Department of Hematology, Complejo Hospitalario Toledo, Hospital Virgen de la Salud, Avenida Barber 30, 45004, Toledo, Spain.
Department of Hematology, Hospital de Sant Pau, Barcelona, Spain.
Int J Hematol. 2011 Apr;93(4):458-464. doi: 10.1007/s12185-011-0825-8. Epub 2011 Apr 8.
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.
本研究旨在通过 326 例血栓形成患者（病例组）和同一家医院的 351 例患者的病例对照研究，评估血栓形成、高同型半胱氨酸血症和维生素 B12 缺乏之间的关系。除了经典的危险因素外，还评估了许多血液学变量，包括血清维生素 B12（B12）、红细胞叶酸（RCF）和血清同型半胱氨酸（Hcy）。还进行了血清甲基丙二酸（MMA）评估和临床研究，以研究 B12 病理学。单变量分析结果表明，血栓形成患者的 B12 水平降低（Student's t 检验，p<0.0001）。在 17.2%、8.6%和 2.2%的血栓栓塞患者中发现维生素 B12 低于 200 pmol/l（LB200）或低于 150 pmol/l（LB150），红细胞叶酸低于 600 nmol/l。在 86 例血栓形成患者中检测到 Hcy 升高（26.3%）。在高同型半胱氨酸血症和血栓形成患者中，80%的患者存在维生素 B12 和/或肾功能异常。MMA 增加表明，在这些血清维生素 B12 水平较低的患者中存在维生素 B12 缺乏，并且 MMA 水平与 Hcy 水平一致。临床研究表明，在大多数 LB200 患者中存在 B12 吸收不良。多变量分析表明，血清维生素 B12（RR 0.998，CI 0.997-0.999）与血栓栓塞中度相关。结果表明，维生素 B12 缺乏在高同型半胱氨酸血症和血栓形成患者中很常见。此外，在大多数血栓形成患者中，高同型半胱氨酸血症是由维生素 B12 缺乏和/或慢性肾衰竭引起的。由于维生素 B12 缺乏的主要原因是维生素吸收不良，因此应给予维生素 B12 或联合叶酸进行治疗。然而，一些病例报告表明，这种治疗方法是否可以预防维生素 B12 缺乏和血栓形成患者的复发性血栓形成，仍有待证实。
