Enhanced risk of thrombotic disease in patients with acquired vitamin B₁₂ and/or folate deficiency: role of hyperhomocysteinemia

Abstract.

A number of studies have identified elevated levels of homocysteine (Hcy) as a risk factor for thrombosis. Given the relationship between Hcy and thrombosis, a high prevalence of thrombosis would be expected in patients with megaloblastic anemia. The aim of our study was to determine whether an acquired vitamin B₁₂/folate deficiency is a risk factor for thrombosis. A retrospective case and control study was performed that included 193 cases with reduced levels of vitamin B₁₂/folate. The cases were divided initially into two groups (105 with serum vitamin B₁₂ ≤150 pmol/l and/or low red cell folate ≤450 nmol/l and 88 with serum vitamin B₁₂ between 150 and 200 pmol/l and/or red cell folate between 450 and 590 nmol/l). The control group consisted of 87 additional patients who had normal levels of serum vitamin B₁₂, red cell folate, and normal renal function. Serum Hcy, thrombotic events, and risk factors were evaluated in all participants. Eight patients (9%) in the control group had had previous vascular events although only three of these events (37.5%) were observed between the vitamin study and 2 years prior to the study. In the case group, 20% of the patients had a history of thrombosis. In contrast with controls, 85% of cases suffered thrombosis between the time they were diagnosed and 2 years prior to the time they were diagnosed as showing a vitamin deficiency. Multivariate analysis demonstrated that vitamin deficiency was a significant risk factor for arterial thrombosis [adjusted odds ratio (OR) 3.3, confidence interval (CI) 1.1–10.2]. However, when hyperhomocysteinemia was included in the analysis, vitamin deficiency was no longer a risk factor, suggesting that hyperhomocysteinemia was responsible for arterial thrombotic risk in these patients (adjusted OR 2.5, CI 1.1–5.8). As a consequence of hyperhomocysteinemia, patients with acquired vitamin deficiency of vitamin B₁₂/folate had a high risk of thrombosis. However, a more extensive study that controls risk variables and genetic factors is needed to sort out the various contributing factors.