochemistryHospital de Sant PauBarcelonaSpain
  4. 4.Department of NeurologyHospital de Sant PauBarcelonaSpain
  5. 5.Department of CardiologyHospital de Sant PauBarcelonaSpain

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